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Learning points Immunoglobulin G4-related disease (IgG4-RD) of the aortic valve may cause aortic regurgitation and heart block. Steroid therapy is effective for regression of the lesion, but can exacerbate aortic regurgitation and cause heart failure. Regardless of whether serum IgG4 level normalizes, sustained increases in inflammatory markers during medication therapy for IgG4-RD may indicate the development of new lesions. Introduction Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized systemic disease characterized by the presence of numerous immunoglobulin G4 (IgG4)-positive plasma cells in lymphoplasmacytic infiltrates and fibrosclerotic tissue.1 IgG4-RD is described in almost every organ system, but rarely the aortic valve. There are only a few reports of IgG4-RD of the aortic valve, which was always associated with aortic stenosis.2,3 We report a patient with an IgG4-related aortic valve lesion that resulted in severe aortic regurgitation, a tumorous lesion in the left ventricular outflow tract (LVOT), and complete atrioventricular block. To our knowledge, this is the first report of a patient with IgG4-RD that developed mixed aortic valve disease with a prevalence of regurgitation and initially received conservative treatment with steroids before surgery. Timeline

We report a patient with an IgG4-related aortic valve lesion that resulted in severe aortic regurgitation, a tumorous lesion in the left ventricular outflow tract (LVOT), and complete atrioventricular block. To our knowledge, this is the first report of a patient with IgG4-RD that developed mixed aortic valve disease with a prevalence of regurgitation and initially received conservative treatment with steroids before surgery. Timeline Day Events 1 Patient presented with general malaise, shortness of breath, and bradycardia 1 year after the initiation of steroid (prednisolone 10 mg/day) administration under suspicion of immunoglobulin G4-related disease Thickened aortic valve with severe aortic regurgitation and complete atrioventricular block was revealed 8 Clinical diagnosis of IgG4-related aortic valve lesion High-dose steroid (methylprednisolone 1 g/day) therapy initiated for 3 days 11 Oral prednisolone dose increased to 30 mg/day 40 Oral prednisolone dose decreased to 25 mg/day 90 Administration of azathioprine (50 mg/day) initiated 100 Heart failure exacerbated due to worsening aortic regurgitation 125 Surgical aortic valve replacement performed Pathological diagnosis of IgG4-related aortic valve lesion Case presentation A 62-year-old man with diabetes presented with general malaise, shortness of breath, and bradycardia. His medical history included retroperitoneal fibrosis, enlargement of the pancreas, and symmetrical swelling of the lacrimal glands with elevated serum IgG4 levels (175 mg/dL). He had received steroid therapy for 1 year for suspected IgG4-RD.

iabetes presented with general malaise, shortness of breath, and bradycardia. His medical history included retroperitoneal fibrosis, enlargement of the pancreas, and symmetrical swelling of the lacrimal glands with elevated serum IgG4 levels (175 mg/dL). He had received steroid therapy for 1 year for suspected IgG4-RD. A physical examination revealed a blood pressure of 90/42 mmHg, a pulse rate of 42 b.p.m., and body temperature of 36.6°C. An early diastolic murmur was noted on auscultation. The laboratory test results revealed elevated levels of white blood cells (WBC, 17 800/mm3), C-reactive protein (CRP, 4.07 mg/dL), and erythrocyte sedimentation rate (ESR, >120 mm) in the first hour. The serum IgG4 level was within the normal range (101 mg/dL) under oral prednisolone treatment (10 mg/day). An electrocardiogram revealed a complete atrioventricular block. A chest radiograph showed a normal cardiac silhouette and clear lung fields. Although echocardiography revealed a normal aortic valve 1 year ago, a transthoracic and transoesophageal echocardiography now revealed a thickened tricuspid aortic valve and the LVOT wall with severe aortic regurgitation, but no evidence of aortic stenosis and LVOT obstruction (Figure 1). The left ventricular (LV) systolic function was preserved, without wall motion abnormalities, and the LV end-diastolic diameter was slightly increased (Table 1). A contrast-enhanced computed tomography (CT) of the chest showed a thickened aortic valve extending to the LVOT wall and normal thickness of the ascending aortic wall (Figure 2A). A cardiovascular magnetic resonance (CMR) revealed a high-intensity signal around the aortic valve in the late gadolinium enhancement, whereas there was no significant change in the myocardium, the ascending aortic wall, and the surrounding structures. Table 1 Time courses of echocardiographic parameters

l (Figure 2A). A cardiovascular magnetic resonance (CMR) revealed a high-intensity signal around the aortic valve in the late gadolinium enhancement, whereas there was no significant change in the myocardium, the ascending aortic wall, and the surrounding structures. Table 1 Time courses of echocardiographic parameters Variables Initial diagnosis Preoperative LVEF (%) 70 59 LVEDD (mm) 55 65 LVESD (mm) 33 44 LVOT diameter (mm) 23.1 23.9 AR jet width (%) 86 100 HDFR in descending aorta Consistent Consistent AV peak velocity (m/s) 1.7 2.3 AV mean gradient (mmHg) 6 11 AR, aortic regurgitation; AV, aortic valve; LVEDD, left ventricular end-diastolic diameter; HDFR, holodiastolic flow reversal; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic diameter; LVOT, left ventricular outflow tract. Figure 1 Transoesophageal echocardiography showing the thickened aortic valve with severe aortic regurgitation (A, aortic valve long-axis; B, aortic valve short-axis). Figure 2 (A) Contrast-enhanced computed tomography at initial diagnosis showing the thickened aortic valve extending to the left ventricular outflow tract wall. (B) The preoperative contrast-enhanced computed tomography showing regression of the thickened aortic valve and left ventricular outflow tract wall.

Figure 1 Transoesophageal echocardiography showing the thickened aortic valve with severe aortic regurgitation (A, aortic valve long-axis; B, aortic valve short-axis). Figure 2 (A) Contrast-enhanced computed tomography at initial diagnosis showing the thickened aortic valve extending to the left ventricular outflow tract wall. (B) The preoperative contrast-enhanced computed tomography showing regression of the thickened aortic valve and left ventricular outflow tract wall. We increased the oral prednisolone to 30 mg/day after three days (1 g/day) of high-dose methylprednisolone for clinically suspected IgG4-RD of the aortic valve. The complete atrioventricular block improved to a first-degree atrioventricular block within a few days. Thus, he avoided permanent pacemaker implantation. He received an angiotensin receptor blocker (olmesartan 10 mg/day) and a long-acting loop diuretic (azosemide 60 mg/day) as a medical therapy for aortic regurgitation-related heart failure. The inflammatory markers CRP and ESR gradually returned to within the normal range, and his serum IgG4 level decreased further (56.3 mg/dL). A follow-up echocardiography demonstrated a slight regression of the thickened aortic valve and the LVOT wall. We thus decreased the oral prednisolone to 25 mg/day after 1 month of administration and initiated azathioprine (50 mg/day).4 A follow-up contrast-enhanced CT showed regression of the thickened aortic valve and the LVOT wall (Figure 2B).

demonstrated a slight regression of the thickened aortic valve and the LVOT wall. We thus decreased the oral prednisolone to 25 mg/day after 1 month of administration and initiated azathioprine (50 mg/day).4 A follow-up contrast-enhanced CT showed regression of the thickened aortic valve and the LVOT wall (Figure 2B). Nevertheless, he presented with worsening shortness of breath and malaise three months after increasing the corticosteroid dose. Plasma brain natriuretic peptide increased from 69 pg/mL to 414 pg/mL, whereas the serum IgG4 level decreased to 27.6 mg/dL. The chest radiograph showed pulmonary congestion and cardiomegaly. The transthoracic echocardiography revealed the progression of aortic regurgitation and an enlarged LV dimension, whereas the aortic valve and LVOT wall thickening regressed. The LV systolic function was preserved, with no evidence of significant aortic stenosis and no LV wall motion abnormalities (Table 1).

diomegaly. The transthoracic echocardiography revealed the progression of aortic regurgitation and an enlarged LV dimension, whereas the aortic valve and LVOT wall thickening regressed. The LV systolic function was preserved, with no evidence of significant aortic stenosis and no LV wall motion abnormalities (Table 1). He underwent aortic valve replacement for severe symptomatic aortic regurgitation and heart failure deterioration. The patient received a bioprosthetic aortic valve (25-mm Carpentier-Edwards PERIMOUNT; Edwards Lifesciences, Irvine, CA, USA), as we were concerned about the risk of anticoagulation-related bleeding and the possibility that there could be problems further down the line with complications from multiple organs and ongoing anticoagulation. During the operation, we observed the thickening and shortening of the tricuspid aortic valve (Figure 3). The entire LVOT wall was also thickened. In contrast, the ascending aorta was normal. The pathological examination of the excised valve leaflets showed a dense lymphoplasmacytic infiltrate mixed with fibrotic tissue. The immunohistochemical staining revealed a ratio of IgG4-positive plasma cells to IgG-positive plasma cells greater than 0.5 (Figure 4). Thus, he was diagnosed with IgG4-RD of the aortic valve. Figure 3 The excised aortic valve leaflets were shortened, with a maximum thickness of 8.0 mm. Figure 4 Immunostaining for (A) immunoglobulin G-positive plasma cells and (B) immunoglobulin G4-positive plasma cells (A, B: original magnification ×400).

He underwent aortic valve replacement for severe symptomatic aortic regurgitation and heart failure deterioration. The patient received a bioprosthetic aortic valve (25-mm Carpentier-Edwards PERIMOUNT; Edwards Lifesciences, Irvine, CA, USA), as we were concerned about the risk of anticoagulation-related bleeding and the possibility that there could be problems further down the line with complications from multiple organs and ongoing anticoagulation. During the operation, we observed the thickening and shortening of the tricuspid aortic valve (Figure 3). The entire LVOT wall was also thickened. In contrast, the ascending aorta was normal. The pathological examination of the excised valve leaflets showed a dense lymphoplasmacytic infiltrate mixed with fibrotic tissue. The immunohistochemical staining revealed a ratio of IgG4-positive plasma cells to IgG-positive plasma cells greater than 0.5 (Figure 4). Thus, he was diagnosed with IgG4-RD of the aortic valve. Figure 3 The excised aortic valve leaflets were shortened, with a maximum thickness of 8.0 mm. Figure 4 Immunostaining for (A) immunoglobulin G-positive plasma cells and (B) immunoglobulin G4-positive plasma cells (A, B: original magnification ×400). The dose of prednisolone was tapered by 2.5 mg every 2 months in combination with azathioprine 50 mg after surgery. The transthoracic echocardiography 1 year after the surgery showed regression of the LV dilatation and normal function of the prosthetic valve.

Figure 4 Immunostaining for (A) immunoglobulin G-positive plasma cells and (B) immunoglobulin G4-positive plasma cells (A, B: original magnification ×400). The dose of prednisolone was tapered by 2.5 mg every 2 months in combination with azathioprine 50 mg after surgery. The transthoracic echocardiography 1 year after the surgery showed regression of the LV dilatation and normal function of the prosthetic valve. Discussion IgG4-RD is a newly recognized systemic disease characterized by tumefactive lesions containing lymphoplasmacytic infiltrate and sclerosis, rich in IgG4-positive plasma cells.1 IgG4-RD was initially reported in 2001 in sclerosing pancreatitis associated with increased levels of serum IgG4.5 Since this original description, IgG4-RD has been described in various organs such as the biliary tree, salivary glands, kidneys, lungs, aorta, and others.6 Cardiovascular involvement may manifest as aortitis, inflammatory aneurysm, periaortitis, cardiac pseudotumors, coronary arteritis and pericarditis, but the aortic valve is rarely affected.7 Although previous reports have shown that aortic valve lesions are associated with aortic stenosis, our patient developed only aortic regurgitation and not significant aortic stenosis.2,3 Furthermore, in previously reported cases, surgical procedures, mainly aortic valve replacement, were performed first. To the best of our knowledge, this is the first report of a case treated with steroid therapy before surgery. Yamauchi et al.8 presented a patient with a pseudotumour in the left atrium, causing aortic regurgitation and heart block, who also underwent aortic valve replacement before steroid administration.

ormed first. To the best of our knowledge, this is the first report of a case treated with steroid therapy before surgery. Yamauchi et al.8 presented a patient with a pseudotumour in the left atrium, causing aortic regurgitation and heart block, who also underwent aortic valve replacement before steroid administration. One of the potential problems related to valve surgery without initial steroid therapy in these individuals is the possibility of leakage and early prosthetic valve failure. Maleszewski et al.2 reported a case, in which aortic valve replacement was performed for aortic stenosis and regurgitation without preoperative steroid therapy, that developed perivalvular leakage approximately 1 year after surgery. Yamauchi et al.8 presented a case in which steroid treatment was started after aortic valve replacement that required redo surgery because of the perivalvular leakage 8 months after the operation. They considered that perivalvular leakage might have resulted from the loosening of the sutures placed in the annulus due to regression of the tumefactive lesion after the initiation of steroid therapy. In our patient, the prosthetic valve was functioning well without leakage around the valve at the 1-year follow-up. The preoperative steroid administration may have contributed to the stability of the prosthetic valve.

d in the annulus due to regression of the tumefactive lesion after the initiation of steroid therapy. In our patient, the prosthetic valve was functioning well without leakage around the valve at the 1-year follow-up. The preoperative steroid administration may have contributed to the stability of the prosthetic valve. Steroid therapy is widely recognized as the first-line therapy for IgG4-RD. A consensus statement from Japan suggested treating patients initially with prednisolone at a dose of 0.6 mg/kg of body weight.4 According to the literature, our patient was started on steroid treatment when he was suspected to have IgG4-related pancreatitis, lacrimal gland enlargement, and retroperitoneal fibrosis approximately 1 year ago. The prednisolone was tapered to 10 mg/day without recurrence of the already known lesions. Although his serum IgG4 level gradually decreased to within the normal range, inflammatory markers (CRP, ESR, and WBC) remained elevated. We should have assessed not only the serum IgG4 level but also inflammatory markers while tapering the steroid doses, to detect the development of new lesions. Our patient responded well to increased prednisolone. The thickening of the aortic valve leaflets regressed due to the intensive steroid therapy after the development of the aortic valve lesion. Heart failure was exacerbated, however, by the progression of aortic regurgitation. The suspected cause of aortic regurgitation, based on echocardiographic findings, is that the shortening and thickening of the valve leaflets might have caused a coaptation failure (Figure 1B). We theorise that changes in the geometry of the aortic valve, resulting from a reduction in the inflammatory infiltrate by steroid therapy, may have exacerbated the aortic regurgitation due to the coaptation failure and, subsequently, the LV dilatation.

valve leaflets might have caused a coaptation failure (Figure 1B). We theorise that changes in the geometry of the aortic valve, resulting from a reduction in the inflammatory infiltrate by steroid therapy, may have exacerbated the aortic regurgitation due to the coaptation failure and, subsequently, the LV dilatation. Multimodality imaging, including echocardiography, multidetector CT, and CMR, has been used for early diagnosis and follow-up of IgG4-related cardiovascular disease.7,9 An echocardiography is particularly useful for the evaluation of valvular involvement as in our patient. It provides structural and functional information about the aortic valve and enables early diagnosis and severity assessment of valvular disease, and is also essential to evaluate cardiac function and heart failure. A multidetector CT allows multiplanar reformation; thus, allowing evaluation of the aortic valve, aortic wall, and myocardium changes. Although the spatial resolution of a CMR is inferior to a CT, a CMR has superior soft tissue characterization, and can evaluate disease activity and response to treatment due to the ability to characterize tissue oedema and fibrosis.

n; thus, allowing evaluation of the aortic valve, aortic wall, and myocardium changes. Although the spatial resolution of a CMR is inferior to a CT, a CMR has superior soft tissue characterization, and can evaluate disease activity and response to treatment due to the ability to characterize tissue oedema and fibrosis. In conclusion, we describe a case of steroid therapy preceding surgery for IgG4-RD of the aortic valve that caused severe aortic regurgitation and complete atrioventricular block. Preoperative steroid treatment may induce regression of the lesion and contribute to the stability of the prosthetic valve after surgery, but it may also carry a risk of heart failure exacerbation due to the progression of aortic regurgitation in patients with aortic valve lesions. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points The patient reported here suggests that acetazolamide could be an alternative diuretic to vasopressin antagonists for some proportion of heart failure (HF) patients with hyponatraemia. This observation is supported by literature describing that the serum sodium concentration is preserved or enhanced in 70% of refractory HF patients undergoing acetazolamide treatment. Large randomized studies are required to re-evaluate the efficiency of this forgotten, but useful agent for the treatment of HF and its potential for correcting hyponatraemia. Introduction Hyponatraemia in acutely decompensated heart failure (HF) is easily corrected by vasopressin receptor antagonists,1–3 but these medications are costly and their use in outpatient clinics is restricted in Japan by government-managed insurance. According to the ‘chloride theory’ for HF pathophysiology,4–6 chloride manipulation, including the use of acetazolamide (Diamox),7–9 may be an essential therapeutic target in HF treatment. Previous reports revealed that chloride is a crucial electrolyte for reabsorption of filtered sodium in the renal tubules to the extracellular space of the body.10–12 Acetazolamide could become an alternative diuretic to an oral vasopressin antagonist for correcting hyponatraemia due to more aquaresis than natriuresis because; (i) this diuretic agent enhances the reabsorption of chloride,5–7 and thus sodium is expected to be reabsorbed concurrently in the cortical collecting tubules10–12 and (ii) might have an ability of increasing the free water clearance in the urinary tubules.13 Timeline

Introduction Hyponatraemia in acutely decompensated heart failure (HF) is easily corrected by vasopressin receptor antagonists,1–3 but these medications are costly and their use in outpatient clinics is restricted in Japan by government-managed insurance. According to the ‘chloride theory’ for HF pathophysiology,4–6 chloride manipulation, including the use of acetazolamide (Diamox),7–9 may be an essential therapeutic target in HF treatment. Previous reports revealed that chloride is a crucial electrolyte for reabsorption of filtered sodium in the renal tubules to the extracellular space of the body.10–12 Acetazolamide could become an alternative diuretic to an oral vasopressin antagonist for correcting hyponatraemia due to more aquaresis than natriuresis because; (i) this diuretic agent enhances the reabsorption of chloride,5–7 and thus sodium is expected to be reabsorbed concurrently in the cortical collecting tubules10–12 and (ii) might have an ability of increasing the free water clearance in the urinary tubules.13 Timeline Day Events 1 The patient was emergently admitted to the hospital due to acutely decompensated heart failure (HF) (NYHA-IV) with hypotension (60/42 mmHg) and bradycardic junctional rhythm (30 b.p.m.) Cardiac transthoracic ultrasound revealed moderate degree of aortic regurgitation (III/IV), but a preserved left ventricular ejection fraction (60%) Blood tests revealed moderately elevated b-type natriuretic peptide (BNP 576 pg/mL), hyponatraemia (128 mEq/L), and hypochloraemia (95 mEq/L)

Day Events 1 The patient was emergently admitted to the hospital due to acutely decompensated heart failure (HF) (NYHA-IV) with hypotension (60/42 mmHg) and bradycardic junctional rhythm (30 b.p.m.) Cardiac transthoracic ultrasound revealed moderate degree of aortic regurgitation (III/IV), but a preserved left ventricular ejection fraction (60%) Blood tests revealed moderately elevated b-type natriuretic peptide (BNP 576 pg/mL), hyponatraemia (128 mEq/L), and hypochloraemia (95 mEq/L) Urgent noradrenaline drip infusion (2–3 μg/kg/h) promptly restored sinus rhythm (70 b.p.m.) and led to recovery from hypotension Low-dose oral acetazolamide (500 mg/day) was prescribed to correct the decompensated HF status and electrolyte disturbance 4 Both the serum sodium and serum chloride concentrations recovered to normal (136 mEq/L and 104 mEq/L, respectively) 14 The patient’s HF status became stable, and the serum BNP concentration returned to normal (55 pg/mL), but the serum sodium was slightly reduced (133 mEq/L) 21 The patient was discharged from the hospital in an acceptable HF status 21 + 2 months The HF status remained to be stable (serum BNP level of 65 pg/mL) and both the serum sodium and chloride concentrations were normal (139 mEq/L and 108 mEq/L, respectively)

14 The patient’s HF status became stable, and the serum BNP concentration returned to normal (55 pg/mL), but the serum sodium was slightly reduced (133 mEq/L) 21 The patient was discharged from the hospital in an acceptable HF status 21 + 2 months The HF status remained to be stable (serum BNP level of 65 pg/mL) and both the serum sodium and chloride concentrations were normal (139 mEq/L and 108 mEq/L, respectively) Case presentation An 83-year-old male patient was emergently admitted to the hospital with the chief complaint of progressive dyspnoea over several days due to acutely decompensated HF (NYHA-IV) with hypotension (60/42 mmHg), bradycardia, and an irregular pulse (30 b.p.m.). The patient was uneventful for recent several years, and was not on any regular medication, including cardiovascular drugs, before the present admission. Table 1 shows the clinical course of his HF-related tests, peripheral blood and urinary tests, and medications given to treat the decongestion and electrolyte disturbance. Physical examination on admission revealed jugular venous distension, systemic oedema, bilateral basal pulmonary rales, distant heart sound, and peripheral coldness. A 12-lead electrocardiogram revealed sinus arrest with a junctional escape rhythm and an irregular heart rate of 30 b.p.m. A chest X-ray revealed mild cardiomegaly (cardiothoracic ratio 55%) and prominent vasculature in the upper lung fields. Transthoracic cardiac ultrasound revealed a moderate degree of aortic regurgitation (III/IV), but the left ventricular ejection fraction (60%) was preserved, and its diastolic volume was almost within the normal range (143 cc). Thoracic and abdominal ultrasound showed massive bilateral pleural effusion and an expanded inferior vena cava with minimal respiratory change. Table 1 Changes in serum and urinary electrolytes before and after the administration of Diamox

preserved, and its diastolic volume was almost within the normal range (143 cc). Thoracic and abdominal ultrasound showed massive bilateral pleural effusion and an expanded inferior vena cava with minimal respiratory change. Table 1 Changes in serum and urinary electrolytes before and after the administration of Diamox Admission to the hospital (24 October 2017) Before Diamox treatment After Diamox treatment Day 1 Day 4 Day 8 Day 14 At admission 8 h later A. Heart failure-related test Urine volume (mL/d) 1000–2100–1400–1000 1400 — Blood pressure (mmHg) 60/42 117/56 118/60/ 106/56 96/59 Heart rate (b.p.m.) 30 70 83 78 68 Electrocardiogram Sinus arrest/escape rhythm NSR/conducted narrow QRS — — NSR/conducted narrow QRS Body fluid retention (physical and ultrasonographic exam) Systemic oedema and pleural effusion — — No B-type natriuretic peptide (pg/mL) 576 — — 55 Renin activity (ng/mL/h) 0.9 — — 2.7 Anti-diuretic hormone (pg/mL) 8.6 — — 1 B. Peripheral blood test Haemoglobin (g/dL) 11.5 10.9 10.9 10.2 Haematocrit (%) 34.4 35.9 35 32.5 MCV (fL) 97 106 104 102 Serum electrolytes Sodium (mEq/L) 128 136 135 133 Potassium (mEq/L) 5.7 4.5 4.1 4.2 Chloride (mEq/L) 95 104 103 103 Blood urea nitrogen (mg/dL) 33 23 23 20 Serum creatinine (mg/dL) 1 0.77 0.6 0.65 C. Urinary test (spot urine) Urinary electrolytes Sodium (mEq/L) 104 — — 113 Potassium (mEq/L) 40 — — 34 Chloride (mEq/L) 100 — — 98 Urinary creatinine (mg/dL) 44 — — 56 Urinary electrolytes corrected by urinary creatinine Sodium/Cr (10 mEq/g·Cr) 2.36 — — 2.02 Potassium/Cr (10 mEq/g·Cr) 0.91 — — 0.61 Chloride/Cr (10 mEq/g·Cr) 2.27 — — 1.75 D. Treatment Noradrenaline 2–3 μg/kg/h Beta stimulant skin patch 2 mg/d (Tulobuterol) Argamate 20% jelly 25 g/d Carbonic anhydrase inhibitor 500 mg/d (Diamox) Cr, Creatinine; d, day; h, hour; MCV, mean corporeal red cell volume; NSR, normal sinus rhythm.

0 mEq/g·Cr) 0.91 — — 0.61 Chloride/Cr (10 mEq/g·Cr) 2.27 — — 1.75 D. Treatment Noradrenaline 2–3 μg/kg/h Beta stimulant skin patch 2 mg/d (Tulobuterol) Argamate 20% jelly 25 g/d Carbonic anhydrase inhibitor 500 mg/d (Diamox) Cr, Creatinine; d, day; h, hour; MCV, mean corporeal red cell volume; NSR, normal sinus rhythm. Urgent initiation of a noradrenaline drip infusion (2–3 μg/kg/h) and beta stimulant adhesive skin patch (Tulobuterol 2 mg/day) promptly restored the sinus rhythm (70 b.p.m.) and the normality of conduction and the QRS complex on electrocardiography, resulting in the recovery from hypotension with a systemic blood pressure of 117/56 mmHg. Blood tests on admission revealed moderately elevated b-type natriuretic peptide (BNP 576 pg/mL; normal range <18.4 pg/mL), hyponatraemia (128 mEq/L; normal range 135–147 mEq/L), hypochloraemia (95 mEq/L; normal range 98–108 mEq/L), hyperkalaemia (5.7 mEq/L, normal range 3.6–5.0 mEq/L), and preserved renal function (creatinine 1.0 mg/dL; normal range 0.61–1.04 mg/dL) under no particular cardiovascular medications. Immediately after resolving the bradycardia and hypotension, low-dose oral acetazolamide (500 mg/day) and 20% polystyrene sulfate-Ca jelly (Argamate 25 g/day for 3 days) were prescribed to correct the decompensated HF status and electrolyte disturbance. Three days later, both the serum sodium and chloride concentrations had recovered to normal levels (136 mEq/L and 104 mEq/L, respectively), and the serum potassium concentration had decreased to 4.5 mEq/L.

(Argamate 25 g/day for 3 days) were prescribed to correct the decompensated HF status and electrolyte disturbance. Three days later, both the serum sodium and chloride concentrations had recovered to normal levels (136 mEq/L and 104 mEq/L, respectively), and the serum potassium concentration had decreased to 4.5 mEq/L. Two weeks later, the patient’s body fluid retention was ameliorated and the serum BNP concentration was near normal (55 pg/mL). Serum chloride and potassium concentrations remained in the normal range, but the serum sodium concentration was slightly reduced (133 mEq/L) compared to that at Day 4 of the hospital admission, which could be managed by changing the diuretic prescription and/or dietary salt adjustment in accordance with the ‘chloride theory’ for HF pathophysiology.6 Three weeks later, the patient was discharged in an acceptable HF status. Two months later after discharge under the same medication, the patient’s HF status remained stable (serum BNP level of 65 pg/mL) and both the serum sodium and chloride concentrations were normal (139 mEq/L and 108 mEq/L, respectively). Discussion The present case indicates that the classical drug acetazolamide not only has a potent chloride-regaining diuretic effect but also has a vasopressin blockade-like effect to enhance the serum sodium concentration presumably through the mechanism of more aquaresis than natriuresis by this diuretic agent. Hyponatraemia was promptly corrected (within 4 days in this case) after acetazolamide monotherapy.

tent chloride-regaining diuretic effect but also has a vasopressin blockade-like effect to enhance the serum sodium concentration presumably through the mechanism of more aquaresis than natriuresis by this diuretic agent. Hyponatraemia was promptly corrected (within 4 days in this case) after acetazolamide monotherapy. Electrolyte abnormalities may be multifactorial and interrelated, resulting from neurohormonal activation, renal dysfunction, medications, and dietary intake.14 In the present study, hyponatraemia and hypochloraemia on admission were associated with enhanced activation of anti-diuretic hormone (8.6 pg/mL; normal range <2.8 pg/mL) and normal renin activity (0.9 ng/mL/h; normal range 0.3–2.9 ng/mL/h). Under the situation of both hyponatraemia and enhanced activation of anti-diuretic hormone, vasopressin receptor blockade would be the primary choice of diuretics.1,2 Acetazolamide was selected for this patient, however, because recent studies have suggested that manipulating the serum chloride concentration is important for improving the haemodynamic and neurohormonal status in HF pathophysiology.3,6 As a consequence, this diuretic strategy using low-dose oral acetazolamide corrected both the hyponatraemia and hypochloraemia in parallel with improvement of the worsening of HF status. Additionally, hyperkalaemia was simultaneously corrected by this agent due to its potential to reduce serum potassium concentration by secreting this electrolyte into the urinary tubules.7–9 At Day 14 of hospitalization and after acetazolamide treatment (Table 1), the plasma renin activity was slightly increased, but it remained normal (2.7 ng/mL/h), and the anti-diuretic hormone level was decreased to normal level (1 pg/mL).

otassium concentration by secreting this electrolyte into the urinary tubules.7–9 At Day 14 of hospitalization and after acetazolamide treatment (Table 1), the plasma renin activity was slightly increased, but it remained normal (2.7 ng/mL/h), and the anti-diuretic hormone level was decreased to normal level (1 pg/mL). The potential of acetazolamide to correct hyponatraemia is expected based on previous studies. The carbonic anhydrase inhibitor acetazolamide has a unique but critical diuretic action, a ‘non-reabsorbable anion-like effect’, that results in the excretion of bicarbonate (HCO3−) into the urinary tubules with interchangeable absorption of filtered chloride into the blood, and concurrent excretion of potassium into the urine.7–9 An earlier study by Relman et al.7 examined the acute effects (3–12 days) of acetazolamide on serum solutes in 26 patients with severe HF (male 73%; age 56.7 ± 12.4 years) and found that the serum sodium concentration was unchanged or increased in 73% of 24 evaluations from the 23 HF patients (Table 2 and Figure 1A). Furthermore, the increased serum sodium concentration correlated positively with the increased serum chloride concentration (Figure 1B), suggesting that the reabsorption of chloride might be enhanced concurrently with the reabsorption of sodium in the urinary tubules to the blood stream.8,10–12 More importantly, acetazolamide might have aquaretic effects,13 presumably through the ‘non-reabsorbable anion-like effect’,8 that might enhance serum sodium concentration. It is required furthermore to examine the exact mechanism(s) for enhancing serum sodium concentration by acetazolamide. Table 2 Distribution of changes in the serum chloride and sodium concentrations under Diamox treatment in 23 refractory heart failure patients

effect’,8 that might enhance serum sodium concentration. It is required furthermore to examine the exact mechanism(s) for enhancing serum sodium concentration by acetazolamide. Table 2 Distribution of changes in the serum chloride and sodium concentrations under Diamox treatment in 23 refractory heart failure patients Change in serum sodium (mEq/L) ≥0 0> Change in serum chloride (mEq/L) ≥0 14 6 0> 2 2 Number of samples = 24; Male 17; Female 6; Age 57 ± 13 years (29–73); Daily dose of Diamox 250 mg–3 g/day; observation period 6.0 ± 2.8 days (3–12 days). Data obtained in the study by Relman et al.7 Figure 1 (A) Scatterplot of changes in the serum sodium concentration after treatment with acetazolamide. (B) Correlation between changes in the serum chloride concentration and serum sodium concentration after treatment with acetazolamide. Data obtained in the study by Relman et al.7 The specific diuretic action of this agent greatly contributes to favourably modulate serum electrolyte disturbances in HF pathophysiology. It should be kept in mind, however, that the efficiency of this diuretic agent to correct hyponatraemia would be modest, so worsening hyponatraemia even with the use of this agent should be carefully evaluated. Fortunately, this effect usually appears promptly, so the strategy can be quickly revised according to the results of blood test monitoring during a short observational period.

retic agent to correct hyponatraemia would be modest, so worsening hyponatraemia even with the use of this agent should be carefully evaluated. Fortunately, this effect usually appears promptly, so the strategy can be quickly revised according to the results of blood test monitoring during a short observational period. Both vasopressin receptor blockade3 and acetazolamide9 have similar effects to enhance the serum chloride concentration via their diuretic actions. Hence, according to my ‘chloride theory’ for HF pathophysiology,6 both diuretics could be expected to have a similar haemodynamic effect of redistributing the body fluid after diuresis, such as increasing or maintaining the plasma volume, and probably fluid drainage from the interstitial space due to changes in the serum osmolality/tonicity, mainly by serum chloride.3,6 While maintaining plasma volume might be beneficial for preserving the blood supply to the kidney and other organs, its persistent burden to the failing heart should be kept in mind3,6 when monitoring HF patients based on changes in BNP levels and haemodynamic parameters.

molality/tonicity, mainly by serum chloride.3,6 While maintaining plasma volume might be beneficial for preserving the blood supply to the kidney and other organs, its persistent burden to the failing heart should be kept in mind3,6 when monitoring HF patients based on changes in BNP levels and haemodynamic parameters. Conclusion It remains to be determined whether or not acetazolamide could be an alternative diuretic to vasopressin antagonists for some HF patients with hyponatraemia; compared with an oral vasopressin antagonist, acetazolamide is less costly and easy to administer both at outpatient clinic and hospitals. A recent pilot study15 has demonstrated that the addition of acetazolamide to the background regimen in patients with chronic HF exacerbations had additional diuretic effects and alleviated dyspnoea. Large randomized studies are required to re-evaluate the efficiency of this forgotten but useful agent for the treatment of HF and its potential for correcting hyponatraemia. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Optimal result can be achieved with the transcatheter aortic valve implantation technique when treating complex anatomy such as bicuspid aortic stenosis and situs inversus totalis. Pre-operative planning and per-operative fluoroscopy image processing can provide valuable guidance when pursuing optimal technical result in complex and unusual anatomy. Introduction Transcatheter aortic valve implantation (TAVI) can be challenging in case of complex anatomy. Transcatheter aortic valve implantation using the Edwards Sapien 3 (Edwards lifesciences, Irvine, CA, USA) valve has been recently reported to be an effective treatment of severe bicuspid aortic valve stenosis,1,2 and its positioning during the procedure is one of the main predictors of peri-prosthetic regurgitation.3 But the bicuspid valve’s angiographic appearance can be irregular and asymmetric and possibly lead to malpositioning. Furthermore, situs inversus yields unusual angiographic anatomical landmarks that could render the transcatheter heart valve’s (THVs) positioning even more hazardous. This report illustrates a successful procedure in a patient with both conditions after careful pre-operative planning and per-operative guidance by means of a novel software. Timeline Case A 71-year-old man Symptomatic severe aortic stenosis of a bicuspid valve Situs inversus totalis Day 1: Pre-operative investigations Pre-operative multi-slice computed tomography: possibility of iliofemoral approach pre-operative planning through three-dimensional reconstruction

Introduction Transcatheter aortic valve implantation (TAVI) can be challenging in case of complex anatomy. Transcatheter aortic valve implantation using the Edwards Sapien 3 (Edwards lifesciences, Irvine, CA, USA) valve has been recently reported to be an effective treatment of severe bicuspid aortic valve stenosis,1,2 and its positioning during the procedure is one of the main predictors of peri-prosthetic regurgitation.3 But the bicuspid valve’s angiographic appearance can be irregular and asymmetric and possibly lead to malpositioning. Furthermore, situs inversus yields unusual angiographic anatomical landmarks that could render the transcatheter heart valve’s (THVs) positioning even more hazardous. This report illustrates a successful procedure in a patient with both conditions after careful pre-operative planning and per-operative guidance by means of a novel software. Timeline Case A 71-year-old man Symptomatic severe aortic stenosis of a bicuspid valve Situs inversus totalis Day 1: Pre-operative investigations Pre-operative multi-slice computed tomography: possibility of iliofemoral approach pre-operative planning through three-dimensional reconstruction Day 2: Intervention Transcatheter aortic valve implantation using a 26 mm Edwards Sapien 3 prosthesis while using per-operative fluoroscopy image processing for guidance Angiographic verification of the absence of periprosthetic leakage Day 3–7: Post-operative care Transthoracic echocardiography: no periprosthetic leakage Electrocardiogram: no atrioventricular block Day 8: Patient discharge Discharge at home

Day 2: Intervention Transcatheter aortic valve implantation using a 26 mm Edwards Sapien 3 prosthesis while using per-operative fluoroscopy image processing for guidance Angiographic verification of the absence of periprosthetic leakage Day 3–7: Post-operative care Transthoracic echocardiography: no periprosthetic leakage Electrocardiogram: no atrioventricular block Day 8: Patient discharge Discharge at home Day 90: Follow-up consultation Improvement of symptoms Case presentation A 71-year-old man was admitted to our hospital with dyspnoea due to severe aortic stenosis complicating a calcified type 0 bicuspid aortic valve. His medical history included diabetes mellitus, atrial fibrillation, chronic respiratory failure, and coronary artery bypass grafting surgery for left main artery stenosis, which uncovered a situs inversus totalis (Figure 1). On physical examination the patient had a systolic murmur predominantly located in the second left intercostal space on cardiac auscultation and bilateral crackles regarding the inferior parts of the lungs on pulmonary auscultation. Because of his medical history and a high Society of Thoracic Surgeons (STS) score of 11.9%, the Heart Team recommended TAVI rather than open surgery. The pre-operative multi-slice computed tomography (MSCT) evaluation of the aorta, and its branches confirmed patency of femoral arteries that allowed transfemoral approach (Figure 2) and absence of significant thoracic aortic aneurysm. Figure 1 Transversal view of a computed tomography scan of the complete situs inversus.

Case presentation A 71-year-old man was admitted to our hospital with dyspnoea due to severe aortic stenosis complicating a calcified type 0 bicuspid aortic valve. His medical history included diabetes mellitus, atrial fibrillation, chronic respiratory failure, and coronary artery bypass grafting surgery for left main artery stenosis, which uncovered a situs inversus totalis (Figure 1). On physical examination the patient had a systolic murmur predominantly located in the second left intercostal space on cardiac auscultation and bilateral crackles regarding the inferior parts of the lungs on pulmonary auscultation. Because of his medical history and a high Society of Thoracic Surgeons (STS) score of 11.9%, the Heart Team recommended TAVI rather than open surgery. The pre-operative multi-slice computed tomography (MSCT) evaluation of the aorta, and its branches confirmed patency of femoral arteries that allowed transfemoral approach (Figure 2) and absence of significant thoracic aortic aneurysm. Figure 1 Transversal view of a computed tomography scan of the complete situs inversus. Figure 2 Three-dimensional computed tomography scan reconstruction of distal aorta, and it’s iliac and femoral branches. The usual transfemoral access was used in our patient.

Case presentation A 71-year-old man was admitted to our hospital with dyspnoea due to severe aortic stenosis complicating a calcified type 0 bicuspid aortic valve. His medical history included diabetes mellitus, atrial fibrillation, chronic respiratory failure, and coronary artery bypass grafting surgery for left main artery stenosis, which uncovered a situs inversus totalis (Figure 1). On physical examination the patient had a systolic murmur predominantly located in the second left intercostal space on cardiac auscultation and bilateral crackles regarding the inferior parts of the lungs on pulmonary auscultation. Because of his medical history and a high Society of Thoracic Surgeons (STS) score of 11.9%, the Heart Team recommended TAVI rather than open surgery. The pre-operative multi-slice computed tomography (MSCT) evaluation of the aorta, and its branches confirmed patency of femoral arteries that allowed transfemoral approach (Figure 2) and absence of significant thoracic aortic aneurysm. Figure 1 Transversal view of a computed tomography scan of the complete situs inversus. Figure 2 Three-dimensional computed tomography scan reconstruction of distal aorta, and it’s iliac and femoral branches. The usual transfemoral access was used in our patient. Pre-operative sizing was performed with the new ValveAssist 2 (Discovery IGS 730, GE Healthcare, Chalfont St Giles, UK) image processing software. Comparatively to the standard fluoroscopy, the new software allows the projection of the MSCT-extracted, manually drawn virtual aortic annulus on the live fluoroscopy screen, and the enhancement of the aortic valve calcifications and aorta calcifications that are used as anatomical landmarks for operator guiding for the positioning of the THV during the procedure (Figures 3–5). A Sapien 3 (Edwards lifesciences, Irvine, CA, USA) 26 mm was directly implanted in a high position (regarding the leaflet extremities rather than the annulus, to reduce the risk of paravalvular regurgitation and need for permanent pacemaker), without post-dilatation, prosthesis constriction and no angiographic leak. The patient did not require permanent pacemaker implantation. A transthoracic echocardiography one week later confirmed an excellent result with no intra or paravalvular regurgitation, and the patient reported improved symptoms. In follow-up consultation 3 months after the procedure the patient reported improved symptoms and had no periprosthetic leak on transthoracic echocardiography.

sthoracic echocardiography one week later confirmed an excellent result with no intra or paravalvular regurgitation, and the patient reported improved symptoms. In follow-up consultation 3 months after the procedure the patient reported improved symptoms and had no periprosthetic leak on transthoracic echocardiography. Figure 3 Computed tomography scan reconstruction of the aortic valve annulus of the bicuspid aortic valve. Figure 4 Per-procedural images with usual fluoroscopy. Figure 5 Per-procedural images with calcification enhancement and aortic annulus fusion on the fluoroscopy screen allowed by Valve Assist 2 software (Discovery IGS 730, GE Healthcare, Chalfont St Giles, UK).

Figure 3 Computed tomography scan reconstruction of the aortic valve annulus of the bicuspid aortic valve. Figure 4 Per-procedural images with usual fluoroscopy. Figure 5 Per-procedural images with calcification enhancement and aortic annulus fusion on the fluoroscopy screen allowed by Valve Assist 2 software (Discovery IGS 730, GE Healthcare, Chalfont St Giles, UK). Discussion To the best of our knowledge, this is the first report of TAVI in a patient with complete situs inversus and bicuspid aortic valve.4 Careful pre-procedural planning and precise THV implantation allowed the achievement of an optimal result despite complex anatomy in the case of our patient. Per-procedural fluoroscopy image processing with calcification enhancement and virtual aortic annulus fusion with new software such as Valve Assist 2 (Discovery IGS 730, GE Healthcare, Chalfont St Giles, UK) could help to achieve optimal results in selected patients with complex anatomy. Indeed, during TAVI the angiographic appearance of the cusps is irregular and asymmetric,1 which can lead to malpositioning, which in turn might increase the risk of paravalvular regurgitation5 and need for pacemaker implantation after TAVI.6 This is most evident in type 0 bicuspid valves where only two cusps exist and the classic angiographic orthogonal view of the three cusps of a tricuspid valve is absent.7 Furthermore, usual anatomical landmarks can be even more disturbed by the situs inversus totalis.4

5 and need for pacemaker implantation after TAVI.6 This is most evident in type 0 bicuspid valves where only two cusps exist and the classic angiographic orthogonal view of the three cusps of a tricuspid valve is absent.7 Furthermore, usual anatomical landmarks can be even more disturbed by the situs inversus totalis.4 We believe that pre-operative three-dimensional reconstruction and per-operative fluoroscopy image processing can provide precious guidance for TAVI in patients with complex and unusual anatomy. This case, along with previously published data,1,4,7 pleads in favour of feasibility of TAVI in patients with bicuspid aortic stenosis and situs inversus totalis with the Sapien 3 THV. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: T.M. is proctor and consultant for Medtronic and Microport. A.S. has served as a consultant for Edwards and Medtronic. All other author declared no conflict of interest.

Case description A 72-year-old man with a history of anteroseptal acute myocardial infarction was admitted to our hospital with acute heart failure. He underwent left ventricular (LV) reconstruction due to LV aneurysm, coronary artery bypass grafting from the left internal thoracic artery to the left anterior descending artery, mitral valvuloplasty with artificial ring for moderate to severe mitral regurgitation, and tricuspid valvuloplasty with artificial ring 18 months earlier. On admission, his blood pressure was 86/55 mmHg, heart rate was 60 b.p.m., and a visible apex beat was present at the 6th left intercostal space just medial to the left mid-clavicular line (Supplementary material online, Video S1). Computed tomography revealed a pseudoaneurysm with mild calcification, protruding outside the thorax around the apex of the heart (Figure 1). Echocardiogram showed akinesis of the anteroseptal wall and a 40 × 27-mm pseudoaneurysm around the apex of the heart, moving in synchrony with the heartbeat, and a 17% LV ejection fraction (Figure 2, Supplementary material online, Video S2). The connection was confirmed between the pseudoaneurysm and the left ventricle with a spontaneous echo contrast. An underlying infection could have contributed to the formation of the pseudoaneurysm. We theorize that as the pseudoaneurysm progressed, the tissue along its path of progression was mechanically damaged. This gradual damage could have resulted in impaired structural integrity of the surrounding tissue which ultimately allowed certain segments of the heart to protrude into regions beyond the normal anatomical confines of the heart. Left ventricular ejection fraction slightly improved from 17% to 25%, before and after the operation, respectively. The patient was discharged after a protracted hospital course. After discharge, the patient is now coming for follow-ups at regular intervals.

o regions beyond the normal anatomical confines of the heart. Left ventricular ejection fraction slightly improved from 17% to 25%, before and after the operation, respectively. The patient was discharged after a protracted hospital course. After discharge, the patient is now coming for follow-ups at regular intervals. Most LV pseudoaneurysm patients present with various clinical observations and abnormal findings on physical examination, such as heart failure, dyspnoea, and chest pain; however, 10% of patients are asymptomatic.1 In the present case, the pseudoaneurysm protruded into the left thoracic cavity with the pericardium and perforated subcutaneously from the intercostal space. Post-myocardial infarction LV pseudoaneurysm has been reported2,3; however, a pseudoaneurysm presenting with a visible apex beat is exceptionally rare. Figure 1 Computed tomography shows a pseudoaneurysm (white arrow) at the apex of the heart, which protruding outside of the thorax. (A) Transverse view. (B) Sagittal view. Figure 2 Transthoracic echocardiogram in a two-chamber view shows a 40 × 27-mm pseudoaneurysm (white arrow), connecting with the left ventricle around the apex of the heart. LV, left ventricle. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Supplementary material is available at European Heart Journal - Case Reports online. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material Supplementary Data Click here for additional data file.

Learning points Accessory mitral valve tissue is a rare congenital anomaly of endocardial cushion development. It rarely causes left ventricular outflow tract obstruction in adults and is often associated with other cardiac and vascular congenital malformations. Accessory mitral valve tissue has been described as parachute-like, sail-shaped, sac-like, leaflet-like, or as a sheet. Introduction Accessory mitral valve tissue (AMVT) is a rare congenital anomaly that develops because of an incomplete separation of the mitral valve from the endocardial cushion tissue.1 AMVT is responsible for left ventricular outflow tract (LVOT) obstruction and is associated with other cardiac and vascular congenital malformations.2 We describe the case of a 22-year-old female patient diagnosed with parachute mitral valve (PMV), ventricular septal defect (VSD), bicuspid aortic valve (BAV), unruptured aneurysm of aortic sinus and LVOT obstruction produced by an AMVT. This combination of symptoms has not been reported previously in an adult. Timeline 24 October 2017 The patient was referred to the Department of Cardiology 26 October 2017 Transthoracic echocardiography was performed 14 November 2017 Surgical treatment was carried out. (The operation time was 09:40–15:10.) A pre-operative and post-operative transoesophageal echocardiography was performed to evaluate surgical curative effects 22 November 2017 The first transthoracic echocardiography was performed after the operation 25 November 2017 The patient discharged from our hospital

arried out. (The operation time was 09:40–15:10.) A pre-operative and post-operative transoesophageal echocardiography was performed to evaluate surgical curative effects 22 November 2017 The first transthoracic echocardiography was performed after the operation 25 November 2017 The patient discharged from our hospital Case report A 22-year-old female patient was referred to the Department of Cardiology with exertional shortness of breath and a history of congenital heart disease with mitral stenosis (MS), VSD and pulmonary hypertension as an outpatient. Five days previously, her condition had deteriorated rapidly, the patient became progressively dyspnoeic and developed orthopnoea, and she was unable to perform daily activities due to severe shortness of breath associated with exertional atypical chest pain. An electrocardiogram showed an ectopic rhythm (78 b.p.m./m), rapid atrial arrhythmias, and a left QRS axis. Upon physical examination, her blood pressure was found to be normal (100/60 mmHg) and the cardiac auscultation showed a 3/6 systolic murmur along the left sternal border. On auscultation of the chest, there were normal vesicular breath sounds. Scoliosis was observed in chest findings. There were no peripheral oedema and jugular venous distention. Blood and biochemical laboratory tests revealed leucocytosis, white blood cell count 10.18 × 109 cells/L (normal value: 3.5–9.5 × 109 cells/L), elevated C-reactive protein levels 25.36 mg/L (normal value: 1–10 mg/L) and NT-proBNP 628 ng/L (normal value: 133–450 ng/L). Chest radiography showed a cardiothoracic ratio of 60%, pulmonary congestion, bilateral pleural thickening and scoliosis.

ood cell count 10.18 × 109 cells/L (normal value: 3.5–9.5 × 109 cells/L), elevated C-reactive protein levels 25.36 mg/L (normal value: 1–10 mg/L) and NT-proBNP 628 ng/L (normal value: 133–450 ng/L). Chest radiography showed a cardiothoracic ratio of 60%, pulmonary congestion, bilateral pleural thickening and scoliosis. Next, we performed a transthoracic echocardiography (TTE) that revealed an abnormal membranous structure (1.3 cm × 1.2 cm) attached to the ventricular side of anterior mitral valve (MV) leaflet, with a subaortic chordal attachment. The abnormal tissue was similar to a MV leaflet. The parasternal short-axis view showed the relationship between the normal MV and the accessory valve (Figure 1). Therefore, we diagnosed it as AMVT. The peak blood flow velocity across LVOT had accelerated to 5.0 m/s (Figure 2). The MV had a parachute-like appearance. There were two normally positioned papillary muscles in the left ventricle, but they did not have chordae tendineae inserted into it. The chordae tendineae were located in the left ventricular wall between the two papillary muscles (Supplementary material online, Video S1). Therefore, we described it as a parachute-like MV. Doppler assessment yielded a peak MV gradient of 27 mmHg and a mean MV gradient of 16 mmHg. Pressure half-time method yielded a valve area of 0.8 cm2. There was also a mild degree of mitral regurgitation. In addition, echocardiography revealed a peri-membranous VSD (Supplementary material online, Videos S2 and S3) and BAV. The diameter of the VSD was 1.0 cm, and the shunt flow through VSD was left-to-right with a peak velocity of 4.5 m/s. From these findings, we hypothesized that LVOT obstruction was due to the accessory MV, MS was due to PMV and the left-to-right shunt was due to VSD. The pulmonary and tricuspid valves were normal. The pulmonary artery systolic pressure was slightly high (44 mmHg). There was also a mild dilatation of the left atrium (4.2 cm) and left ventricle (left ventricle end-diastolic diameter = 5.2 cm). Systolic function of the left ventricle was estimated to be within normal limits (ejection fraction = 60%). right ventricle function as well as the dimensions and morphology of the aortic arch and the ascending and descending aorta were normal.

.2 cm) and left ventricle (left ventricle end-diastolic diameter = 5.2 cm). Systolic function of the left ventricle was estimated to be within normal limits (ejection fraction = 60%). right ventricle function as well as the dimensions and morphology of the aortic arch and the ascending and descending aorta were normal. Figure 1 The parasternal long-axis view showed a fixed accessory mitral valve tissue attached to the anterior leaflet, which caused left ventricular outflow tract obstruction. Figure 2 Apical five-chamber view: continuous wave Doppler examination showed the peak flow velocity across left ventricular outflow tract was 5.04 m/s. In addition, we performed transoesophageal echocardiography (TOE) that confirmed the TTE findings, showing a fixed, membrane-like structure arising from the anterior mitral leaflet causing the LVOT obstruction (Supplementary material online, Video S4). This also confirmed the presence of PMV and VSD (Supplementary material online, Videos S5 and S6). Transoesophageal echocardiography showed a BAV with only two sinuses: left coronary and right coronary. The right coronary sinus appeared aneurysmal, but not ruptured (Supplementary material online, Video S7). The valve area of BAV was 2.5 cm2 by planimetry, BAV was functioning normally with no aortic valve stenosis or regurgitation.

l echocardiography showed a BAV with only two sinuses: left coronary and right coronary. The right coronary sinus appeared aneurysmal, but not ruptured (Supplementary material online, Video S7). The valve area of BAV was 2.5 cm2 by planimetry, BAV was functioning normally with no aortic valve stenosis or regurgitation. After a comprehensive clinical evaluation, elective surgical treatment was performed because of the presence of VSD, severity of the MV stenosis and LVOT obstruction. The BAV was functioning normally and was not replaced. The operative findings correlated with the imaging diagnosis. During the operation, excision of the AMV and MV replacement were performed. In addition, the peri-membranous VSD and aneurysm of the aortic sinus were repaired. Grossly, the membranous structure specimens confirmed that it was AMVT (Figure 3). Histological examination showed valvular tissue associated with mucous degeneration and inflammatory cell infiltration. Figure 3 AMVT and PMV after resection. AMVT, accessory mitral valve tissue; PMV, parachute mitral valve.

After a comprehensive clinical evaluation, elective surgical treatment was performed because of the presence of VSD, severity of the MV stenosis and LVOT obstruction. The BAV was functioning normally and was not replaced. The operative findings correlated with the imaging diagnosis. During the operation, excision of the AMV and MV replacement were performed. In addition, the peri-membranous VSD and aneurysm of the aortic sinus were repaired. Grossly, the membranous structure specimens confirmed that it was AMVT (Figure 3). Histological examination showed valvular tissue associated with mucous degeneration and inflammatory cell infiltration. Figure 3 AMVT and PMV after resection. AMVT, accessory mitral valve tissue; PMV, parachute mitral valve. A post-operative echocardiography showed complete resection of AMV, no residual shunt, no left ventricular outflow gradient or mitral regurgitation. The mosaic flow signals in the left ventricular outflow were diminished using colour Doppler, and the peak blood flow velocity decreased to 1.4 m/s. The peak pressure of rapid filling phase and atrial systolic phase across the prosthetic MV were 16 mmHg and 4 mmHg, respectively. The post-operative course was uneventful, and the patient was most recently reviewed 1 week, 1 month, 3 months after the surgical procedure by ultrasound, electrocardiogram, and chest radiography. The function of BAV was evaluated by ultrasound regularly. In the most recent follow-up, the patient’s shortness of breath disappeared, with no further episodes of chest pain.

tient was most recently reviewed 1 week, 1 month, 3 months after the surgical procedure by ultrasound, electrocardiogram, and chest radiography. The function of BAV was evaluated by ultrasound regularly. In the most recent follow-up, the patient’s shortness of breath disappeared, with no further episodes of chest pain. In this study, we report an extremely rare case of AMVT causing LVOT obstruction associated with PMV, VSD, BAV, and an unruptured aneurysm of the aortic sinus. This combination of symptoms has not been previously reported in literature.

tient was most recently reviewed 1 week, 1 month, 3 months after the surgical procedure by ultrasound, electrocardiogram, and chest radiography. The function of BAV was evaluated by ultrasound regularly. In the most recent follow-up, the patient’s shortness of breath disappeared, with no further episodes of chest pain. In this study, we report an extremely rare case of AMVT causing LVOT obstruction associated with PMV, VSD, BAV, and an unruptured aneurysm of the aortic sinus. This combination of symptoms has not been previously reported in literature. Discussion Accessory mitral valve tissue is a rare congenital anomaly of endocardial cushion development and is commonly associated with other congenital cardiac anomalies. Accessory mitral valve tissue arises from the anterior mitral leaflet and causes LVOT obstruction. Transthoracic echocardiography and TOE are considered the primary imaging modalities for AMVT diagnosis and patient follow-up.3 We performed TTE and TOE that revealed AMVT attached to the anterior mitral leaflet, with a subaortic chordal attachment, resulting in a severe increase in LVOT gradient (118 mmHg). Accessory mitral valve tissue has been described as parachute-like, sail-shaped, sac-like, leaflet-like, or as a sheet. Prifti et al.4 classified this abnormality into a fixed type (Type I) or mobile type (Type II) depending on the morphology of the abnormal tissue. Fixed and mobile types were further divided into the nodular type (Type IA) and the membranous type (Type IB) and into the pedunculated (Type IIA) type and the leaflet type (Type IIB), respectively. The leaflet type was subdivided into the rudimentary chordae tendineae type (Type IIB1) and the well-developed chordae tendineae type (Type IIB2). Our patient had a fixed membranous type leaflet-like structure directly attached to the endocardium with chordae tendineae; therefore, our case was classified as Type IB.

y. The leaflet type was subdivided into the rudimentary chordae tendineae type (Type IIB1) and the well-developed chordae tendineae type (Type IIB2). Our patient had a fixed membranous type leaflet-like structure directly attached to the endocardium with chordae tendineae; therefore, our case was classified as Type IB. Accessory mitral valve tissue is associated with other cardiac abnormalities. Manganaro et al.5 identified 104 patients who were diagnosed with AMVT from 1963 to 2012. Most patients (86.6%) had signs of LVOT obstruction, and AMVT was frequently associated with VSD (19.2%), followed by subaortic membrane (9.6%), LV hypertrophy (8.6%), and transposition of the great arteries (7.7%). In this case study, we report the first and the rarest presentation of AMVT in a 22-year-old female patient diagnosed with PMV, VSD, BAV, an unruptured aneurysm of the aortic sinus, and LVOT obstruction produced by AMVT. The obstruction can occur in the early period of life due to continued deposition of fibrous tissues within LVOT. Accessory mitral valve tissue is usually diagnosed in the first or second decade of life, and the main symptoms are exercise intolerance with dyspnoea, chest pain, and syncope.6 Patients with AMVT become symptomatic when the mean pressure gradient across LVOT reaches >50 mmHg.7 The peak LVOT pressure gradient of our patient was 100 mmHg, and LVOT stenosis was confirmed to be severe in the parasternal short-axis images. From a surgical point of view, early surgical removal is recommended because the pressure gauge gradient might increase with age.

essure gradient across LVOT reaches >50 mmHg.7 The peak LVOT pressure gradient of our patient was 100 mmHg, and LVOT stenosis was confirmed to be severe in the parasternal short-axis images. From a surgical point of view, early surgical removal is recommended because the pressure gauge gradient might increase with age. Conclusion Accessory mitral valve tissue rarely causes LVOT obstruction in adults. It is often associated with other cardiac and vascular congenital malformations. It should be considered a rare but important cause of LVOT obstruction. Supplementary Material Supplementary Video 1 Click here for additional data file. Supplementary Video 2 Click here for additional data file. Supplementary Video 3 Click here for additional data file. Supplementary Video 4 Click here for additional data file. Supplementary Video 5 Click here for additional data file. Supplementary Video 6 Click here for additional data file. Supplementary Video 7 Click here for additional data file. Acknowledgements The authors are grateful to the patients and families who participated in this study. Team members who supported the subject are as follows: Cuiying Cui, Yuanyuan Liu, Ying Wang, Deguang Feng, Feng Wang, and Bin Lin. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Concomitant acute myocardial infarction and pulmonary embolism is rare but a potentially fatal combination. Early recognition of this clinical entity can facilitate delivery of targeted therapy, adapted for the specific clinical presentation, and may avert a fatal outcome. Type I respiratory failure in the context of acute myocardial infarction and lack of heart failure signs should prompt thinking of second pathology like pulmonary embolism. Introduction Concomitant acute myocardial infarction (MI) and pulmonary embolism (PE) is rare, but establishing this dual diagnosis early is essential, since delay in appropriate therapy may lead to a fatal outcome. Right ventricular (RV) infarction in the setting of inferior ST-segment elevation MI (STEMI) coupled with acute massive PE confers a particular risk due to acute RV failure and cardiogenic shock.1 We report a rare case of concomitant PE and inferior STEMI, where early recognition prompted simultaneous right coronary artery (RCA) thrombectomy and administration of thrombolytic therapy to treat pulmonary embolism. Timeline

Introduction Concomitant acute myocardial infarction (MI) and pulmonary embolism (PE) is rare, but establishing this dual diagnosis early is essential, since delay in appropriate therapy may lead to a fatal outcome. Right ventricular (RV) infarction in the setting of inferior ST-segment elevation MI (STEMI) coupled with acute massive PE confers a particular risk due to acute RV failure and cardiogenic shock.1 We report a rare case of concomitant PE and inferior STEMI, where early recognition prompted simultaneous right coronary artery (RCA) thrombectomy and administration of thrombolytic therapy to treat pulmonary embolism. Timeline Time Events Initial presentation (Day 1) Onset of chest pain and initial assessment revealing inferior ST-segment elevation myocardial infarction. Transfer to cardiac catheter laboratory where coronary angiography took place via the right radial artery. Administration of tissue plasminogen activator (tPA) via the intracoronary route, followed by systemic dose intravenously. Subsequently, multiple aspirations using an Export thrombectomy catheter was performed. Transfer to radiology department for computed tomography pulmonary angiogram (CTPA), which confirmed acute pulmonary embolism. Day 2 Transthoracic echocardiogram with bubble-agitated saline revealed a patent foramen ovale (PFO). 2 months Right heart catheterization showing mean pulmonary arterial pressure of 33, wedge pressure of 11, cardiac output of 4.7 L/min (index 2.35) with pulmonary vascular resistance of 5.3 Wood units. The patient managed 80 m on 6-min walk test. Follow-up (6 months) Pulmonary endarterectomy with subsequent successful PFO closure. Outpatient clinic (12 months) Marked improvement in patient’s symptomatic status, including significant improvements in 6-min walking test (411 m).

ry vascular resistance of 5.3 Wood units. The patient managed 80 m on 6-min walk test. Follow-up (6 months) Pulmonary endarterectomy with subsequent successful PFO closure. Outpatient clinic (12 months) Marked improvement in patient’s symptomatic status, including significant improvements in 6-min walking test (411 m). Patient information A 43-year-old woman presented with a history of 2 h of central chest pain associated with breathlessness. She had no cardiac risk factors. Her medical history was significant for PE (diagnosed 5 years ago), managed with apixaban, but with poor adherence. Physical examination On arrival, the patient was profoundly hypotensive with a blood pressure of 60/30 mmHg. She was tachycardiac with a heart rate 115 b.p.m. and peripherally shut down. Cardiovascular examination revealed a parasternal heave, but no murmurs were audible. The lung fields were clear. There was no clinical evidence of deep vein thrombosis. Diagnostic assessment A 12-lead electrocardiogram (ECG) showed inferior ST-segment elevation in leads II, III, and aVF, in keeping with acute MI. An arterial blood gas (on room air) demonstrated acute Type I respiratory failure with an arterial partial pressure of oxygen of 5.5 kPa.

Physical examination On arrival, the patient was profoundly hypotensive with a blood pressure of 60/30 mmHg. She was tachycardiac with a heart rate 115 b.p.m. and peripherally shut down. Cardiovascular examination revealed a parasternal heave, but no murmurs were audible. The lung fields were clear. There was no clinical evidence of deep vein thrombosis. Diagnostic assessment A 12-lead electrocardiogram (ECG) showed inferior ST-segment elevation in leads II, III, and aVF, in keeping with acute MI. An arterial blood gas (on room air) demonstrated acute Type I respiratory failure with an arterial partial pressure of oxygen of 5.5 kPa. Interventions The patient was transferred urgently to the Cardiac Catheter Laboratory. Coronary angiography via the right radial artery showed complete occlusion of the RCA, with a large thrombus straddling a bifurcation in the proximal artery (RCA). The left coronary system was normal. A guidewire was passed across the occlusion, and the origin of the right ventricular branch was identified (Figure 1A). Given the history of PE and poor compliance with anticoagulant therapy, acute Type I respiratory failure with clear lung fields, a concurrent diagnosis of acute PE was suspected. Empirical intracoronary tissue plasminogen activator (tPA; alteplase, 15 mg) was given via the intracoronary route. Multiple aspirations (including of the RV marginal branch) using an Export thrombectomy catheter (Medtronic Vascular, Minneapolis, MN, USA) obtained three large clots (Figure 1B). This established thrombolysis in myocardial infarction (TIMI) III flow downstream in the RCA. The lack of angiographic evidence of atherosclerotic plaque suggested a possible thrombo-embolic infarct. Concurrently, the blood pressure started to improve reaching the systolic pressure of 100 mmHg but with residually poor oxyhaemoglobin saturation of 75%.

myocardial infarction (TIMI) III flow downstream in the RCA. The lack of angiographic evidence of atherosclerotic plaque suggested a possible thrombo-embolic infarct. Concurrently, the blood pressure started to improve reaching the systolic pressure of 100 mmHg but with residually poor oxyhaemoglobin saturation of 75%. Figure 1 Paradoxical embolism leading to occluded right coronary artery (successfully aspirated) and extensive pulmonary embolism. After stabilization, the patient was transferred directly from the Cardiac Catheter Lab for urgent computed tomography pulmonary angiogram. This confirmed acute PE with extensive clot burden in the proximal right pulmonary artery (Figure 1D and E). The full tPA protocol was completed intravenously. A subsequent transthoracic echocardiogram with bubble-agitated saline revealed a patent foramen ovale (PFO) (Figure 1F), with preserved left ventricular function, but a dilated right ventricle with elevated pulmonary artery pressure. The patient was electively scheduled for right heart catheterization, which demonstrated mean pulmonary arterial pressure of 33 mmHg, wedge pressure of 11 mmHg, cardiac output of 4.7 L/min (index 2.35) with pulmonary vascular resistance of 5.3 Wood units. Follow-up and outcomes The patient underwent surgery for pulmonary endarterectomy (leading to reduction in her pulmonary pressure from 47 mmHg to 18 mmHg) and PFO closure 6 months after the index presentation and was symptomatically well on 12 months of follow-up. Her 6-min walk test was significantly improved from 80 m to 411 m.

nd outcomes The patient underwent surgery for pulmonary endarterectomy (leading to reduction in her pulmonary pressure from 47 mmHg to 18 mmHg) and PFO closure 6 months after the index presentation and was symptomatically well on 12 months of follow-up. Her 6-min walk test was significantly improved from 80 m to 411 m. Discussion Coronary embolism is a recognized cause of acute MI; however, paradoxical embolism is relatively rare.2 In an autopsy series of more than 1000 MI patients, coronary embolism accounted for only 5% of the events, with no cases due to paradoxical embolism.2 The high prevalence of PFO in echocardiographic studies makes definitive diagnosis of paradoxical embolism challenging.3 Rather, three criteria have been proposed to make a presumptive diagnosis: (i) embolisation that was not sourced from left heart but (ii) had originated from the venous system and was (iii) associated with abnormal communication between the venous and arterial circulations, in the form of atrial septal defect or PFO.4 The combination of paradoxical embolism with concomitant PE is extremely rare. Acute PE is frequently implicated as detrimental driver for embolism to travel across a PFO.5 This may be explained by the pathophysiological changes that occur following PE. A large PE results in elevated right atrial pressures and systemic hypotension, promoting reversed (right-to-left) blood flow across the PFO.5 In a study of 139 patients with a large PE, the presence of a PFO significantly increased the risk of stroke, peripheral embolism, and mortality.6

anges that occur following PE. A large PE results in elevated right atrial pressures and systemic hypotension, promoting reversed (right-to-left) blood flow across the PFO.5 In a study of 139 patients with a large PE, the presence of a PFO significantly increased the risk of stroke, peripheral embolism, and mortality.6 The similarities in clinical presentations between acute PE and MI make a joint diagnosis very challenging, and more often symptoms, and even ECG changes, are attributed to one pathology.7 Profound hypotension in the context of acute MI is usually due to cardiac pump failure or mechanical complications such as mitral regurgitation, ventricular septal defect, or wall rupture.8 However, in our case, the diagnosis of PE was prompted by extreme hypotension combined with profound hypoxaemia, without pulmonary oedema and out of keeping with an acute inferior MI. The combination of inferior/RV infarctions and pulmonary arterial obstruction with increased pulmonary vascular resistance was considered particularly adverse. The haemodynamic benefits are greatest when thrombolysis was initiated as early as possible, reinforcing the importance of the immediate recognition of this problem and delivering appropriate treatment.9,10

pulmonary arterial obstruction with increased pulmonary vascular resistance was considered particularly adverse. The haemodynamic benefits are greatest when thrombolysis was initiated as early as possible, reinforcing the importance of the immediate recognition of this problem and delivering appropriate treatment.9,10 The use of thrombus aspiration has been proposed as adjunctive treatment to restore coronary perfusion in the context of STEMI.11 In the latest European Society of Cardiology (ESC) guidelines, the routine use of thrombectomy catheter is no longer recommended; however, it has to be targeted towards specific group of patients. In a recent meta-analysis, patients with a large thrombus burden undergoing thrombectomy demonstrated mortality benefits.12 Whether intracoronary lytic therapy may facilitate successful thrombus aspiration is currently being studied in the T-Time trial.13 During the acute setting, closure of PFO is controversial and should be individualized. Although theoretically it may help prevent further recurrence of paradoxical emboli, the PFO may serve to offset the elevated right pressure and maintain cardiac output at the expense of low systemic saturation.14,15 In fact, some reports recommend against PFO closure in the setting of right elevated pressure.14 However, in our case, a successful pulmonary endarterectomy leading to reduction in pulmonary pressure has rationalized the decision to close PFO.

and maintain cardiac output at the expense of low systemic saturation.14,15 In fact, some reports recommend against PFO closure in the setting of right elevated pressure.14 However, in our case, a successful pulmonary endarterectomy leading to reduction in pulmonary pressure has rationalized the decision to close PFO. In conclusion, we reported a rare case of concurrent acute MI caused by paradoxical emboli, associated with, and likely triggered by acute PE. In this case, prompt clinical diagnosis and simultaneous delivery of targeted therapies adapted for the specific clinical presentation have led to an excellent long-term outcome. Funding NIHR Oxford Biomedical Research Centre (R.P.C. and M.A.). Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Systemic thrombosis can develop in patients with cancer despite being on optimal warfarin anticoagulation therapy. Direct oral anticoagulants (DOACs) have been reported to be as safe and effective as conventional therapy for treating venous thromboembolism in patients with cancer. On the other hand, the effect of DOACs on left atrial appendage thrombi is not well understood. More cases and larger scale data are needed to investigate if factor Xa inhibitors are useful for treating systemic thrombosis in patients with cancer. Introduction Venous thromboembolism (VTE) is the third leading cause of cardiovascular mortality.1 Venous thromboembolism commonly occurs in patients with cancer. Left atrial appendage (LAA) thrombi are associated with non-haemorrhagic stroke and systemic embolic events in patients with non-valvular atrial fibrillation (AF). Vitamin K antagonists (VKAs) were the standard of care for patients with VTE or AF. Direct oral anticoagulants (DOACs) are approved to treat VTE and prevent ischaemic stroke in patients with AF. There are no previous reports of simultaneous VTE and LAA thrombus during optimal anticoagulation treatment with VKAs. Timeline Time Event 3 years ago Prostate cancer and atrial fibrillation were diagnosed Over the past 2 years The patient’s international normalized ratio on warfarin was almost always within the therapeutic range Prostate cancer was in remission with medical treatment

Introduction Venous thromboembolism (VTE) is the third leading cause of cardiovascular mortality.1 Venous thromboembolism commonly occurs in patients with cancer. Left atrial appendage (LAA) thrombi are associated with non-haemorrhagic stroke and systemic embolic events in patients with non-valvular atrial fibrillation (AF). Vitamin K antagonists (VKAs) were the standard of care for patients with VTE or AF. Direct oral anticoagulants (DOACs) are approved to treat VTE and prevent ischaemic stroke in patients with AF. There are no previous reports of simultaneous VTE and LAA thrombus during optimal anticoagulation treatment with VKAs. Timeline Time Event 3 years ago Prostate cancer and atrial fibrillation were diagnosed Over the past 2 years The patient’s international normalized ratio on warfarin was almost always within the therapeutic range Prostate cancer was in remission with medical treatment Day 1 The patient presented with left lower extremity oedema. Enhanced computed tomography (CT) confirmed pulmonary embolism (PE), deep vein thrombosis (DVT), and left atrial appendage (LAA) thrombus. Anticoagulation was switched to unfractionated heparin instead of warfarin Day 10 Because of his refractory symptoms, systemic thrombolysis with urokinase was initiated Day 17 Ultrasonography of the lower extremities showing no residual DVT The patient was prescribed apixaban

Day 1 The patient presented with left lower extremity oedema. Enhanced computed tomography (CT) confirmed pulmonary embolism (PE), deep vein thrombosis (DVT), and left atrial appendage (LAA) thrombus. Anticoagulation was switched to unfractionated heparin instead of warfarin Day 10 Because of his refractory symptoms, systemic thrombolysis with urokinase was initiated Day 17 Ultrasonography of the lower extremities showing no residual DVT The patient was prescribed apixaban Follow-up (1 month) Follow-up CT imaging revealed complete resolution of PE, DVT, and LAA thrombus Outpatient clinic (12 months) Marked improvement in the patient’s clinical status. No recurrence of venous thromboembolism and LAA thrombus Case presentation An 85-year-old man was referred to our hospital for the treatment of left lower extremity oedema. His past medical history included localized prostate cancer and cardiogenic cerebral infarction caused by AF. He was taking warfarin (1.5 mg daily) at the time. His prothrombin time-international normalized ratio (PT-INR) was checked monthly by his primary care physician. It was almost always between 2 and 3 over the past 2 years. The most recent PT-INR, approximately 2 months before admission, was 2.66. Three years ago, after prostate cancer was diagnosed, an anti-androgenic agent and a luteinising hormone-releasing hormone agonist were started. Prostate cancer was in remission with these medicines. He had no other risk factors for VTE.

years. The most recent PT-INR, approximately 2 months before admission, was 2.66. Three years ago, after prostate cancer was diagnosed, an anti-androgenic agent and a luteinising hormone-releasing hormone agonist were started. Prostate cancer was in remission with these medicines. He had no other risk factors for VTE. On admission, he was afebrile, heart rate was 96 b.p.m., blood pressure was 170/104 mmHg, and respiratory rate was 24 b.p.m. His oxygen saturation was 96% on room air. There was no obvious jugular venous distention or audible murmurs. The lung fields were clear. His left lower extremity was erythematous and swollen. Laboratory tests revealed high levels of inflammation, as evidenced by the high white blood cell count, 11 100/μL (reference range 3500–8000/μL); C-reactive protein level, 7.55 mg/dL (<0.2 mg/dL); and d-dimer level, 37.0 μg/dL (<1.0 μg/dL). He had normal antinuclear antibody titres. Lupus anticoagulant, anticardiolipin IgG antibodies, and anti-β2-glycoprotein titres were negative. His serum creatinine level was 0.86 mg/dL (0.5–1.2 mg/dL) and his creatinine clearance was 62 mL/min (70–130 mL/min). At presentation, PT-INR was 3.75 (0.9–1.1). Electrocardiography showed AF and inverted T waves in V1 and V2. Computed tomography (CT) with contrast revealed intraluminal filling defects in the LAA, right pulmonary artery, and from the left superficial femoral vein (SFV) to the left popliteal vein (Figure 1A, C, E).

n). At presentation, PT-INR was 3.75 (0.9–1.1). Electrocardiography showed AF and inverted T waves in V1 and V2. Computed tomography (CT) with contrast revealed intraluminal filling defects in the LAA, right pulmonary artery, and from the left superficial femoral vein (SFV) to the left popliteal vein (Figure 1A, C, E). Figure 1 Time course of the pulmonary embolism (A and B), left atrial appendage thrombus (C and D), and deep venous thrombosis (E and F) on contrast-enhanced computed tomography. (A) A thrombus was detected in the right pulmonary artery (arrow). (B) This thrombus had completely disappeared by 1 month after discharge. (C) A thrombus was detected in the left atrial appendage (arrow). (D) No thrombi were detected at 1 month after discharge. (E) A thrombus was detected in the left superficial femoral vein (arrow). (F) No thrombi were detected at 1 month after discharge.

is thrombus had completely disappeared by 1 month after discharge. (C) A thrombus was detected in the left atrial appendage (arrow). (D) No thrombi were detected at 1 month after discharge. (E) A thrombus was detected in the left superficial femoral vein (arrow). (F) No thrombi were detected at 1 month after discharge. Anticoagulation was switched from warfarin to unfractionated heparin (UFH). The target activated partial thromboplastin time was 60–80 s (25–40 s). We administered UFH for 1 week, with no changes in symptoms. No obvious decrease in the size of the thrombi was observed on follow-up CT. Given the patient’s refractory symptoms, refusal to undergo catheter-directed thrombolysis, and no absolute contraindications to urokinase, we decided to perform systemic thrombolysis (360 000 to 540 000 units/day of urokinase) for 1 week to improve his acute lower extremity symptoms and prevent post-thrombotic syndrome. He was then switched to a DOAC after complete symptom resolution and ultrasonography showed no lower extremity thrombi. The direct factor Xa inhibitor apixaban was started at 5 mg twice daily. Enhanced CT approximately 1 month after hospital discharge showed complete resolution of the LAA thrombus, deep vein thrombosis (DVT), and pulmonary embolism (Figure 1B, D, F). During 12 months of follow-up, the patient was doing well with significant improvement in his quality of life. Venous thromboembolism and LAA thrombus were not detected by enhanced CT at 12 months.

Anticoagulation was switched from warfarin to unfractionated heparin (UFH). The target activated partial thromboplastin time was 60–80 s (25–40 s). We administered UFH for 1 week, with no changes in symptoms. No obvious decrease in the size of the thrombi was observed on follow-up CT. Given the patient’s refractory symptoms, refusal to undergo catheter-directed thrombolysis, and no absolute contraindications to urokinase, we decided to perform systemic thrombolysis (360 000 to 540 000 units/day of urokinase) for 1 week to improve his acute lower extremity symptoms and prevent post-thrombotic syndrome. He was then switched to a DOAC after complete symptom resolution and ultrasonography showed no lower extremity thrombi. The direct factor Xa inhibitor apixaban was started at 5 mg twice daily. Enhanced CT approximately 1 month after hospital discharge showed complete resolution of the LAA thrombus, deep vein thrombosis (DVT), and pulmonary embolism (Figure 1B, D, F). During 12 months of follow-up, the patient was doing well with significant improvement in his quality of life. Venous thromboembolism and LAA thrombus were not detected by enhanced CT at 12 months. Discussion The pathogenesis of cancer-related thrombosis is poorly understood, but it is likely to be multifactorial. Virchow’s triad is thought to play a central role in the induction of thrombosis, which may be accompanied by other comorbid factors that increase hypercoagulability. Nakamura et al.2 showed that 27.0% of patients with VTE in Japan have a history of cancer. Low molecular weight heparins (LMWHs) alone have been shown to be more effective and as safe as LMWH followed by VKAs. Thus, LMWHs have become the standard of care for treating VTE in patients with cancer, but cannot be used for VTE in Japan because of insurance coverage issues. In addition, long-term injection therapy is associated with substantial costs and injection fatigue. In recent years, DOACs have been reported to be as safe and effective as conventional VTE therapy in patients with cancer. Vedovati et al.3 conducted a meta-analysis of randomised controlled trials that assessed the safety and efficacy of DOACs in patients with cancer-associated VTE. In their study, VTE recurred in 3.9% of patients with cancer treated with DOACs, compared with 6.0% patients who received conventional treatment (odds ratio 0.63; 95% confidence interval 0.37–1.10). Direct oral anticoagulants are an attractive alternative for treating VTE in patients with cancer. In this case, we selected a DOAC as maintenance therapy.

9% of patients with cancer treated with DOACs, compared with 6.0% patients who received conventional treatment (odds ratio 0.63; 95% confidence interval 0.37–1.10). Direct oral anticoagulants are an attractive alternative for treating VTE in patients with cancer. In this case, we selected a DOAC as maintenance therapy. It is important to reduce thrombus volume during early stages of treatment. Thus, we performed thrombolysis prior to DOAC administration. Schweitzer et al.4 reported that systemic thrombolytic therapy results in significantly fewer closed vein segments 12 months after acute DVT than conventional treatment. They administered urokinase for up to 7 days, while monitoring for bleeding and lower extremity symptoms. Similarly, we administered urokinase for 7 days and frequently evaluated the extent of thrombus dissolution using ultrasonography. When thrombus was no longer detected in the left SFV on Day 7, thrombolysis was discontinued. On the other hand, most thromboembolisms associated with AF originate in the LAA. The effect of DOACs on LAA thrombi is not well understood. There are several case reports about the effects of DOACs on LAA thrombi,5–9 but no meta-analyses or prospective studies. To the best of our knowledge, there have been no previous reports of simultaneous VTE and LAA thrombosis during optimal anticoagulation treatment with VKAs.

Cs on LAA thrombi is not well understood. There are several case reports about the effects of DOACs on LAA thrombi,5–9 but no meta-analyses or prospective studies. To the best of our knowledge, there have been no previous reports of simultaneous VTE and LAA thrombosis during optimal anticoagulation treatment with VKAs. Warfarin and factor Xa inhibitors have different mechanisms of action. Warfarin inhibits vitamin K-dependent coagulation factors (factors II, VII, IX, and X). It also inhibits vitamin K-dependent gamma-carboxylation of proteins C and S; both have anticoagulant effects. On the other hand, factor Xa inhibitors do not consume proteins C and S. Instead, they have complementary anticoagulant actions. The mechanisms underlying hypercoagulability in patients with malignancy are not sufficiently understood. Tumour-specific activation of factor X may be an important step in the activation of the coagulation cascade in patients with malignancy.10 Factor Xa inhibitors might be effective for treating systemic thrombosis during VKA therapy.

erlying hypercoagulability in patients with malignancy are not sufficiently understood. Tumour-specific activation of factor X may be an important step in the activation of the coagulation cascade in patients with malignancy.10 Factor Xa inhibitors might be effective for treating systemic thrombosis during VKA therapy. We chose apixaban for the following reasons. First, apixaban has higher trough concentrations and smaller peak-to-trough fluctuations in plasma as well as anti-factor Xa activity.11 Second, factor Xa inhibitors reportedly do not change levels of existing thrombin and will not completely suppress thrombin production.12 Therefore, a small amount of thrombin might be sufficient to activate high-affinity thrombin receptors on platelets to maintain haemostasis. Miwa et al.6 reported the case of a patient in whom apixaban resolved LAA thrombus refractory to warfarin and dabigatran. This case demonstrates the importance of awareness of systemic thrombosis in patients with cancer regardless of VKA therapy. More cases and larger scale data are needed to investigate if factor Xa inhibitors are useful for treating systemic thrombosis in patients with cancer. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material Supplementary Data Click here for additional data file.

Learning points Veno-arterial extracorporeal membrane oxygenation can restore haemodynamic stability in patients with transient severe left ventricular outflow tract obstruction following cardiac arrest and cardiogenic shock. Veno-arterial extracorporeal membrane oxygenation improves systemic circulation and oxygenation. Introduction Obstruction of the left ventricular outflow tract (LVOTO) is most frequently seen as a consequence of septal myocardial hypertrophy in hypertrophic obstructive cardiomyopathy and in hypertensive heart disease. Systolic anterior motion (SAM) often accompanies LVOTO and is the result of high velocity blood flow in mid-systole, displacing the anterior mitral leaflet to the hypertrophied septum causing a dynamic obstruction throughout systole accompanied by mitral regurgitation (MR).1 Left ventricular outflow tract obstruction is associated with increased risk of sudden cardiac death, exercise intolerance, angina, and syncope. Left ventricular outflow tract obstruction is a dynamic condition and dependent on loading conditions of the left ventricle (LV) with worsening of the obstruction with reduced preload, decreased afterload, and increased contractility.1,2 Timeline Day 1 Out of hospital Cardiac arrest intubation and respiratory support. Primary coronary intervention revealed chronic left anterior descending artery lesion. Echocardiogram with severe left ventricular outflow tract obstruction (LVOTO).

Introduction Obstruction of the left ventricular outflow tract (LVOTO) is most frequently seen as a consequence of septal myocardial hypertrophy in hypertrophic obstructive cardiomyopathy and in hypertensive heart disease. Systolic anterior motion (SAM) often accompanies LVOTO and is the result of high velocity blood flow in mid-systole, displacing the anterior mitral leaflet to the hypertrophied septum causing a dynamic obstruction throughout systole accompanied by mitral regurgitation (MR).1 Left ventricular outflow tract obstruction is associated with increased risk of sudden cardiac death, exercise intolerance, angina, and syncope. Left ventricular outflow tract obstruction is a dynamic condition and dependent on loading conditions of the left ventricle (LV) with worsening of the obstruction with reduced preload, decreased afterload, and increased contractility.1,2 Timeline Day 1 Out of hospital Cardiac arrest intubation and respiratory support. Primary coronary intervention revealed chronic left anterior descending artery lesion. Echocardiogram with severe left ventricular outflow tract obstruction (LVOTO). Day 1–3 Severe pulmonary congestion and low cardiac output with increasing lactate due to severe LVOTO and severe MR despite effort to increase afterload. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Day 4 Echocardiogram revealed cessation of MR and LVOTO. VA-ECMO removed. Day 5–12 Stabilization at intensive care unit. Sedation weaning and patient extubation Day 13 Implantable cardioverter-defibrillator implantation Day 16 Discharged to cardiac rehabilitation

Day 1–3 Severe pulmonary congestion and low cardiac output with increasing lactate due to severe LVOTO and severe MR despite effort to increase afterload. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Day 4 Echocardiogram revealed cessation of MR and LVOTO. VA-ECMO removed. Day 5–12 Stabilization at intensive care unit. Sedation weaning and patient extubation Day 13 Implantable cardioverter-defibrillator implantation Day 16 Discharged to cardiac rehabilitation Case presentation A 74-year-old female with a history of hypertension and mild to moderate valvular aortic stenosis (AS) (mean gradient 20 mmHg) suffered cardiac arrest due to ventricular fibrillation (VF) at a restaurant. Bystander cardio pulmonary resuscitation was initiated immediately, and after two defibrillations she was cardioverted to atrial fibrillation. Return of spontaneous circulation was achieved after 10 min of CPR. The patient was intubated on site and transferred to the nearest primary coronary intervention centre. During transport she showed signs of awakening and was sedated with propofol. Adrenaline infusion was titrated to a mean arterial pressure (MAP) >70 mmHg.

n of spontaneous circulation was achieved after 10 min of CPR. The patient was intubated on site and transferred to the nearest primary coronary intervention centre. During transport she showed signs of awakening and was sedated with propofol. Adrenaline infusion was titrated to a mean arterial pressure (MAP) >70 mmHg. The coronary angiogram showed severe proximal left anterior descending (LAD) artery stenosis. Complete revascularization was achieved after implantation of a single drug-eluting stent in the LAD artery. Troponin T values were only mildly elevated (257 ng/L) and the electrocardiogram without ST-segment elevation. The bedside transthoracic echocardiogram showed a hyperdynamic and hypertrophic left ventricle with ejection fraction of 50–60%. There were signs of LVOTO, SAM, and moderate MR, but no aortic regurgitation (AR). The patient was transferred to the intensive care unit (ICU) for haemodynamic stabilization. Targeted temperature management was omitted due to haemodynamic instability and because the patient had been partly awake.

The coronary angiogram showed severe proximal left anterior descending (LAD) artery stenosis. Complete revascularization was achieved after implantation of a single drug-eluting stent in the LAD artery. Troponin T values were only mildly elevated (257 ng/L) and the electrocardiogram without ST-segment elevation. The bedside transthoracic echocardiogram showed a hyperdynamic and hypertrophic left ventricle with ejection fraction of 50–60%. There were signs of LVOTO, SAM, and moderate MR, but no aortic regurgitation (AR). The patient was transferred to the intensive care unit (ICU) for haemodynamic stabilization. Targeted temperature management was omitted due to haemodynamic instability and because the patient had been partly awake. Within 6 h her haemodynamics deteriorated further with tachycardia 110–130 b.p.m., lactic acidosis (9.2 mmol/L), increasing demand for vasopressor therapy (norepinephrine: 0.7 μg/kg/min) to maintain MAP >60 mmHg and concurrent severe pulmonary oedema with a fall in peripheral oxygenation saturation to 60% despite 100% oxygenation supply and titration of positive end expiratory pressure settings of the mechanical ventilator. Efforts to increase pre- and afterload by volume and additional vasopressor therapy (vasopressin 1.0 U/kg/d) only worsened the degree of congestion. Repeated transthoracic and transoesophageal echocardiograms revealed progression of LVOTO and SAM resulting in severe MR and pulmonary oedema (Figure 1; Supplementary material online, Videos S1–S4).

Within 6 h her haemodynamics deteriorated further with tachycardia 110–130 b.p.m., lactic acidosis (9.2 mmol/L), increasing demand for vasopressor therapy (norepinephrine: 0.7 μg/kg/min) to maintain MAP >60 mmHg and concurrent severe pulmonary oedema with a fall in peripheral oxygenation saturation to 60% despite 100% oxygenation supply and titration of positive end expiratory pressure settings of the mechanical ventilator. Efforts to increase pre- and afterload by volume and additional vasopressor therapy (vasopressin 1.0 U/kg/d) only worsened the degree of congestion. Repeated transthoracic and transoesophageal echocardiograms revealed progression of LVOTO and SAM resulting in severe MR and pulmonary oedema (Figure 1; Supplementary material online, Videos S1–S4). Figure 1 Transoesophageal echocardiographic systolic long-axis images. (A and B) Acquired before, and (C and D) Immediately after initiation of veno-arterial extracorporeal membrane oxygenation. (A) White arrow shows severe systolic anterior motion and (B) left ventricular outflow tract obstruction causing severe mitral regurgitation (red arrow). After initiation of veno-arterial extracorporeal membrane oxygenation systolic anterior motion, left ventricular outflow tract obstruction and mitral regurgitation disappeared.

arrow shows severe systolic anterior motion and (B) left ventricular outflow tract obstruction causing severe mitral regurgitation (red arrow). After initiation of veno-arterial extracorporeal membrane oxygenation systolic anterior motion, left ventricular outflow tract obstruction and mitral regurgitation disappeared. After a multidisciplinary team conference, it was decided to attempt to establish mechanical circulatory support with femoro-femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for oxygenation and restoration of tissue perfusion. Right femoral vein and artery was cannulated via Seldinger’s technique and VA-ECMO established using a Cardiohelp ECMO system. A 21 Fr venous catheter was placed in the right atrium guided by transoesophageal echocardiography for venous drainage. A 17 Fr arterial cannula was placed in the femoral artery and advanced for return of oxygenated blood. Veno-arterial extracorporeal membrane oxygenation blood flow was set at 4.0 L/min. This led to immediate improvement in haemodynamics and resolved SAM. Lactate was normalized within 24 h and oxygenation improved. Demand for vasopressor therapy was minimized. On Day 4, haemodynamics had been restored. The echocardiogram revealed cessation of MR severity to mild and after VA-ECMO flow had been reduced to 1.5 L/min it was removed. After 5 days sedation weaning and extubation was achieved without complications despite intermittent use of low-dose norepinephrine to maintain MAP >70 mmHg.

haemodynamics had been restored. The echocardiogram revealed cessation of MR severity to mild and after VA-ECMO flow had been reduced to 1.5 L/min it was removed. After 5 days sedation weaning and extubation was achieved without complications despite intermittent use of low-dose norepinephrine to maintain MAP >70 mmHg. A Day 13, the patient was discharged from the ICU to the coronary care unit. She was neurologically intact without echocardiographic signs of LVOTO or SAM. Overall, the patient was hospitalized for 16 days. She was discharged with beta-blocking agents after implantation of secondary prophylactic implantable cardioverter-defibrillator (ICD) to ambulatory cardiac rehabilitation. At 6 months of follow-up, the patient was in high spirit and fully asymptomatic. Transthoracic echocardiogram demonstrated normal ejection fraction, mild septal hypertrophy, and unchanged mild AS and discrete AR. No Doppler signs of MR. Pressure gradient in LVOT at rest was not elevated. However during Valsalva manoeuvre the gradient in the LVOT increased to 42 mmHg, suggesting a latent LVOTO. The patient gave informed consent and all identifiable information has been removed.

A Day 13, the patient was discharged from the ICU to the coronary care unit. She was neurologically intact without echocardiographic signs of LVOTO or SAM. Overall, the patient was hospitalized for 16 days. She was discharged with beta-blocking agents after implantation of secondary prophylactic implantable cardioverter-defibrillator (ICD) to ambulatory cardiac rehabilitation. At 6 months of follow-up, the patient was in high spirit and fully asymptomatic. Transthoracic echocardiogram demonstrated normal ejection fraction, mild septal hypertrophy, and unchanged mild AS and discrete AR. No Doppler signs of MR. Pressure gradient in LVOT at rest was not elevated. However during Valsalva manoeuvre the gradient in the LVOT increased to 42 mmHg, suggesting a latent LVOTO. The patient gave informed consent and all identifiable information has been removed. Discussion Several reports have described that dynamic LVOTO may develop as complication in both ST-elevation myocardial infarction and Takotsubo cardiomyopathy in subjects with no previous history of LVOTO.3 In hypertrophic cardiomyopathy, the severity of LVOTO is associated with increased risk of sudden cardiac death. The risk increases with the severity of the obstruction and in symptomatic patients there is an indication for prophylactic ICD implantation.4 This patient had a history of mild to moderate AS and hypertensive heart disease, but no previous signs of hypertrophic cardiomyopathy with LVOTO.

risk of sudden cardiac death. The risk increases with the severity of the obstruction and in symptomatic patients there is an indication for prophylactic ICD implantation.4 This patient had a history of mild to moderate AS and hypertensive heart disease, but no previous signs of hypertrophic cardiomyopathy with LVOTO. Severe dynamic LVOTO may as in the present case mimic cardiogenic shock with inadequate tissue perfusion due to inadequate cardiac output and increased left ventricular filling pressures. This explains why our patient developed cardiogenic shock despite near to normal LVEF. Displacement of the anterior mitral leaflet in systole resulted not only in LVOTO worsening but also in coaptation failure of the anterior and posterior mitral leaflets with subsequent severe MR aggravating pulmonary oedema. Subvalvular LVOTO often occurs in combination with valvular AS. With AS, increased afterload tend to cause LV hypertrophy and subsequent of LVOTO. In hypertrophic obstructive cardiomyopathy, AS may appear by coincidence.5,6 The combined haemodynamic effects of valvular AS and LVOTO are low output syndrome and these effects might be synergistic. However, in this case, AS was only mild to moderate, suggesting haemodynamic instability was due to true LVOTO.

f LVOTO. In hypertrophic obstructive cardiomyopathy, AS may appear by coincidence.5,6 The combined haemodynamic effects of valvular AS and LVOTO are low output syndrome and these effects might be synergistic. However, in this case, AS was only mild to moderate, suggesting haemodynamic instability was due to true LVOTO. The post-cardiac arrest syndrome is characterized by disturbed pre- and afterload conditions, and in our patient systemic vascular resistance was low despite attempt to increase afterload with norepinephrine. Some case reports highlight that the use of inotropes like dobutamine attenuates dynamic obstruction causing a vicious circle.7

arrest syndrome is characterized by disturbed pre- and afterload conditions, and in our patient systemic vascular resistance was low despite attempt to increase afterload with norepinephrine. Some case reports highlight that the use of inotropes like dobutamine attenuates dynamic obstruction causing a vicious circle.7 The Impella transvalvular device was considered unsuitable in the current situation due to SAM and hyperdynamic LV function and TandemHeart is not available at our centre thus VA-ECMO was chosen. Veno-arterial extracorporeal membrane oxygenation is a supportive treatment for cardiopulmonary resuscitation in patients with cardiogenic shock due to myocardial infarction, myocarditis, or pulmonary embolus with haemodynamic compromise and in some situations as bridge to decision for transplant or other definitive strategies.8 Veno-arterial extracorporeal membrane oxygenation establishes a right-to-left shunt by draining blood from the right atrium, blood is then oxygenated and warmed and returned to the arterial circulation in the iliac arteries.9 The purpose of the VA-ECMO is to improve systemic circulation and oxygenation, this at the cost of increased afterload that in the severely compromised heart may lead to inadequate myocardial unloading. Draining of venous blood from the right atrium using VA-ECMO reduce preload with potential of LVOTO aggravation and pulmonary congestion.9 However, LVOTO is not a contraindication to VA-ECMO as with severe AR. In the present case, VA-ECMO broke the vicious circle by restoring circulation and after weaning of mechanical circulatory support, and possibly due to increased afterload both the LVOTO and MR ceased.

of LVOTO aggravation and pulmonary congestion.9 However, LVOTO is not a contraindication to VA-ECMO as with severe AR. In the present case, VA-ECMO broke the vicious circle by restoring circulation and after weaning of mechanical circulatory support, and possibly due to increased afterload both the LVOTO and MR ceased. To our knowledge, this is the first reported case of the use of VA-ECMO in severe dynamic LVOTO with haemodynamic compromise after cardiac arrest with primary VF without myocardial infraction. However, one case report describes the use of VA-ECMO in a patient with sustained cardiogenic shock due to dynamic LVOTO in Takotsubo cardiomyopathy (LVEF 25%). Veno-arterial extracorporeal membrane oxygenation completely reverted cardiogenic shock.2 Conclusion Veno-arterial extracorporeal membrane oxygenation can restore haemodynamic stability in patients with true dynamic LVOTO following cardiac arrest and cardiogenic shock. Thus, VA-ECMO can be used as potential bridge to recovery treatment in patients with cardiovascular collapse due to severe dynamic LVOTO. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material Supplementary Data Click here for additional data file.

Learning points In patients with a midaortic syndrome: The stenosis may only be found below the diaphragm. Involvement of the renal arteries can cause severe arterial hypertension. Stepwise dilation with a drug-eluting balloon is an option to treat. Introduction Interventional dilation with drug-eluting balloons (DEB) is an established therapeutic option in coronary and peripheral arterial disease in adults.1 With successful results in adults, the use in paediatric patients with congenital stenosis has begun. Besides a few clinical trials in pulmonary vein stenosis,2 only a single case with the use of a paclitaxel eluting balloon in a child with Takayasu’s disease and renal artery stenosis has been published.3 The midaortic syndrome is a rare diagnosis and is defined as segmental narrowing of the proximal abdominal aorta. It can be acquired or congenital. The reduced blood perfusion to the renal arteries causes severe renovascular hypertension. Effective therapeutic options are surgical with different modifications of aortoaortic bypass grafts4,5 or interventional with the implantation of stents,6,7 but results are not always satisfactory, particularly on long-term follow-up. Timeline Date Procedures Time difference 10 February 2015 Suspected diagnosis because of syncope, episodes of headache, nose bleeding, and blood pressure difference between arms and legs. Age 15 years

The midaortic syndrome is a rare diagnosis and is defined as segmental narrowing of the proximal abdominal aorta. It can be acquired or congenital. The reduced blood perfusion to the renal arteries causes severe renovascular hypertension. Effective therapeutic options are surgical with different modifications of aortoaortic bypass grafts4,5 or interventional with the implantation of stents,6,7 but results are not always satisfactory, particularly on long-term follow-up. Timeline Date Procedures Time difference 10 February 2015 Suspected diagnosis because of syncope, episodes of headache, nose bleeding, and blood pressure difference between arms and legs. Age 15 years Diagnosis by echocardiography with left ventricular hypertrophy and a narrow long segment of the abdominal aorta proximal to and involving the renal arteries 12 February 2015 Dilation with 7 mm drug-eluting balloons (DEB) 2 days 19 April 2015 Dilation with 8 mm DEB 9.4 weeks 22 June 2015 Dilation with 10 mm DEB 9.1 weeks 28 October 2015 Dilation with 12 mm DEB 18.2 weeks 20 June 2018 Control magnetic resonance imaging demonstrated no evidence of recurrence of stenosis. The blood pressure was 139/64 mmHg at the right arm and 127/65 mmHg at the right leg under therapy with atenolol and amlodipine. 2.64 years

tion with 10 mm DEB 9.1 weeks 28 October 2015 Dilation with 12 mm DEB 18.2 weeks 20 June 2018 Control magnetic resonance imaging demonstrated no evidence of recurrence of stenosis. The blood pressure was 139/64 mmHg at the right arm and 127/65 mmHg at the right leg under therapy with atenolol and amlodipine. 2.64 years Case presentation A 15-year-old female patient (bodyweight 50 kg, height 160 cm) presented with syncope. Severe arterial hypertension was diagnosed (178/147 mmHg left arm, 102/83 mmHg left leg). She reported previous episodes of exercise independent headaches and nose bleeds. Auscultation revealed no cardiac murmurs, but an accentuated second heart sound and reduced pulses in the lower limbs. There were no clinical signs to suggest Alagille or William’s syndrome or clinical evidence of neurofibromatosis. Blood tests showed normal inflammatory markers and normal creatinine. The urine dip showed no markers for blood or protein. No regular medication was taken at the time she presented. The electrocardiogram showed normal sinus rhythm, no significant signs of left ventricular (LV) hypertrophy or abnormal repolarization. Echocardiography detected a severe concentric LV hypertrophy (14 mm diastolic septal diameter, 15 mm diastolic diameter of the LV posterior wall) and a long hypoplastic segment in the abdominal aorta with massive arterial collateralization. Cardiac catheterization confirmed the diagnosis of a midaortic syndrome with a minimum diameter of <1.5 mm and a gradient of 50 mmHg between the aortic arch and the femoral arteries (Figure 1A). The narrow part began directly under the diaphragm above the truncus coeliacus and continued down to the bifurcation of the arteriae iliacae including the renal arteries, with reversed flow in the caudal aorta up to the renal arteries. Because of the extraordinary length of the hypoplastic segment of 23 cm, we decided for a stepwise interventional therapy with a paclitaxel covered balloon. No additional computed tomography scan or magnetic resonance imaging (MRI) was performed. Consultation with our surgeon, supported the interventional approach. The proposed procedure was reviewed and approved by our institutional review board, extensively discussed with the patient’s family, and informed consent was obtained before proceeding.

mography scan or magnetic resonance imaging (MRI) was performed. Consultation with our surgeon, supported the interventional approach. The proposed procedure was reviewed and approved by our institutional review board, extensively discussed with the patient’s family, and informed consent was obtained before proceeding. Figure 1 (A) Initial presentation of the abdominal aorta with subtotal occlusion caused by a 1.7 mm catheter passing through the stenosis. There is a massive collateralization and only minimal contrast opacification of the right renal artery. The white arrow marks the upper entrance to the tubular coarctation of the abdominal aorta, and the black arrows mark the course of the left and right renal artery, if visible. (B) Anatomy after the first dilation with a Paclitaxel covered balloon. (C) After the fourth intervention using a 12 mm drug-eluting balloon an endothelial lesion and intra mural contrast was noted (white asterisk). (D) Magnetic resonance imaging at latest follow-up 2.7 years after this last intervention shows an unobstructed aorta without collateralization.

h a Paclitaxel covered balloon. (C) After the fourth intervention using a 12 mm drug-eluting balloon an endothelial lesion and intra mural contrast was noted (white asterisk). (D) Magnetic resonance imaging at latest follow-up 2.7 years after this last intervention shows an unobstructed aorta without collateralization. After balloon interrogation of the long stenotic abdominal aorta using a 6 × 20 mm Tyshak balloon (NuMED Inc., Hopkinton, NY, USA) to differentiate between rigid stenosis and hypoplastic parts, serial balloon dilation with a 7 × 40 mm paclitaxel covered In.Pact balloon (Medtronic, Minneapolis, MN, USA) (3 µg/mm2 Paclitaxel on the balloon) was performed (Figure 1B) from end to end of the stenosis. Planned redilations, to stepwise improve the aortic compliance and reduce the risk of dissection, were performed after 2, 4, and 8 months with Elutax balloons ranging from 8 mm to 12 mm diameter (Aachen Resonance, Düsseldorf, Germany) (2 µg/mm2 Paclitaxel). At the end of the last interventional procedure, a mild endothelial lesion at the former narrowest point of the aorta was noticed (Figure 1C). This lesion healed and after 2.7 years MRI showed a stable and adequate result (Figure 1D). Today the girl is in unrestricted physical condition. The blood pressure has markedly improved (139/64 mmHg right arm and 127/65 mmHg right leg) under therapy with atenolol and amlodipine. The patient and patient’s family consented to the publication of this case’s history and the images presented.

After balloon interrogation of the long stenotic abdominal aorta using a 6 × 20 mm Tyshak balloon (NuMED Inc., Hopkinton, NY, USA) to differentiate between rigid stenosis and hypoplastic parts, serial balloon dilation with a 7 × 40 mm paclitaxel covered In.Pact balloon (Medtronic, Minneapolis, MN, USA) (3 µg/mm2 Paclitaxel on the balloon) was performed (Figure 1B) from end to end of the stenosis. Planned redilations, to stepwise improve the aortic compliance and reduce the risk of dissection, were performed after 2, 4, and 8 months with Elutax balloons ranging from 8 mm to 12 mm diameter (Aachen Resonance, Düsseldorf, Germany) (2 µg/mm2 Paclitaxel). At the end of the last interventional procedure, a mild endothelial lesion at the former narrowest point of the aorta was noticed (Figure 1C). This lesion healed and after 2.7 years MRI showed a stable and adequate result (Figure 1D). Today the girl is in unrestricted physical condition. The blood pressure has markedly improved (139/64 mmHg right arm and 127/65 mmHg right leg) under therapy with atenolol and amlodipine. The patient and patient’s family consented to the publication of this case’s history and the images presented. Discussion The midaortic syndrome is rare, but its severe form, with involvement of the renal arteries, is associated with significant morbidity and mortality.8 The results of routine measurement of the blood pressure in children should raise suspicion. Because of the non-causal treatment using antihypertensive drug combinations and poor long-term results in endovascular intervention, surgical treatment is widely accepted as the treatment of choice.4,9 However, the implantation of an aortoaortic bypass can become a very complex operation with a high intraoperative risk,5 frequently followed by the need for re-interventions.

e drug combinations and poor long-term results in endovascular intervention, surgical treatment is widely accepted as the treatment of choice.4,9 However, the implantation of an aortoaortic bypass can become a very complex operation with a high intraoperative risk,5 frequently followed by the need for re-interventions. If the midaortic syndrome is interpreted as a local aortic wall disease, a combined medical and endovascular treatment might be a reasonable therapeutic option. Drug-eluting balloons and stents have proven to be safe and effective in coronary artery diseases. Paclitaxel, a cytostatic drug, which is lipophilic, anti-proliferative and irreversibly stops the cell division between meta- and Ana-phase is widely used to cover DEB. In children some reports showed a minor and normally tolerable drug-toxicity of paclitaxel after local therapy.2,10

ective in coronary artery diseases. Paclitaxel, a cytostatic drug, which is lipophilic, anti-proliferative and irreversibly stops the cell division between meta- and Ana-phase is widely used to cover DEB. In children some reports showed a minor and normally tolerable drug-toxicity of paclitaxel after local therapy.2,10 In our patient, the hypoplastic segment of the aorta was very long and included all origins from the coeliac trunk to the iliac vessels. Survival was only possible because of massive collateralization. Using stents in this setting, overstenting of nearly all side branches would have been unavoidable. Surgical therapy with an aortic bypass graft of this long segment would have generated a high risk because of endangered vascular supply of all abdominal organs. Endovascular treatment with a DEB to enlarge the aortic diameter and reduce the risk for re-stenoses was seen as the best therapeutic option in this setting. As the initial result was promising, repeated re-dilations with a stepwise increasing diameter of the DEB were justified. The latest measured residual gradient of <10 mmHg could not prevent from a persistent arterial hypertension as known from late diagnosed coarctation, so antihypertensive medication was required.

In our patient, the hypoplastic segment of the aorta was very long and included all origins from the coeliac trunk to the iliac vessels. Survival was only possible because of massive collateralization. Using stents in this setting, overstenting of nearly all side branches would have been unavoidable. Surgical therapy with an aortic bypass graft of this long segment would have generated a high risk because of endangered vascular supply of all abdominal organs. Endovascular treatment with a DEB to enlarge the aortic diameter and reduce the risk for re-stenoses was seen as the best therapeutic option in this setting. As the initial result was promising, repeated re-dilations with a stepwise increasing diameter of the DEB were justified. The latest measured residual gradient of <10 mmHg could not prevent from a persistent arterial hypertension as known from late diagnosed coarctation, so antihypertensive medication was required. Conclusion This is a single case experience with an intervention-free clinical follow-up and an adequate local result. Repeated balloon dilations with paclitaxel eluting balloons have demonstrated to be an effective and safe therapeutic option in this patient with a severe and long segment midaortic syndrome. This treatment needs to be applied in comparable situations to better judge its value for similar patients. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

Conclusion This is a single case experience with an intervention-free clinical follow-up and an adequate local result. Repeated balloon dilations with paclitaxel eluting balloons have demonstrated to be an effective and safe therapeutic option in this patient with a severe and long segment midaortic syndrome. This treatment needs to be applied in comparable situations to better judge its value for similar patients. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material Supplementary Data Click here for additional data file.

Learning points Renal artery intramural haematoma (IMH) is a rare cause of renal artery obstructed after stenting. Intravascular ultrasound could be useful for qualifying and treating renal artery IMH. Percutaneous transluminal angioplasty from distal to proximal and another stent implantation is an important strategy for treating IMH. Introduction Stent implantation is a treatment for renovascular hypertension due to atherosclerotic renal artery stenosis.1 Renal artery intramural haematoma (IMH) is a rare complication after renal artery stenting.2 It can be diagnosed using intravascular ultrasound (IVUS) instead of computed tomography angiography (CTA) and renal artery angiography (RAG). If severe renal artery IMH causes a non-functional kidney, intervention may be indicated. Balloon dilatation or stent closure is known to be more successful for managing severe renal artery IMH.

ed using intravascular ultrasound (IVUS) instead of computed tomography angiography (CTA) and renal artery angiography (RAG). If severe renal artery IMH causes a non-functional kidney, intervention may be indicated. Balloon dilatation or stent closure is known to be more successful for managing severe renal artery IMH. Timeline Day Hour Events 0 09:00 Right renal artery stent successfully 3 06:58 Sudden right lower abdominal pain 3 09:00 Ultrasound (US): the main trunk of the right renal artery was not clear, and the blood flow was significantly reduced 3 10:00 Computed tomography angiography: the right renal artery stent was unobstructed, but the middle segment was severely obstructed, and the right renal perfusion was light 3 15:00 Dual glomerular filtration rate (GFR) examination discovered that the right kidney was non-functional (GFR: right 0.6; left 75.6) 4 09:00 Renal artery angiography: the right renal artery stent was patent and severe new stenosis of the middle part of the renal artery with two branches involved; however, there was no dissection or thrombus formation 4 09:10 IVUS: the IMH originated at the distal end of the stent, without an identifiable entry point 4 09:20 Percutaneous transluminal angioplasty form far to near and another stent implantation 30 Follow-up: the abdominal pain symptoms had disappeared, and the blood pressure and renal function were normal 90 US: the right renal artery was unobstructed Case presentation A 62-year-old man, a heavy smoker, was admitted with resistant hypertension. He had been a known hypertensive for >10 years; the highest systolic and diastolic blood pressure was 220 and 140 mmHg, respectively. Treatment with oral calcium channel blocker, beta blockers, and diuretics had not controlled the blood pressure. Other medical history included new-onset diabetes for the last 2 months and hyperlipidaemia and coronary heart disease for the last 10 years. No abdominal and cardiovascular abnormalities were found. Conn’s syndrome was excluded by negative aldosterone screening in horizontal position and no abnormal adrenal CT scan. The creatinine level was 84.3 µmol/L (44–133 µmol/L). Renal artery US showed a peak systolic velocity of 358 cm/s, indicating severe stenosis of the right renal artery. Renal artery CTA showed local and ostial stenosis (95%) of the right renal artery (Figure 1A). RAG showed 95% ostial stenosis of the right renal artery (Figure 2A) using a 6 F RDC catheter.

44–133 µmol/L). Renal artery US showed a peak systolic velocity of 358 cm/s, indicating severe stenosis of the right renal artery. Renal artery CTA showed local and ostial stenosis (95%) of the right renal artery (Figure 1A). RAG showed 95% ostial stenosis of the right renal artery (Figure 2A) using a 6 F RDC catheter. The stenosis was pre-dilated with a 4 × 20 mm balloon (Sapphire) at a maximal pressure of 18 atm and implanted with a 6 × 14 mm stent (Express SD) at a maximal pressure of 15 atm through a Fielder guided wire. The intervention was successful without any complications (Figure 2B,Supplementary material online, Video S1). Dual antiplatelet therapy was then administered (aspirin 100 mg, one time daily, clopidogrel 75 mg, one time daily). Figure 1 Preoperative renal artery computed tomography angiography shows that the right renal artery stenosis (red arrow) was 95% (A). Two days after renal artery stenting, reconstruction of renal artery computed tomography angiography showed the lumen of the middle part of the right renal artery was occluded (red arrow) and right renal perfusion was not restored (B). The transverse section highlights a long linear filling defect of the right renal artery (red arrow) with full filling of the left renal artery (yellow arrow) and no filling with contrast media in the right renal cortex (blue arrow) with full filling with contrast media in the left renal cortex (green arrow) (C).

(B). The transverse section highlights a long linear filling defect of the right renal artery (red arrow) with full filling of the left renal artery (yellow arrow) and no filling with contrast media in the right renal cortex (blue arrow) with full filling with contrast media in the left renal cortex (green arrow) (C). Figure 2 Renal artery angiography shows that the right renal artery stenosis (red arrow) was 95% (A). The right renal artery stent is perfect (red arrow), without any complications (B). The obstructed renal artery (red arrow) near the first stent (C). The patency of the right renal artery (red arrow) after PTA and stent re-implantation (D).

ary auscultation with oxygen saturation at 100%, and no more pain. The patient was considered for open cardiac surgery but was evaluated at a high mortality risk based on his age, his medical history, and significant calcifications on his aorta. Our vascular surgical team decided then to perform an endovascular repair. In emergency, an off the shelf endovascular stent graft was used. The rupture measured 12 mm and was located at just a few millimetres proximal to the IA. The ascending aorta measured 8 cm from the coronary sinuses to the IA. The largest diameter measured along the length of the ascending aorta was 33 mm (Figure 1). The shortest available off the shelf thoracic stent graft was the 10 cm length Conformable GORE® TAG® Thoracic Endoprothesis (WL Gore & associates, Flagstaff, AZ, USA).

angiography shows that the right renal artery stenosis (red arrow) was 95% (A). The right renal artery stent is perfect (red arrow), without any complications (B). The obstructed renal artery (red arrow) near the first stent (C). The patency of the right renal artery (red arrow) after PTA and stent re-implantation (D). After 3 days, the patient developed sudden right lower abdominal pain. The abdominal and renal examination was negative, but defaecation had stopped. The electrocardiogram, myocardial enzyme levels, and myocardial infarction marker levels were all normal. Pancreatitis was excluded because the amylase levels were normal. The serum creatinine level increased slightly, to 100–108 µmol/L, the urine protein was weakly positive (+1), and the blood pressure was maintained at 110/70 mmHg. To determine the cause of abdominal pain, renal artery US was performed, which showed that the main trunk of the right renal artery was not clear, and the blood flow was significantly reduced. This indicated a possible complication of right renal artery stenting. Renal artery CTA showed an unobstructed right renal artery stent, a severely stenosed middle segment, and light right renal perfusion (Figure 1B and C, Supplementary material online, Video S2). Considering a diagnosis of thrombosis or dissection of the renal artery, treatment with low-molecular weight heparin anticoagulant and rehydration was administered. Simultaneously, examining the dual glomerular filtration rate (GFR) using nuclear imaging discovered a non-functional right kidney (GFR: right 0.6; left 75.6; Figure 4A). Therefore, RAG was repeated to identify the cause of blood flow reduction and rescuing kidney function; the right renal artery stent was found patent. Severe stenosis (90–95%) of the middle part of the renal artery with two branches involved was seen; however, there was no dissection or thrombus formation (Figure 2C, Supplementary material online, Video S3). To further determine the aetiology of the new lesion, IVUS was used, which showed that the IMH originated at the distal end of the stent, without an identifiable entry point, and the length was about 40 mm (Figure 3, Supplementary material online, Video S4).

rmation (Figure 2C, Supplementary material online, Video S3). To further determine the aetiology of the new lesion, IVUS was used, which showed that the IMH originated at the distal end of the stent, without an identifiable entry point, and the length was about 40 mm (Figure 3, Supplementary material online, Video S4). Figure 3 The original images of intravascular ultrasound (A). The schematic images of intravascular ultrasound shows a strong pulsatile echo area (red arrow) between the intima (blue line) and media (green line) of the right renal artery, resulting in the compression of the true lumen, and no obvious entry and exit of the interlayer and haematoma (B).

ntravascular ultrasound (A). The schematic images of intravascular ultrasound shows a strong pulsatile echo area (red arrow) between the intima (blue line) and media (green line) of the right renal artery, resulting in the compression of the true lumen, and no obvious entry and exit of the interlayer and haematoma (B). After clarifying the cause of the new stenosis, we first used a 2.5 × 20 mm balloon, followed by a 4 × 20 mm balloon (Sapphire) at a low pressure to push out the haematoma and dilate the compressed renal artery from the proximal to the distal end. The cavity of the compressed renal artery increased gradually, and the blood flow improved. However, the residual stenosis was still more than 50%, limiting the blood flow. Therefore, another stent (5 × 19 mm Express SD) was implanted near the first stent; the distal segment of the renal artery was seen to be well-developed (Figure 2D, Supplementary material online, Video S5). After reoperation, dual GFR revealed that the right kidney function had partially recovered (GFR: right 10.3; left 66.3; Figure 4A), the creatinine reduced to 91 µmol/L, and the urine protein was negative (Figure 4C). After discharge, the patient continued to maintain dual antiplatelet therapy. At the third month follow-up, the abdominal pain symptoms had disappeared, the serum creatinine level was 79 µmol/L, the urine protein was negative, and the blood pressure was maintained at 125/83 mmHg without any antihypertension drug. Renal artery US showed that the right renal artery was unobstructed.

telet therapy. At the third month follow-up, the abdominal pain symptoms had disappeared, the serum creatinine level was 79 µmol/L, the urine protein was negative, and the blood pressure was maintained at 125/83 mmHg without any antihypertension drug. Renal artery US showed that the right renal artery was unobstructed. Figure 4 Dual glomerular filtration rate was measured 4 days after the first renal artery stenting, which revealed that the right kidney was non-functional (A). Dual glomerular filtration rate was measured 2 days after the second renal artery stenting, which revealed that the right kidney function had partially recovered. (B). The serum creatinine and urine protein of the patient were normal before the operation and there was no abnormality after primary renal artery stenting. Creatinine increased, and urine protein was weakly positive when the patient had sudden abdominal pain, but both values returned to normal after renal artery re-intervention (C).

reatinine and urine protein of the patient were normal before the operation and there was no abnormality after primary renal artery stenting. Creatinine increased, and urine protein was weakly positive when the patient had sudden abdominal pain, but both values returned to normal after renal artery re-intervention (C). Discussion Stent implantation is a treatment for renovascular hypertension due to atherosclerotic renal artery stenosis.1 Rare complications3,4 such as renal capsule haemorrhage and acute aortic IMH are reported. However, IMH of the renal artery is an extremely rare complication; there is only one report on renal artery IMH immediately caused by a cover stent that was used for treating renal artery dissection after the first renal artery stent implantation.2 In this case, IMH after renal artery stenting occurred late because the first stent was likely oversized; therefore, we report the rare complication of subacute IMH after renal artery stenting.

y caused by a cover stent that was used for treating renal artery dissection after the first renal artery stent implantation.2 In this case, IMH after renal artery stenting occurred late because the first stent was likely oversized; therefore, we report the rare complication of subacute IMH after renal artery stenting. Numerous studies5,6 have reported on coronary artery and aorta IMH after stent implantation. Arteriography is sometimes inadequate in diagnosing IMH. IVUS could observe the location of the IMH, detect interlayer fractures, and determine the reason for the narrowing vascular lumen.7 Due to the lack of outlet, IMH can quickly enlarge, and severe compression of the lumen could cause coronary artery stenosis. Therefore, once coronary artery IMH is diagnosed, emergency treatment must be implemented,8 a cutting balloon dilatation to promote the transformation of typical dissection9 or stent closure.10 The pressure should be expanded properly from the distal to the proximal end to avoid expansion of the IMH,7 which is called a milking sandwich.6

onary artery IMH is diagnosed, emergency treatment must be implemented,8 a cutting balloon dilatation to promote the transformation of typical dissection9 or stent closure.10 The pressure should be expanded properly from the distal to the proximal end to avoid expansion of the IMH,7 which is called a milking sandwich.6 In this case, the obstructed renal artery after renal artery stenting compromised the renal blood perfusion, resulting in serious impairment of renal function, which was the indication for re-intervention. However, it was difficult to identify the reasons for lumen narrowing on performing US, CTA, and RAG. IVUS could provide a clear diagnosis of renal artery IMH and help determine the treatment. To prevent haematoma extending to the distal end, the important strategy was that the renal artery dilatation was carried out from the distal to the proximal end. The diameter of the compressed lumen subsequently improved. However, the residual stenosis of the lumen remained more than 50%. To avoid re-enlargement of haematoma, we implanted the second stent. Subsequently, the blood flow was satisfactory, and the distal segment of the lumen was unobstructed. If RAG and IVUS had not been performed, this case would have been misdiagnosed as dissection or thrombosis of the renal artery, leading to incorrect treatment and further aggravation of the renal injury.

e second stent. Subsequently, the blood flow was satisfactory, and the distal segment of the lumen was unobstructed. If RAG and IVUS had not been performed, this case would have been misdiagnosed as dissection or thrombosis of the renal artery, leading to incorrect treatment and further aggravation of the renal injury. To our knowledge, this is the first case report of the rare complication of subacute renal artery IMH after successful renal artery stenting. Owing to the diagnosis and treatment under the guidance of IVUS, the clinical outcomes were satisfactory. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The authors confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz014_Supplementary_Video Click here for additional data file.

A 62-year-old man with a history of ascending aortic replacement for aortic dissection 3 years ago was referred to our hospital with 3 months of dyspnoea. His past medical history of hypertension was well-controlled by medication. The patient is 173 cm in height and weighs 69 kg, and his physical examination showed holo-diastolic murmur (Levine III/VI) in the third left sternal border, neck vein distention, and leg oedema. His echocardiogram showed preserved left ventricular ejection fraction, right sided heart enlargement, and trivial aortic regurgitation, but no shunt flow was observed. Unfortunately, the patient refused transoesophageal echocardiography, the images of which would have been optimal to visualize and evaluate this patient’s cardiac structures. Thus, other tests were performed, including cardiac catheterization, showing step-up of blood oxygen in the right atrium, and a pulmonary-systemic flow ratio of 4.1. The left anterior oblique view of aortography showed a regurgitant jet from aorta to right atrium which occurred in diastole (Supplementary material online, Video S1), but the ruptured site remained still unclear. Therefore, electrocardiogram (ECG)-gated cardiac computed tomography (CCT) was done and revealed sinus of Valsalva aneurysm (SVA) of non-coronary cusp which ruptured to the right atrium (Figure 1). Further, cine mode reconstruction of CCT showed flap motion of rupture site which opened only during diastole (Figures 2 and 3, Supplementary material online, Video S2). With an estimated aortic root diameter of 60 mm, the decision for the patient to undergo aortic root replacement was made. Following this surgery, the patient experienced a full recovery and was discharged from the hospital.

e which opened only during diastole (Figures 2 and 3, Supplementary material online, Video S2). With an estimated aortic root diameter of 60 mm, the decision for the patient to undergo aortic root replacement was made. Following this surgery, the patient experienced a full recovery and was discharged from the hospital. Figure 1 The coronal reconstruction of cardiac computed tomography showed dilated Valsalva sinus of non-coronary cusp which ruptured to the right atrium (white arrow). Ao, aorta; LV, left ventricle; RA, right atrium; RV, right ventricle. Figure 2 The cine mode reconstruction of cardiac computed tomography showed the flap-type rupture, which was opened to the right atrium in diastole. Ao, aorta; LV, left ventricle; RA, right atrium; RV, right ventricle. Figure 3 The cine mode reconstruction of cardiac computed tomography showed the flap-type rupture, which was closed in systole. Ao, aorta; LV, left ventricle; RA, right atrium; RV, right ventricle.

Figure 2 The cine mode reconstruction of cardiac computed tomography showed the flap-type rupture, which was opened to the right atrium in diastole. Ao, aorta; LV, left ventricle; RA, right atrium; RV, right ventricle. Figure 3 The cine mode reconstruction of cardiac computed tomography showed the flap-type rupture, which was closed in systole. Ao, aorta; LV, left ventricle; RA, right atrium; RV, right ventricle. Sinus of Valsalva aneurysm is a congenital or acquired cardiac anomaly, yet the history of ascending aortic replacement might be considered as a risk for SVA in this case.1 Rupture of SVA usually occurs to the right atrium or ventricle, and typically causes a continuous murmur.2 Rupture of SVA with only a diastolic murmur, as shown in this case, is very rare. While ECG-gated CCT has already been established to diagnose SVA3, cine mode reconstruction of CCT was very useful for the detection of detailed flap motion at the rupture site which opened only during diastole. During systole, the flap might be closed because of low intra-Valsalva pressure (caused by Venturi effect created by the elevated cardiac output), whereas left-to-right shunt might have occurred only in diastole because the pressure in the aortic sinuses was maximal during diastole. Supplementary Material ytz070_Supplementary_Video.zip Click here for additional data file. Acknowledgements The authors thank Heidi N. Bonneau, RN, MS, CCA for review of this report.

Sinus of Valsalva aneurysm is a congenital or acquired cardiac anomaly, yet the history of ascending aortic replacement might be considered as a risk for SVA in this case.1 Rupture of SVA usually occurs to the right atrium or ventricle, and typically causes a continuous murmur.2 Rupture of SVA with only a diastolic murmur, as shown in this case, is very rare. While ECG-gated CCT has already been established to diagnose SVA3, cine mode reconstruction of CCT was very useful for the detection of detailed flap motion at the rupture site which opened only during diastole. During systole, the flap might be closed because of low intra-Valsalva pressure (caused by Venturi effect created by the elevated cardiac output), whereas left-to-right shunt might have occurred only in diastole because the pressure in the aortic sinuses was maximal during diastole. Supplementary Material ytz070_Supplementary_Video.zip Click here for additional data file. Acknowledgements The authors thank Heidi N. Bonneau, RN, MS, CCA for review of this report. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Constrictive pericarditis may be a complication of dermatomyositis. The interventricular septum bulging (or septal bounce) detected by echocardiography is the most striking finding of this type of complication. Introduction Dermatomyositis (DM) is a systemic idiopathic inflammatory myopathy, characterized by an inflammatory infiltrate primarily affecting skeletal muscle and skin, with typical cutaneous lesions2 accompanying, or more often preceding, muscle weakness. The reported incidence of DM ranges from 1.2 to 17 new cases per 1 000 000 inhabitants with a prevalence between 5 and 11 cases per 100 000 individuals.3 Dermatomyositis typically demonstrates a bimodal age distribution with both juvenile and adult forms.4 Pericardial involvement is less common in DM than other connective tissue diseases (<10%) and it nearly always manifests as acute pericarditis, pericardial effusion and cardiac tamponade.5 To our knowledge, only one published case of constrictive pericarditis (CP) in DM6 is available in the medical literature. Timeline 15 January 2016 Hospitalization Clinical history Constitutional symptoms (started 3 months before): progressive weakness and arthralgia Physical examination Gottron’s papules Hepatomegaly Congested jugular veins BP 90/60 mmHg HR 82 b.p.m. (regular) Lower limb oedema Labs Positive anti-Jo1 antibodies Increase of alanine transaminase and creatine phosphokinase Investigations (results) Electromyography (pattern suggestive of dermatomyositis) Muscular magnetic resonance (generalized muscular oedema, atrophy, and adipose infiltration).

Congested jugular veins BP 90/60 mmHg HR 82 b.p.m. (regular) Lower limb oedema Labs Positive anti-Jo1 antibodies Increase of alanine transaminase and creatine phosphokinase Investigations (results) Electromyography (pattern suggestive of dermatomyositis) Muscular magnetic resonance (generalized muscular oedema, atrophy, and adipose infiltration). Muscular biopsy (muscle fibre degeneration due to microvascular damage) Diagnosis Dermatomyositis Treatment Corticosteroids and methotrexate Time two (20 January 2016) Cardiac evaluation Investigations and results Electrocardiogram Sinus rhythm and multiple ventricular premature beats Transthoracic echocardiogram Interventricular septal bounce Significant reduction in mitral inflow velocity and an increase of tricuspid inflow velocity during inspiration Tissue Doppler imaging-E Normal eʹ velocity from the medial mitral annulus (12 cm/s) Transoesophageal echocardiogram Interventricular septal bounce Markedly thickened and calcified pericardium

Diagnosis Dermatomyositis Treatment Corticosteroids and methotrexate Time two (20 January 2016) Cardiac evaluation Investigations and results Electrocardiogram Sinus rhythm and multiple ventricular premature beats Transthoracic echocardiogram Interventricular septal bounce Significant reduction in mitral inflow velocity and an increase of tricuspid inflow velocity during inspiration Tissue Doppler imaging-E Normal eʹ velocity from the medial mitral annulus (12 cm/s) Transoesophageal echocardiogram Interventricular septal bounce Markedly thickened and calcified pericardium Diagnosis Constrictive pericarditis 21 February 2016 Treatment Surgical treatment Pericardial resection 21 April 2016 Outcome After pericardial resection cardiovascular symptoms disappeared and patient went back to normal life 20 February 2018 2 years follow-up Patient was asymptomatic with a NYHA class 1 Case presentation A 16-year-old man was referred to our institution with progressive weakness and arthralgia, mainly involving proximal part of superior limbs. He developed these symptoms during the last 3 months in association with intermittent fever and weight loss. As the patient reported, a skin rash was present for 6 months. He had not received any therapy for these symptoms and signs. At admission he had a temperature of 37.4°C. Physical examination demonstrated significant hepatomegaly. Mucocutaneous examination showed lichenoid papules on the dorsal surface of the hands, typical of Gottron papules.

Diagnosis Constrictive pericarditis 21 February 2016 Treatment Surgical treatment Pericardial resection 21 April 2016 Outcome After pericardial resection cardiovascular symptoms disappeared and patient went back to normal life 20 February 2018 2 years follow-up Patient was asymptomatic with a NYHA class 1 Case presentation A 16-year-old man was referred to our institution with progressive weakness and arthralgia, mainly involving proximal part of superior limbs. He developed these symptoms during the last 3 months in association with intermittent fever and weight loss. As the patient reported, a skin rash was present for 6 months. He had not received any therapy for these symptoms and signs. At admission he had a temperature of 37.4°C. Physical examination demonstrated significant hepatomegaly. Mucocutaneous examination showed lichenoid papules on the dorsal surface of the hands, typical of Gottron papules. His jugular venous pressure was raised and his heart sounds were normal. The chest was clear to auscultation. His blood pressure was 90/60 mmHg with a heart rate of 82 b.p.m. The respiratory rate was 16 breaths per minute and the oxygen saturation was 98%. Blood investigations revealed: High alanine transaminase (78 IU/l) (reference range <35 IU/l) Very high creatine phosphokinase (736 UI/l) (reference range 60–174) Positive Rose-Waaler test. Positive anti-Jo1 antibody High NT-proBNP (3150 ng/l) (upper limit of normal: 900 ng/l).

His jugular venous pressure was raised and his heart sounds were normal. The chest was clear to auscultation. His blood pressure was 90/60 mmHg with a heart rate of 82 b.p.m. The respiratory rate was 16 breaths per minute and the oxygen saturation was 98%. Blood investigations revealed: High alanine transaminase (78 IU/l) (reference range <35 IU/l) Very high creatine phosphokinase (736 UI/l) (reference range 60–174) Positive Rose-Waaler test. Positive anti-Jo1 antibody High NT-proBNP (3150 ng/l) (upper limit of normal: 900 ng/l). In the proximal muscles, electromyography showed small, short, polyphasic actions potentials, with early recruitment motor unit action potentials, indicative of membrane irritability. These findings were more pronounced in the upper limbs. These findings suggested a diagnosis of DM. A right quadriceps femoris biopsy showed B cells inflammatory infiltrated involving perivascular spaces and interfascicular septae, compatible with muscle fibre degeneration due to microvascular damage. Muscular magnetic resonance showed generalized muscular oedema associated with atrophy and adipose infiltration. The patient was diagnosed as having DM (Bohan and Peter’s criteria)7 and was started on corticosteroids therapy (1 mg/kg/day of oral prednisolone) together with methotrexate (15 mg, orally, once a week). The 12-leads electrocardiogram showed a sinus rhythm with multiple ventricular premature beats.

Muscular magnetic resonance showed generalized muscular oedema associated with atrophy and adipose infiltration. The patient was diagnosed as having DM (Bohan and Peter’s criteria)7 and was started on corticosteroids therapy (1 mg/kg/day of oral prednisolone) together with methotrexate (15 mg, orally, once a week). The 12-leads electrocardiogram showed a sinus rhythm with multiple ventricular premature beats. The transthoracic echocardiogram (TTE) showed an atypical interventricular septal bounce into the left ventricular cavity because of ventricular interaction (Supplementary material online, Video S1). Left ventricle and right ventricle (RV) systolic function was normal. Transoesophageal echocardiogram showed a markedly thickened and calcified pericardium and demonstrated very clearly the interventricular septal bounce (Supplementary material online, Video S2). TTE-transvalvular PW Doppler flow studies showed a significant reduction of 31% in mitral inflow velocity and an increase of 25% in tricuspid inflow velocity during inspiration (Figures 1and2). The increase in tricuspid flow during inspiration was less significant than mitral inflow velocity reduction. In contrast, an increase of mitral inflow velocity was noted during expiration with a reduced filling velocity to the right heart (Figures 1and2). The aortic flow velocity decreased during inspiration and increased during expiration. Figure 1 Respiratory variation of mitral inflow. Figure 2 Respiratory variation of tricuspid inflow.

TTE-transvalvular PW Doppler flow studies showed a significant reduction of 31% in mitral inflow velocity and an increase of 25% in tricuspid inflow velocity during inspiration (Figures 1and2). The increase in tricuspid flow during inspiration was less significant than mitral inflow velocity reduction. In contrast, an increase of mitral inflow velocity was noted during expiration with a reduced filling velocity to the right heart (Figures 1and2). The aortic flow velocity decreased during inspiration and increased during expiration. Figure 1 Respiratory variation of mitral inflow. Figure 2 Respiratory variation of tricuspid inflow. Tissue Doppler imaging (TDI) showed a medial eʹ velocity of 12 cm/s and a lateral eʹ velocity of 9 cm/s (annulus reversus). E/eʹ ratio (using average eʹ) was 9 (annulus paradoxus). The echocardiographic findings were in keeping with constrictive pericarditis (CP).8 Patient was diagnosed as having a CP. At the time of diagnosis the NYHA class was 3 (dyspnoea induced by mild exertion). The patient underwent radical pericardiectomy by total median sternotomy without significant post-operative complications. He was discharged on day 10 with a medical therapy consisting of diuretics (furosemide orally 20 mg BID); corticosteroids (5 mg per day of oral prednisone), methotrexate (15 mg orally, once per week), antibiotics (amoxicillin orally 3 g/day for 2 weeks) and paracetamol (maximum 4000 mg/day, orally). Hepatomegaly disappeared 4 weeks after operation together with alanine transaminase normalization.

osemide orally 20 mg BID); corticosteroids (5 mg per day of oral prednisone), methotrexate (15 mg orally, once per week), antibiotics (amoxicillin orally 3 g/day for 2 weeks) and paracetamol (maximum 4000 mg/day, orally). Hepatomegaly disappeared 4 weeks after operation together with alanine transaminase normalization. After pericardial resection, the interventricular septum bulging and the respiratory variation of filling velocities completely disappeared (Supplementary material online, Video S3) (see also Table 1). On follow-up 2 years later, the patient had no symptoms. Discussion In 1899 Oppenheim reported for the first time, according to the current literature, cardiac involvement in polymyositis and DM.9 The pathophysiology of pericardial involvement is similar in all systemic inflammatory diseases. Immune complexes and inflammatory cytokines, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, seem to be related to pericardial involvement, even if their role is not completely cleared.10 Karatolios et al. report that the concentrations of VEGF in pericardial effusion and serum blood were significantly greater in subjects with systemic autoimmune inflammatory disease than in those with coronary artery disease. They also found VEGF levels in pericardial effusion positively correlated with markers of pericardial inflammation, such as lactate dehydrogenase and leucocytes.11 Chronic inflammation may lead to fibrosis, calcification and organization of pericardial fluid with a possible evolution towards pericardial constriction.5

They also found VEGF levels in pericardial effusion positively correlated with markers of pericardial inflammation, such as lactate dehydrogenase and leucocytes.11 Chronic inflammation may lead to fibrosis, calcification and organization of pericardial fluid with a possible evolution towards pericardial constriction.5 Approximately 5–15% of patients with acute or recurrent pericarditis may have a systemic autoimmune disease, either overt or underlying. Pericardial involvement is common in all connective tissue diseases, rheumatoid arthritis and systemic vasculitis, but it might be less common in sarcoidosis and inflammatory bowel diseases. More specifically, while CP may complicate the rheumatoid arthritis, we know it is extremely rare in systemic lupus erythematosus.12 In DM, pericardial involvement usually expresses itself as an acute pericarditis, pericardial effusion, and cardiac tamponade.5 In 1998, Tamir et al.6 reported, for the first time, a case of a 54-year-old man who developed CP 12 years after the diagnosis of DM. The patient presented with progressive weakness, anasarca, and moderate anaemia. To our knowledge, this may be the only case like ours ever reported.

In DM, pericardial involvement usually expresses itself as an acute pericarditis, pericardial effusion, and cardiac tamponade.5 In 1998, Tamir et al.6 reported, for the first time, a case of a 54-year-old man who developed CP 12 years after the diagnosis of DM. The patient presented with progressive weakness, anasarca, and moderate anaemia. To our knowledge, this may be the only case like ours ever reported. The patient’s clinical history may raise a discussion about the relatively rapid development of the constriction picture, within 3 months from the constitutional symptoms onset, even if the patient presented an indefinite skin rash for 6 months. The 2015 ESC Guidelines for the diagnosis and management of pericardial diseases13 reported that the delay between the initial pericardial inflammation and the onset of pericardial constriction is variable and that it is possible to define the clinical picture as persistent constriction after 3–6 months from the onset of symptoms. Imazio et al.14 reported that a warning sign of a possible rapid evolution towards CP is a failure of empirical anti-inflammatory therapy. For this reason, in our patient, a lack of specific therapy in the previous 3 months may have lead to a rapid development of CP. An important issue is how to correctly diagnose pericardial constriction. Oh et al.8 described very accurately the echo-Doppler features of pericardial constriction compared with myocardial restriction.

Imazio et al.14 reported that a warning sign of a possible rapid evolution towards CP is a failure of empirical anti-inflammatory therapy. For this reason, in our patient, a lack of specific therapy in the previous 3 months may have lead to a rapid development of CP. An important issue is how to correctly diagnose pericardial constriction. Oh et al.8 described very accurately the echo-Doppler features of pericardial constriction compared with myocardial restriction. In CP, the most striking findings are ventricular septal motion abnormalities (septal bounce), which do not occur in restriction.15 In the reported case, this finding allowed us to make an early diagnosis. Respiratory variation in ventricular filling arises from the dissociation of intrathoracic and intracardiac pressure change and enhanced ventricular interaction in CP. As we know, inspiration reduces intrathoracic pressure which usually is fully transmitted to intracardiac pressures. On the contrary, in constriction, the intracardiac pressures fall much less than intrathoracic pressure because of pericardial constraint. This difference in pressure change with inspiration results in reduced filling to left side of the heart. The reduction in left heart filling during inspiration causes a reduction in mitral inflow velocity and a shift of the interventricular septum towards the left ventricle. With expiration, left heart filling increases which shifts the interventricular septum back towards the RV, leading to reduced filling to right side of the heart and a late-diastolic reversal of flow in the hepatic veins.

n in mitral inflow velocity and a shift of the interventricular septum towards the left ventricle. With expiration, left heart filling increases which shifts the interventricular septum back towards the RV, leading to reduced filling to right side of the heart and a late-diastolic reversal of flow in the hepatic veins. In CP the eʹ velocity from TDI of the medial mitral annulus is 9 cm/s or greater while it is usually 6 cm/s or less in patients with a restrictive cardiomyopathy. Furthermore, the medial mitral annular eʹ velocity is usually greater than the lateral mitral annular eʹ, since the lateral motion of the heart is limited by the constrictive pericardium. This finding is recognized as “annulus reversus”.8 This again stands in contrast to what is expected in other forms of heart failure, and may reflect tethering of the lateral annulus by the constrictive process.8 Despite elevated LV filling pressures (restrictive transmitral flow pattern) E/e′ remains low in CP (annulus paradoxus). These findings, together with an inferior vena cava plethora and little respiratory variations, are important echocardiographic signs of pericardial constriction.8 As reported in the European Association of Cardio-Vascular Imaging (EACVI) position paper,15 other imaging techniques are useful to make a diagnosis of pericardial constriction. Cardiac computed tomography and cardiac magnetic resonance (CMR) usually detect very accurately pericardial calcification and, in a clinical setting of suspected constriction, they have an essential role in making a correct diagnosis. However, calcification alone does not allow making a diagnosis of ‘pericardial constriction’. In addition, real-time cine CMR demonstrates dilated right atrium, elongated RV and ventricular interdependence.15 At the same time, pericardial adhesions between the thickened pericardium and the epicardial surface of the myocardium with reduced mobility of the myocardium may be highlighted by tagged cine CMR imaging.15

ng aorta measured 8 cm from the coronary sinuses to the IA. The largest diameter measured along the length of the ascending aorta was 33 mm (Figure 1). The shortest available off the shelf thoracic stent graft was the 10 cm length Conformable GORE® TAG® Thoracic Endoprothesis (WL Gore & associates, Flagstaff, AZ, USA). In a hybrid operative room, first we performed an IA debranching with a left to right common carotid bypass through a cervicotomy using GORETEX vascular graft (8 mm). Via a transfemoral approach, the IA was embolized with a plug emplatzer (16 mm). Then, we considered a femoral approach to place the stent graft, but due to bad femoral access and after determining the working length of the delivery catheter would be insufficient to reach the most proximal landing in the ascending aorta, we decided a transapical approach would be necessary. A 24-Fr introducer sheath was placed through a left ventricular transapical approach by using a mini-thoracotomy. The endograft was deployed under rapid pacing with three-dimensional image fusion-guided thoracic endovascular aortic repair (Figure2). The intra-procedural aortography demonstrated a well-positioned endograft with successful seal of the rupture.

addition, real-time cine CMR demonstrates dilated right atrium, elongated RV and ventricular interdependence.15 At the same time, pericardial adhesions between the thickened pericardium and the epicardial surface of the myocardium with reduced mobility of the myocardium may be highlighted by tagged cine CMR imaging.15 Conclusion It is well known that, among cardiovascular complications due to DM, pericardial involvement is rare and usually it manifests as acute pericarditis, pericardial effusion, and/or cardiac tamponade. The reported case demonstrates that CP is a possible complication of DM. A very important point is to correctly using all imaging techniques today available in order to make a correct diagnosis of pericardial constriction. Supplementary Material ytz034_Supplementary_Video Click here for additional data file. Acknowledgements Patient gave his informed consent to use information about his pathological condition in order to write this case report. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The authors confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Cardiogenic shock still represents a challenge condition to diagnose and managing. Multimodality fast access imaging should be used in the non-typical cases of cardiogenic shock to clarify their aetiology. A high level of clinical suspicion is needed for some challenging cases of cardiogenic shock. Introduction Cardiogenic shock is defined by a decrease in cardiac output and evidence of tissue hypoxia despite adequate intravascular volume.1 The reduced cardiac output induces compensatory mechanisms that are usually not satisfactory and if no interventions are undertaken, multi-organ failure and death occur.2 In the contemporary era, cardiogenic shock patients’ management remains challenging. The most frequent cause for this condition is still ischaemic heart disease with a prevalence of 6–10% following ST-elevation myocardial infarction.3 Moreover, despite all advances in medical therapy, percutaneous coronary intervention and left ventricular (LV) assist devices, in-hospital mortality rate remains high.4

The most frequent cause for this condition is still ischaemic heart disease with a prevalence of 6–10% following ST-elevation myocardial infarction.3 Moreover, despite all advances in medical therapy, percutaneous coronary intervention and left ventricular (LV) assist devices, in-hospital mortality rate remains high.4 Timeline Investigations Findings Clinical presentation Acute dyspnoea and haemodynamic collapse Electrocardiogram Right bundle branch block and lateral ST elevation Coronary angiogram No coronary artery occlusion Echocardiogram Left ventricular dysfunction and kinetic changes Computed tomography scan No pulmonary embolism. Left ventricle and pulmonary artery invading tumour Case presentation A 74-year-old woman with past medical history of left breast cancer submitted to radical mastectomy 10 years ago was admitted to the emergency department for acute dyspnoea. Clinical observation showed tachycardia, blood pressure 89/54 mmHg, regular heart sounds, no heart murmurs, arterial oxygen saturation of 85%, tachypnoea, accessory respiratory muscles use, and bilateral rales with left hemithorax dullness at percussion. Electrocardiogram showed sinus tachycardia, right bundle brunch block, and left anterior hemiblock with 2 mm ST-elevation in leads aVL, aVR, and I (Figure 1). Clinical condition deteriorated requiring intensive care unit admission, inotropic and vasopressor support, and mechanical ventilation. Bedside transthoracic echocardiogram (TTE) showed impaired LV function with anterior and lateral wall akinesia. A presumptive diagnosis of myocardial infarction (MI) presenting as cardiogenic shock was made and antithrombotic therapy including loading doses of aspirin (250 mg), ticagrelor (180 mg), and heparin (5000 UI) were administered. Emergent coronary angiogram was performed and showed diffuse non-significative three-vessels disease (Figure 2). Cardiac biomarkers were elevated (high sensitivity troponin I 32 ng/mL, for a normal <0.07 ng/mL and BNP 528 pg/mL, for a normal <100 pg/mL). Based on radiological chest imaging, a mass in the left lung was suspected; TTE imaging review showed LV lateral and anterior wall akinesis due to infiltration by a heterogeneous echogenic mass (Figure 3). Transoesophageal echocardiogram confirmed TTE findings, showing mild mitral regurgitation and a large mass invading the lateral LV wall.

chest imaging, a mass in the left lung was suspected; TTE imaging review showed LV lateral and anterior wall akinesis due to infiltration by a heterogeneous echogenic mass (Figure 3). Transoesophageal echocardiogram confirmed TTE findings, showing mild mitral regurgitation and a large mass invading the lateral LV wall. An urgent computed tomography (CT) scan was performed showing a neoformation located in the lower and mid sections of the left hemithorax, invading the lateral LV wall, pulmonary artery left branch, left pulmonary bronchi and anterior thoracic wall, compatible with an advanced lung cancer (Figure 4). Despite supportive care, clinical status worsened and the patient died in the following hours. Figure 1 Patient’s 12-lead electrocardiogram at presentation shows sinus tachycardia, right bundle brunch block, and left anterior hemiblock with 2 mm ST-elevation in leads aVL, aVR, and I. Figure 2 Coronary angiography shows three vessel diffuse disease with TIMI flow III in all vessels. Figure 3 Transthoracic echocardiography four-chamber subcostal view showing a echogenic mass adjacent to the lateral left ventricular wall. Figure 4 Thoracic computed tomography scan showing a heterogeneous mass, with necrotic material, originating from the inferior left lung lobe invading the anterior and lateral wall of the left ventricle, left branch of the pulmonary artery, left bronchi and anterior chest wall.

rative computed tomography with off the shelf thoracic stent graft Conformable GORE® TAG® Thoracic Endoprothesis (WL Gore & associates, Flagstaff, AZ, USA) with rupture exclusion. (F) The shelf thoracic stent graft Conformable GORE® TAG® Thoracic Endoprothesis (WL Gore & associates, Flagstaff, AZ, USA) covering the IA. He had a significant past medical history: end-stage renal failure undergoing dialysis, and myocardial infarctions with previous stentings (the last infarction dating back 10 months). Earlier in the day, the patient had presented with severe retrosternal chest pain for which a myocardial infarction was initially suspected, but the electrocardiography and the transthoracic echography performed in emergency excluded the diagnosis. A CT scan was realized and showed a local aortic plaque rupture of the ascending aorta with active contrast leakage, the patient was then transferred to our institution. At admission the patient was haemodynamically stable with good blood pressure, a normal pulmonary auscultation with oxygen saturation at 100%, and no more pain. The patient was considered for open cardiac surgery but was evaluated at a high mortality risk based on his age, his medical history, and significant calcifications on his aorta. Our vascular surgical team decided then to perform an endovascular repair.

Figure 3 Transthoracic echocardiography four-chamber subcostal view showing a echogenic mass adjacent to the lateral left ventricular wall. Figure 4 Thoracic computed tomography scan showing a heterogeneous mass, with necrotic material, originating from the inferior left lung lobe invading the anterior and lateral wall of the left ventricle, left branch of the pulmonary artery, left bronchi and anterior chest wall. Discussion To the authors; knowledge, this is the first report of lung cancer mimicking a MI with cardiogenic shock. Despite the absence of typical chest pain, the present case was at first assessed as a cardiogenic shock complicating a MI. The electrocardiogram and echocardiogram findings, and later the cardiac enzymes, suggested left ventricle ongoing ischaemia. However, the coronary angiography revealed no coronary artery occlusion or significant stenosis explaining the clinical presentation. Coronary arteries presented diffuse disease with small vessels and a rich collateral circulation. Revision of the echocardiography images revealed a suspicious mass attached to the left ventricle, what immediately conducted to further imaging modalities. Both transoeosophageal echocardiogram and CT scan were helpful to the diagnosis and haemodynamic impact of a tumoural mass invading the LV wall and pulmonary artery. We believe that the cardiogenic shock mechanism in this case is explained in part by the dysfunction caused by the LV anterior and lateral akinesia with LV dysfunction, but also by the pulmonary artery obstruction which impairs adequate pre-load to the left ventricle. Moreover, the pro-inflammatory and high metabolic rate status that characterizes an advanced and invasive tumour might also contribute for the haemodynamic collapse.

LV anterior and lateral akinesia with LV dysfunction, but also by the pulmonary artery obstruction which impairs adequate pre-load to the left ventricle. Moreover, the pro-inflammatory and high metabolic rate status that characterizes an advanced and invasive tumour might also contribute for the haemodynamic collapse. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz009_Slide_Set Click here for additional data file.

Learning points An endovascular approach to the management of a ruptured plaque in the ascending aorta may be an alternative to open surgery in high-risk patients. There are very few stent grafts able to fit the ascending aorta and in emergency cases, most medical teams have been limited to current thoracic aortic endografts, the shortest ones measure 10 cm. We reported a solution to perform an endovascular repair by extending the length of the aortic coverage by debranching the brachiocephalic artery. Introduction An endovascular approach of a ruptured penetrating atherosclerotic ulcer in the ascending aorta may be an alternative to open surgery in high-risk patients. There are very few stent grafts able to fit the ascending aorta and in emergency cases, most medical teams have been limited to current thoracic aortic endografts, the shortest ones measure 10 cm. Here, we describe a case of endovascular repair of the ascending aorta extending the length of the aortic coverage by debranching the innominate artery (IA).

le to fit the ascending aorta and in emergency cases, most medical teams have been limited to current thoracic aortic endografts, the shortest ones measure 10 cm. Here, we describe a case of endovascular repair of the ascending aorta extending the length of the aortic coverage by debranching the innominate artery (IA). Timeline 14 November 2017 09:00 AM The patient had severe retrosternal chest pain 14 November 2017 03:00 PM Computed tomography (CT) scan: acute plaque rupture of the ascending aorta with active contrast leakage. The leak is located close to the innominate artery 14 November 2017 06:00 PM Transferred to intensive care unit of our institution 14 November 2017 07:00 PM Surgical treatment was carried out. First step: innominate artery debranching with a left to right common carotid bypass. Second step: thoracic endovascular aortic repair with transapical access 15 November 2017 Sudden right hemiparesis for 48 h followed by complete recovery. Normal cerebral CT scan. 04 December 2017 Discharged from the intensive care unit. 14 December 2017 Control CT scan: successful exclusion of the rupture. 15 December 2017 Discharged from our hospital. 26 June 2018 Good clinical evolution: the patient was asymptomatic and doing well without any chest pain and without any neurological sequelae. Case presentation A 79-year-old man was admitted to the intensive care unit on November 2017 for a ruptured penetrating atherosclerotic ulcer of the ascending aorta identified on CT scan (Figure1).

nical evolution: the patient was asymptomatic and doing well without any chest pain and without any neurological sequelae. Case presentation A 79-year-old man was admitted to the intensive care unit on November 2017 for a ruptured penetrating atherosclerotic ulcer of the ascending aorta identified on CT scan (Figure1). Figure 1 (A–D) Initial computed tomography (A and C) and post-operative implantation (B and D). (E and F) Three-dimensional volume rendering reconstruction of initial computed tomography (E) and post-operative computed tomography (F). (A, C, and E) Local aortic plaque rupture of the ascending aorta with active contrast leakage. The leak is located close to the innominate artery (yellow arrow). (B and D) Post-operative computed tomography with off the shelf thoracic stent graft Conformable GORE® TAG® Thoracic Endoprothesis (WL Gore & associates, Flagstaff, AZ, USA) with rupture exclusion. (F) The shelf thoracic stent graft Conformable GORE® TAG® Thoracic Endoprothesis (WL Gore & associates, Flagstaff, AZ, USA) covering the IA.

ough a left ventricular transapical approach by using a mini-thoracotomy. The endograft was deployed under rapid pacing with three-dimensional image fusion-guided thoracic endovascular aortic repair (Figure2). The intra-procedural aortography demonstrated a well-positioned endograft with successful seal of the rupture. Figure 2 Periprocedural angiography in the hybrid operating room with 3-dimensional image fusion-guided thoracic endovascular aortic repair (see Supplementary material online, Videos). Red points were positioned on the coronary ostia, on the ostium of the innominate artery, and on the rupture. (A) Angiography before stent graft exclusion showing the aortic plaque rupture (yellow arrow). (B and C) Stent graft implantation. (D) Angiography after stent graft implantation with rupture exclusion. During post-operative period, the patient underwent an ischaemic stroke with sudden right hemiparesis for 48 h followed by complete recovery. The patient was discharged from the intensive care unit at 19 days and from the hospital at 30 days with an antiplatelet therapy (aspirin 75 mg). The post-operative CT scan showed a successful exclusion of the rupture (Figure3). Eight months after surgical treatment, the patient is in an excellent neurological condition without sequelae, and he recovers a quality of life equivalent to the previous state. Figure 3 Control computed tomography scan: endovascular stent graft covering the innominate artery in acute aortic plaque rupture.

The post-operative CT scan showed a successful exclusion of the rupture (Figure3). Eight months after surgical treatment, the patient is in an excellent neurological condition without sequelae, and he recovers a quality of life equivalent to the previous state. Figure 3 Control computed tomography scan: endovascular stent graft covering the innominate artery in acute aortic plaque rupture. Discussion The decision to use endovascular repair for treatment of aortic ascending pathologies is not an obvious choice because of its unknown results. More than 50% of these procedures described in the literature were completed for Type A dissections with only three acute ruptured aortas described in a review in 2018.1–3 In our case, regarding the high risk of mortality associated with open surgery and cross-clamping of the aorta (13.30% using the European System for Cardiac Operative Risk Evaluation, EuroSCORE). Our cardiovascular surgical team decided to perform an endovascular repair instead of risking the patient to cardiopulmonary bypass. There are few stent grafts able to fit the ascending aorta and in emergency cases, most medical teams have been limited to current thoracic aortic endografts.2 The shortest measure 10 cm. In our case, we describe a solution to extend the length of the aortic distal neck by debranching the IA to provide adequate coverage over the rupture as well as enough length for placement of the thoracic endoprosthesis. We had to cover the IA because the rupture was located very close (<10 mm) to its ostium.

e 10 cm. In our case, we describe a solution to extend the length of the aortic distal neck by debranching the IA to provide adequate coverage over the rupture as well as enough length for placement of the thoracic endoprosthesis. We had to cover the IA because the rupture was located very close (<10 mm) to its ostium. Due to bad femoral access and the size of the introducer (24 Fr), we decided on a transapical approach.4 Deployment of the endograft in the ascending aorta can be challenging and requires precise placement. In our opinion, the procedure is only possible in a hybrid operative room using three-dimensional image superposition and must be performed by a team with experience in the field of endovascular interventions. We believe rapid pacing reduces the risk of graft migration during deployment.1 The patient’s post-operative complication is comparable to what is described in the literature.5 His 19 day long in-hospital stay in intensive care unit was necessary due to his severe morbidities and the need for invasive ventilation for post-operative pulmonary congestion. The patient was discharge from the hospital after 30 days with a quality of life equivalent to the previous state, an open sternotomy with a cardiopulmonary bypass would have further complicated his recovery with possible additional complications.1,4

eed for invasive ventilation for post-operative pulmonary congestion. The patient was discharge from the hospital after 30 days with a quality of life equivalent to the previous state, an open sternotomy with a cardiopulmonary bypass would have further complicated his recovery with possible additional complications.1,4 Endovascular treatment of the ascending aorta is at its infancy and needs further research. This option will continue to be inevitable due to the number of elderly patients unfit for open cardiac surgery. New stent grafts designed for the ascending aorta are in progress and should increase the numbers of interventions in the years to come. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz043_Supplementary_Video Click here for additional data file.

Learning points Constrictive pericarditis (CP) has a long symptom-free period that may take weeks to decades to develop and it is often a clinical diagnosis made with routine investigations. The symptoms and signs of CP are sometimes ignored, leading to a misdiagnosis or delayed diagnosis. Echocardiography has an important diagnostic role in patients with CP. Surgical pericardectomy can improve the symptoms and quality of life of patients with CP.

Constrictive pericarditis (CP) has a long symptom-free period that may take weeks to decades to develop and it is often a clinical diagnosis made with routine investigations. The symptoms and signs of CP are sometimes ignored, leading to a misdiagnosis or delayed diagnosis. Echocardiography has an important diagnostic role in patients with CP. Surgical pericardectomy can improve the symptoms and quality of life of patients with CP. Introduction The symptoms and signs of constrictive pericarditis (CP) are often elusive at onset, with a long symptom-free period that may take weeks to decades to develop after an episode of CP or pericardial injury, leading to a misdiagnosis or a delayed diagnosis.1–3 CP can be secondary to any pericardial disease and, its course is affected by various diseases.4 Data from developed countries indicate that idiopathic and viral pericarditis account for 42–49% of CP cases, and infection (tuberculous or purulent pericarditis) accounts for 3–6% of CP cases.5 Tuberculosis (TB) is a primary aetiological factor of CP in developing countries.6 The diagnosis of CP is based on the clinical manifestations, imaging, and cardiac catheterization.4 Here, we present a case of a patient initially complaining of lower extremity fatigue, intermittent chest tightness, and shortness of breath. He was first misdiagnosed as neuropathy, later unsuccessfully treated as ischaemic heart disease, because the symptoms of chest tightness and shortness of breath were thought to be partially due to severe stenosis of the diagonal branch of left anterior descending artery, which was confirmed by computed tomography angiography (CTA). He was diagnosed as CP after carefully reading the initial computed tomography (CT) scan and finally confirmed by pericardectomy. However, the mechanism underlying large haemorrhagic pericardial effusions remains unclear. His symptoms gradually disappeared after surgical pericardectomy. By reporting this case, we aimed to highlight the important diagnostic role of echocardiography and CT in patients with CP and the potential of surgical pericardectomy in treating CP, promoting the management of this disease.

l effusions remains unclear. His symptoms gradually disappeared after surgical pericardectomy. By reporting this case, we aimed to highlight the important diagnostic role of echocardiography and CT in patients with CP and the potential of surgical pericardectomy in treating CP, promoting the management of this disease. Timeline Time Events 0 month Chief complaint of lower extremity fatigue, severe pitting oedema over both legs and much worse over the right leg, intermittent, and mild chest tightness. 2 months First misdiagnosed as neuropathy: visited the clinic of neuropathy. The computer tomography, diffusion-weighted imaging, and angiography were unremarkable. The initial transthoracic echocardiogram indicated left ventricular ejection fraction (LVEF) of 72%, fractional shortening (FS) 42%, stroke volume (SV) 88 mL, and cardiac output (CO) 10.9 L/min. Moderate pericardial effusion was detected and the depth of liquid in left ventricular apex was 5 mm and diaphragmatic surface of right ventricle was 12 mm. After the treatment with diuretic, there was little improvement of lower extremity fatigue, oedema of lower extremity, and chest tightness. 4 months The symptoms of fatigue, chest tightness, and dyspnoea were unsuccessfully treated as ischaemic heart disease: computed tomography angiography showed that the diagonal branch of left anterior descending artery was severely narrow, pleural effusion, mild pericardial effusion, and the thickening pericardium (all evidences of the thickening pericardium were ignored by the radiologist at this time). However, these syndromes were unsuccessfully treated as ischaemic heart disease. The oedema and shortness of breath was significantly improved after thoracentesis. After removing the drainage tube due to the concerns of iatrogenic infection and discomfort; however, the bilateral pleural effusion shortly reappeared. 5 months Received a diagnosis of constrictive pericarditis (CP): visited the clinic of pulmonary medicine and complained of cough, expectoration, progressive dyspnoea, and pitting oedema over both legs. After reviewing the initial results, the thickened pericardium in high-resolution CT was observed. Constrictive pericarditis is under consideration though there was no Kussmaul sign. This urged the physicians to get informed consent for pericardectomy. 5 months + 1 week The gross pathology during pericardectomy indicating fibrinous pericarditis, massive haemorrhagic pericardial effusion, and thickened pericardium.

. Constrictive pericarditis is under consideration though there was no Kussmaul sign. This urged the physicians to get informed consent for pericardectomy. 5 months + 1 week The gross pathology during pericardectomy indicating fibrinous pericarditis, massive haemorrhagic pericardial effusion, and thickened pericardium. After extensive work excluding malignancy and tuberculosis, the patient finally received a diagnosis of idiopathic CP, though the mechanism underlying it remains unproved. 5 months + 2 weeks All symptoms disappeared 6 months The echocardiogram indicated normal left ventricular function with the data of LVEF 76%, FS 44%, SV 75 mL, and CO 7.8 L/min. 12 months At the most recent follow-up, the patient complained of no discomfort. Case presentation A 58-year-old man was brought to the local hospital with chief complaints of lower extremity fatigue, severe bilateral lower extremity pitting oedema, particularly of the right leg, and intermittent, mild chest tightness. He first visited the neuropathy clinic. The CT, diffusion-weighted imaging, and angiography were unremarkable. Haemoglobin was 108 g/L (normal range within 130–175 g/L), urine protein was 0.43 g/24 h (normal range within 0.00–0.15 g/24 h), and albumin was 34.7 g/L (normal range within 40.0–55.0 g/L). Thyroid function was unremarkable.

the neuropathy clinic. The CT, diffusion-weighted imaging, and angiography were unremarkable. Haemoglobin was 108 g/L (normal range within 130–175 g/L), urine protein was 0.43 g/24 h (normal range within 0.00–0.15 g/24 h), and albumin was 34.7 g/L (normal range within 40.0–55.0 g/L). Thyroid function was unremarkable. The initial transthoracic echocardiogram indicated the internal diameter of the ascending aorta 32 mm, right ventricular outflow 30 mm, the left atrium 30 mm, left ventricular (LV) end − diastolic/systolic dimension 50 mm/29 mm, LV dimension 18 mm, and LV function was normal with an ejection fraction (LVEF) of 72%, fractional shortening (FS) of 42%, stroke volume (SV) of 88 mL, and cardiac output (CO) of 10.9 L/min. A moderate pericardial effusion was detected, and the depth of liquid at the left ventricular apex was 5 mm. The diaphragmatic surface of the right ventricle was 12 mm. After the treatment with diuretic, there was little improvement in lower extremity fatigue, oedema of the lower extremities, or chest tightness.

L/min. A moderate pericardial effusion was detected, and the depth of liquid at the left ventricular apex was 5 mm. The diaphragmatic surface of the right ventricle was 12 mm. After the treatment with diuretic, there was little improvement in lower extremity fatigue, oedema of the lower extremities, or chest tightness. Therefore, the patient visited the outpatient clinic of cardiology for further treatment after new facial and ankle oedema appeared and his shortness of breath persisted. On admission to the cardiology department, a chest X-ray revealed bilateral pleural effusions (Figure1A). Echocardiogram showed normal left ventricular function with an LVEF of 65%, FS of 35%, SV of 76 mL, CO of 9.2 L/min, a small-medium pericardial effusion (left ventricular posterior wall 6.4 mm, right ventricular anterior wall 7.7 mm, apex of the heart 6 mm, right ventricular free wall 17 mm, left ventricular free wall 6 mm), increased size of the right heart (right atrial diameter 36 mm × 46 mm, right ventricle internal dimension 40 mm × 70 mm), dilation of the inferior vena cava (24 mm) and respiratory variation of the mitral peak E velocity of >25% (Figure2). Electrocardiography showed sinus tachycardia, and T wave inversion (Figure3). The coronary CTA and computed tomography pulmonary angiogram (CTPA) showed severe narrowing of the diagonal branch of left anterior descending artery (Figure4A), as well as the presence of pleural effusion (Figure4B) and peritoneal effusion. Thoracentesis of the left thoracic cavity using imaging guidance was performed to determine the cause of the excess pleural effusions and to relieve his shortness of breath. A total of an estimated 1180 mL of fluid was drained from the pleural effusion during hospitalization. Laboratory tests of the pleural effusion indicated leakage fluid with the following results: light yellow turbid liquid, Rivalta test (+), total cells count 152 × 106, monocytes accounting for 90% of total white blood cells, white blood cells count 140 × 106, protein 27.7 g/L, glucose 11.87 mmol/L, lactate dehydrogenase (LDH) 106 U/L, and adenosine deaminase (ADA) 4 U/L. Thoracentesis of the right thoracic cavity was also performed later. A total of 3050 mL of fluid was drained from the pleural effusion during hospitalization.

blood cells, white blood cells count 140 × 106, protein 27.7 g/L, glucose 11.87 mmol/L, lactate dehydrogenase (LDH) 106 U/L, and adenosine deaminase (ADA) 4 U/L. Thoracentesis of the right thoracic cavity was also performed later. A total of 3050 mL of fluid was drained from the pleural effusion during hospitalization. Laboratory tests of the pleural effusion indicated leakage fluid with the following results: light yellow turbid liquid, Rivalta test (+), total cells count 352 × 106, monocytes accounting for 72% of total white blood cells, white blood cell count 287 × 106, protein 31.6 g/L, glucose 12.55 mmol/L, LDH 111 U/L, and ADA 4 U/L. Hyperplastic mesothelial cells and lymphocytes were found in the pleural effusion. The oedema and shortness of breath was significantly improved after thoracentesis. After removing the drainage tube due to the concerns of iatrogenic infection and discomfort, however, the bilateral pleural effusions quickly reappeared. Based on the CTA result indicating the severe stenosis of the diagonal branch of left anterior descending artery, antiplatelet and lipid-lowering medications, and a beta-blocker were prescribed because the symptoms of fatigue, chest tightness, and dyspnoea were partially thought to be due to ischaemic heart disease. However, these symptoms were unsuccessfully treated as ischaemic heart disease.

of left anterior descending artery, antiplatelet and lipid-lowering medications, and a beta-blocker were prescribed because the symptoms of fatigue, chest tightness, and dyspnoea were partially thought to be due to ischaemic heart disease. However, these symptoms were unsuccessfully treated as ischaemic heart disease. Figure 1 The chest X-ray on admission (A) showed high density involving both lungs symmetrically and massive pleural effusion, and chest X-ray (B) after pericardectomy indicated significant improvement. Red arrow indicates pleural effusion. Figure 2 Echocardiogram showed (A) small-medium pericardial effusion (red arrows) with the data of left ventricular posterior wall 6.4 mm, right ventricular anterior wall 7.7 mm, apex of heart 6 mm, right ventricular free wall 17 mm, left ventricular free wall 6 mm, and thickened parietal pericardium (blue arrow); however, which was not observed by the sonographer. (B) Dilation of the inferior vena cava (24 mm). (C) Respiratory variation of the mitral peak E velocity of >25%. Figure 3 Electrocardiography showed sinus tachycardia and T wave inversion (25 mm/s, 10 mm/mv).

Figure 2 Echocardiogram showed (A) small-medium pericardial effusion (red arrows) with the data of left ventricular posterior wall 6.4 mm, right ventricular anterior wall 7.7 mm, apex of heart 6 mm, right ventricular free wall 17 mm, left ventricular free wall 6 mm, and thickened parietal pericardium (blue arrow); however, which was not observed by the sonographer. (B) Dilation of the inferior vena cava (24 mm). (C) Respiratory variation of the mitral peak E velocity of >25%. Figure 3 Electrocardiography showed sinus tachycardia and T wave inversion (25 mm/s, 10 mm/mv). Figure 4 Computed tomography angiography scan on admission showed severe stenosis of the diagonal branch of left anterior descending artery (A), pleural effusion (B), mild pericardial effusion and the thickening pericardium (C–E). However, all evidences of the thickening pericardium were ignored by the radiologist. White arrows indicate irregular fluid levels and encapsulated effusion, supporting the chronic process. Red arrows indicate thickening pericardium. The pericardial thickness by high-resolution computed tomography was more than 4.5 mm. Red asterisks indicate pericardial effusion.

cardium were ignored by the radiologist. White arrows indicate irregular fluid levels and encapsulated effusion, supporting the chronic process. Red arrows indicate thickening pericardium. The pericardial thickness by high-resolution computed tomography was more than 4.5 mm. Red asterisks indicate pericardial effusion. After being discharged from the department of cardiology without a clear aetiology, the patient complained of cough, expectoration, progressive dyspnoea, and bilateral lower extremity pitting oedema. He then visited the department of pulmonary medicine. After reviewing the initial CT results, a thickened pericardium was observed (Figure4C–E). Though there was no evident Kussmaul sign, CP was considered and this urged the physicians to get informed consent to perform a pericardectomy. The gross view of the heart in situ originally observed during pericardectomy indicated fibrinous pericarditis, a massive haemorrhagic pericardial effusion, and thickened pericardium (Figure5A and Supplementary material Video S1). The maximum thickness of the pericardium was more than 6 mm (Figure5B). Haematoxylin and eosin (H&E) staining of the pericardial tissue biopsy obtained from five different regions of the thickened pericardium showed massive chronic inflammatory cell infiltration (phlogocytes and leucomonocytes) and fibroid necrosis (hyaline degeneration). There were no pathological characteristics of TB or malignancy (Figure 6). The patient was diagnosed as idiopathic pericarditis. Chronic, non-specific vascular inflammation was proposed to be responsible for the haemorrhagic pericardial effusion. All of the symptoms gradually disappeared 1 week after pericardectomy. Prior to discharge, the repeated X-ray (Figure 1B) indicated disappearance of the cavity effusion. At the first scheduled follow-up visit 1 month after pericardectomy, the echocardiogram indicated normal left ventricular function with an EF of 76%, FS of 44%, SV of 75 mL, and CO of 7.8 L/min. At the 2-, 5-, 7-, and 12-month follow-ups, the patient had no complaints of discomfort.

isappearance of the cavity effusion. At the first scheduled follow-up visit 1 month after pericardectomy, the echocardiogram indicated normal left ventricular function with an EF of 76%, FS of 44%, SV of 75 mL, and CO of 7.8 L/min. At the 2-, 5-, 7-, and 12-month follow-ups, the patient had no complaints of discomfort. Figure 5 (A) The gross view of heart in situ originally observed at the time of pericardectomy indicated fibrinous pericarditis, massive haemorrhagic pericardial effusion, and thickened pericardium. (B) The maximum thickness of the pericardium is more than 6 mm. Black arrows indicate thickened pericardium, white arrows indicate haemorrhagic pericardial effusion, and white box indicates massive fibrinous pericarditis. Figure 6 Histopathology, haematoxylin and eosin staining of the pericardial tissue biopsy at different magnification of 4×, 10×, 20×, 40×, and 100×, respectively, shows massive chronic inflammatory cell infiltration (phlogocytes and leucomonocytes) and fibrinoid necrosis (hyaline degeneration). Red and black arrows indicate the outer and interior of cardiac pericardium, respectively.

ricardial tissue biopsy at different magnification of 4×, 10×, 20×, 40×, and 100×, respectively, shows massive chronic inflammatory cell infiltration (phlogocytes and leucomonocytes) and fibrinoid necrosis (hyaline degeneration). Red and black arrows indicate the outer and interior of cardiac pericardium, respectively. Discussion Our case shows the symptoms and signs of right-sided heart failure, including shortness of breath, pleural effusion, ascites, pericardial effusion, and ankle oedema, all of which are non-specific for the diagnosis of CP. The signs and symptoms of predominantly right-sided heart failure were present with shortness of breath, jugular venous distention, oedema, and ascites, which are seen in 24.7, 89.0, 89.0, and 62.0% of the cases of CP.7 The percentages of total CP patients without the sign of Kussmaul’s respirations, pulsus paradoxus, and pericardial knock are 21.0, 20.0, and 20.0, respectively.8 In our case, decreasing the amount of pleural and pericardial fluid effectively relieve the patient’s shortness of breath but all symptoms reappeared shortly. CP should have been considered.

nts without the sign of Kussmaul’s respirations, pulsus paradoxus, and pericardial knock are 21.0, 20.0, and 20.0, respectively.8 In our case, decreasing the amount of pleural and pericardial fluid effectively relieve the patient’s shortness of breath but all symptoms reappeared shortly. CP should have been considered. Pericardial thickness was present in 37% of CP patients evaluated by echocardiography and 72% by CT.9 A threshold of pericardial thickness >3–4 mm, respectively yielded a sensitivity and specificity of 83–91% and 100% for the diagnosis of CP.10 Increased pericardial thickness of 3 mm was observed in all patients with CP.11 In our patient, the pericardial thickness was more than 4.5 mm by high-resolution CT (Figure4C–E) and more than 6.0 mm by directly pathological observation (Figure 5 and Supplementary material Video S1), leading to the diagnosis of CP. However, the presence of thickened pericardium on CT was missed in the initial diagnosis, in part, because the thickened pericardium was not significant on CT (4 mm) and was complicated by the presence of pericardial effusion (Figure4C–E). It is easy to overlook a slightly thickened pericardium and pericardial effusions when mixed with cellulose exudate and blood components which were proved during pericardectomy.

, because the thickened pericardium was not significant on CT (4 mm) and was complicated by the presence of pericardial effusion (Figure4C–E). It is easy to overlook a slightly thickened pericardium and pericardial effusions when mixed with cellulose exudate and blood components which were proved during pericardectomy. In patients with CP, the outer layer of the myocardium has decreased motion similar to the pericardium, while the motion of the inner layer of the myocardium is stronger than that of the outer layer myocardium.12 The echocardiogram did suggest the CP, although it showed a small-medium pericardial effusion, an increase in right heart size, dilation of the inferior vena cava, and respiratory variation of the mitral peak E velocity of >25% in our patient. The observed signs could also be caused by an existing pericardial effusion. We did not observe septal bounce, or abnormal motion of the myocardium, which could be related to the various clinical manifestations of CP at different stages or the experience of the individual performing the echocardiogram.

in our patient. The observed signs could also be caused by an existing pericardial effusion. We did not observe septal bounce, or abnormal motion of the myocardium, which could be related to the various clinical manifestations of CP at different stages or the experience of the individual performing the echocardiogram. The common causes of large haemorrhagic pericardial effusion are TB and malignancy.13,14 In patients those underwent a pericardiocentesis to relieve cardiac tamponade, 64% had a bloody pericardial effusion. The causes of bloody pericardial effusion are iatrogenic disease (31%), malignancy (26%), complications of atherosclerotic heart disease (particularly acute myocardial infarction) (11%), and idiopathic disease (10%).15 Some cases of idiopathic pericarditis present with large haemorrhagic pericardial effusions.16,17 In this case, there was no evidence of TB, malignancy, or autoimmune diseases by laboratory tests and pericardial biopsy except for the infiltration of massive, scattered lymphocytes, and fibroid necrosis in the pericardial tissue (Figure6). Taking into account the aforementioned data, we diagnosed this case as idiopathic CP associating with large haemorrhagic pericardial effusion though the mechanism underlying it remains unproved. Lead author biography

The common causes of large haemorrhagic pericardial effusion are TB and malignancy.13,14 In patients those underwent a pericardiocentesis to relieve cardiac tamponade, 64% had a bloody pericardial effusion. The causes of bloody pericardial effusion are iatrogenic disease (31%), malignancy (26%), complications of atherosclerotic heart disease (particularly acute myocardial infarction) (11%), and idiopathic disease (10%).15 Some cases of idiopathic pericarditis present with large haemorrhagic pericardial effusions.16,17 In this case, there was no evidence of TB, malignancy, or autoimmune diseases by laboratory tests and pericardial biopsy except for the infiltration of massive, scattered lymphocytes, and fibroid necrosis in the pericardial tissue (Figure6). Taking into account the aforementioned data, we diagnosed this case as idiopathic CP associating with large haemorrhagic pericardial effusion though the mechanism underlying it remains unproved. Lead author biography Guoliang Li, MD, PhD, research work focuses on cardiac electrophysiology. He achieved the bachelor degree in medicine and PhD degree from Xi’an Jiaotong University. He studied as a joint training PhD candidate in Institut de Cardiologie of Hôpital de la Salpêtrière in Paris, France. Now, he is a clinical fellow in cardiac electrophysiology in Fuwai hospital in Beijing. Supplementary Material ytz064_Supplementary_Video Click here for additional data file.

Guoliang Li, MD, PhD, research work focuses on cardiac electrophysiology. He achieved the bachelor degree in medicine and PhD degree from Xi’an Jiaotong University. He studied as a joint training PhD candidate in Institut de Cardiologie of Hôpital de la Salpêtrière in Paris, France. Now, he is a clinical fellow in cardiac electrophysiology in Fuwai hospital in Beijing. Supplementary Material ytz064_Supplementary_Video Click here for additional data file. Acknowledgements We extend our gratitude to Dr Shuanliang Fan from Dr Forensic Medical College of Xi'an Jiaotong University, Prof. Limei Chen from Department of Hematopathology, Prof. Guanjun Zhang from Department of Pathology, Prof. Danjun Zhu, Ke Han and Chaofeng Sun from Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Prof. Xinli Li from Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, for their contribution for discussion of the diagnosis. We extend our gratitude to Dr Ryan Yuan from Overlake Medical Center for his revising this manuscript. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Case description A 50-year-old hypertensive male presented to the emergency room with unstable angina (rest angina Class IIB as per the Braunwald classification). Electrocardiogram showed pathological Q-waves and T-wave inversion in the inferior limb leads (Supplementary material online, Figure S1). Transthoracic echocardiogram showed no wall motion abnormality and a left ventricular ejection fraction of 60%. Coronary angiogram revealed normal left coronary artery, while the right coronary artery (RCA) could not be localized despite using various diagnostic catheters such as Amplatz Right (AR1), Amplatz Left (AL1), Judkins Right (JR), and an aortic root angiogram by a pigtail catheter (Supplementary material online, Videos S1 and S2). A computed tomography coronary angiogram revealed an anomalous high origin of RCA from the ascending aorta, 3 cm above the sino-tubular junction on the right side (Figure 1) and significant stenosis of the proximal and distal RCA. The RCA was cannulated at the ascending aorta using a 6-Fr AL1 coronary guide catheter. There was a high take-off of RCA from the ascending aorta (Supplementary material online, Video S3) and diffuse disease in the proximal segment and from the distal segment to the posterior left ventricular (PLV) branch (Supplementary material online, Video S4). Optical coherence tomography (OCT) showed a fibro-fatty plaque with a thin-cap atheroma (Figure 2 and Supplementary material online, Video S5). Two overlapping Xience Prime stents (Abbott Vascular, Santa Clara, CA, USA) of 3 × 38 mm and 2.75 × 38 mm were deployed in the distal RCA-PLV segment and a 4 × 33 mm Xience Prime stent was deployed in the proximal RCA with a good angiographic end-result (Supplementary material online, Video S6). Repeat OCT imaging after the intervention revealed well-apposed stent struts with no significant residual stenosis or edge dissection. He was discharged on Day 3 on dual antiplatelet therapy (aspirin 300 mg and clopidogrel 75 mg), along with atorvastatin 40 mg, metoprolol succinate 50 mg, and Telmisartan 80 mg. He remained asymptomatic during 18 months of clinical follow-up.

pposed stent struts with no significant residual stenosis or edge dissection. He was discharged on Day 3 on dual antiplatelet therapy (aspirin 300 mg and clopidogrel 75 mg), along with atorvastatin 40 mg, metoprolol succinate 50 mg, and Telmisartan 80 mg. He remained asymptomatic during 18 months of clinical follow-up. Figure 1 A volume-rendered computed tomography reconstructed image shows high take-off of the right coronary artery from the ascending aorta with a funnel-shaped ostium, while the left coronary artery is arising from the sino-tubular junction at the left aortic sinus. Figure 2 Optical coherence tomography image shows a thin-cap fibroatheroma (white arrow) with a dense lipid pool (red arrow), cholesterol crystals (green arrow), and fibrous tissue (asterisk) in the proximal right coronary artery. To the best of our knowledge, there are only five described cases with very high take-off of RCA from the ascending aorta above the sino-tubular junction on the right side.1–4 This is the first case where PCI with intravascular imaging was done for this rare anomaly. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz139_Supplementary_Data Click here for additional data file.

Learning points Spontaneous coronary artery dissection could be associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) syndrome. Spontaneous coronary artery dissection is a result of arteriopathy and CADASIL syndrome is a result of angiopathy both similarly affecting the vascular system causing ischaemia and infarction. Introduction Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) syndrome is an autosomal dominant inherited angiopathy thought to be caused by mutations in the NOTCH3 gene.1 The NOTCH3 gene encodes for the NOTCH3 receptor protein, modulating vascular smooth muscle activity. Mutations in the gene are thought to result in loss of vascular smooth muscle cells, vascular dysfunction, and the associated subsequent vascular ischaemic events. Its prevalence is estimated as between 2 and 5 in 100 000.2 Migraine with aura and cerebral infarctions, with later progressive features of leucoencephalopathy is the most recognized form of presentation.3 Histological examination shows granular osmiophilic material (GOM) in arterial walls.4 Magnetic resonance imaging shows white matter abnormalities, lacunar infarcts, and micro-bleeds.5

ith aura and cerebral infarctions, with later progressive features of leucoencephalopathy is the most recognized form of presentation.3 Histological examination shows granular osmiophilic material (GOM) in arterial walls.4 Magnetic resonance imaging shows white matter abnormalities, lacunar infarcts, and micro-bleeds.5 We present a case of a patient with CADASIL syndrome who presented with an acute coronary syndrome; subsequent coronary angiography was highly suggestive of spontaneous coronary dissection (SCAD). Spontaneous coronary artery dissection is characterized by a false lumen forming within the layers of the coronary arterial wall restricting blood flow. The underlying mechanism for SCAD is unclear but it is regarded as a manifestation of a more widespread arteriopathy resulting in coronary arterial wall degradation with increased risk of development of compressive intramural haematoma due to vaso vasorum bleeding or frank intimal tear and subsequent ischaemic coronary events.6

lying mechanism for SCAD is unclear but it is regarded as a manifestation of a more widespread arteriopathy resulting in coronary arterial wall degradation with increased risk of development of compressive intramural haematoma due to vaso vasorum bleeding or frank intimal tear and subsequent ischaemic coronary events.6 Timeline Time Events 5 October 2018 Emergency admission for ST-elevation myocardial infarction. Angiogram showed spontaneous coronary dissection. 6 October 2018 Started on IV glyceryl trinitrate (GTN) infusion in view of chest pain. 7 October 2018 GTN infusion stopped. 9 October 2018 Discharged with dual antiplatelets for 3 months and Aspirin lifelong thereafter. Awaiting follow up in clinic. Case presentation A 61-year-old woman who was normally fit and well with a background history of CADASIL syndrome presented to the emergency department with chest pain and feeling dizzy and unwell. She had no other risk factors for coronary artery disease. CADASIL diagnosis was made in a regional specialist neurological centre and she was under follow-up. Her cardiovascular examination revealed an initial blood pressure of 167/81 mmHg, heart rate of 81 b.p.m., and her electrocardiogram showed anterior ST-segment elevation (Figure 1) with a raised initial high-sensitivity troponin level which was 1551 ng/L (0–15 ng/L). On auscultation, her chest was clear and heart sounds were essentially normal. Jugular venous pressure was normal and there was no peripheral oedema present. Her bedside focused transthoracic echocardiography showed anterolateral regional wall motion abnormalities with akinesia in the anterior segments with a visually estimated left ventricular ejection fraction of 35%. She underwent emergency radial coronary angiography which showed an abnormal appearance of the left anterior descending artery (LAD) suggestive of SCAD. She had a long segment of irregular filling of the mid anterior descending artery with a tubular stenosis. The proximal LAD, the circumflex, and right coronary arteries were angiographically normal. Given the appearance of thrombolysis in myocardial infarction Grade 3 flow in the LAD territory and recognizing the potential risks of percutaneous intervention in the setting of SCAD, she was, therefore, managed medically with dual antiplatelets (Aspirin and Clopidogrel) for 3 months, Bisoprolol, Ramipril, and Atorvastatin (Figures 2 and 3).

thrombolysis in myocardial infarction Grade 3 flow in the LAD territory and recognizing the potential risks of percutaneous intervention in the setting of SCAD, she was, therefore, managed medically with dual antiplatelets (Aspirin and Clopidogrel) for 3 months, Bisoprolol, Ramipril, and Atorvastatin (Figures 2 and 3). The duration of dual-antiplatelet therapy was limited as no stent was deployed and a reported natural history of vascular healing in SCAD. Intravascular imaging was not used to confirm the suspected angiographic diagnosis given the reported vascular complications with instrumentations in SCAD such as extending the coronary dissection with wire or imaging catheter and guide catheter iatrogenic dissection.7,8 A repeat transthoracic echocardiogram has not been performed yet. Figure 1 Electrocardiogram on admission. Figure 2 Angiogram of the left anterior descending artery showing spontaneous coronary artery dissection in the mid left anterior descending artery. Figure 3 Angiogram showing a normal right coronary artery.

The duration of dual-antiplatelet therapy was limited as no stent was deployed and a reported natural history of vascular healing in SCAD. Intravascular imaging was not used to confirm the suspected angiographic diagnosis given the reported vascular complications with instrumentations in SCAD such as extending the coronary dissection with wire or imaging catheter and guide catheter iatrogenic dissection.7,8 A repeat transthoracic echocardiogram has not been performed yet. Figure 1 Electrocardiogram on admission. Figure 2 Angiogram of the left anterior descending artery showing spontaneous coronary artery dissection in the mid left anterior descending artery. Figure 3 Angiogram showing a normal right coronary artery. Discussion Progressive arterial fibrosis and loss of vascular smooth muscle cells, together with deposition of GOM, is the proposed mechanism for the neurological vascular events seen with CADASIL. This pathophysiological phenomenon is seldom described outside the central nervous system, and its association with coronary arteries remains unknown. Coronary arterial changes of a similar pathophysiological nature would explain the potential risk of intramural haematoma or coronary artery dissection developing and the associated myocardial infarctions seen. This would be in the absence of traditional cardiovascular risk factors.9,10

ronary arteries remains unknown. Coronary arterial changes of a similar pathophysiological nature would explain the potential risk of intramural haematoma or coronary artery dissection developing and the associated myocardial infarctions seen. This would be in the absence of traditional cardiovascular risk factors.9,10 Conclusion Here, we describe a case of likely intravascular haematoma and SCAD in a patient with CADASIL syndrome. CADASIL syndrome is an angiopathy associated with predominately central nervous system vascular events. Spontaneous coronary artery dissection as discussed is also regarded as a manifestation of an underlying arteriopathy. We present a case of a patient with CADASIL experiencing SCAD. To our knowledge, an association between the two has not been described, but given the similar underlying pathophysiological mechanisms, further investigation could be warranted. Further invasive angiography was not performed. Lead author biography Nikolaos Tsanaxidis is a Senior Interventional Fellow in Cardiology at New Cross Hospital, Heart & Lung tertiary Centre, Royal Wolverhampton NHS Trust, UK. He is a Board Certified Cardiologist in UK and Greece since 2018; also PhD candidate in Larissa University Hospital, Greece. He is a Professional member of European Society of Cardiology (ESC) and EAPCI and member of British Cardiovascular Intervention Society (BCIS). Supplementary material Supplementary material is available at European Heart Journal - Case Reports online.

Lead author biography Nikolaos Tsanaxidis is a Senior Interventional Fellow in Cardiology at New Cross Hospital, Heart & Lung tertiary Centre, Royal Wolverhampton NHS Trust, UK. He is a Board Certified Cardiologist in UK and Greece since 2018; also PhD candidate in Larissa University Hospital, Greece. He is a Professional member of European Society of Cardiology (ESC) and EAPCI and member of British Cardiovascular Intervention Society (BCIS). Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz136_Supplementary_Slide_Set Click here for additional data file.

Learning points Although coconut left atrium (LA) has long been believed as the result of rheumatic heart disease or an unusual complication after mitral valve replacement, tuberculous pericarditis could be a possible aetiology. In stiff LA syndrome resulting from atrial calcification, the LA can no longer function as a reservoir or booster pump but merely act as a conduit. Giant v wave with steep ascending limb is an important clue for the diagnosis of stiff LA syndrome. Introduction Calcification of the left atrium (LA) is a rare condition and can be the result of long-standing rheumatic mitral stenosis1,2 or an unusual complication after mitral valve replacement.3,4 Cases with massive LA calcification are referred to as those with ‘coconut LA’5 or ‘porcelain LA’.3 This condition leads to the crucial impairment of LA compliance and thus a significant increase in LA pressure, which eventually results in intractable heart failure.6 Here, we report a rare case with stiff LA syndrome caused by both coconut LA and vertebral compression, with no history of rheumatic heart disease or cardiac surgery. Timeline Time Events Six years ago The patient became conscious of exertional dyspnoea and leg oedema. Initial presentation She came to our hospital because of the chest discomfort. Chest radiography showed bilateral pulmonary oedema and pleural effusion, which was consistent with decompensated heart failure.

Introduction Calcification of the left atrium (LA) is a rare condition and can be the result of long-standing rheumatic mitral stenosis1,2 or an unusual complication after mitral valve replacement.3,4 Cases with massive LA calcification are referred to as those with ‘coconut LA’5 or ‘porcelain LA’.3 This condition leads to the crucial impairment of LA compliance and thus a significant increase in LA pressure, which eventually results in intractable heart failure.6 Here, we report a rare case with stiff LA syndrome caused by both coconut LA and vertebral compression, with no history of rheumatic heart disease or cardiac surgery. Timeline Time Events Six years ago The patient became conscious of exertional dyspnoea and leg oedema. Initial presentation She came to our hospital because of the chest discomfort. Chest radiography showed bilateral pulmonary oedema and pleural effusion, which was consistent with decompensated heart failure. Admission Echocardiography revealed the presence of significant pulmonary hypertension and markedly reduced left atrial (LA) reservoir and booster pump function. Multidetector row computed tomography revealed that LA was encased by dense calcification and compressed by vertebral body. By cardiac catheter examination, prominent v wave with giant peak of 43 mmHg was observed in pulmonary capillary wedge pressure waveform. Patient was managed conservatively with loop diuretics and tolvaptan which led to amelioration of heart failure symptoms.

Admission Echocardiography revealed the presence of significant pulmonary hypertension and markedly reduced left atrial (LA) reservoir and booster pump function. Multidetector row computed tomography revealed that LA was encased by dense calcification and compressed by vertebral body. By cardiac catheter examination, prominent v wave with giant peak of 43 mmHg was observed in pulmonary capillary wedge pressure waveform. Patient was managed conservatively with loop diuretics and tolvaptan which led to amelioration of heart failure symptoms. After discharge Fortunately, the patient can lead her daily life without worsening of heart failure symptoms under oral administration of diuretics. Case presentation A 75-year-old woman was referred to our hospital because of chest discomfort and exertional dyspnoea. She had no remarkable medical history of rheumatic fever or cardiac surgery, except for a history of tuberculosis when she was 10 years old. On auscultation, a Grade 2/6 systolic murmur at the left lower sternal border was observed. On visual inspection, she was found to have systemic oedema and jugular distension. Electrocardiography showed sinus tachycardia with incomplete right bundle branch block and right-axis deviation. A chest radiography showed bilateral pulmonary oedema and pleural effusion, which was consistent with decompensated heart failure. Interestingly, however, laboratory findings showed a disproportionally low serum brain natriuretic peptide concentration of 63.4 pg/mL. And the qualitative analysis of Troponin T was negative at initial check-up. On the other hand, echocardiography revealed an unusual finding of the linear high-echoic lesion along the posterior LA wall, suggesting dense calcium deposition (Figure 1A and B and Supplementary material online, Video S1). There was moderate tricuspid regurgitation, with a peak pressure gradient of 54 mmHg, and the configuration of the ventricular septum was distorted to a D-shape in systole, which was consistent with significant pulmonary hypertension (Figure 1C and D and Supplementary material online, Video S2). However, there were no remarkable aortic and mitral valve dysfunctions, and her left ventricular (LV) contractile function was preserved with an ejection fraction of 78% (Supplementary material online, Video S3). Transmitral and mitral annular velocities disclosed the presence of severely elevated LV filling pressure with an early diastolic and atrial wave velocity (E/A) and E/e’ ratios of 1.9 and 35.5, respectively. Of note, her pulmonary venous flow showed a significantly blunted systolic forward flow (S) and retrograde flow during atrial contraction (Ar), conversely, a prominent diastolic wave (D) was observed (Figure 2).

essure with an early diastolic and atrial wave velocity (E/A) and E/e’ ratios of 1.9 and 35.5, respectively. Of note, her pulmonary venous flow showed a significantly blunted systolic forward flow (S) and retrograde flow during atrial contraction (Ar), conversely, a prominent diastolic wave (D) was observed (Figure 2). Despite the presence of these severe LA functional abnormalities, interestingly, her LA was not dilated at all (LA volume index of 25.5 mL/m2). The patient underwent cardiac catheter examination for further investigation of her strange hemodynamic state. Her pulmonary capillary wedge pressure (PCWP) waveform was impressive as shown in Figure 3. Especially, the morphology and the magnitude of v wave, which consisted of a steep ascending limb with giant peak of 43 mmHg (mean pressure of 15 mmHg), was consistent with an extremely stiff LA. Multidetector row computed tomography (MDCT) clearly revealed that the dense calcifications were predominantly distributed along the roof and bottom of the LA wall: therefore, the LA was sandwiched between the dense calcifications (Figure 4). Furthermore, the LA posterior wall was posteriorly compressed by the vertebral body (Figure 5). Integration of these functional and anatomical findings ultimately led to the diagnosis of stiff LA syndrome caused by both coconut LA and vertebral compression.

LA was sandwiched between the dense calcifications (Figure 4). Furthermore, the LA posterior wall was posteriorly compressed by the vertebral body (Figure 5). Integration of these functional and anatomical findings ultimately led to the diagnosis of stiff LA syndrome caused by both coconut LA and vertebral compression. Figure 1 (A) Parasternal long-axis view showing a linear high-echoic lesion along the posterior left atrial wall (red arrows), which was demonstrated to be left atrium calcification by multidetector row computed tomography (B). A continuous-wave Doppler signal of tricuspid regurgitation is shown (C). Peak pressure gradient across the tricuspid valve was measured as 54 mmHg, and configuration of the ventricular septum (red triangle) was distorted to a D-shape in diastole (D), suggesting significant pulmonary hypertension. Figure 2 Transmitral (A) and mitral annular velocities (B) disclosed the presence of the severely elevated ventricular filling pressure (E/e' ratio of 35.5). Pulmonary venous flow showed a significantly blunted systolic forward flow and retrograde flow reversal during atrial contraction, and conversely, a prominent diastolic wave velocity was observed (C). Ar, pulmonary venous atrial reversal flow; PVD, pulmonary venous flow in diastole; PVS, pulmonary venous flow in systole.

lmonary venous flow showed a significantly blunted systolic forward flow and retrograde flow reversal during atrial contraction, and conversely, a prominent diastolic wave velocity was observed (C). Ar, pulmonary venous atrial reversal flow; PVD, pulmonary venous flow in diastole; PVS, pulmonary venous flow in systole. Figure 3 Waveforms of pulmonary capillary wedge pressure and right atrial pressures are shown. The a wave, v wave, and mean pressure were 13, 43, and 15 mmHg, respectively. A prominent v wave of the pulmonary capillary wedge pressure waveform was impressive. Note the marked contrast with right atrial pressure waveform. ECG, electrocardiogram; PCWP, pulmonary capillary wedge pressure; RA, right atrial; SpO2, saturation of percutaneous oxygen. Figure 4 Volume-rendered images from the multidetector row computed tomography are shown (A). The structures coloured in light green indicate the left atrium and pulmonary veins, and blue structures represent calcium deposition. Note that the left atrium calcifications were predominantly distributed both at the roof (B) and bottom (C) of the atrial wall, thereby sandwiching the left atrium. Figure 5 Multiplanar reconstruction images from multidetector row computed tomography are shown. The left atrium is sandwiched between dense calcification (A). Moreover, the posterior wall (red arrow) is compressed by the vertebral body (B). LA, left atrium; VB, vertebral body.

Figure 4 Volume-rendered images from the multidetector row computed tomography are shown (A). The structures coloured in light green indicate the left atrium and pulmonary veins, and blue structures represent calcium deposition. Note that the left atrium calcifications were predominantly distributed both at the roof (B) and bottom (C) of the atrial wall, thereby sandwiching the left atrium. Figure 5 Multiplanar reconstruction images from multidetector row computed tomography are shown. The left atrium is sandwiched between dense calcification (A). Moreover, the posterior wall (red arrow) is compressed by the vertebral body (B). LA, left atrium; VB, vertebral body. After the administration of diuretics, with azosemide 30 mg daily and tolvaptan 7.5 mg daily, her systemic oedema and heart failure symptoms gradually ameliorated, without worsening of renal function. Although this therapeutic trial was effective, her heart failure symptom was still presented in New York Heart Association II. We thus proposed surgery after medical management. However, she refused cardiac surgery and was discharged after 25 days and continued to receive close outpatient follow-ups.

of renal function. Although this therapeutic trial was effective, her heart failure symptom was still presented in New York Heart Association II. We thus proposed surgery after medical management. However, she refused cardiac surgery and was discharged after 25 days and continued to receive close outpatient follow-ups. Discussion Calcified LA is usually anecdotally reported as ‘coconut LA’5 or ‘porcelain LA’3 and has been diagnosed mostly in long-standing rheumatic mitral stenosis1,2 or patients with previous mitral valve replacement.3,4 Thus, prolonged inflammation and excessive extension of the LA wall may lead to LA calcification.2 In this case, however, the patient had a history of tuberculosis when she was 10 years old but no history of rheumatic fever or cardiac surgery. Therefore, we hypothesized that the tuberculous pericarditis led to the calcified LA due to long-lasting mural inflammation.

sion of the LA wall may lead to LA calcification.2 In this case, however, the patient had a history of tuberculosis when she was 10 years old but no history of rheumatic fever or cardiac surgery. Therefore, we hypothesized that the tuberculous pericarditis led to the calcified LA due to long-lasting mural inflammation. From a haemodynamical point of view, Doppler findings of the pulmonary venous flow velocities, which consisted of a significantly blunted systolic forward flow and a retrograde flow during atrial contraction as well as a prominent diastolic wave, indicated that her LA could no longer function as a reservoir or booster pump but merely act as a conduit. The PCWP waveform also clearly revealed the hemodynamic characteristics of this special case. Generally, the v wave on the PCWP trace reflects LA filling during ventricular systole, and thus the morphology and magnitude of the v wave is determined principally by the pressure–volume relationships of the LA. In a stiff LA, a given increase in LA volume during ventricular systole will produce a much larger increase in LA pressure and result in a large v wave. As observed in this case, the giant v wave with steep ascending limb was consistent with extremely stiff LA.

rincipally by the pressure–volume relationships of the LA. In a stiff LA, a given increase in LA volume during ventricular systole will produce a much larger increase in LA pressure and result in a large v wave. As observed in this case, the giant v wave with steep ascending limb was consistent with extremely stiff LA. From an anatomical point of view, her LA was sandwiched by dense calcifications and compressed posteriorly by the vertebral body. These anatomical situations surrounding her LA may be the reason for why her LA could not be enlarged, even when her LA pressure was elevated. We speculated that her LA pressure could easily elevate, even with a slight haemodynamic load7 and especially while excerting, and thus can easily lead to decompensation. Especially, since her heart failure syndrome was not related to LV dysfunction but originated from a stiff LA, brain natriuretic peptide levels did not increase. A previous report described successful management of stiff LA syndrome through surgical resection of the calcified atrial endothelium.8 In general, the atrial calcification does not extend beyond the atrial endocardium in patients with porcelain LA, thus the preferred surgical approach for left atrial calcification has been reported to be a total endoatrioectomy for these patients.5

drome through surgical resection of the calcified atrial endothelium.8 In general, the atrial calcification does not extend beyond the atrial endocardium in patients with porcelain LA, thus the preferred surgical approach for left atrial calcification has been reported to be a total endoatrioectomy for these patients.5 In conclusion, we report a unique case with stiff LA syndrome caused by both coconut LA and vertebral compression. Echocardiography was a key tool that was used to initially identify this unique pathophysiology of LA, and the complementary modalities including cardiac catheter examination and MDCT were useful for a definite diagnosis. To the best of our knowledge, this is the first reported case of stiff LA syndrome caused by both coconut LA and vertebral compression that was diagnosed using multimodality imaging. Lead author biography After graduating from university in 2008, Junichi Ooka went into the path of cardiology after 2 years of residency. After studying general cardiology for 3 years, he have conducted research activities focusing on echocardiography for 4 years at Kobe University. Supplementary Material ytz154_Supplementary_Data Click here for additional data file. Acknowledgements The authors would like to thank Toshihiko Taya, Yoshiaki Shimoda, Toru Mazaki, Mariko Tanaka, and Tetsuya Tanaka for assistance. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

Supplementary Material ytz154_Supplementary_Data Click here for additional data file. Acknowledgements The authors would like to thank Toshihiko Taya, Yoshiaki Shimoda, Toru Mazaki, Mariko Tanaka, and Tetsuya Tanaka for assistance. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Evaluation of not only fibrous cap thickness but also coronary plaque morphology including cholesterol crystal may enable to predict the occurrence of acute coronary syndrome (ACS). Randomized control trials will be required to investigate whether additional therapeutic approach modulating cholesterol crystal could prevent future ACS events. Introduction Cholesterol crystal is a morphological feature of atherosclerotic plaques and is frequently observed at the culprit lesions of acute coronary syndrome (ACS).1 These crystals form through the accumulation of excessive amount of cholesterol materials within vessel walls. Biologically, the formation of cholesterol crystals activates the nucleotide-binding domain and leucine-rich repeat protein-3 inflammasome and then stimulates the secretion of interleukin-1β, which promotes atherogenesis.2,3 This observation suggests that cholesterol crystal may be morphological features of vulnerable plaques due to its pro-inflammatory property and needle-like structure. Optical coherence tomography (OCT) imaging enables the visualization of cholesterol crystals within vessel walls in vivo.4 Coronary atheroma containing cholesterol crystal is characterized by the presence of lipid-rich plaque.5 This clinical finding also indicates that the formation of cholesterol crystals may promote plaque instability. However, whether or not cholesterol crystal formation is associated with future coronary events remains to be determined yet. Here, we report a case in which ACS occurred repeatedly due to plaques containing cholesterol crystals.

also indicates that the formation of cholesterol crystals may promote plaque instability. However, whether or not cholesterol crystal formation is associated with future coronary events remains to be determined yet. Here, we report a case in which ACS occurred repeatedly due to plaques containing cholesterol crystals. Timeline Time points Events 2016 November Severe, prolonged (6-h) chest pain. Electrocardiogram revealed anterior wall myocardial infarction with ST-segment elevation. Coronary angiography showed one obstructive and another non-obstructive stenotic lesion in the left anterior descending artery (LAD). The obstructive lesion was treated with a drug-eluting stent. The non-obstructive lesion harbored cholesterol crystals and had a thick fibrous cap, as demonstrated by optical coherence tomography imaging. 2016 December Non-contrast T1-weighted magnetic resonance imaging showed a high-intensity signal corresponding to the non-obstructive lesion containing cholesterol crystals. Patient discharged on standard medical therapy, including dual antiplatelets and rosuvastatin. 2017 December Recurrence of chest pain at rest. Coronary angiography showed substantial progression of the non-obstructive lesion containing cholesterol crystals. Optical coherence tomography imaging showed severe LAD narrowing at the lesion site due to overlying tissues that presumably consisted of thrombus. Near-infrared spectroscopy imaging visualized a considerable amount of lipidic materials at the lesion, reflected by a maximum 4-mm lipid core burden index of 809. Drug-eluting stent successfully implanted.

Optical coherence tomography imaging showed severe LAD narrowing at the lesion site due to overlying tissues that presumably consisted of thrombus. Near-infrared spectroscopy imaging visualized a considerable amount of lipidic materials at the lesion, reflected by a maximum 4-mm lipid core burden index of 809. Drug-eluting stent successfully implanted. Patient discharged with further lipid-lowering therapy with ezetimibe. 2018 December Last follow-up; uneventful clinical course.

Near-infrared spectroscopy imaging visualized a considerable amount of lipidic materials at the lesion, reflected by a maximum 4-mm lipid core burden index of 809. Drug-eluting stent successfully implanted. Patient discharged with further lipid-lowering therapy with ezetimibe. 2018 December Last follow-up; uneventful clinical course. Case presentation A 60-year-old man with a history of dyslipidaemia presented to our hospital due to 6 h of central chest pain at rest, with radiation into his left shoulder. He had not previously received any medication for dyslipidaemia. His vital signs were stable, and he had no cardiac murmurs, jugular vein distension, or pitting oedema (heart rate, 81 beats per minute; blood pressure, 169/109 mmHg; respiratory rate, 16/min; oxygen saturation, 98% on ambient room air). Electrocardiogram showed ST-segment elevation in the anterior leads (V2–V6), with reciprocal changes in the inferior leads (II, III, aVf). Transthoracic echocardiography identified severe hypokinesis of the left ventricular anterior wall (left ventricular ejection fraction, 40%). Emergent coronary angiography revealed a severely stenotic lesion (=culprit lesion) and another non-obstructive lesion in the proximal and middle segments of the left anterior descending artery (LAD), respectively (Figure 1A, Supplementary material online, Video S1). Optical coherence tomography imaging (Dragonfly OPTISTM; Abbott, Chicago, IL, USA) was conducted after manual thrombus aspiration to evaluate the lesions. The culprit lesion exhibited lipid-rich plaques that contained multiple cholesterol crystals and caused severe narrowing (Figure 1B, Supplementary material online, Video S2). The surface of the culprit lesion was covered by homogeneous tissue that was considered to be a thrombus. The non-obstructive lesion in the middle segment of the LAD also contained cholesterol crystals and had a thick fibrous cap (thickness, 230 μm) (Figure 1C, Supplementary material online, Video S2). One 3.5 mm × 18 mm Resolute Integrity® zotarolimus-eluting stent (Medtronic, Minneapolis, MN, USA) was successfully implanted at the culprit lesion under OCT guidance (Figure 2D, Supplementary material online, Video S3).

d had a thick fibrous cap (thickness, 230 μm) (Figure 1C, Supplementary material online, Video S2). One 3.5 mm × 18 mm Resolute Integrity® zotarolimus-eluting stent (Medtronic, Minneapolis, MN, USA) was successfully implanted at the culprit lesion under OCT guidance (Figure 2D, Supplementary material online, Video S3). Since the patient had a high level of low-density lipoprotein cholesterol (LDL-C) on admission (LDL-C, 4.1 mmol/L; total cholesterol, 6.3 mmol/L; triglyceride, 0.7 mmol/L; high-density lipoprotein cholesterol (HDL-C), 1.8 mmol/L; glycated haemoglobin, 5.0%), rosuvastatin 10 mg was commenced, in addition to aspirin 100 mg, clopidogrel 75 mg, enalapril 2.5 mg, and carvedilol 10 mg. Non-contrast T1-weighted magnetic resonance imaging (T1WI-MRI) 10 days after PCI showed a high-intensity signal distal to the implanted stent, corresponding to the non-obstructive lesion containing cholesterol crystals that was visualized by OCT (Figure 2E and F, Supplementary material online, Video S4). Since a stress myocardial perfusion scan did not show any residual myocardial ischaemia, this lesion was medically managed.

al distal to the implanted stent, corresponding to the non-obstructive lesion containing cholesterol crystals that was visualized by OCT (Figure 2E and F, Supplementary material online, Video S4). Since a stress myocardial perfusion scan did not show any residual myocardial ischaemia, this lesion was medically managed. Figure 1 (A) Coronary angiography prior to percutaneous coronary intervention. One severe stenosis (a–d) and another non-obstructive lesion (e–h) were identified in the proximal and middle segments of left anterior descending artery, respectively. (a–h) corresponds to optical coherence tomography images in (B). (B) Optical coherence tomography Images prior to percutaneous coronary intervention. Culprit lesion (a–d) exhibited lipid-rich plaque (L) with cholesterol crystal (arrow head). Homogeneous high-intensity signal area at the surface of this lesion was observed [arrow in (b)]. Fibrous cap thickness was 110 μm. At another non-obstructive lesion (e–h), lipid-rich plaque (L), multiple cholesterol crystals (arrow head), and small calcification (C) were visualized. The thickness of its fibrous cap was 230 μm. SB, septal branch.

ignal area at the surface of this lesion was observed [arrow in (b)]. Fibrous cap thickness was 110 μm. At another non-obstructive lesion (e–h), lipid-rich plaque (L), multiple cholesterol crystals (arrow head), and small calcification (C) were visualized. The thickness of its fibrous cap was 230 μm. SB, septal branch. Figure 2 (A) Coronary angiography after percutaneous coronary intervention. Zotarolimus-eluting stent [dashed line: (3.5 × 18 mm Resolute Integrity®, Medtronic, Minneapolis, MN, USA)] was successfully implanted at culprit lesion. The non-obstructive lesion with cholesterol crystal (arrow) was medically managed. (B) Non-contrast T1-weighted magnetic resonance imaging after percutaneous coronary intervention (sagittal view). (C) Non-contrast T1-weighted magnetic resonance imaging after percutaneous coronary intervention (coronal view). High-intensity signal (yellow arrow) was observed at the coronary lesion distal to the implanted stent (dashed line), which corresponded to the non-obstructive plaque in left anterior descending artery. Ao, aorta; LA, left atrium; LV, left ventricle; PA, pulmonary artery; SB, septal branch.

intervention (coronal view). High-intensity signal (yellow arrow) was observed at the coronary lesion distal to the implanted stent (dashed line), which corresponded to the non-obstructive plaque in left anterior descending artery. Ao, aorta; LA, left atrium; LV, left ventricle; PA, pulmonary artery; SB, septal branch. Twelve months later, the patient was hospitalized again due to 3 days of intermittent central chest pain at rest. There were no abnormalities on physical examination (heart rate, 63 b.p.m.; blood pressure, 115/61 mmHg; respiratory rate, 14/min; oxygen saturation, 97% on ambient room air). The patient was still taking dual-antiplatelet therapy (aspirin 100 mg and clopidogrel 75 mg) with 10 mg rosuvastatin, 2.5 mg enalapril, and 10 mg carvedilol (LDL-C, 2.2 mmol/L; total cholesterol, 4.6 mmol/L; triglyceride, 0.9 mmol/L; HDL-C, 1.9 mmol/L; glycated haemoglobin, 5.3%). Despite a normal troponin T level (0.01 ng/mL) and no ST-T changes on electrocardiogram or new regional left ventricular wall motion abnormality on echocardiogram, coronary angiography revealed substantial progression of the non-obstructive lesion containing cholesterol crystals, whereas the implanted zotarolimus-eluting stent did not show restenosis (Figure 3G, Supplementary material online, Video S5). Optical coherence tomography and near-infrared spectroscopy (NIRS) imaging were used to evaluate the culprit lesion prior to PCI. On OCT imaging, this lesion was severely narrowed due to the overlying tissue that presumably consisted of thrombus (Figure 3H, Supplementary material online, Video S6). In addition, a considerable amount of lipidic material at this lesion was visualized by NIRS imaging [maximum 4-mm lipid core burden index (LCBI) = 809] (Figure 3I). An additional 3.5 mm × 24 mm Synergy® everolimus-eluting stent (Boston Scientific, Marlborough, MA, USA) was successfully implanted. Since an increased dose of rosuvastatin would only lower LDL-C levels by ∼6%, 10 mg ezetimibe was added instead to achieve the Japanese target LDL-C level (<1.8 mmol/L). The patient’s course was uneventful in the 12 months after the second PCI. Her LDL-C level under rosuvastatin and ezetimibe was 1.6 mmol/L.

implanted. Since an increased dose of rosuvastatin would only lower LDL-C levels by ∼6%, 10 mg ezetimibe was added instead to achieve the Japanese target LDL-C level (<1.8 mmol/L). The patient’s course was uneventful in the 12 months after the second PCI. Her LDL-C level under rosuvastatin and ezetimibe was 1.6 mmol/L. Figure 3 (A) Coronary angiography 12 months after the first percutaneous coronary intervention. While in-stent restenosis did not occur within the previously implanted stent (dashed line), progression of the non-obstructive plaque was observed (e′–h′). (e′–h′) corresponds to optical coherence tomography images in (B) and near-infrared spectroscopy images in (C). Two asterisks (*) shows the evaluated segment on near-infrared spectroscopy imaging (C). (B) Optical coherence tomography imaging prior to the second percutaneous coronary intervention. Cholesterol-crystalized lesion (arrow head) was severely narrowed due to large lipid-rich plaque (L) and its overlying tissues presumably consisting of thrombus (arrow). (C) Near-infrared spectroscopy imaging prior to the second percutaneous coronary intervention. Near-infrared spectroscopy imaging visualized the presence of extensive amount of lipidic materials at the progressive cholesterol-crystalized lesion (maximum 4-mm lipid core burden index = 809). C, calcification; LAD, left anterior descending artery; SB, septal branch.

to the second percutaneous coronary intervention. Near-infrared spectroscopy imaging visualized the presence of extensive amount of lipidic materials at the progressive cholesterol-crystalized lesion (maximum 4-mm lipid core burden index = 809). C, calcification; LAD, left anterior descending artery; SB, septal branch. Discussion Vulnerable plaque, considered to be an important driver of acute coronary events, has been defined by histopathological studies as a lesion with a thin fibrous cap overlying a large necrotic core. In our case, however, ACS occurred due to the rapid progression of the lesion with associated cholesterol crystallization and a thick fibrous cap. This observation suggests that plaque containing cholesterol crystals may be another precursor lesion associated with ACS.

thin fibrous cap overlying a large necrotic core. In our case, however, ACS occurred due to the rapid progression of the lesion with associated cholesterol crystallization and a thick fibrous cap. This observation suggests that plaque containing cholesterol crystals may be another precursor lesion associated with ACS. Increased cholesterol content within vessel walls affects lipid metabolism in macrophages, leading to the deposition of cholesterol crystals within plaques.1–3 Cholesterol crystals have been shown to directly stimulate the production of interleukin-1β, suggesting their potential to destabilize plaques.2,3 In our case, the culprit lesion underlying the initial ST-segment elevation myocardial infarction episode contained cholesterol crystals in its overlying thrombus. Additionally, the second ACS event occurred due to rapid progression and thrombus formation at the other lesion with associated cholesterol crystallization. Given that interleukin-1βinduce plaque rupture and its thrombus formation via the increased expression of matrix metalloproteinase, tissue factor, and monocyte chemoattractant protein-1,6,7 cholesterol crystals may increase lesion vulnerability and increase the risk of acute coronary events.

holesterol crystallization. Given that interleukin-1βinduce plaque rupture and its thrombus formation via the increased expression of matrix metalloproteinase, tissue factor, and monocyte chemoattractant protein-1,6,7 cholesterol crystals may increase lesion vulnerability and increase the risk of acute coronary events. T1-weighted magnetic resonance imaging and NIRS imaging provide mechanistic insights into the association of cholesterol crystals with ACS. In the current case, a high-intensity signal on T1WI-MRI was identified at the lesion that caused the second ACS event. One recent study using OCT imaging reported that coronary plaques with high-intensity signals on T1WI-MRI were associated with lipid-rich plaque and healed plaque rupture but not with a thin fibrous cap.8 Considering that coronary plaque characterized by a high-intensity signal is associated with future coronary events,9 progression of the high-intensity signal plaque in our case suggests that cholesterol crystals may be an important feature of precursor lesions that may induce coronary events. Near-infrared spectroscopy imaging is an intravascular plaque imaging modality that quantitatively measures lipidic materials within coronary atheromas in vivo.10 The NIRS-derived LCBI has been validated by several histopathological studies that compared NIRS images with coronary specimens.10,11 LCBImax4mm >400 has been considered as the presence of a high-risk plaque containing lipidic materials.10 Since the accumulation of lipidic materials within the vessel wall is a driver of cholesterol crystal formation, very high LCBImax4mm at rapidly progressive plaques containing cholesterol crystals may account for the further development of cholesterol crystals in vivo.

a high-risk plaque containing lipidic materials.10 Since the accumulation of lipidic materials within the vessel wall is a driver of cholesterol crystal formation, very high LCBImax4mm at rapidly progressive plaques containing cholesterol crystals may account for the further development of cholesterol crystals in vivo. In our case, the coronary plaques associated with ACS events did not have thin fibrous caps. This is inconsistent with postmortem studies that demonstrated that fibrous caps with thicknesses <65 μm were a major feature of culprit lesions in patients with acute coronary events.12,13 A recent in vivo OCT imaging study reported that the rupture of fibrous caps did not necessarily occur at their thinnest site.14 Of note, the median thickness of the fibrous cap overlying most ruptured plaques was below 188 μm. These findings suggest that ACS occurs even if the fibrous cap at the coronary plaque is not thin. Imaging assessment not just of fibrous cap thickness but also of plaque microstructure, including cholesterol crystals, may be important to identify high-risk lesions causing ACS.

g most ruptured plaques was below 188 μm. These findings suggest that ACS occurs even if the fibrous cap at the coronary plaque is not thin. Imaging assessment not just of fibrous cap thickness but also of plaque microstructure, including cholesterol crystals, may be important to identify high-risk lesions causing ACS. The current case indicates the need for preventive management in patients with plaques containing cholesterol crystals. While an in vitro study reported that a statin modulated the density of cholesterol crystals, recurrence of ACS occurred due to progression of lesions containing cholesterol crystals despite rosuvastatin use.15 Further investigation is warranted to determine if more potent lipid-lowering agents, such as proprotein convertase subtilisin/kexin type 9 inhibitors, affect cholesterol crystals. The canakinumab anti-inflammatory thrombosis outcomes (CANTOS) study demonstrated a significant reduction of atherosclerotic cardiovascular events by an anti-inflammatory agent that modifies interleukin-1β.16 Considering that cholesterol crystals themselves promote the secretion of interleukin-1β, this therapeutic approach may be another valid strategy to prevent coronary events associated with cholesterol crystals. Conclusions In conclusion, coronary plaques characterized by the presence of cholesterol crystals and thick fibrous caps were associated with the occurrence of ACS. Our findings suggest that cholesterol crystals may be an important feature of ACS precursor lesions and may require additional anti-atherosclerotic management.

lusions In conclusion, coronary plaques characterized by the presence of cholesterol crystals and thick fibrous caps were associated with the occurrence of ACS. Our findings suggest that cholesterol crystals may be an important feature of ACS precursor lesions and may require additional anti-atherosclerotic management. Lead author biography Hiroki Sugane was born in Chiba, Japan, in 1987. He graduated from Kochi Medical University and received the MD degree in 2012. He was working as a Cardiology fellow at Chikamori hospital from 2014. Then, he became a cardiovascular interventional fellow at Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Japan from 2017. He experienced a large number of PCI cases as well as analysis of intravascular imaging. From 2019, he serves as a staff cardiologist at Chikamori hospital, Kochi, Japan. His research interest is percutaneous coronary intervention and intravascular imaging. Supplementary Material ytz128_Supplementary_Data Click here for additional data file. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Dapsone has the potential to cause ventricular arrhythmias in patients with ischaemic cardiomyopathy. When a patient’s care is at the end stages of recognized treatment to consider withdrawal of medication as an appropriate action. Introduction There are over 4 million global deaths per year due to sudden cardiac death and ventricular arrhythmia (VA).1 The substrates for VA include scar-related re-entry, prolonged QTC and drugs.1,2 Here, we present a first case presentation of dapsone reducing the threshold of VA, leading to intractable, recurrent VA despite maximal pharmacological anti-arrhythmic agents. The underlying mechanism by which dapsone acted as a substrate for VA is not known but prolongation of the QT interval was not seen in this case.

re, we present a first case presentation of dapsone reducing the threshold of VA, leading to intractable, recurrent VA despite maximal pharmacological anti-arrhythmic agents. The underlying mechanism by which dapsone acted as a substrate for VA is not known but prolongation of the QT interval was not seen in this case. Timeline Day Events 0 A 52-year-old man was admitted with pneumocystis pneumonia, requiring inotropic, and ventilatory support. He was discharged on dapsone 100 mg prophylaxis. During admission, interrogation of his implantable cardioverter-defibrillator (ICD) showed multiple episodes of non-sustained ventricular tachycardia; non-requiring ICD therapy. 14 One appropriate ICD shock for ventricular fibrillation. Oral anti-arrhythmics uptitrated. 35–56 Recurrent polymorphic ventricular tachycardia requiring six shocks from his ICD despite optimized oral and intravenous anti-arrhythmics and revascularization. The patient was accepted for end-stage treatment with cervical sympathectomy. Whilst waiting for the surgery, medications were reviewed and dapsone alone was held. After 96 h, he had no further ventricular arrhythmia (VA). Cervical sympathectomy was avoided and he was discharged. 6 months later No further episodes of VA detected. Case presentation A 52-year-old taxi driver with a background history of ischaemic cardiomyopathy with a primary prevention implantable cardioverter-defibrillator (ICD) and pancreatic cancer under surveillance after chemotherapy, presented 2 weeks after initiation of dapsone with ventricular fibrillation (VF) requiring an ICD shock. At this stage, he had recently been discharged from hospital after being treated for pneumocystis pneumonia, which had required intubation and prophylaxis of subsequent infections with dapsone. Initial examination and investigations were normal with no evidence of electrolyte disturbance or infection. Transthoracic echocardiogram on presentation showed an unchanged ejection fraction of 30%. Figure 1 shows his resting electrocardiogram. The ICD shock was treated with uptitration of his mexiletine from 100 to 200 mg b.i.d. and he was subsequently discharged. He represented 5 weeks later with further VF requiring an ICD shock. Initial investigations showed no specific substrate and his mexiletine dose was increased to 300 mg t.d.s. He was discharged and represented a third time with further VF episodes and he was initiated on an amiodarone infusion.

subsequently discharged. He represented 5 weeks later with further VF requiring an ICD shock. Initial investigations showed no specific substrate and his mexiletine dose was increased to 300 mg t.d.s. He was discharged and represented a third time with further VF episodes and he was initiated on an amiodarone infusion. Figure 1 The resting 12-lead electrocardiogram showing sinus bradycardia and a normal QTc. He continued to have multiple ICD shocks secondary to VF, whilst on the amiodarone infusion and so this was switched to a lidocaine infusion. Figure 2 shows an example of captured VA. Figure 3 demonstrates his ICD interrogation. During each admission with VA, it was noted he was also not doing any physical exercise during the shocks and the episodes did not have a temporal concordance with daily medications. The patient also did not have any additional symptoms other than those related to the VA on any of the occasions pre-admission. On the third admission, to exclude an ischaemic cause, he had an angiogram which showed a moderate small mid-right coronary artery with a 70% narrowing, which was stented in the absence of any other reversible causes. Figure 2 A rhythm strip showing the onset of ventricular fibrillation.

He continued to have multiple ICD shocks secondary to VF, whilst on the amiodarone infusion and so this was switched to a lidocaine infusion. Figure 2 shows an example of captured VA. Figure 3 demonstrates his ICD interrogation. During each admission with VA, it was noted he was also not doing any physical exercise during the shocks and the episodes did not have a temporal concordance with daily medications. The patient also did not have any additional symptoms other than those related to the VA on any of the occasions pre-admission. On the third admission, to exclude an ischaemic cause, he had an angiogram which showed a moderate small mid-right coronary artery with a 70% narrowing, which was stented in the absence of any other reversible causes. Figure 2 A rhythm strip showing the onset of ventricular fibrillation. Figure 3 An example of an implantable cardioverter-defibrillator interrogation showing multiple ventricular arrhythmias requiring shocks. (A) Overview of an implantable cardioverter-defibrillator interrogation over a 48 h period where nine episodes of ventricular arrhythmias were detected. Five were terminated with shocks after they reached 15 s in duration. (B) Ventricular arrhythmias detection demonstrated on an R-R interval graph, where the threshold of 320 ms is reached and ventricular arrhythmias detected. It was subsequently terminated with a 35.1 J shock. (C) Electromyography of ventricular arrhythmias detection and treatment with a shock. EMG, electromyography; FS, fibrillation sense; J, joule; RV, right ventricle; VS, ventricular sense.

h, where the threshold of 320 ms is reached and ventricular arrhythmias detected. It was subsequently terminated with a 35.1 J shock. (C) Electromyography of ventricular arrhythmias detection and treatment with a shock. EMG, electromyography; FS, fibrillation sense; J, joule; RV, right ventricle; VS, ventricular sense. He was discharged but unfortunately was readmitted 3 days later with a collapse and polymorphic ventricular tachycardia (VT). He was recommenced on a lidocaine infusion but because of continued VAs, he was listed for a cervical sympathectomy. Cervical sympathectomy acts by reducing the effect of sympathetic hyperactivity on the myocardium. Studies have demonstrated that there is hyperinnervation at the border of the normal myocardium and scars which acts to increase the action of the sympathetic overdrive seen in VA.3 There is now evidence that video-assisted thoracoscopic sympathectomy is a safe and effective treatment to reduce VA burden in patients with life-threatening arrhythmias due to catecholaminergic polymorphic VT or long QT syndrome.3 However, in ischaemic cardiomyopathy, there are currently no guidelines to recommend cervical sympathectomy.1 Ablation was not possible in this gentleman as the VT was polymorphic. Pacing the atria to achieve less ectopy via the ICD was not considered as he did not have an atrial lead. A cardiac magnetic resonance imaging to assess for scar burden and inducible ischaemia was not possible due to a non-compatible ICD. At this stage, his medications were re-reviewed with an open mind and dapsone was stopped in case there was any interaction that had not been recognized. He had no further runs of VA and was discharged home without the need for the sympathectomy. He was not changed onto a different prophylactic antibiotic agent, as he had a previous severe allergy to the alternative option: co-trimoxazole. During this month of admission for VA, he did not receive any chemotherapy, antibiotics, or other drugs not mentioned that could have contributed to a pro-arrhythmogenic environment. There was also no evidence of decompensated heart failure, electrolyte, or hormone imbalance during this time. His QTc was 420–450 ms throughout the admissions. He has subsequently been VA free for 6 months with a reducing regime of amiodarone.

mentioned that could have contributed to a pro-arrhythmogenic environment. There was also no evidence of decompensated heart failure, electrolyte, or hormone imbalance during this time. His QTc was 420–450 ms throughout the admissions. He has subsequently been VA free for 6 months with a reducing regime of amiodarone. Discussion In the literature, the effect of dapsone on the heart has only been described twice.4,5 Both have been clinical case reports of patients who have developed dapsone hypersensitivity syndrome. This syndrome is an idiosyncratic drug reaction which occurs in 0.5–3.6% of patients treated with dapsone. It is a triad of fever, rash and systemic involvement; usually, hepatic and haematological. In these two patients, dapsone caused myocarditis; in one case, this was fatal. In our case report, there was no evidence of dapsone hypersensitivity syndrome and a different mechanism of cardiac involvement is likely to have been involved whilst inducing VA. Dapsone, a synthetic derivative of diamino-sulfone has anti-inflammatory and anti-bacterial properties. It is commonly used in the treatment of mycobacterium leprosae, pneumocystitis pneumonia, and dermatological conditions such as dermatitis herpetiformis. It inhibits dihydropteroate synthase, an enzyme important in folate synthesis which subsequently interferes with DNA synthesis. Dapsone also interferes with myeloperoxidase (important in oxidative stress pathways) in neutrophils and inhibits chemotaxis in neutrophils. This is the likely mechanism for its anti-inflammatory effects.6

ihydropteroate synthase, an enzyme important in folate synthesis which subsequently interferes with DNA synthesis. Dapsone also interferes with myeloperoxidase (important in oxidative stress pathways) in neutrophils and inhibits chemotaxis in neutrophils. This is the likely mechanism for its anti-inflammatory effects.6 Interestingly, animal studies have shown inhibition of neutrophils and myeloperoxidase is VA protective. Studies using CD11b/CD18-integrin-deficient mice, subjected to ischaemia and reperfusion show reduced neutrophil infiltration and cardiac myeloperoxidase deposition was significantly protective against VA.7,8 This was also the case with knockout myeloperoxidase rabbits which have shown an alteration of cardiomyocyte ion channels, specifically a reduction in action potential amplitude and a reduction in VA.7,8 These studies have however been in Phase 2 arrhythmia post ischaemia (subacute), which may or may not have been important in our case, as he was developing VA’s without any ischaemic event. There have not been any studies researching the effects of neutrophils/myeloperoxidase on VA in non-ischaemic, scar burdened cardiomyocyte models. It is also important to note that the pathways of oxidative stress are complex, not yet fully elucidated and the interaction of dapsone on folate and myeloperoxidase on cardiomyocytes has not yet been explored.

rching the effects of neutrophils/myeloperoxidase on VA in non-ischaemic, scar burdened cardiomyocyte models. It is also important to note that the pathways of oxidative stress are complex, not yet fully elucidated and the interaction of dapsone on folate and myeloperoxidase on cardiomyocytes has not yet been explored. In cardiomyopathy patients, there is often an unfavourable environment and a small change in this can lead to arrhythmias. This case highlights the importance of questioning all prescribed medications for the safety of our patients especially in cases where there are life-threatening intractable arrhythmias. Patient perspective It is well established that ICD shocks can cause significant psychological stress.9 The majority of his ICD shocks occurred when he was unconscious, which may have reduced his anxiety and fear. Despite the multiple ICD shocks and re-admissions, our patient states: ‘on reflection, I felt an over-riding theme of reassurance, confidence in my management and a personalized service’. He felt he had an excellent rapport and trust in the consultants and team looking after him. He states that they all knew his case very well and the communication and management were excellent. In his words: ‘Out of their work, I am still alive’.

of reassurance, confidence in my management and a personalized service’. He felt he had an excellent rapport and trust in the consultants and team looking after him. He states that they all knew his case very well and the communication and management were excellent. In his words: ‘Out of their work, I am still alive’. Lead author biography Dr Bethany Wong is a cardiology specialist registrar and lecturer for Royal College of Surgeons in Dublin, Ireland. She graduated from Imperial College School of Medicine and obtained First Class honours in her BSc in cardiovascular sciences. She has authored research in both basic science and clinical cardiology including in transcriptional and translational regulation in cardiomyocytes exposed to oxidative stress and in balloon valvuloplasty in transcatheter aortic valve implantation patients. She is currently completing a diploma in health professions education to extend her interest in teaching. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz158_Supplementary_Slide_Set Click here for additional data file.

Learning points Prosthetic valve endocarditis (PVE) can often be a major diagnostic challenge owing to the difficulties in the interpretation of conventional echocardiography, particularly in patients with low-to-intermediate probability for PVE based on the modified Duke criteria. We describe a case of PVE complicated by perivalvular abscess where the combination of 18F-fluorodeoxyglucose positron emission tomography and computed tomography angiography aided in the diagnosis of PVE and its complications, shedding light on the additional roles of the new imaging modalities. Introduction Definitive diagnosis of prosthetic valve endocarditis (PVE) is clinically challenging because of its varying clinical presentation, microorganisms involved and patient profile. Prosthetic valve endocarditis entails high initial mortality and morbidity rates with a high risk of complications, including perivalvular abscess and fistulae during follow-up and often requires surgical intervention.1 Therefore, the diagnosis and management of PVE necessitates a collaborative approach involving cardiologists, infectious disease physicians, cardiac imaging specialists, cardiovascular surgeons, and microbiologists.2

including perivalvular abscess and fistulae during follow-up and often requires surgical intervention.1 Therefore, the diagnosis and management of PVE necessitates a collaborative approach involving cardiologists, infectious disease physicians, cardiac imaging specialists, cardiovascular surgeons, and microbiologists.2 Recently, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been advocated as an alternative diagnostic imaging modality for PVE, particularly when echocardiography and blood culture results are inconclusive in reaching a definitive PVE diagnosis.3 Furthermore, 18F-FDG PET/CT can detect distant emboli, metastatic infections and perivalvular involvement along with coronary anatomy when combined with CT coronary angiography.4 Additionally, complementary information obtained from less invasive tests are vital for patients with PVE who require early surgery. Herein, we present a challenging case of PVE complicated with perivalvular abscess.

s and perivalvular involvement along with coronary anatomy when combined with CT coronary angiography.4 Additionally, complementary information obtained from less invasive tests are vital for patients with PVE who require early surgery. Herein, we present a challenging case of PVE complicated with perivalvular abscess. Timeline 12 years before admission 25-mm mechanical aortic valve implantation owing to severe aortic regurgitation. 3 days before admission Fever at night and general fatigue initiated. Day of admission Initial transthoracic echocardiography revealed no dysfunction of the mechanical aortic prosthesis, and no embolic events were detected on the whole-body computed tomography (CT). Three blood culture tests were performed and intravenous antibiotic therapy with ceftriaxone (2 g/day) was initiated. Hospital Day 5 Transoesophageal echocardiography was inconclusive and fever persisted. Hospital Day 8 All blood culture tests were negative. 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT revealed considerable uptake of 18F-FDG surrounding the aortic annulus; intensive antibiotic therapy was initiated with intravenous ampicillin (8 g/day) and gentamicin (180 mg/day). Hospital Day 14 The infected prosthetic valve was surgically replaced with a 25-mm bioprosthesis with extensive debridement of perivalvular abscess. Hospital Day 51 The patient was discharged well. 6 months after discharge A 6-month of outpatient oral antibiotic therapy with amoxicillin (750 mg/day) was completed without any recurrences. Case presentation A 64-year-old man presented to our outpatient clinic with complaints of general fatigue and high fever (>38°C) at night that persisted for 3 days. He had previously undergone 25-mm mechanical aortic valve implantation (St. Jude Medical Regent; St. Jude Medical, Inc., St. Paul, MN) 12 years prior because of severe aortic regurgitation. Upon examination, no focus of infection could be identified, and he was admitted to our heart centre to exclude the possibility of PVE. After three sets of blood culture were obtained, intravenous ceftriaxone (2 g/day) was empirically initiated. Initial transthoracic echocardiography (TTE) revealed no dysfunction of the mechanical aortic prosthesis, and whole-body CT revealed no embolic events. The patient recovered to a low-grade fever (37–38°C) 48 h after the initial antibiotics therapy and showed improved C-reactive protein level (from 13 to 6.3 mg/dL) in the first 5 days.

over revascularization in case of preserved flow and absence of high-risk features like left main dissection, ongoing ischaemia, electrical, or haemodynamic instability.1–3,12 In this case, angina was controlled medically, furthermore, percutaneous intervention was not possible because of the small size of the vessel. There is little evidence for medical treatment of SCAD, current recommendations are based upon expert opinion. Dual antiplatelet therapy with aspirin and clopidogrel was started in this case, as recommended by most experts (1–12 months) because of evidence that high-grade stenosis can be associated with true luminal thrombus in SCAD patients. However, in contrast with a classic ACS, clopidogrel is preferred over newer P2Y12 inhibitors like ticagrelor and prasugrel because of lack of data and their higher associated bleeding risk. Here, clopidogrel was interrupted because of the progression of the dissection, indicating that the need for DAPT should be evaluated on a patient by patient basis. Given the LV impairment, beta-blockers, and ACE-inhibitors were indicated in this patient.1–3 Statins are not routinely recommended since the aetiology of SCAD is not atherosclerotic. Furthermore, a small retrospective cohort demonstrated a higher recurrence rate in statin users, therefore, their use should be reserved for patients with conventional indications for statins.1–3

racic echocardiography (TTE) revealed no dysfunction of the mechanical aortic prosthesis, and whole-body CT revealed no embolic events. The patient recovered to a low-grade fever (37–38°C) 48 h after the initial antibiotics therapy and showed improved C-reactive protein level (from 13 to 6.3 mg/dL) in the first 5 days. Subsequently, transoesophageal echocardiography (TOE) performed on the 5th day of hospitalization revealed a 6–11 mm mobile echogenic mass attached to the prosthetic valve and a thickened area within the posterior annular region with a low echogenic appearance at the level of the non-coronary sinus of Valsalva (Figure 1). At this point, the patient met two minor diagnostic criteria (predisposing heart condition of prior prosthetic valve implantation and high fever) in the modified Duke diagnostic criteria for infective endocarditis because the TOE findings were considered inconclusive. Subsequently, combined 18F-FDG PET/CT and CT coronary angiography revealed intense hyper-metabolism above the aortic valve prosthesis with greater intensity at the posterior end and absence of obstructive coronary artery, thereby confirming the diagnosis of aortic PVE complicated with perivalvular abscess (Figure 2). Following a comprehensive discussion with the endocarditis team, including an infectious disease specialist, a microbiologist (pathologist) and cardiovascular surgeons, we decided to switch from intravenous ceftriaxone to appropriate antibiotic therapy [intravenous ampicillin (8 g/day) and gentamicin (180 mg/day)] for blood culture-negative patients with PVE based on the current ESC guideline5 and withheld specific serological tests or polymerase chain reaction (PCR) assays for unusual but potential microorganisms as long as the patient’s clinical course was not out of track and the antibiotics therapy appeared clinically effective. Following 1 week of intensive antibiotic treatment, we finally decided to perform surgery mainly because the PVE was complicated with perivalvular abscess, as evidenced by 18F-FDG PET/CT with all negative blood culture tests. On the 14th day of hospitalization, prosthetic valve was surgically replaced with a 25-mm bioprosthesis (25A Trifecta™; St. Jude Medical, Inc., St. Paul, MN, USA) with extensive debridement of the infected and necrotic tissues surrounding the aortic annulus (Figure 3A and B).

T/CT with all negative blood culture tests. On the 14th day of hospitalization, prosthetic valve was surgically replaced with a 25-mm bioprosthesis (25A Trifecta™; St. Jude Medical, Inc., St. Paul, MN, USA) with extensive debridement of the infected and necrotic tissues surrounding the aortic annulus (Figure 3A and B). Surgically excised tissue was subjected to microbiological and pathological analysis; however, no evidence of bacterial organisms was found (Figure 3C and D) and blood culture tests were negative. Post-operative TTE revealed a normally functioning aortic valve, and he was discharged on the 51st day. Based on the international guideline,5 antibiotic therapy was continued for 6 weeks until hospital discharge, although gentamicin was discontinued in the first 3 weeks because of nephrotoxicity. Furthermore, intravenous antibiotic treatment was followed by 6-month outpatient oral antibiotic therapy with amoxicillin (750 mg/day) without any recurrences. Figure 1 Transoesophageal echocardiography showing a thickened area along the aortic root behind the non-coronary sinus of Valsalva (arrowheads) and a mobile echogenic mass attached to the prosthetic valve leaflet (arrow).

Surgically excised tissue was subjected to microbiological and pathological analysis; however, no evidence of bacterial organisms was found (Figure 3C and D) and blood culture tests were negative. Post-operative TTE revealed a normally functioning aortic valve, and he was discharged on the 51st day. Based on the international guideline,5 antibiotic therapy was continued for 6 weeks until hospital discharge, although gentamicin was discontinued in the first 3 weeks because of nephrotoxicity. Furthermore, intravenous antibiotic treatment was followed by 6-month outpatient oral antibiotic therapy with amoxicillin (750 mg/day) without any recurrences. Figure 1 Transoesophageal echocardiography showing a thickened area along the aortic root behind the non-coronary sinus of Valsalva (arrowheads) and a mobile echogenic mass attached to the prosthetic valve leaflet (arrow). Figure 2 (A) 18F-fluorodeoxyglucose positron emission tomography/computed tomography showing significant 18F-fluorodeoxyglucose uptake (arrowheads) at the level of the mechanical aortic valve with inhibition of the rest of the cardiac metabolism, indicating perivalvular abscess. (B) The combination of 18F-fluorodeoxyglucose positron emission tomography and computed tomography angiography provides additional information regarding the accurate location of the vegetation behind the valve surface (arrow) and distribution of the affected perivalvular tissue (arrowheads), in addition to characterizing the coronary arteries, aortic valve, root, and ascending aorta. LMCA, left main coronary artery; RCA, right coronary artery.

nal information regarding the accurate location of the vegetation behind the valve surface (arrow) and distribution of the affected perivalvular tissue (arrowheads), in addition to characterizing the coronary arteries, aortic valve, root, and ascending aorta. LMCA, left main coronary artery; RCA, right coronary artery. Figure 3 (A) Visualization of the mobile vegetation attached to the aortic mechanical prosthesis (arrow). (B) Surgical view of an aortic perivalvular abscess (arrow). (C) Haematoxylin–eosin (H&E)-stained histological section of the mobile vegetation attached to the aortic mechanical prosthesis showing fibrin-rich thrombi and infiltration of neutrophils and macrophages without any evidence of bacteria or tumour tissue. (D) Magnified H&E-stained section of mobile vegetation (square in C) showing microorganisms that were absent in the thrombotic vegetation.

egetation attached to the aortic mechanical prosthesis showing fibrin-rich thrombi and infiltration of neutrophils and macrophages without any evidence of bacteria or tumour tissue. (D) Magnified H&E-stained section of mobile vegetation (square in C) showing microorganisms that were absent in the thrombotic vegetation. Discussion The modified Duke criteria have been recommended for PVE diagnosis since its proposal by Durack et al.6 Notwithstanding the presence of well-established clinical criteria, PVE diagnosis poses some challenges. There is a common concern regarding the interpretation of echocardiographic findings, despite TTE or TOE being the primary diagnostic approach.7 As observed in the patient in this study, echocardiographic findings can often be inconclusive, which can be primarily attributed to the similar appearance of both the thrombus and pannus on the prosthetic valves, which cannot be distinguished from vegetation.7 This inconclusive diagnosis can lead to difficulty or delay in surgical decisions, particularly in patients with low-to-intermediate likelihood of PVE, such as those with negative blood culture tests. 18F-fluorodeoxyglucose positron emission tomography/computed tomography is an established diagnostic modality in patients with suspected PVE that is used when conventional diagnostic tools fail to provide a definitive diagnosis.5 In the present patient, perivalvular involvement was a key observation because intense 18FDG uptake confined to the aortic annulus above the prosthesis as revealed by 18F-FDG PET/CT images was compatible with the thickened area within the aortic annular region observed in TOE examinations, implying perivalvular abscess formation. Additionally, detecting perivalvular involvement by utilizing 18F-FDG PET/CT allowed us to improve the diagnostic accuracy of PVE.

rosthesis as revealed by 18F-FDG PET/CT images was compatible with the thickened area within the aortic annular region observed in TOE examinations, implying perivalvular abscess formation. Additionally, detecting perivalvular involvement by utilizing 18F-FDG PET/CT allowed us to improve the diagnostic accuracy of PVE. As a preoperative risk assessment, CT angiography is more advantageous and safer than invasive coronary angiography in PVE cases involving the aortic valve because invasive coronary angiography potentially involves risks of vegetation embolization or haemodynamic decompensation. Also, CT angiography can provide further information on the valve size, anatomy, and calcification of aortic valve, which are essential for surgical planning.8 Furthermore, compared with the TOE findings, the combination of PET and CT angiography enhances the accuracy of identification of the infected location, in addition to the delineation of coronary anatomy and detection of fistulae and abscess, distal embolic complications and infected aneurysms at other sites.4

anning.8 Furthermore, compared with the TOE findings, the combination of PET and CT angiography enhances the accuracy of identification of the infected location, in addition to the delineation of coronary anatomy and detection of fistulae and abscess, distal embolic complications and infected aneurysms at other sites.4 Another important case discussion was on how to manage the blood culture-negative patient with PVE with appropriate antibiotic therapy and/or surgical intervention if needed. The patient was initially treated with ceftriaxone in empirical therapy for unexplained fever following three sets of blood culture tests. Although the patient’s condition stabilised in the first week, with improvement in fever and general appearance, we switched ceftriaxone to intravenous ampicillin and gentamicin because the findings of 18F-FDG PET/CT imaging were highly suggestive of PVE. These antibiotic regimens for initial empirical treatment of late PVE were determined based on the current ESC guideline5 and consultation with the endocarditis team. In a recent review,9 Viridans group streptococci, coagulase-negative staphylococci (CNS), Enterococcus spp. and Streptococcus bovis were reported to be the most common pathogens in patients with PVE. We carefully selected a combination of ampicillin and gentamicin to mainly treat staphylococci, streptococci, and enterococci. We assumed that the patient’s clinical course was relatively subacute and less destructive with no major complications such as heart failure and systematic embolism and ceftriaxone seemed to be clinically effective. Considering this, PVE triggered by Staphylococcus aureus or CNS was slightly less likely to occur in the patient. Blood culture-negative infective endocarditis (BCNIE) can be caused by fungi or fastidious slow-growing bacteria, notably obligatory intracellular bacteria.1 Among them, nutritionally variant Streptococcus spp. and HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella) could be the potential causative microbes in the present case; therefore, we selected a combination of ampicillin and gentamicin for treatment based on the local epidemiology. Indeed, we were ready to perform systemic serological testing for less common microorganisms in BCNIE patients, such as Coxiella burnetii, Bartonella spp., Aspergillus spp., Mycoplasma pneumonia, Brucella spp., and Legionella pneumophila, followed by specific PCR assays.

n for treatment based on the local epidemiology. Indeed, we were ready to perform systemic serological testing for less common microorganisms in BCNIE patients, such as Coxiella burnetii, Bartonella spp., Aspergillus spp., Mycoplasma pneumonia, Brucella spp., and Legionella pneumophila, followed by specific PCR assays. However, we kept the samples and did not perform these tests because the patient’s condition had gradually recovering after the initiation of intravenous ampicillin and gentamicin during the whole hospital stay, including the perioperative period. Additionally, both the blood and tissue PCR tests, which are not covered by Japan’s national health insurance, generally take a considerable amount of time and cost. A 6-month outpatient oral antibiotic therapy was completed because we emphasized on the remarkable findings: PVE was complicated with perivalvular abscess formation and unidentified microorganisms. In summary, we report a case regarding a patient with blood culture-negative PVE complicated with perivalvular abscess, with a low-to-intermediate likelihood of PVE based on the modified Duke criteria, in whom 18F-FDG PET/CT successfully provided a definitive diagnosis of perivalvular abscess and infective endocarditis, leading to subsequent surgical intervention within an appropriate timeframe.

VE complicated with perivalvular abscess, with a low-to-intermediate likelihood of PVE based on the modified Duke criteria, in whom 18F-FDG PET/CT successfully provided a definitive diagnosis of perivalvular abscess and infective endocarditis, leading to subsequent surgical intervention within an appropriate timeframe. Lead author biography Dr Shiro Miura is working as a chief interventional cardiologist at one of the most outstanding cardiovascular centers in Hokkaido in Japan named Hokkaido Ohno Memorial Hospital with remarkable achievements specializing in interventions on ischemic heart diseases and structural heart disease in the management of inpatients and outpatients with heart failure following the postgraduate course named ‘MSc Statistics with Applications in Medicine’ in University of Southampton in the UK where I was rewarded the Dean’s List Awards for exceptional performance for both the regular term exams and final dissertation. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz171_Supplementary_Slide_Set Click here for additional data file.

Learning points Gradual rise in implantable cardioverter-defibrillator shock impedance may be caused by encapsulation fibrosis; this may be seen in isolation and in the absence of electrical failure. Synchronized shock through the device can be used to determine whether a true lead integrity issue exists and requires replacement. Low-voltage subthreshold measurements may be deceptive and small changes to true impedance can be amplified. Only a true shock impedance can give an accurate impedance reading. Introduction Effective defibrillation requires sufficient current across the myocardial mass to reset the action potentials of a critical number of myocardial cells. An implantable cardioverter-defibrillator (ICD) system with a high impedance will have greater resistance to current flow and defibrillation may be unsuccessful. Ensuring ongoing integrity of the high-voltage (HV) system is an essential part of the device monitoring process. Defibrillation impedance (also termed shock or HV impedance) can be measured in two different ways: either through a high output therapy—termed true shock impedance (TSI); or through a calculated value derived using a low voltage sub-threshold measurement (LVSM).2–4 True shock impedance is rarely performed as a routine test as it requires sedating the patient to deliver a shock through the device. The normal range for HV impedance is approximately 30–110 Ω from a single coil circuit and 20–70 Ω in a dual coil circuit, with a small variance between lead designs.5

urement (LVSM).2–4 True shock impedance is rarely performed as a routine test as it requires sedating the patient to deliver a shock through the device. The normal range for HV impedance is approximately 30–110 Ω from a single coil circuit and 20–70 Ω in a dual coil circuit, with a small variance between lead designs.5 Acute impedance rises can occur post-implantation due to incomplete pin engagement or from a pneumothorax and gradual changes in HV impedance up to 12 Ω have been described in the first 3 months of follow up.6 This could be due to lead movement or because of initial encapsulation of the right ventricular (RV) coil, which reduces its contact with the blood pool, increasing the coil shock impedance. There is limited evidence on gradual changes in impedance beyond 1 year.6,7 Causes for this have been attributed to metal ion oxidization (MIO) and environmental stress cracking (ESC).5 Metal ion oxidization is a degradation process caused by exposure of polyurethane to metal ions released by the conductor elements. This can be due to chemical oxidization, solvation, galvanic, or electrolytic corrosion. These ions cause cracks that expose the metal conductor elements to body fluids creating a chain reaction and gradually increasing impedance.5 Environmental stress cracking is caused by shocking coil oxidation which weakens the surface structure causing brittle microcracks. These cracks are then exposed to further chemical reactions that cause a gradual rise in impedance.

r elements to body fluids creating a chain reaction and gradually increasing impedance.5 Environmental stress cracking is caused by shocking coil oxidation which weakens the surface structure causing brittle microcracks. These cracks are then exposed to further chemical reactions that cause a gradual rise in impedance. Here, we present a case series of patients implanted with Boston Scientific ICDs, all of whom exhibited a significant, but gradual, rise in HV impedance above the upper limit of normality. We compared these cases to our historical ICD dataset of similar devices from the same manufacturer to identify any differences.

r elements to body fluids creating a chain reaction and gradually increasing impedance.5 Environmental stress cracking is caused by shocking coil oxidation which weakens the surface structure causing brittle microcracks. These cracks are then exposed to further chemical reactions that cause a gradual rise in impedance. Here, we present a case series of patients implanted with Boston Scientific ICDs, all of whom exhibited a significant, but gradual, rise in HV impedance above the upper limit of normality. We compared these cases to our historical ICD dataset of similar devices from the same manufacturer to identify any differences. Timeline Patient 1 Pre-implantation Hypertrophic cardiomyopathy, primary prevention dual chamber implantable cardioverter-defibrillator (ICD) Implant 2007 A dual coil right ventricular (RV) lead was implanted The high-voltage (HV) impedance (low-voltage sub-threshold measurement, LVSM) at implant was 58 Ω in dual coil configuration February 2017 The HV impedance (LVSM) begins to rise June 2017 The HV impedance (LVSM) had risen to 167 Ω in dual coil configuration August 2017 A full output synchronized shock was performed showing a true shock impedance (TSI) of 116 Ω in dual coil configuration May 2018 Right ventricular lead was replaced at time of upgrade to cardiac resynchronization defibrillator (CRT-D) New implant HV impedance (LVSM) of 53 Ω Patient 2 Pre-implantation Hypertrophic cardiomyopathy, primary prevention dual chamber ICD Implant 2012 A single coil RV lead was implanted The HV impedance (LVSM) at implant was 50 Ω June 2016 The HV impedance (LVSM) begins to rise January 2018 The HV impedance (LVSM) had risen to 118 Ω February 2018 A full output synchronized shock was performed showing a TSI of 76 Ω in dual coil configuration Continued monitoring of RV lead as TSI normal Patient 3 Pre-implantation Hypertrophic cardiomyopathy, primary prevention dual chamber ICD Implant 2006 A dual coil RV lead was implanted The HV impedance (LVSM) at implant was 38 Ω in dual coil configuration October 2015 The HV impedance (LVSM) begins to rise April 2018 The HV impedance (LVSM) had risen to 126 Ω in dual coil configuration June 2018 A full output synchronized shock was performed showing a TSI of 78 Ω in dual coil configuration Continued monitoring of RV lead as TSI normal Patient 4 Pre-implantation Long QT syndrome, secondary prevention dual chamber ICD Implant 2013 A single coil RV lead was implanted The HV impedance (LVSM) at implant was 55 Ω May 2016 The HV impedance (LVSM) begins to rise January 2017 The HV impedance (LVSM) had risen to 125 Ω February 2017 A full output synchronized shock was performed showing a TSI of 90 Ω August 2017 Right ventricular lead extraction was elected after discussion with guardians Extraction unsuccessful, unable to retrieve RV coil

The HV impedance (LVSM) begins to rise January 2017 The HV impedance (LVSM) had risen to 125 Ω February 2017 A full output synchronized shock was performed showing a TSI of 90 Ω August 2017 Right ventricular lead extraction was elected after discussion with guardians Extraction unsuccessful, unable to retrieve RV coil and tip due to fibrous adhesions with a mechanical sheath.

The HV impedance (LVSM) begins to rise January 2017 The HV impedance (LVSM) had risen to 125 Ω February 2017 A full output synchronized shock was performed showing a TSI of 90 Ω August 2017 Right ventricular lead extraction was elected after discussion with guardians Extraction unsuccessful, unable to retrieve RV coil and tip due to fibrous adhesions with a mechanical sheath. New HV impedance (LVSM) of 54 Ω Patient 5 Pre-implantation Hypertrophic cardiomyopathy, secondary prevention dual chamber ICD Implant 2003 A dual coil RV lead was implanted The HV impedance (LVSM) at implant was 55 Ω in dual coil configuration December 2015 The HV impedance (LVSM) begins to rise March 2018 The HV impedance (LVSM) had risen to 107 Ω in dual coil configuration and 135 Ω in single coil configuration April 2018 A full output synchronized shock was performed showing a TSI of 76 Ω in single coil configuration Continued monitoring of RV lead as TSI normal Patient 6 Pre-implantation Left ventricular non-compaction, primary prevention dual chamber ICD Implant 2005 A dual coil RV lead was implanted The HV impedance (LVSM) at implant was 56 Ω in dual coil configuration February 2008 The HV impedance (LVSM) begins to rise February 2018 The HV impedance (LVSM) had risen to 137 Ω in dual coil configuration and 154 Ω in single coil configuration March 2018 A full output synchronized shock was performed showing a TSI of 121 Ω in single coil configuration A new RV lead was added at time of box change as patient declined extraction Results This case series describes six patients (Table 1) with low-voltage sub-threshold measurement (LVSM) values significantly higher than at initial implant (Figure 1). After reviewing each case in turn, the impedance rise did not correlate with any specific clinical event such as decompensated heart failure, pulmonary oedema, pneumothorax, or trauma, nor as a result of any change in medication. Furthermore, blood tests confirmed no electrolyte abnormalities in any of our patients. All leads had Gore polytetrafluoroethylene (ePTFE) coated coils. Chest radiographs showed no macroscopic appearances of a lead insulation breaches (Figure 2) and for the three patients that had procedures, there was no evidence of pocket calcification. Echocardiography was unable to demonstrate any evidence of exaggerated lead fibrosis for all cases. Patient 4 was the first patient presented in this series. Following an open discussion with the patient and their parents, a decision for attempted extraction and reimplantation was made.

vidence of pocket calcification. Echocardiography was unable to demonstrate any evidence of exaggerated lead fibrosis for all cases. Patient 4 was the first patient presented in this series. Following an open discussion with the patient and their parents, a decision for attempted extraction and reimplantation was made. Figure 1 Shock impedance and bipolar right ventricular impedance (Ω) trends for each patient over the past year. aHighlights the when a high-voltage therapy was performed. Figure 2 Anteroposterior chest radiographs performed for each patient. Table 1 Summary of patient details with shock impedance values measured in DC or SC

vidence of pocket calcification. Echocardiography was unable to demonstrate any evidence of exaggerated lead fibrosis for all cases. Patient 4 was the first patient presented in this series. Following an open discussion with the patient and their parents, a decision for attempted extraction and reimplantation was made. Figure 1 Shock impedance and bipolar right ventricular impedance (Ω) trends for each patient over the past year. aHighlights the when a high-voltage therapy was performed. Figure 2 Anteroposterior chest radiographs performed for each patient. Table 1 Summary of patient details with shock impedance values measured in DC or SC Patient ID Age Aetiology ECG indication Device position Implant Lead details Coils Access LVSM at implant (Ω) Rate of rise in LVSM (Ω/month) LVSM prior to shock (Ω) TSI (Ω) Management 1 43 HCM Primary prevention, LBBB Sub-pec 01 March 2007 Guidant 0185 Dual coil Subclavian 58 (DC) 6 (DC) 167 (DC) 116 (DC) New RV lead added at time of upgrade to CRT. New LVSM 53 Ω 2 22 HCM Primary prevention, normal QRS Sub-pec 20 December 2012 Boston Scientific 0292 Single coil Axillary 50 (SC) 4.24 (SC) 118 (SC) 76 (SC) Continued monitoring 3 38 HCM Primary prevention, LBBB Sub-pec 18 July 2006 Guidant 0165 Dual coil Cephalic 38 (DC) 2.93 (DC) 126 (DC) 78 (DC) Continued monitoring 4 12 Long QT Secondary prevention, normal QRS Sub-pec February 2013 Boston Scientific 0692 Single coil Axillary 55 (SC) 4.25 (SC) 140 (SC) 90 (SC) Attempted RV lead extraction and lead replacement, unable to retrieve RV coil. New LVSM 54 Ω 5 27 HCM Secondary prevention, RBBB Sub-pec 16 October 2003 Guidant 0165 Dual Coil Cephalic 55 (DC) 1.01 (DC) 107 (DC) 135 (SC) 76 (SC) Continued monitoring 6 32 Non- compaction Primary prevention, normal QRS Sub-cut 01 September 2005 Guidant 0165 Dual coil Cephalic 56 (DC) 0.51 (DC) 137 (DC) 154 (SC) 121 (SC) New RV lead added at time of box change. New LVSM 52 Ω DC, dual coil; SC, single coil.

Coil Cephalic 55 (DC) 1.01 (DC) 107 (DC) 135 (SC) 76 (SC) Continued monitoring 6 32 Non- compaction Primary prevention, normal QRS Sub-cut 01 September 2005 Guidant 0165 Dual coil Cephalic 56 (DC) 0.51 (DC) 137 (DC) 154 (SC) 121 (SC) New RV lead added at time of box change. New LVSM 52 Ω DC, dual coil; SC, single coil. Mean change in impedance amongst implantable cardioverter-defibrillators We used our historical data from patients previously implanted with Boston Scientific ICDs (n1,477) using the Latitude system to document the mean change in shock impedance over the course of a 12-month period. Any patients with suspected shock conductor fractures were excluded from this calculation. Using an unpaired t-test, the change in impedance per month was significantly higher amongst our case series of patients compared with the cohort with Boston Scientific ICDs (3.2 ± 1.9 Ω/month vs. 0.0008 ± 0.005 Ω/month, P < 0.001).

patients with suspected shock conductor fractures were excluded from this calculation. Using an unpaired t-test, the change in impedance per month was significantly higher amongst our case series of patients compared with the cohort with Boston Scientific ICDs (3.2 ± 1.9 Ω/month vs. 0.0008 ± 0.005 Ω/month, P < 0.001). Discussion True shock impedance vs. low-voltage subthreshold impedance measurements There are distinct differences between a TSI and a LVSM. Device-based diagnostics now place greater demands on battery current and many manufacturers have reduced the energy used to obtain the LVSM. Since the Teligen generation of Boston Scientific ICDs, Boston Scientific used a smaller electrical impulse of 80 µA@ 156 µs to measure the LVSM. This impulse was less than previous models which used 15 mA @ 60 µs.8 Of note, Abbott and Biotronik devices also use small current impulses (750 µA@ 19 ms, 1 mA @ 30 µs, respectively). These smaller current calculated values can be affected by subtle changes to current flow, causing minor variation in impedance values day to day. These are caused by external and internal factors such as; positional, external electromagnetic interference, and electrolyte balance. Medtronic ICDs use a higher sub-threshold constant voltage stimulus (1 V @90 µs) coupled with mathematical scaling to arrive at the projected HV therapy pulse, making it less variable. In our patients, whilst the shock impedance trends show daily fluctuations (due to causes described above), the ongoing rising trend in impedance suggests an additional contributing factor (Figure 1).

us (1 V @90 µs) coupled with mathematical scaling to arrive at the projected HV therapy pulse, making it less variable. In our patients, whilst the shock impedance trends show daily fluctuations (due to causes described above), the ongoing rising trend in impedance suggests an additional contributing factor (Figure 1). What is the mechanism of rising high-voltage impedance? Patients assessed in device clinic where provocative manoeuvres (arm manipulation, pectoral muscle contraction, pocket manipulation, deep expiration, and inspiration both standing and supine) were performed showed no signs of lead malfunction or baseline wander on right ventricle and far field electrograms. For dual coil leads, individual vector breakdown showed stable SVC coil measurements and abnormally high RV coil measurements. Furthermore, in all cases, the rise in HV impedance correlated with a Superior Vena Cava (SVC), gradual rise in RV pacing impedance over time. This is logical as all six leads have integrated bipolar design, which measures the RV pacing impedance between the RV tip and RV coil. This isolates the problem to the RV coil.

Furthermore, in all cases, the rise in HV impedance correlated with a Superior Vena Cava (SVC), gradual rise in RV pacing impedance over time. This is logical as all six leads have integrated bipolar design, which measures the RV pacing impedance between the RV tip and RV coil. This isolates the problem to the RV coil. Two mechanisms have previously been described for gradual rises in shock impedance, MIO, and ESC. These mechanisms, however, do not fit this presentation, because the TSI should be an abnormally high measurement, not a normalised one, as the coil conductor is damaged. One explanation for our findings could be encapsulation of the RV coil by endocardium and an additional tissue fibrotic process. Tissue growth around endocardial defibrillator leads has been widely reported in the literature, from extraction studies, post-transplant and post-mortem examination. It is likely to be the cause of the rise in LVSM post-implant.5,10–16 However, proving that there is a definitive fibrotic or calcification process in these patients is difficult without surgical lead extraction. Imaging modalities such as echocardiography, cardiac magnetic resonance imaging and cardiac computed tomography suffer from artefact as a consequence of the metal lead conductors.

wever, proving that there is a definitive fibrotic or calcification process in these patients is difficult without surgical lead extraction. Imaging modalities such as echocardiography, cardiac magnetic resonance imaging and cardiac computed tomography suffer from artefact as a consequence of the metal lead conductors. Encapsulation may cause a falsely high LVSM; due to rising tissue density surrounding the coil. However, the TSI would be less affected as the value is not scaled, producing a reduced, normalised value. This would also explain why this phenomenon is only being seen in newer generation devices that have smaller LVSM energy outputs. Furthermore, four relatively young patients in this series have a diagnosis of hypertrophic cardiomyopathy; one may postulate that a more aggressive fibrotic reaction in these patients may exacerbate the fibrotic process contributing to endocardial encapsulation.17 One commonality between all patients is that they all had GORE ePTFE coated coils. When GORE ePTFE coated coils were initially produced there was a warning that one may expose the coil by damaging the coating if not implanted correctly. This could prove an additional theory as it may result in infiltration of the exposed conductor and a rise in impedance.18 However, we observed no electrical abnormality and an exposed coil should produce an abnormal TSI.

ere was a warning that one may expose the coil by damaging the coating if not implanted correctly. This could prove an additional theory as it may result in infiltration of the exposed conductor and a rise in impedance.18 However, we observed no electrical abnormality and an exposed coil should produce an abnormal TSI. Another theory is ionic build up around the RV coil. This may be caused by the anodal shock vector attracting free floating electrons to the RV coil, causing a gradual rise in shock impedance. An HV shock would dissipate these ions, producing a value comparable to implant. However, in our series, all values of TSI have been raised compared to implant suggesting that there is an underlying issue surrounding the RV coil. Also, all patients had normal blood electrolyte values which would make this theory less likely to be the sole cause. Ionic build up that is dissipated with synchronised shock may prove a reason as to why the LVSM transiently drops post-shock before increasing once more. From our case series, we have only observed this phenomenon in Boston Scientific devices and leads. Whether this is a unique problem applicable to Boston leads remains uncertain as this manufacturer makes up the largest proportion of the ICDs implanted at our centre. Therefore, our findings may extend to other manufacturers with time and increased volume.

served this phenomenon in Boston Scientific devices and leads. Whether this is a unique problem applicable to Boston leads remains uncertain as this manufacturer makes up the largest proportion of the ICDs implanted at our centre. Therefore, our findings may extend to other manufacturers with time and increased volume. Management of defibrillator systems with rising high-voltage impedance A full clinical assessment is an essential part of the investigative process. One may speculate that one could predict such an issue from the rate of increase in the impedance, however, from just six cases, there is insufficient data to make such inferences. Over the past 12 months, the average rise in LVSM per month of 3.2 ± 1.9 Ω/month was seen across the six cases. This certainly appears higher than the trends from our historical Boston ICD dataset. A suggested management flow diagram is demonstrated in Figure 3. Of note, if patients are to be considered for transvenous lead extraction, one may consider this a higher risk procedure, due to potentially more extensive tissue fibrosis or infiltration of the RV coil. Interestingly, we were unable to retrieve the RV coil with a mechanical sheath in Patient 4 due to extensive tethering to the intracardiac tissue. For patients that have normal TSI the active monitoring will continue with synchronised shocks needing to be performed as the LVSM is inaccurate. Whilst this does not resolve the problem, it may prevent unnecessary lead extraction and replacement.

eath in Patient 4 due to extensive tethering to the intracardiac tissue. For patients that have normal TSI the active monitoring will continue with synchronised shocks needing to be performed as the LVSM is inaccurate. Whilst this does not resolve the problem, it may prevent unnecessary lead extraction and replacement. Figure 3 Flow diagram of suggested management for patients with high-voltage impedance measurements on Boston Scientific ICDs. HV, high voltage; LVSM, low-voltage sub-threshold measurement. Conclusion Gradual rises in LVSM may be attributed to encapsulation of RV coils as well as MIO and ESC. The phenomena can be distinguished by a normalized TSI when measured with a full output synchronised shock compared to the LVSM. Managing these leads requires vigorous testing and replacement may be necessary. For those who have normal TSI, close monitoring is required to ensure a sufficient impedance to effectively defibrillate the patient. Lead author biography Christopher Monkhouse, BSc CCDS. Cardiac electrophysiology has been my passion since starting my training in 2011. Being a cardiac patient, myself has given me special insight into the patient’s perspective of health services, driving me to provide the highest level of evidence-based care for patients within Cardiac Rhythm Management, in particular device therapy and arrhythmia. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

Lead author biography Christopher Monkhouse, BSc CCDS. Cardiac electrophysiology has been my passion since starting my training in 2011. Being a cardiac patient, myself has given me special insight into the patient’s perspective of health services, driving me to provide the highest level of evidence-based care for patients within Cardiac Rhythm Management, in particular device therapy and arrhythmia. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: C.M. has received speaker fees from Abbott Ltd. A.W.C. has received grant fees from Abbott Ltd. J.B. is an associate editor of EHJ-Case Reports, received speaker fees from Abbott Ltd and research grant from Boston Scientific. Supplementary Material ytz220_Supplementary_Slide_Set Click here for additional data file.

Learning points There are many cases of acute aortic dissection with out-of-hospital cardiopulmonary arrest that can be diagnosed using non-contrast computed tomography (CT), and it is often possible to estimate the direct cause of death. Acute phase CT cannot completely replace conventional autopsy. However, it is useful because it can be performed in many cases because of its convenience and non-invasiveness. Introduction With the progress in medical technology, the prognosis of patients admitted for acute aortic dissection (AAD) has remarkably improved;1 however, it may demonstrate a high mortality rate, because many cases with AAD are considered as patients with out-of-hospital cardiopulmonary arrest (OHCPA).2 Thus, the exact causes of death might often be unclear. The incidence of AAD, as known currently, has been mainly calculated from hospitalized patients. Therefore, it is extremely important to investigate AAD cases, including OHCPA patients to accurately assess the prognosis of AAD cases. The aim of our report was to validate the findings of non-contrast computed tomography (CT) in three cases of AAD with OHCPA and to propose that CT diagnosis be actively performed as a way of determining the cause of death in OHCPA patients. The CT images were acquired on an 80-slice multidetector scanner (Aquilion ONE, Canon Medical Systems, Tochigi, Japan) with a thickness of 5 mm, tube voltage of 120 kVp, and auto exposure control. The CT values for bloody pericardial effusion and haematoma of the thoracic cavity are shown in Hounsfield units (HUs).

ts. The CT images were acquired on an 80-slice multidetector scanner (Aquilion ONE, Canon Medical Systems, Tochigi, Japan) with a thickness of 5 mm, tube voltage of 120 kVp, and auto exposure control. The CT values for bloody pericardial effusion and haematoma of the thoracic cavity are shown in Hounsfield units (HUs). Timeline Patient 1 16 min prior Disturbance of consciousness, abnormal respiration 0 min [cardiopulmonary arrest CPA)] Bystander cardiopulmonary resuscitation (CPR) performed by his family 3 min later Emergency medical service (EMS) arrival at the scene, initial electrocardiogram (ECG): pulseless electrical activity (PEA) 37 min later Arrival at the hospital 58 min later Discontinuation of CPR 77 min later Computed tomography (CT) performed Patient 2 [Day of admission] About 15 min prior Discomfort Unknown (CPA) Witness (+), Bystander CPR (−) 0 min (EMS arrival at the scene) CPR initiated by EMS, Initial ECG: PEA 38 min later Return of spontaneous circulation [Hospital Day 2] (Emergency operation not performed) 0 min (CPA) CPR started, Initial ECG: PEA 28 min later Discontinuation of CPR 44 min later CT performed Patient 3 0 min (CPA) Collapsed suddenly in front of her family (Bystander CPR +) 9 min later EMS arrival at the scene, Initial ECG: ventricular fibrillation (VF) 40 min later Arrival at hospital 69 min later Venoarterial extracorporeal membrane oxygenation (VA-ECMO) established because of incessant VF 195 min later CT performed, (impossible systematic circulation maintenance) Case presentation Patient 1 Our first patient, a man in his early 80s, presented with hypertension, sequelae of left hemiparesis owing to cerebral haemorrhage, and severe chronic obstructive pulmonary disease. Home oxygen therapy was introduced, and he was provided with home medical care.

matic circulation maintenance) Case presentation Patient 1 Our first patient, a man in his early 80s, presented with hypertension, sequelae of left hemiparesis owing to cerebral haemorrhage, and severe chronic obstructive pulmonary disease. Home oxygen therapy was introduced, and he was provided with home medical care. One evening, his family noticed deterioration of his consciousness and stertorous respiration while at home. Just prior to arrival of the emergency medical services (EMS), cardiopulmonary arrest (CPA) occurred, and bystander cardiopulmonary resuscitation (CPR) was initiated by the family. The initial electrocardiogram (ECG) showed pulseless electrical activity (PEA) at the time of arrival of the EMS. Thereafter, CPR was continued for 55 min; however, the return of spontaneous circulation (ROSC) could not be achieved. Computed tomography imaging after discontinuation of CPR showed an intimomedial flap localized to the ascending aorta and an inward shift of the calcified intima into a portion of the aortic lesion (Figure 1). The diameter of the false lumen was 26.6 mm from the maximum short axis diameter of 48.0 mm, and the enlarged false lumen was pushed against the true lumen. Increased attenuation was seen along the wall of the bilateral pulmonary artery, probably owing to ‘haemorrhagic infiltration through the common aortopulmonary adventitia’3 when the aortic rupture occurred. Moreover, a large amount of bloody pericardial effusion was confirmed, and the direct cause of death was considered to be cardiac tamponade.

een along the wall of the bilateral pulmonary artery, probably owing to ‘haemorrhagic infiltration through the common aortopulmonary adventitia’3 when the aortic rupture occurred. Moreover, a large amount of bloody pericardial effusion was confirmed, and the direct cause of death was considered to be cardiac tamponade. Figure 1 Computed tomography image of Patient 1 after the discontinuation of cardiopulmonary resuscitation shows an intimomedial flap localized to the ascending aorta (A-arrow), inward shift of the calcified intima (B/C-arrows), increased bilateral pulmonary artery wall attenuation (B/C-arrowheads), and large amount of bloody pericardial effusion (D-asterisk). The computed tomography values of bloody pericardial effusion were 40–52 HUs.

momedial flap localized to the ascending aorta (A-arrow), inward shift of the calcified intima (B/C-arrows), increased bilateral pulmonary artery wall attenuation (B/C-arrowheads), and large amount of bloody pericardial effusion (D-asterisk). The computed tomography values of bloody pericardial effusion were 40–52 HUs. Patient 2 A male patient in his early 80s presented with hypertension. He complained of discomfort while driving a car with his wife. The car slowly bumped onto the guardrail and stopped. Immediately, his wife requested EMS, and CPA was confirmed upon arrival of the EMS at the scene. The initial ECG at the scene showed PEA. After 38 min of CPR, ROSC was confirmed. Non-contrast CT imaging showed ‘crescentic hyperattenuating intramural fluid collection’4 from the ascending aorta to the arch, along with an inward shift of the calcified intima into a portion of the aortic lesion (Figure 2). In addition, bleeding into the left thoracic cavity was noted. An emergency operation was not performed owing to the poor prognosis regarding brain function. On Day 2 of admission, he developed CPA again, and CPR was performed immediately. However, he died without ROSC. The initial ECG obtained at the time of the CPA showed PEA, while that obtained after discontinuation of CPR showed a significant increase in the left pleural haematoma.

r prognosis regarding brain function. On Day 2 of admission, he developed CPA again, and CPR was performed immediately. However, he died without ROSC. The initial ECG obtained at the time of the CPA showed PEA, while that obtained after discontinuation of CPR showed a significant increase in the left pleural haematoma. Figure 2 Computed tomography image of Patient 2 after return of spontaneous circulation (ROSC) on the day of admission shows crescentic hyperattenuating intramural fluid collection from the ascending aorta to the arch (A-arrow) and left pleural haematoma (A-asterisk). Computed tomography image after discontinuation of cardiopulmonary resuscitation on Day 2 of admission shows inward shift of the calcified intima (B-arrowhead), significant increase in the left pleural haematoma (B-asterisk), and crescentic intramural fluid collection revealing more hyperattenuation (B-arrow). The computed tomography values of left pleural haematoma were 33–43 HUs on admission and 45–60 HUs on Day 2 of admission.

rd shift of the calcified intima (B-arrowhead), significant increase in the left pleural haematoma (B-asterisk), and crescentic intramural fluid collection revealing more hyperattenuation (B-arrow). The computed tomography values of left pleural haematoma were 33–43 HUs on admission and 45–60 HUs on Day 2 of admission. Patient 3 A female patient in her late 60s had a medical history of hypertension and diabetes. She collapsed in front of her family, and bystander CPR was performed. The initial ECG on arrival of the EMS at the scene showed ventricular fibrillation (VF). CPR was continued, and defibrillation was repeatedly performed. Since VF was sustained even after arrival at the emergency room, venoarterial extracorporeal membrane oxygenation was established. However, it was impossible to maintain the systemic circulation. The CT showed aortic dissection extending from the root of the ascending aorta to the common iliac artery (Figure 3). Although there were no findings suggestive of a rupture of the aorta, the true lumen from the ascending aorta to the descending thoracic aorta was pushed and completely collapsed because of the enlarged false lumen. Based on these findings, myocardial ischaemia owing to occlusion of the coronary artery ostium was considered to be the direct cause of death.

tive of a rupture of the aorta, the true lumen from the ascending aorta to the descending thoracic aorta was pushed and completely collapsed because of the enlarged false lumen. Based on these findings, myocardial ischaemia owing to occlusion of the coronary artery ostium was considered to be the direct cause of death. Figure 3 Computed tomography imaging of Patient 3 shows aortic dissection extending from the root of the ascending aorta to the common iliac artery. The true lumen from the ascending aorta to the descending thoracic aorta completely collapsed due to the enlarged false lumen (A/B-arrowheads) and inward shift of the calcified intima at the abdominal aorta (C-arrow). No findings, such as bloody pericardial effusion and haemothorax, suggesting a rupture of the aorta (D). Discussion The three patients with OHCPA we experienced could be diagnosed with type A AAD and the direct causes of death could be easily determined using the clinical course of the condition and non-contrast CT findings.

Figure 3 Computed tomography imaging of Patient 3 shows aortic dissection extending from the root of the ascending aorta to the common iliac artery. The true lumen from the ascending aorta to the descending thoracic aorta completely collapsed due to the enlarged false lumen (A/B-arrowheads) and inward shift of the calcified intima at the abdominal aorta (C-arrow). No findings, such as bloody pericardial effusion and haemothorax, suggesting a rupture of the aorta (D). Discussion The three patients with OHCPA we experienced could be diagnosed with type A AAD and the direct causes of death could be easily determined using the clinical course of the condition and non-contrast CT findings. In past reports,5–7 the diagnostic criteria for AAD by non-contrast CT performed after CPA were as follows: (a) intimomedial flap; (b) inward shift of the calcified intima; (c) double sedimentation in the true and false lumen caused by hypostasis; and (d) the presence of intramural haematoma (IMH). In each paper, either criteria a, b, and c or criteria a, b, and d were adopted. Additionally, IMH is precisely defined as ‘a variant of dissection characterized by the absence of an intimal tear’ caused by haemorrhage of the aortic vasa vasorum into the aortic wall.8 However, as it is usually difficult to distinguish the tear itself using non-contrast CT, we interpreted the criterion (d) as ‘crescentic hyperattenuating intramural fluid collection’.4 The ‘intimomedial flap’ was detected in Cases 1 and 3, the ‘inward shift of the calcified intima’ was observed in all cases, and the ‘crescentic hyperattenuating intramural fluid collection’ was only detected in Case 2. On the other hand, ‘double sedimentation in the true and false lumen caused by hypostasis’ was not observed in any case. This is considered to be the reason for marginal influence of post-mortem changes in all cases because CT was performed immediately after discontinuation of CPR. In fact, few other post-mortem changes except for hypostasis were also observed in these patients.9,10 Furthermore, we diagnosed the direct causes of death in the three cases as follows: Case 1, cardiac tamponade because of aortic rupture into the pericardium; Case 2, left pleural haematoma due to aortic rupture into the left pleural cavity; and Case 3, myocardial ischaemia due to coronary artery occlusion as incessant VF and complete collapsed true lumen were observed without evidence of aortic rupture. All three cases described above could be easily diagnosed with AAD, and the associated direct causes of death could also be diagnosed.

eft pleural cavity; and Case 3, myocardial ischaemia due to coronary artery occlusion as incessant VF and complete collapsed true lumen were observed without evidence of aortic rupture. All three cases described above could be easily diagnosed with AAD, and the associated direct causes of death could also be diagnosed. Ampanozi et al.5 reported that out of 33 cases diagnosed with AAD at autopsy, 25 (about 76%) could be diagnosed with AAD using non-contrast CT performed before autopsy. In their other study, they also reported that among 11 cases of AAD with bloody pericardial effusion, 8 cases could be correctly diagnosed using non-contrast CT performed before autopsy. At the time, the sensitivity and specificity were 72.7% and 100%, respectively.6 Although the number of cases is small, these reports indicate that non-contrast CT alone is insufficient to diagnose AAD. In fact, when using non-contrast CT, post-mortem changes such as hypostasis can lead to false positives. Moreover, severe collapse of the aorta due to aortic rupture can lead to a false negative. In such cases, it is necessary to perform other imaging procedures, such as CT angiography11 or MRI,12 and autopsy because diagnosis of AAD with non-contrast CT alone is particularly difficult.

stasis can lead to false positives. Moreover, severe collapse of the aorta due to aortic rupture can lead to a false negative. In such cases, it is necessary to perform other imaging procedures, such as CT angiography11 or MRI,12 and autopsy because diagnosis of AAD with non-contrast CT alone is particularly difficult. In past reports based on autopsy,13,14 the incidence of AAD in patients with non-traumatic OHCPA was ∼3%. However, Tanaka et al. investigated the cause of death with acute phase CT. Thereafter, they reported that the type A AAD patients constituted ∼7% of the non-traumatic OHCPA cases. Moreover, Moriwaki et al.15 reported that AAD (including both type A and type B) cases were found in 9.17% of non-traumatic OHCPA cases, mainly in the study that conducted diagnoses by perimortem CT. The incidence of AAD in their report was much higher than that in the previous reports based on autopsy. Although autopsy is the most reliable procedure for identifying the cause of sudden death, it is difficult to cover all cases owing to staff shortages, potential risks, and ethical and religious issues. Therefore, diagnostic imaging, in particular non-contrast CT, is considered to be superior to autopsy in terms of convenience and non-invasiveness. Although the sensitivity of non-contrast CT is insufficient, the technique is considered extremely useful to understand the morbidity and mortality associated with AAD.

es. Therefore, diagnostic imaging, in particular non-contrast CT, is considered to be superior to autopsy in terms of convenience and non-invasiveness. Although the sensitivity of non-contrast CT is insufficient, the technique is considered extremely useful to understand the morbidity and mortality associated with AAD. Thus, this case series presented three cases of AAD that showed typical mechanisms leading to death. We could determine the presence of AAD and its serious complications using non-contrast CT alone. There are not enough reports on the effectiveness of perimortem imaging including non-contrast CT, and few studies have investigated the detailed cause of death based on the features of the images. Our study, which is validated based on the features of detailed images, is considered to be useful for the diagnosis of AAD cases with OHCPA and the epidemiological study of AAD using non-contrast CT. Lead author biography Shinsuke Takeuchi graduated from Kyorin University Medical School in 2009. He have been at a Medical Staff (Cardiologist) at the Division of Cardiology, Second Department of Internal Medicine, Kyorin University School of Medicine, since 2015. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

Lead author biography Shinsuke Takeuchi graduated from Kyorin University Medical School in 2009. He have been at a Medical Staff (Cardiologist) at the Division of Cardiology, Second Department of Internal Medicine, Kyorin University School of Medicine, since 2015. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: Consent for publication was not obtained by the authors for the patients in this case series. However, the authors provided a means of opting out to the family of the deceased. Every effort has been made to ensure that patients are not identifiable in this publication. Conflict of interest: none declared. Supplementary Material ytz218_Supplementary_Slide_Set Click here for additional data file.

Learning points Spontaneous coronary artery dissection (SCAD) patients often have little or no traditional cardiovascular risk factors. Autosomal dominant polycystic kidney disease associated arteriopathy can predispose to SCAD. Corticosteroids can trigger the event. Treatment of SCAD is usually conservative because of the high probability of spontaneous healing, while intervention is reserved for cases with high-risk features like left main dissection, ongoing ischaemia, electrical, or haemodynamic instability. Prolonged inpatient monitoring (5–7 days) is recommended because of the risk of progression of the dissection. The need for dual antiplatelet therapy should be carefully evaluated in conservatively treated SCAD patients.

Treatment of SCAD is usually conservative because of the high probability of spontaneous healing, while intervention is reserved for cases with high-risk features like left main dissection, ongoing ischaemia, electrical, or haemodynamic instability. Prolonged inpatient monitoring (5–7 days) is recommended because of the risk of progression of the dissection. The need for dual antiplatelet therapy should be carefully evaluated in conservatively treated SCAD patients. Introduction Spontaneous coronary artery dissection (SCAD) is defined as a spontaneous (non-traumatic, non-iatrogenic, and non-atherosclerotic) separation of the coronary artery wall by intramural haemorrhage resulting in myocardial ischaemia. It is elicited by an intimal tear or a spontaneous intramural haemorrhage. Patients can present with the whole spectrum of acute coronary syndromes (ACS). The prevalence in the general population has been underestimated as a result of underdiagnosis. Recently, the condition is gaining recognition and recent angiographic data report an incidence of SCAD in 1–4% of patients presenting with ACS.1,2 The aetiology of SCAD appears to be multifactorial but patients often have a predisposing condition and, in many cases, a precipitating trigger is recognized. Predisposing conditions include heritable connective tissue disorders, fibromuscular dysplasia, systemic inflammatory disease, and pregnancy-related hormonal changes, as they can cause weakening of the arterial wall. Emotional and extreme physical stress have been described as possible triggers, while hormonal therapy and corticosteroids have been identified as both predisposing factors and precipitating triggers (see Table 1).3

atory disease, and pregnancy-related hormonal changes, as they can cause weakening of the arterial wall. Emotional and extreme physical stress have been described as possible triggers, while hormonal therapy and corticosteroids have been identified as both predisposing factors and precipitating triggers (see Table 1).3 Table 1 Possible predisposing conditions and triggers for spontaneous coronary artery dissection Case patient Known predisposing conditions for SCAD Inherited arteriopathy and connective tissue disorder ADPKD Systemic inflammatory disease No evidence Fibromuscular dysplasia No evidence Exogenous hormones Was recently on high-dose steroid therapy (tapered 1 month before) Pregnancy and multiparity No (recent) pregnancy, one daughter Known triggers for SCAD Extreme emotional stress Present Intense exercise Not recent Active hormonal therapy Was recently on high-dose steroid therapy (tapered 1 month before) Recreational drugs None Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder. It is caused by mutations in PKD1 and -2 genes, coding for polycystin 1 and 2, proteins with an important role in the development and maintenance of the vascular system.4 Cystic malformation leads to progressive loss of kidney function over decades.4,5 It is a systemic disorder with polycystic liver disease being the most common extrarenal manifestation.4 Intracranial aneurysms are the most common vascular manifestation.5 Common cardiac manifestations include mitral valve prolapse and aortic insufficiency.4

eads to progressive loss of kidney function over decades.4,5 It is a systemic disorder with polycystic liver disease being the most common extrarenal manifestation.4 Intracranial aneurysms are the most common vascular manifestation.5 Common cardiac manifestations include mitral valve prolapse and aortic insufficiency.4 Timeline Day Events 1 Consultation abdominal surgery after recent liver transplant: complaints of intermittent chest pain, cardiological workup planned. 4 Admission to the emergency room: persisting heavy chest pain. Electrocardiogram (ECG) showed a normal sinus rhythm without ST segment or T-wave abnormalities. Blood samples revealed elevated cardiac troponins T (53 pg/mL) but without evolution. Transthoracic echocardiogram (TTE) showed a non-dilated ventricle wild mild septal hypertrophy, normal regional, and global left ventricular function without significant valvulopathy. Coronary angiography was performed and showed a diffuse stenosis of the distal left anterior descending artery (LAD) compatible with a spontaneous coronary artery dissection. Conservative treatment with dual antiplatelet therapy, low-dose statin, and beta-blocker was started. The patient was admitted to the intensive cardiac care unit for further evaluation. 6 New episode of chest pain: ECG showed diffuse ST segment and repolarization abnormalities. A new TTE showed apicoseptal hypokinesia. A new coronary angiography showed a more proximal and prominent dissection of the LAD (75–95% stenosis) with preserved distal flow. No percutaneous coronary intervention because of small vessel size. Transdermal nitrates were associated, clopidogrel was interrupted and a small dose of angiotensin-converting-enzyme inhibition was initiated. Afterwards, the patient remained pain free. 7 Prolonged monitoring reveals a single asymptomatic episode of non-sustained ventricular tachycardia. 10 Discharge under medical treatment with close follow-up. 33 Follow-up outpatient visit, no problems. Initiation of cardiac rehabilitation. Case presentation A 44-year-old woman was referred by her gastrointestinal surgeon to the emergency room (ER) because of multiple episodes of chest pain. She was, like her mother, known with ADPKD as well as polycystic liver disease, without (intracranial) aneurysms. Two months earlier, a liver transplantation had been performed because of dyspnoea caused by the liver cysts.

gastrointestinal surgeon to the emergency room (ER) because of multiple episodes of chest pain. She was, like her mother, known with ADPKD as well as polycystic liver disease, without (intracranial) aneurysms. Two months earlier, a liver transplantation had been performed because of dyspnoea caused by the liver cysts. She was under treatment with antirejection medication (tacrolimus, mycophenolate mofetil, and steroids that were tapered recently). She did not smoke and there were no other cardiovascular risk factors but stress. The chest pain started during sleep, radiated to the left arm and subsided spontaneously after 5 min. The electrocardiogram (ECG) in the ER showed a normal sinus rhythm without ST segment or T-wave abnormalities. Patient was afebrile, with a blood pressure of 137/74 mmHg and a regular pulse of 77 b.p.m. On auscultation heart sounds were normal and lungs were clear. There was no peripheral oedema and peripheral pulsations were normal. Chest X-ray was normal. Blood samples showed a chronic but stable kidney disease (eGFR 36 mL/min/1.73 m2), absence of inflammation or anaemia. High-sensitive troponin T-level was significantly elevated (53 pg/mL) but showed no significant evolution after 3 h. A transthoracic echocardiogram (TTE) demonstrated a non-dilated ventricle (end-diastolic diameter 41 mm) with mild septal hypertrophy (14 mm), normal regional contractility, a preserved left ventricular (LV) systolic function and absence of significant valvulopathy. A coronary angiography was performed and showed diffuse narrowing of the distal left anterior descending artery (LAD) with ‘stick insect’ aspect, compatible with a SCAD Type 2 with preserved distal flow6 (Figure 1). The patient was admitted to the intensive cardiac care unit for further observation and treatment. Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin was started, as well as pravastatin and a low dose of bisoprolol. During the following days, the troponin level steadily rose with stable kidney function. Three days later, chest pain redeveloped for which IV nitrates were associated but these were quickly interrupted because of headache. The ECG was progressively abnormal with diffuse biphasic T waves in the anterior leads (V2–5). A repeat TTE now showed apicoseptal hypokinesia. A new coronary angiography showed a more proximal and prominent dissection of the mid and distal LAD (75–95% stenosis), with preserved distal flow (Figure 2).

ause of headache. The ECG was progressively abnormal with diffuse biphasic T waves in the anterior leads (V2–5). A repeat TTE now showed apicoseptal hypokinesia. A new coronary angiography showed a more proximal and prominent dissection of the mid and distal LAD (75–95% stenosis), with preserved distal flow (Figure 2). Transdermal nitrates were associated after which the pain subsided. Clopidogrel was interrupted because of the progression under DAPT and a small dose of angiotensin-converting-enzyme (ACE)-inhibition was initiated because of the depressed LV function. Prolonged monitoring revealed a single episode of non-sustained ventricular tachycardia. The patient remained asymptomatic and the rest of the stay was uneventful. She was discharged after 10 days and was still doing well at follow-up after 1 month with cardiac enzymes that returned to baseline levels. Cardiac rehabilitation, including psychological support, was initiated. Figure 1 Coronary angiogram Day 0: apical 0°, cranial 35° demonstrating diffuse stenosis of the mid and distal LAD with ‘stick insect’ aspect (arrows). Figure 2 Coronary angiogram Day 4: apical 0°, cranial 38° demonstrating more proximal and prominent dissection (arrow).

Transdermal nitrates were associated after which the pain subsided. Clopidogrel was interrupted because of the progression under DAPT and a small dose of angiotensin-converting-enzyme (ACE)-inhibition was initiated because of the depressed LV function. Prolonged monitoring revealed a single episode of non-sustained ventricular tachycardia. The patient remained asymptomatic and the rest of the stay was uneventful. She was discharged after 10 days and was still doing well at follow-up after 1 month with cardiac enzymes that returned to baseline levels. Cardiac rehabilitation, including psychological support, was initiated. Figure 1 Coronary angiogram Day 0: apical 0°, cranial 35° demonstrating diffuse stenosis of the mid and distal LAD with ‘stick insect’ aspect (arrows). Figure 2 Coronary angiogram Day 4: apical 0°, cranial 38° demonstrating more proximal and prominent dissection (arrow). Discussion We report a SCAD in an ADPKD patient, an association of which only eight cases have been described in the literature.7,8 A recent nationwide retrospective analysis of 66 360 SCAD cases, however, identified 60 patients (0.09%) with ADPKD.9 The association between SCAD and inherited arteriopathy and connective tissue disorder is known.1–3 Autosomal dominant polycystic kidney disease is a known predisposing factor for vascular abnormalities, especially cerebral aneurysms.4 Our patient did not have intracranial aneurysms or vascular abnormalities in the thorax or abdomen. The recent treatment with corticosteroids and the associated stress may have triggered the SCAD and to our knowledge, this is the first case of SCAD in a recently transplanted ADPKD patient.

pecially cerebral aneurysms.4 Our patient did not have intracranial aneurysms or vascular abnormalities in the thorax or abdomen. The recent treatment with corticosteroids and the associated stress may have triggered the SCAD and to our knowledge, this is the first case of SCAD in a recently transplanted ADPKD patient. Most (>90%) SCAD patients are women and typically have a low cardiovascular risk profile, which may cause delayed diagnosis.1,3 However, thanks to increasing awareness and the introduction of high-sensitive troponins diagnosis has improved.10 The management of SCAD differs from that of atherosclerotic coronary artery disease.1–3 In our case, no other classical risk factors but chronic kidney disease and emotional stress were identified. She was on steroid antirejection therapy the month before, which is a possible precipitating factor for SCAD.1–3

Most (>90%) SCAD patients are women and typically have a low cardiovascular risk profile, which may cause delayed diagnosis.1,3 However, thanks to increasing awareness and the introduction of high-sensitive troponins diagnosis has improved.10 The management of SCAD differs from that of atherosclerotic coronary artery disease.1–3 In our case, no other classical risk factors but chronic kidney disease and emotional stress were identified. She was on steroid antirejection therapy the month before, which is a possible precipitating factor for SCAD.1–3 Coronary angiography is the gold standard for the diagnosis of SCAD with intracoronary imaging (optical coherence tomography or intravascular ultrasound) being preserved for uncertain diagnosis. The commonly used angiographic classification consists of three types. Type 1 represents the pathognomonic form with multiple radiolucent lumens and extraluminal contrast staining. Type 2, the commonest type, refers to a diffuse stenosis of varying length (usually >20 mm), while a Type 3 SCAD is a focal or tubular and usually short (<20 mm) stenosis that mimics atherosclerosis. In addition, a Type 4 presentation characterized by a total occlusion, usually of a distal vessel is described in the European position paper on SCAD.1 Some familiarity with these angiographic appearances is needed to recognize SCAD but further intracoronary imaging can be necessary, especially in Type 3 presentations. The LAD is the most affected vessel and there is a predisposition for distal segments, as seen in this case.1,3

n the European position paper on SCAD.1 Some familiarity with these angiographic appearances is needed to recognize SCAD but further intracoronary imaging can be necessary, especially in Type 3 presentations. The LAD is the most affected vessel and there is a predisposition for distal segments, as seen in this case.1,3 There is increasing evidence of angiographic healing with medical treatment and percutaneous intervention is associated with a high complication rate.11 Therefore, medical treatment is preferred over revascularization in case of preserved flow and absence of high-risk features like left main dissection, ongoing ischaemia, electrical, or haemodynamic instability.1–3,12 In this case, angina was controlled medically, furthermore, percutaneous intervention was not possible because of the small size of the vessel.

were indicated in this patient.1–3 Statins are not routinely recommended since the aetiology of SCAD is not atherosclerotic. Furthermore, a small retrospective cohort demonstrated a higher recurrence rate in statin users, therefore, their use should be reserved for patients with conventional indications for statins.1–3 In 5–10% of SCAD patients on medical treatment, extension of dissection occurs in the early phase, as in our case. Therefore prolonged inpatient monitoring (5–7 days) is recommended in SCAD patients.1–3 Despite a favourable 30 days survival, 30-day major adverse cardiovascular events rate is high (9%).2,13 Recurrent SCAD can complicate the long-term course and has been reported to be as high as 30% in older series. Unfortunately, there is no treatment strategy that has shown to reduce this risk. In a recent prospective cohort study, this risk was substantially lower (10.4% over a 3-year time course), and therapy with beta-blockade seemed to reduce recurrence risk, probably by lowering the coronary arterial wall stress through decrease in myocardial contractility and blood pressure.14 It is very important to acknowledge the impact of SCAD on psychological well-being. Rates of depression and anxiety in SCAD patients are similar to those of non-SCAD myocardial infarction patients.15 Therefore, specific rehabilitation programmes including psychological support are strongly recommended.16 Patient groups active on social media, such as Beat SCAD-UK and SCAD Alliance, aim to support SCAD patients and their families and raise awareness of SCAD.

lar to those of non-SCAD myocardial infarction patients.15 Therefore, specific rehabilitation programmes including psychological support are strongly recommended.16 Patient groups active on social media, such as Beat SCAD-UK and SCAD Alliance, aim to support SCAD patients and their families and raise awareness of SCAD. Conclusion Autosomal dominant polycystic kidney disease associated arteriopathy predisposes to SCAD and high doses of corticosteroids, given in the transplant setting, may trigger the event. Caregivers should be aware of this association when evaluating ADPKD patients with chest pain. Most cases can be managed conservatively with medical management. Dual antiplatelet therapy with aspirin and clopidogrel is recommended by experts but should be evaluated on an individual basis. Lead author biography Ezther Verlaeckt received her medical degree at Ghent University in 2019. She then started her residency in internal medicine. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz216_Supplementary_Slide_Set Click here for additional data file.

Learning points Quadfurcation of single coronary artery from the right is extremely rare anomaly. Always activate heart team while managing such patients for a better outcome and treatment strategy. During coronary angiogram always look for associated congenital anomalies. The use of 5-Fr catheter is advisable as majority cases have done successfully without any complications. We have treated the patient with the help of 6-Fr catheter without any complications and the choice should be left to the interventional cardiologist. Introduction Single coronary artery (SCA) is a condition in which the entire left coronary arterial system arises from right coronary sinus.1 Among the congenital coronary anomalies, SCA arising from the right aortic cusp is rare with a prevalence during coronary angiogram between 0.02% and 0.05%.2

The use of 5-Fr catheter is advisable as majority cases have done successfully without any complications. We have treated the patient with the help of 6-Fr catheter without any complications and the choice should be left to the interventional cardiologist. Introduction Single coronary artery (SCA) is a condition in which the entire left coronary arterial system arises from right coronary sinus.1 Among the congenital coronary anomalies, SCA arising from the right aortic cusp is rare with a prevalence during coronary angiogram between 0.02% and 0.05%.2 Timeline 28 August 2016 Presented to emergency room as case ST-elevation in myocardial infarction. 28 August 2016 Single coronary artery arising from the right was noted. Primary percutaneous coronary intervention is done to proximal right coronary artery, ostial right posterior descending artery, and right posterior atrioventricular artery with one drug eluting stent in each artery. 30 August 2016 Staged angioplasty was done to first obtuse marginal and to proximal left circumflex coronary artery. 1 September 2016 Discharged with appointment for computed tomography coronary angiogram. 13 October 2016 Contrast-enhanced multidetector computed tomography 64 slices coronary angiogram was performed. Case presentation A 56-year-old Bangladeshi male with no prior medical history presented with an inferior wall ST-elevation myocardial infarction with Killip Class II (Figure 1). The cardiopulmonary examination was normal and the total ischaemic time was 90 min. Figure 1 Electrocardiogram diagnostic for inferior wall myocardial infarction.

Timeline 28 August 2016 Presented to emergency room as case ST-elevation in myocardial infarction. 28 August 2016 Single coronary artery arising from the right was noted. Primary percutaneous coronary intervention is done to proximal right coronary artery, ostial right posterior descending artery, and right posterior atrioventricular artery with one drug eluting stent in each artery. 30 August 2016 Staged angioplasty was done to first obtuse marginal and to proximal left circumflex coronary artery. 1 September 2016 Discharged with appointment for computed tomography coronary angiogram. 13 October 2016 Contrast-enhanced multidetector computed tomography 64 slices coronary angiogram was performed. Case presentation A 56-year-old Bangladeshi male with no prior medical history presented with an inferior wall ST-elevation myocardial infarction with Killip Class II (Figure 1). The cardiopulmonary examination was normal and the total ischaemic time was 90 min. Figure 1 Electrocardiogram diagnostic for inferior wall myocardial infarction. Baseline laboratory investigations showed hs-Troponin-i ≥100 ng/mL (Ref. range: 0.01–0.04 ng/mL). Urgent cardiac catheterization was performed which revealed the presence of an SCA arising from the right aortic sinus which quadfurcated into left anterior descending (LAD) coronary artery, first diagonal (D1), left circumflex coronary artery (LCx), and right coronary artery (RCA).

ng/mL (Ref. range: 0.01–0.04 ng/mL). Urgent cardiac catheterization was performed which revealed the presence of an SCA arising from the right aortic sinus which quadfurcated into left anterior descending (LAD) coronary artery, first diagonal (D1), left circumflex coronary artery (LCx), and right coronary artery (RCA). Multiple atherosclerotic lesions were present with 70–90% stenosis in the distal LAD and a severely calcified 70–90% stenosis in the D1 with reference diameter of the vessel at this level less than 1.5 mm. About 70–90% stenosis was present in the proximal circumflex (LCx) and had a 90–99% stenosis in the first obtuse marginal (OM1). Proximal RCA had an acute occlusion (Figure 2). The crux of the RCA had a bifurcation lesion with MEDINA (0,1,1) of 90–99% (Supplementary material online, Video S1). Percutaneous coronary intervention (PCI) was performed on the RCA with the deployment of three stents. First, one stent was implanted into the proximal RCA and two stents were implanted at the level of crux of RCA with inverted TAP stenting strategy. Full anti-ischaemic treatment including dual antiplatelet therapy was initiated. Figure 2 Acute occlusion of proximal right coronary artery. After 48 h, repeated PCI of the first obtuse marginal (OM1) and proximal LCx were performed (Supplementary material online, Video S2 and Figure 3). Figure 3 The final angiographic results with TIMI III flow and trident appearance.

Multiple atherosclerotic lesions were present with 70–90% stenosis in the distal LAD and a severely calcified 70–90% stenosis in the D1 with reference diameter of the vessel at this level less than 1.5 mm. About 70–90% stenosis was present in the proximal circumflex (LCx) and had a 90–99% stenosis in the first obtuse marginal (OM1). Proximal RCA had an acute occlusion (Figure 2). The crux of the RCA had a bifurcation lesion with MEDINA (0,1,1) of 90–99% (Supplementary material online, Video S1). Percutaneous coronary intervention (PCI) was performed on the RCA with the deployment of three stents. First, one stent was implanted into the proximal RCA and two stents were implanted at the level of crux of RCA with inverted TAP stenting strategy. Full anti-ischaemic treatment including dual antiplatelet therapy was initiated. Figure 2 Acute occlusion of proximal right coronary artery. After 48 h, repeated PCI of the first obtuse marginal (OM1) and proximal LCx were performed (Supplementary material online, Video S2 and Figure 3). Figure 3 The final angiographic results with TIMI III flow and trident appearance. Post-PCI transthoracic echocardiography revealed preserved left ventricle systolic function with an ejection fraction of 55–60%. Mild hypokinesia of the entire inferior wall, inferior septum, and infero-lateral wall detected. We did coronary computed tomography to study the anatomy. Single coronary ostium arising from the right was confirmed. It was found to have three abnormal courses of coronary arteries. Only RCA had a normal course. LCx was found to have retro-aortic course, LAD coronary artery had pre-pulmonic course, and D1 had a sub-pulmonic (septal) course. There was no interarterial course found in this case (Figure 4).

rom the right was confirmed. It was found to have three abnormal courses of coronary arteries. Only RCA had a normal course. LCx was found to have retro-aortic course, LAD coronary artery had pre-pulmonic course, and D1 had a sub-pulmonic (septal) course. There was no interarterial course found in this case (Figure 4). Figure 4 Volume rending three-dimensional computed tomography coronary angiogram shows single coronary ostium arising from the right with three abnormal courses of coronary arteries and only right coronary artery was found to have a normal course. Left circumflex coronary artery was found to have retro-aortic course, left anterior descending artery had pre-pulmonic course, and first diagonal had a sub-pulmonic (septal) course. The patient was discharged on the fourth day from admission. The post-PCI period was uneventful. Discussion Anomalous origin of the coronary arteries, and, in particular, SCA arising from the right aortic cusp is rare.3 In our case, an SCA, with the entire right and left coronaries originating from right sinus of Valsalva was an incidental finding at the time of cardiac catheterization for acute coronary syndrome. There was no history of any congenital or valvular heart disease. However, SCA is associated with congenital anomalies such as bicuspid aortic valve, coronary arteriovenous fistula, and transposition of the great vessels.4

lva was an incidental finding at the time of cardiac catheterization for acute coronary syndrome. There was no history of any congenital or valvular heart disease. However, SCA is associated with congenital anomalies such as bicuspid aortic valve, coronary arteriovenous fistula, and transposition of the great vessels.4 Our case of an SCA originating from right sinus of Valsalva, with a single ostium that quadrifurcated into LAD, D1, LCx, and a dominant RCA highlights some of the challenges encountered during a PCI in these patients. Associated coarctation has to be ruled out and aortogram is vital in such cases. A DOT sign on left ventricular angiography may be a clue to the presence of an anomalous coronary artery.5 In our case, we did not perform left ventricular angiography due to the need for emergency PCI. An SCA originating from the right sinus has the following distribution: (i) anterior to aorta and pulmonary artery, (ii) interarterial, (iii) interseptal, and (iv) retroaortic.6 In our case, we had all three abnormal courses except interarterial. Volume rending three-dimensional computed tomography coronary angiogram of our case confirmed an SCA arising from the right coronary sinus giving rise to right coronary artery (RCA) normal course, LCX with retro-aortic course, the diagonal artery (D1) with subpulmonic (septal) course, and LAD with pre-pulmonic course. Our patient does not fall in any of the types described in Lipton’s classification.7

Volume rending three-dimensional computed tomography coronary angiogram of our case confirmed an SCA arising from the right coronary sinus giving rise to right coronary artery (RCA) normal course, LCX with retro-aortic course, the diagonal artery (D1) with subpulmonic (septal) course, and LAD with pre-pulmonic course. Our patient does not fall in any of the types described in Lipton’s classification.7 Hence, we propose a modified version of this classification of SCA—Type IV (Rajan’s and Vladimir’s) an extremely rare presentation SCA which quadfurcated into RCA, LAD, D1, and LCx. Abnormal coronary anatomy in SCA accounts for 15% ischaemic events. The risk of having ischaemic heart diseases in SCA is high due to8: Acute-angle take-off Atherosclerosis Coronary spasm Interarterial course with associated hypoplasia Intramural course (at the aortic wall) with lateral compression or exercise-related narrowing Ostial ridge Slit-like ostium. Conclusion Single coronary artery arising from the right aortic cusp with quadfurcation into RCA, LAD, D1, and LCx is rare. In view of the absence of inter-arterial course in our case, the need for surgical correction was not required. For such rare type of SCA, it is always wise to activate the heart team for proper assessment and better outcome.

tery arising from the right aortic cusp with quadfurcation into RCA, LAD, D1, and LCx is rare. In view of the absence of inter-arterial course in our case, the need for surgical correction was not required. For such rare type of SCA, it is always wise to activate the heart team for proper assessment and better outcome. Lead author biography Dr Mohammed Al Jarallah is currently the head of cardiology at Sabah al Ahmed cardiac center, Kuwait. He obtained his M.B.Bch form the faculty of medicine, Kuwait University in 1999. Then, he went to do his Internal medicine training at McGill University, Quebec, Canada from the year 2001 to 2004. During which he was certified with the American board of internal medicine in 2004 and became a fellow of the Royal College of Physicians of Canada for internal medicine in 2005. He did his cardiology fellowship at McGill University from 2004 to 2007 followed by a year of fellowship in echocardiography. He was certified with the American board of cardiovascular diseases and became a fellow of the royal college of physicians of Canada for cardiology in 2007. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Supplementary Material ytz197_Supplementary_Data Click here for additional data file. Acknowledgements The authors did not received any kind of honorarium for this article. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

Supplementary material is available at European Heart Journal - Case Reports online. Supplementary Material ytz197_Supplementary_Data Click here for additional data file. Acknowledgements The authors did not received any kind of honorarium for this article. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points It is important to distinguish between acute myocardial infarction and takotsubo cardiomyopathy as this will dictate the patient’s requirement for secondary prevention and counselling regarding the aftermath of the two different conditions. Clinicians should be aware of the possibility of recurrent episodes of takotsubo cardiomyopathy in the same individual with multiple variant morphologies. Introduction Takotsubo cardiomyopathy mimics acute myocardial infarction in its presentation and has a recognized recurrence rate.1,2 So far, the literature focused on the re-occurrence of the syndrome in populations without particular attention to the number of recurrences in a certain individual. We, hereby, present a case of a patient having three confirmed recorded recurrences at the same institution on the background of another three previous (historic) admissions at the same institution, which most likely represented takotsubo episodes but mislabelled as ‘myocardial infarction’ according to the contemporaneous knowledge at the time. She had preserved ejection fraction after each recovery.

at the same institution on the background of another three previous (historic) admissions at the same institution, which most likely represented takotsubo episodes but mislabelled as ‘myocardial infarction’ according to the contemporaneous knowledge at the time. She had preserved ejection fraction after each recovery. Timeline Time Events 1986 Presented with chest pain. Electrocardiogram (ECG) showed widespread anterolateral T-wave inversion and prolonged QTc. Angiogram revealed normal coronary arteries. 1988 Represented similarly with chest pain and similar electrocardiographic changes as 1986. 1998 Admitted with chest discomfort. Elevated creatine kinase to 233. Electrocardiogram showed similar changes as 1986. Normal left and right coronary arteries. January 2014 Presented with chest pain following recent bereavement of neighbour. Raised cardiac markers and normal coronary arteries. Electrocardiogram showed obvious hyperacute T wave in anterior leads. Apical ballooning noted on echocardiogram. Cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement ruled out myocardial infarction. June 2015 With ongoing stress at home, she once again presented with chest pain, ECG showed widespread hyperacute T waves in anterolateral leads, raised cardiac enzymes, and normal coronaries. June 2018 Represented with chest pain, ECG showed T-wave inversion in lateral leads and prolonged QTc, with no known precipitating events. Cardiac MRI demonstrate focal lateral wall ballooning. Case presentation A 76-year-old ex-smoker White Scottish woman first presented in 2014 via Emergency Department, with central chest pain in the context of recent bereavement. Her admission troponin was increased to 8.6 times the upper limit of normal contemporary range. Her B-type natriuretic peptide was 1220 pg/mL. All other laboratory test were unremarkable. Her admission electrocardiogram (ECG) showed in Figure 1A. Coronary angiography revealed normal coronary arteries (Figure 1B and C) but the left ventriculogram showed extensive apical ballooning (Figure 1D–E). An echocardiogram demonstrated apical ballooning (Supplementary material online, Movie M4). Cardiac magnetic resonance imaging (MRI) ruled out a myocardial infarction (Figure 1F–H). Her left ventricular ejection fraction recovered entirely after 4 months and she had a classical diagnosis of apical takostubo. Her InterTak diagnostic score was 61, with 58.6% probability of takotsubo.

material online, Movie M4). Cardiac magnetic resonance imaging (MRI) ruled out a myocardial infarction (Figure 1F–H). Her left ventricular ejection fraction recovered entirely after 4 months and she had a classical diagnosis of apical takostubo. Her InterTak diagnostic score was 61, with 58.6% probability of takotsubo. Figure 1 (A) Presenting electrocardiogram. (B and C) Left and right coronary arteries, respectively, (D and E) End-systolic and end-diastolic frames of the left ventriculogram demonstrating extensive apical ballooning. (F–H) Late gadolinium enhancement ruling out any myocardial infarction. The patient had a significant family history of ischaemic heart disease with sister and brother dying of myocardial infarction in their 6th decade of life. Her past medical history included hypercholesterolaemia and three previous episodes which were labelled ‘myocardial infarctions’ in 1986, 1988, and 1998. These historic presenting ECG’s are shown in Figure 2A–C, respectively. Her cardiac enzymes in 1986 and 1988 were unremarkable but in 1998 her initial creatine kinase was raised to 1.7 times the upper limit of normal contemporary range. She underwent coronary angiography which demonstrated normal coronary arteries on each occasion. Digitized images of 1998 left and right coronary arteries shown in Figure 2D. In 1998, she was admitted directly from her son’s wedding. The InterTak diagnostic score and probability in 1998 was the same as in 2014.

range. She underwent coronary angiography which demonstrated normal coronary arteries on each occasion. Digitized images of 1998 left and right coronary arteries shown in Figure 2D. In 1998, she was admitted directly from her son’s wedding. The InterTak diagnostic score and probability in 1998 was the same as in 2014. Figure 2 (A–C) Presenting electrocardiograms in 1986, 1988, and 1998, respectively. (D) Digitalized left and right coronary arteries in 1998. Subsequently, she represented with central chest pain in 2015, on the background of being the main carer of her husband who had a stroke. Initial troponin was 75 times more than the upper limit of normal and the repeat 12 h troponin was 48 times the upper limit of normal contemporary range. Electrocardiogram on admission is shown in Figure 3A. Again, coronary arteries were normal as shown in Figure 3B and C. She had a left ventriculogram demonstrated probable mild area of hypokinesis in the inferior apical wall, supporting the diagnosis of apical Takotsubo. Her InterTak diagnostic score was 67, with a 79.8% probability of takotsubo. Figure 3 (A) Presenting electrocardiogram 2015, Qtc 560 ms. (B and C) Left and right coronary arteries, respectively. See also Supplementary material online, Movie M5: left coronary artery 2015; Supplementary material online, Movie M6: right coronary artery 2015.

Subsequently, she represented with central chest pain in 2015, on the background of being the main carer of her husband who had a stroke. Initial troponin was 75 times more than the upper limit of normal and the repeat 12 h troponin was 48 times the upper limit of normal contemporary range. Electrocardiogram on admission is shown in Figure 3A. Again, coronary arteries were normal as shown in Figure 3B and C. She had a left ventriculogram demonstrated probable mild area of hypokinesis in the inferior apical wall, supporting the diagnosis of apical Takotsubo. Her InterTak diagnostic score was 67, with a 79.8% probability of takotsubo. Figure 3 (A) Presenting electrocardiogram 2015, Qtc 560 ms. (B and C) Left and right coronary arteries, respectively. See also Supplementary material online, Movie M5: left coronary artery 2015; Supplementary material online, Movie M6: right coronary artery 2015. Further, in 2018, she had another episode of chest pain. Ambulance ECG is shown in Figure 4A with widespread T-wave inversion in the lateral leads and QTc of 527 ms. Initial troponin on admission was increased to 61 times the upper limit of normal contemporary range and repeat troponin 6 h later was again raised to 59 times the upper limit of normal contemporary range. InterTak diagnostic score was raised to 67, with a probability of 79.8%. Angiogram revealed normal coronary arteries and a focal phenotype of takotsubo cardiomyopathy best illustrated on cardiac MRI (Figure 4B–D) which once again ruled out any myocardial infarction. Figure 4E and F shows the end-diastolic and end-systolic phase, respectively. Red arrow in Figure 4F illustrates mid-cavity focal ballooning. A four-chamber cardiac magnetic resonance is shown in Supplementary material online, Movie M7. Once again she made a good recovery.

nce again ruled out any myocardial infarction. Figure 4E and F shows the end-diastolic and end-systolic phase, respectively. Red arrow in Figure 4F illustrates mid-cavity focal ballooning. A four-chamber cardiac magnetic resonance is shown in Supplementary material online, Movie M7. Once again she made a good recovery. Figure 4 (A) Ambulance electrocardiogram 2018. (B–D) Focal phenotype of Takotsubo. (E and F) End-diastolic and end-systolic, respectively. Red arrow in F shows mid-cavity focal ballooning. Supplementary material online, Movie M7: four-chamber cardiac magnetic resonance cine demonstrating the focal lateral wall ballooning. Clinical follow-up 3 months after the 2018 episode confirmed good clinical recovery, unremarkable clinical examination, and normal left ventricular ejection fraction with no regional wall motion abnormalities. Based on the local policy of not medicating these patients due to the lack of supporting evidence, she was discharged on no specific therapy. Discussion Here, we present a case of most likely six recurrences of takotsubo cardiomyopathy spanning over 33 years. At least three presentations had different left ventricular morphological types (apical, apical-to-mid-cavity, and focal) some were triggered by obvious and declared stress, while some were not. Recurrence of Takotsubo Cardiomyopathy is a well-known reported long-term issue in the takotsubo cohort. The recurrence rate is ∼5–6% at 6 years.3,4

tions had different left ventricular morphological types (apical, apical-to-mid-cavity, and focal) some were triggered by obvious and declared stress, while some were not. Recurrence of Takotsubo Cardiomyopathy is a well-known reported long-term issue in the takotsubo cohort. The recurrence rate is ∼5–6% at 6 years.3,4 To date, early cardiac catheterization is the only definite way to distinguish between acute coronary syndrome and takotsubo. However, to better guide initial evaluation, the non-invasive novel InterTak diagnostic score has been proposed.5 It helps distinguish takotsubo from acute coronary syndrome with good sensitivity and specificity using seven variables each with an assigned score value. Three episodes were potentially mislabelled as ‘myocardial infarction’ in the past, despite showing normal coronary arteries on each occasion and no evidence of myocardial injuries noted on subsequent cardiac magnetic resonance. The diagnosis of takotsubo was only discovered in 1991,6 hence it is understandable that this diagnosis was not recognized during the 1986 and 1988 episodes. The diagnosis of takotsubo could not be confirmed in 1998 due to the historic limitations with the lack of cardiac magnetic resonance and non-specific cardiac enzymes used. Clinicians must retain increased awareness on the possibility of multiple recurrences within the same individual, their shifting morphological variants on presentation and the possibility of previous episodes which may have been mislabelled in the past.

Three episodes were potentially mislabelled as ‘myocardial infarction’ in the past, despite showing normal coronary arteries on each occasion and no evidence of myocardial injuries noted on subsequent cardiac magnetic resonance. The diagnosis of takotsubo was only discovered in 1991,6 hence it is understandable that this diagnosis was not recognized during the 1986 and 1988 episodes. The diagnosis of takotsubo could not be confirmed in 1998 due to the historic limitations with the lack of cardiac magnetic resonance and non-specific cardiac enzymes used. Clinicians must retain increased awareness on the possibility of multiple recurrences within the same individual, their shifting morphological variants on presentation and the possibility of previous episodes which may have been mislabelled in the past. We would like to highlight the need for more multicentre prospective clinical trials and registries of takotsubo cases to further explore the best management and follow-up strategy of similar cases. Lead author biography Dr Shekinah Chandy (MBChB Aberdeen) currently an Internal Medical Trainee Year 1 in Aberdeen Royal Infirmary, with a keen interest in cardiology and research. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Funding This patient’s clinical investigation course was supported by the British Heart Foundation Project [PG/15/108/31928]. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

Supplementary material is available at European Heart Journal - Case Reports online. Funding This patient’s clinical investigation course was supported by the British Heart Foundation Project [PG/15/108/31928]. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz191_Supplementary_Data Click here for additional data file.

Learning points Acute myocardial infarction is an unusual complication in the days to months following aortic root replacement with coronary reimplantation (including Bentall and David procedures) and can be due to obstruction of the reimplanted artery. PCI can be considered as a salvage treatment for these patients. Cardiothoracic centres should perform complex aortic root surgery within the setting of an experienced multidisciplinary team involving cardiac surgeons, cardiologists with allied health professional input.

Acute myocardial infarction is an unusual complication in the days to months following aortic root replacement with coronary reimplantation (including Bentall and David procedures) and can be due to obstruction of the reimplanted artery. PCI can be considered as a salvage treatment for these patients. Cardiothoracic centres should perform complex aortic root surgery within the setting of an experienced multidisciplinary team involving cardiac surgeons, cardiologists with allied health professional input. Introduction Coronary ostial stenosis is an uncommon but recognized complication of aortic root surgery involving reimplantation of the coronaries to a graft and usually presents within the first 6 months following aortic root surgery.1 Ischaemia may become apparent immediately post-procedure, and this is generally managed with immediate reoperation with resiting of coronary button or bypass grafting.2 However, immediate grafting may not always be possible for technical reasons and decisions about revascularization become more complicated in patients who develop acute ischaemia in the weeks following the index procedure. We report a case series where urgent percutaneous coronary intervention (PCI) was used in the setting of acute myocardial infarction in patients who had recently undergone aortic root replacement as a valve-sparing procedure. The purpose of this report is to raise awareness of this complication and utility of PCI as a treatment option. This is particularly important for patients where surgery may not be technically possible or those who present in extremis.

nts who had recently undergone aortic root replacement as a valve-sparing procedure. The purpose of this report is to raise awareness of this complication and utility of PCI as a treatment option. This is particularly important for patients where surgery may not be technically possible or those who present in extremis. Timeline Case 1 Case 2 Indication for operation Marfan’s syndrome. Dilated aortic root at 5.7 cm Bicuspid aortic valve with aortic regurgitation (AR). Worsening symptoms with progressive AR and dilated aortic root at 7 cm Time from diagnosis to operation 2 months 3 weeks Operation Valve sparing root replacement (David procedure) Aortic root replacement and repair of native valve Immediate post- operative recovery Unremarkable, discharged 5 days later Angina type pain on mobilizing Time: index operation to ischaemic presentation 2 weeks 4 days Diagnosis of coronary ostial stenosis Inferior ST-elevation myocardial infarction. IVUS confirmed extrinsic compression of neo-ostium. Computed tomography coronary angiography suggests mechanical distortion of proximal right coronary artery (RCA) Procedure 1 × drug-eluting stent (DES) to proximal RCA 1 × DES proximal RCA Follow-up Echocardiography (ECHO) shows moderate left ventricular (LV) systolic dysfunction, with fatigue being only ongoing symptom No ongoing symptoms, most recent ECHO shows mild left ventricular systolic dysfunction Case presentation Patient 1 This 38-year-old woman with background of Marfan’s syndrome was admitted to hospital following an episode of syncope. Echocardiography (ECHO) showed severe dilation of the ascending aorta with mild mitral and aortic regurgitation (AR) and normal left ventricular systolic function. Computed tomography confirmed dilation at 57 mm. Valve sparing aortic root replacement (David procedure) was carried out 2 months later after which she made an unremarkable recovery, being discharged home 5 days post -operatively. She was not on any regular medications prior to admission and refused any medications on discharge from hospital.

irmed dilation at 57 mm. Valve sparing aortic root replacement (David procedure) was carried out 2 months later after which she made an unremarkable recovery, being discharged home 5 days post -operatively. She was not on any regular medications prior to admission and refused any medications on discharge from hospital. She was readmitted 10 days post -operatively directly from home to interventional cardiology via our regional optimal reperfusion service with an inferior ST-elevation myocardial infarction (STEMI) and cardiogenic shock [electrocardiogram (ECG) shown in Figure 1]. Prior to this, she had experienced a short history of exertional chest pain. Angiography showed the right coronary artery (RCA) was occluded proximally with thrombus and appearance of mechanical disruption of the aorto-ostial anastomosis (Figure 2). Reperfusion was achieved after wiring and export of a large thrombus, followed by ventricular fibrillation (VF) cardiac arrest after which an intra-aortic balloon pump was inserted and the patient intubated. After discussion with the multidisciplinary team (MDT) in the catheterization lab, the decision was to proceed with intravascular ultrasound (IVUS)-guided percutaneous intervention. IVUS confirmed extrinsic mechanical compression at the right coronary neo-ostium with no atherosclerosis present. This was successfully treated with one drug-eluting stent (DES) (Figure 2). Emergency ECHO in the catheterization lab showed severe right and left ventricular systolic dysfunction (LVSD). She was extubated the next day. Echocardiography on the 8th day of admission showed a dilated left ventricle with moderate segmental function and notably dilated failing right ventricle. Her recovery was complicated by ventilator acquired pneumonia and atrial fibrillation (AF) and she was discharged home after 3-week hospital admission.

the next day. Echocardiography on the 8th day of admission showed a dilated left ventricle with moderate segmental function and notably dilated failing right ventricle. Her recovery was complicated by ventilator acquired pneumonia and atrial fibrillation (AF) and she was discharged home after 3-week hospital admission. Figure 1 Electrocardiogram taken on admission to catheterization lab after patient admitted directly from home through the optimal reperfusion service. Electrocardiogram shows an inferior-posterior ST-elevation myocardial infarction. Figure 2 A 38-year-old woman with Marfan’s syndrome underwent elective David procedure. Ten days post-operatively, she developed an inferior ST-segment elevation myocardial infarction. The emergency coronary angiography shows extrinsic compression of the neo-ostium with resultant thrombosis of the right coronary artery. The right sided projection of the coronary artery shows the compression and thrombus (red arrow) corresponding with IVUS image showing thrombus and reduced luminal area. The mid-right coronary artery is large and normal without any atherosclerosis or compression (green arrow with corresponding IVUS image, bottom left). A drug-eluting stent implantation was successful with excellent final angiographic result. At 18 months of follow-up, her symptoms and ventricular function had significantly improved [New York Heart Association I–II and mild systolic impairment without right ventricular (RV) impairment].

Figure 2 A 38-year-old woman with Marfan’s syndrome underwent elective David procedure. Ten days post-operatively, she developed an inferior ST-segment elevation myocardial infarction. The emergency coronary angiography shows extrinsic compression of the neo-ostium with resultant thrombosis of the right coronary artery. The right sided projection of the coronary artery shows the compression and thrombus (red arrow) corresponding with IVUS image showing thrombus and reduced luminal area. The mid-right coronary artery is large and normal without any atherosclerosis or compression (green arrow with corresponding IVUS image, bottom left). A drug-eluting stent implantation was successful with excellent final angiographic result. At 18 months of follow-up, her symptoms and ventricular function had significantly improved [New York Heart Association I–II and mild systolic impairment without right ventricular (RV) impairment]. Patient 2 This 53-year-old gentleman with known bicuspid aortic valve and dilated aortic root developed decompensated heart failure related to severe AR in the setting of severely dilated aortic root (70 mm). His left ventricular (LV) function was moderately impaired which improved with medical therapy prior to operation. Computed tomography coronary angiography (CTCA) showed trivial plaque without obstructive coronary artery disease. Three weeks later after optimizing his medical treatment, he underwent aortic valve repair with valve-sparing aortic root replacement (David procedure). Post-procedure ECHO showed no AR with good LV function. Aspirin was started in the post -operative period with plan to continue for 3 months. After developing AF, he commenced on treatment dose low- molecular-weight heparin, amiodarone, and beta-blocker. His other medications included an angiotensin-converting enzyme inhibitor, statin, and omeprazole.

with good LV function. Aspirin was started in the post -operative period with plan to continue for 3 months. After developing AF, he commenced on treatment dose low- molecular-weight heparin, amiodarone, and beta-blocker. His other medications included an angiotensin-converting enzyme inhibitor, statin, and omeprazole. His inpatient recovery was complicated by recurrent chest pain on mobilizing. Levels of high-sensitivity troponin remained elevated at levels higher than expected in the post-operative period ( high-sensitivity troponin T peak 489 ng/mL) raising clinical concern regarding ongoing ischaemia. ECG showed AF with an uncontrolled ventricular rate and new right bundle branch block (Figure 3). Therefore, a CTCA was performed which was suggestive of distortion of the proximal RCA (Figure 4). Urgent invasive angiography showed proximal RCA stenosis which was treated with one DES with good angiographic results. Echocardiography at Day 5 showed basal to mid-infero-lateral akinesia with overall moderate LVSD. The right ventricle size was normal with mildly impaired systolic function. Recovery was complicated by lower respiratory tract infection and ongoing AF but he was discharged home 12 days later. At clinic review 2 months post-operatively, he was well with no symptoms of angina or syncope and with mild shortness of breath only on moderate exertion. At follow-up, there was moderate segmental LVSD (consistent with the target vessel infarction), whilst RV function was normal.

he was discharged home 12 days later. At clinic review 2 months post-operatively, he was well with no symptoms of angina or syncope and with mild shortness of breath only on moderate exertion. At follow-up, there was moderate segmental LVSD (consistent with the target vessel infarction), whilst RV function was normal. Figure 3 Electrocardiogram taken in recovery period from David procedure when the patient complained of chest pain while mobilizing. Electrocardiogram shows new right bundle branch block and new atrial flutter with uncontrolled ventricular rate. Figure 4 A 53-year-old man with a bicuspid aortic valve underwent elective cardiac surgery involving the David procedure. Four days post-operatively developed non-ST-elevation myocardial infarction. Gated computed tomography angiography suggested distortion of the proximal right coronary artery marked with a blue arrow (A). This corresponds with the stenosis marked with blue arrows in diagnostic invasive angiography images (B). There was a good result following implantation of a drug-eluting stent with the stented area marked by the green arrow (C).

y suggested distortion of the proximal right coronary artery marked with a blue arrow (A). This corresponds with the stenosis marked with blue arrows in diagnostic invasive angiography images (B). There was a good result following implantation of a drug-eluting stent with the stented area marked by the green arrow (C). Discussion Composite valve-graft replacement of the aortic root including variations on the Bentall procedure has traditionally been considered the gold standard surgical approach for treatment of aortic root dilatation. When it is possible to retain the native valve, valve-sparing procedures such as the David procedure may improve quality of life and avoid complications relating to degeneration of the bioprosthesis and issues with anticoagulation.3 Both approaches require reimplantation of the coronary buttons. Coronary ostial stenosis is a rare but recognized complication of aortic root surgery involving reimplantation of the coronaries. Incidence is difficult to ascertain but has previously been given as between 5% and 6% in original Bentall procedure1 and between 1% and 5% for patients undergoing aortic valve replacement only.4 A systematic review of the Bentall procedure gave an early mortality of 5.6% with 5.9% of these caused by myocardial infarction,5 some of which may be caused by early coronary ostial obstruction.

tween 5% and 6% in original Bentall procedure1 and between 1% and 5% for patients undergoing aortic valve replacement only.4 A systematic review of the Bentall procedure gave an early mortality of 5.6% with 5.9% of these caused by myocardial infarction,5 some of which may be caused by early coronary ostial obstruction. There are several distinct mechanisms of ostial obstruction proposed. These include damage during instrumentation and delivery of cardioplegia and issues with sutures to the coronary button.2 Hardening and organization of clot could cause mechanical compression. Positioning of the anastomosis can result in tension through the coronary.6 Careful reimplantation of the coronary button is likely to reduce this risk.7 Specific techniques to facilitate tension-free button attachment include identifying the site for the RCA button after the anastomosis of the distal graft to the aorta is complete although there is debate about the best approach.6,8 Others have suggested potential undiagnosed coronary artery disease or development of oedema at the coronary reimplantation site.9 Surgical glue used to secure the anastomosis has also been implicated, either by directly exerting external pressure10 or through abnormal patient inflammatory response to the glue.11 Coronary vasospasm is another potential cause of ischaemia in patients following bypass surgery and is a common cause of angina.12

ite.9 Surgical glue used to secure the anastomosis has also been implicated, either by directly exerting external pressure10 or through abnormal patient inflammatory response to the glue.11 Coronary vasospasm is another potential cause of ischaemia in patients following bypass surgery and is a common cause of angina.12 There are several individual case reports describing the use of PCI in patients who present with ischaemia having undergone aortic root replacement with coronary button re-implantation. This case series demonstrates two heterogeneous presentations linked by the choice of PCI as a salvage option for emergency myocardial revascularization. Each of these cases was discussed with the multidisciplinary team including cardiologists, cardiothoracic surgeons, and cardiac anaesthetists. The collective decision was that PCI was felt to be the most appropriate management in the emergency setting.

PCI as a salvage option for emergency myocardial revascularization. Each of these cases was discussed with the multidisciplinary team including cardiologists, cardiothoracic surgeons, and cardiac anaesthetists. The collective decision was that PCI was felt to be the most appropriate management in the emergency setting. The mechanism of ischaemia related to dynamic coronary obstruction is likely to have occurred subacutely given that RCA occlusion and related RV infarction would prohibit weaning off bypass. The options of surgical re-intervention may have advantages and is potentially less challenging than late redo surgery due to lack of adhesions. A mechanical complication (e.g. excess tension through the ostium or external compression by haematoma or surgical glue) may be identified and corrected including possible refashioning of the coronary button. If this is not possible bypass may be an alternative, however, long-term outcome of a graft may be reduced given the potential for competitive flow through the coronary ostium which would vary through the cardiac cycle.

rgical glue) may be identified and corrected including possible refashioning of the coronary button. If this is not possible bypass may be an alternative, however, long-term outcome of a graft may be reduced given the potential for competitive flow through the coronary ostium which would vary through the cardiac cycle. PCI was felt to offer the best emergency salvage and the acute success of the procedure was supported by prompt improvement in haemodynamics with ST-segment resolution. In general, minimization of time to revascularization is the primary driver behind choice of revascularization in STE MI with cardiac bypass surgery being considered when the patient is not suitable for PCI.13 In this situation, the dynamic change on the stent may lead to altered wall stress and propensity to restenosis or stent fracture in the longer term. Clearly, more evidence is needed with careful longer-term follow-up against repeat surgical button reimplantation as the gold standard approach. Cardiovascular teams looking after these patients will need to be vigilant to any symptoms suggestive of ischaemia. Cardiogenic shock in these cases may result from the target vessel myocardial infarction with contribution from potential suboptimal myocardial protection which is of vital importance in lengthy aortic root reconstructions (e.g. the lengthy David procedure).14

PCI was felt to offer the best emergency salvage and the acute success of the procedure was supported by prompt improvement in haemodynamics with ST-segment resolution. In general, minimization of time to revascularization is the primary driver behind choice of revascularization in STE MI with cardiac bypass surgery being considered when the patient is not suitable for PCI.13 In this situation, the dynamic change on the stent may lead to altered wall stress and propensity to restenosis or stent fracture in the longer term. Clearly, more evidence is needed with careful longer-term follow-up against repeat surgical button reimplantation as the gold standard approach. Cardiovascular teams looking after these patients will need to be vigilant to any symptoms suggestive of ischaemia. Cardiogenic shock in these cases may result from the target vessel myocardial infarction with contribution from potential suboptimal myocardial protection which is of vital importance in lengthy aortic root reconstructions (e.g. the lengthy David procedure).14 Of note, Patient 1 was not on antiplatelet or anticoagulation at time of discharge postoperatively having refused medications. Patient 2 was started on Aspirin post -operatively with a plan to continue for 3 months. Often post -operative patients would be treated with either antiplatelet or anticoagulation for 3 months to reduce the risk of thromboembolic complication and this may have contributed to the acute presentation of Patient 1 .15

ns. Patient 2 was started on Aspirin post -operatively with a plan to continue for 3 months. Often post -operative patients would be treated with either antiplatelet or anticoagulation for 3 months to reduce the risk of thromboembolic complication and this may have contributed to the acute presentation of Patient 1 .15 Alongside early revascularization, both patients were treated with IV fluid to expand plasma volumes and treat RV infarction. In patients with RV infarction, hypotension and absence of pulmonary oedema should be treated with plasma expansion, ideally with invasive monitoring. Both these patients also had a degree of LV impairment which can make resuscitation more challenging as RV dilatation can increase diastolic LV pressures and contribute to low output state.16 Case 1 demonstrated the use of intra-aortic balloon pump counter pulsation in initial management of RV infarction. Intra-aortic balloon pump can improve haemodynamics in this setting.17 Given the acuity of her presentation the ECMO team were activated in anticipation of the need to further escalate her care. These cases demonstrate the potential efficacy of PCI in management of both emergency STEMI and a high-risk non-STEMI. Prompt diagnosis and early multidisciplinary team discussion including with the operating surgeon allowed the patients to receive early and successful revascularization with PCI. Good communication was key to each of these decisions specifically collaboration between the surgical and cardiology teams.

h-risk non-STEMI. Prompt diagnosis and early multidisciplinary team discussion including with the operating surgeon allowed the patients to receive early and successful revascularization with PCI. Good communication was key to each of these decisions specifically collaboration between the surgical and cardiology teams. Conclusions Acute myocardial infarction is an uncommon but important complication following aortic root replacement with coronary reimplantation. Extrinsic compression or distortion of the replanted coronary neo-ostium may result in vessel occlusion. Urgent PCI may facilitate emergency revascularization in these patients. Lead author biography Dr Carly Adamson graduated with MBChB from the University of Dundee in 2013. She has developed a keen interest in pursuing a career in cardiology during general medical training and is currently working as a Cardiology Clinical Fellow. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Funding This study received grant funding from the British Heart Foundation (RE/13/5/30177). Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz181_Supplementary_Slide_Set Click here for additional data file.

Learning points Immunotherapy is effective in reducing cardiac metastasis of malignant melanoma without causing adverse cardiac events in the majority of patients. Therapy-induced colitis constitutes a significant clinical problem in this patient population. Melanoma patients with elevated troponin, N-terminal pro-B-type brain natriuretic peptide, or electrocardiogram changes should be referred for cardiac evaluation. Introduction Melanoma carries a dismal prognosis with an increasing incidence reaching 19 cases per 100 000 in Northern Europe and thus constitutes a burden to public health.1 Cardiac metastasis has been documented in 47.2% of patients with melanoma post-mortem but in the majority of cases it was clinically silent.2–4 When cardiac involvement is diagnosed ante-mortem, symptoms are often related to tumour location and varies from functional dyspnoea, chest pain to dizziness, or syncope.5 Since the introduction of immunotherapy in melanoma management, survival has improved significantly for metastatic disease however when cardiac involvement is present data are lacking in regard to prognosis and response to treatment.6

r location and varies from functional dyspnoea, chest pain to dizziness, or syncope.5 Since the introduction of immunotherapy in melanoma management, survival has improved significantly for metastatic disease however when cardiac involvement is present data are lacking in regard to prognosis and response to treatment.6 Timeline Time Event Findings August 2018 Fatigue and dyspnoea. September 3 Clinical evaluation by general practitioner. September 27 Computed tomography (CT) scan of chest and abdomen. Tumour infiltration in left ventricle and multiple enlarged lymph nodes in the mediastinum and retro peritoneum. October 2 Hospital consultation and echocardiography (Figure 1C). Tumour in the right ventricle and ventricular septum. October 8 Fluorodeoxyglucose positron emission tomography scan (Figure 1D). Multiple fluorodeoxyglucose positive masses in the heart, right lung, and lymph nodes in the groin. October 9 Biopsy from lymph nodes. October 13 Pathology shows malignant melanoma. October 18 Cardiac evaluation and echocardiography (Figures 1E and 2A–C). Blurred vision, referred to cerebral magnetic resonance imaging (MRI). Commences prednisolone treatment. Multiple cardiac metastases were found on contrast echocardiography. Cerebral MRI shows metastasis in left occipital and temporal lope. October 24 Pathology shows no BRAF mutation or PD-L1 expression. October 25 Cardiac MRI (Figure 1F). Extensive metastatic infiltration in the left ventricle. November 1 First treatment with ipilimumab 78 mg and nivolumab 235 mg. November 23 Second treatment with ipilimumab 78 mg and nivolumab 235 mg. December 14 Third treatment with ipilimumab 78 mg and nivolumab 235 mg. December 17 Cardiac evaluation with echocardiography (Figure 2D–F). Regression in metastatic size. December 20 Diarrhoea. January 7, 2019 Persistent diarrhoea, commences infliximab. January 29 Routine cerebral MRI and CT scan of the chest and abdomen after commencing immunotherapy. Echocardiography (Figure 3B and C). Progression of metastasis on cerebral MRI. Computed tomography scan reveals progression of extra-cardiac metastasis. Echocardiography shows persistent reduction in cardiac metastasis and improvement in global longitudinal strain score. February 1 Referred to palliative care. Case presentation A 65-year-old Caucasian male was referred from his general practitioner after complaining of fatigue and shortness of breath at moderate exertion for 3–5 weeks.

shows persistent reduction in cardiac metastasis and improvement in global longitudinal strain score. February 1 Referred to palliative care. Case presentation A 65-year-old Caucasian male was referred from his general practitioner after complaining of fatigue and shortness of breath at moderate exertion for 3–5 weeks. He had no prior medical history and did not use any prescribed medication. A computed tomography (CT) scan of the chest and abdomen revealed multiple enlarged lymph nodes in the mediastinum and retro peritoneum. A large infiltrating tumour was found in the left ventricle along with a small pericardial effusion (Figure 1A) and sub-segmental pulmonary atelectasis.

use any prescribed medication. A computed tomography (CT) scan of the chest and abdomen revealed multiple enlarged lymph nodes in the mediastinum and retro peritoneum. A large infiltrating tumour was found in the left ventricle along with a small pericardial effusion (Figure 1A) and sub-segmental pulmonary atelectasis. At physical examination, heart and lung auscultations were unremarkable and no signs of ascites or peripheral oedema were present. No cutaneous lesions were found though multiple hard subcutaneous masses were felt on palpation of the chest and abdomen. Saturation was 96% while breathing ambient air. Blood pressure was 123/85 mmHg and heart rate 100 b.p.m. The electrocardiogram (ECG) showed sinus rhythm with low voltage and T-wave inversion in the inferior leads suggestive of myocardial involvement (Figure 1B).7 Echocardiogram revealed masses in the right ventricle and ventricular septum (Figure 1C), with normal left ventricular ejection fraction >60% and preserved diastolic function. A positron emission tomography (PET) scan revealed multiple fluorodeoxyglucose (FDG) positive masses in the heart (Figure 1D), right lung, and lymph nodes in the thorax and groin. Consistent with the FDG-PET scan multiple cardiac metastases were found on contrast echocardiography (Figure 1E) and extensive myocardial infiltration was present on cardiac magnetic resonance imaging (MRI, Figure 1F). No involvement of the cardiac valves was found on echocardiography, cardiac MRI, or FDG-PET.

d groin. Consistent with the FDG-PET scan multiple cardiac metastases were found on contrast echocardiography (Figure 1E) and extensive myocardial infiltration was present on cardiac magnetic resonance imaging (MRI, Figure 1F). No involvement of the cardiac valves was found on echocardiography, cardiac MRI, or FDG-PET. Figure 1 (A) Computed tomography scan of the chest showing an infiltrating tumour (arrow) in the interventricular septum. IVS, interventricular septum; LV, left ventricle; RV, right ventricle. (B) Electrocardiogram with low voltage and inverted T waves in inferior leads (II, III, and aVF). (C) Echocardiogram showing metastasis in the interventricular septum and right ventricle (arrows). (D) Fluorodeoxyglucose positron emission tomography combined with computed tomography in the same region as shown in A in addition to the tumour located in the interventricular septum additional metastatic processes are visible in the myocardium of both right and left ventricles. (E) Contrast echocardiography showing multiple metastasis in the septum and left ventricle (arrows). (F) Cardiac magnetic resonance imaging showing extensive melanoma infiltration in left ventricle (T1 weighted sequence).

m additional metastatic processes are visible in the myocardium of both right and left ventricles. (E) Contrast echocardiography showing multiple metastasis in the septum and left ventricle (arrows). (F) Cardiac magnetic resonance imaging showing extensive melanoma infiltration in left ventricle (T1 weighted sequence). Biopsies taken from FDG positive lymph nodes showed malignant melanoma and subsequent analysis did not reveal BRAF mutation or PD-L1 expression. Shortly after, the patient developed blurred vision and a cerebral MRI revealed metastasis in the left occipital and temporal lobe. To manage symptoms, the patient commenced treatment with prednisolone 50 mg once daily and was subsequently reduced to 12.5 mg daily during the following weeks. Due to the patient’s metastatic disease with cerebral involvement, he was referred for combination therapy with ipilimumab 78 mg (anti-CTLA 4 antibody) and nivolumab 235 mg (anti-PD-1 antibody) every third week while on steroid treatment.8 Cardiac evaluation before ipilimumab and nivolumab treatment showed progression of metastasis in the right ventricle (Figure 2A and B). Strain analysis revealed reduced global longitudinal strain (GLS) to −15.4% on average and apical sparing consistent with infiltrative disease (Figure 2C).9 Laboratory studies showed elevated N-terminal pro-B-type brain natriuretic peptide (NT-pro-BNP) 1391 ng/L (<300 ng/L) and troponin T, 21 ng/L (<14 ng/L). At the time of second treatment, NT-pro-BNP and troponin T increased to 3774 ng/L and 62 ng/L, respectively, suggestive of myocardial injury secondary to immunotherapy. After completing the third treatment, the patient felt a complete relief of his initial symptoms of dyspnoea and fatigue. Clinical evaluation showed reduction in subcutaneous metastasis and the ECG revealed sinus rhythm with normalization of T waves in the inferior leads. Subsequent echocardiography confirmed reduction in the size of cardiac metastasis (Figure 2D and E) however GLS score did not improve (−12.9%) on average (Figure 2F). Laboratory studies showed reduced NT-pro-BNP 1074 ng/L and TnT 20 ng/L. Following cardiac evaluation, the patient developed severe colitis for which immunotherapy was discontinued and his gastrointestinal symptoms managed by one treatment of TNF-alpha antibody (infliximab 5 mg/kg) and methylprednisolone 80 mg daily for 1 week.

ry studies showed reduced NT-pro-BNP 1074 ng/L and TnT 20 ng/L. Following cardiac evaluation, the patient developed severe colitis for which immunotherapy was discontinued and his gastrointestinal symptoms managed by one treatment of TNF-alpha antibody (infliximab 5 mg/kg) and methylprednisolone 80 mg daily for 1 week. The patient subsequently resumed oral steroid treatment initially with prednisolone 75 mg once daily and was gradually reduced during the following weeks to 25 mg daily. Figure 2 (A) Echocardiography before treatment with ipilimumab and nivolumab shows tumour in the right ventricle (arrow) with traced area of 7.1 cm2 (B). (C) Global longitudinal strain was reduced with apical sparing. (D) Echocardiography following third treatment with ipilimumab and nivolumab (6 weeks after treatment initiation) shows substantial regression in tumour size (arrow) with traced area reduced to 3.1 cm2 (E). No improvement in global longitudinal strain was noted at this time (F).

strain was reduced with apical sparing. (D) Echocardiography following third treatment with ipilimumab and nivolumab (6 weeks after treatment initiation) shows substantial regression in tumour size (arrow) with traced area reduced to 3.1 cm2 (E). No improvement in global longitudinal strain was noted at this time (F). A routine MRI scan performed 3 months after treatment initiation revealed progression of cerebral metastasis and CT scan of the thorax and abdomen showed increase in extra-cardiac metastasis, a small peripheral pulmonary embolus, and no pleural effusions. Clinical evaluation revealed unremarkable ECG (Figure 3A), persistent reduction in cardiac metastasis on echocardiography (Figure 3B) and a notable improvement in GLS score to −14.9% on average with normalization of contraction pattern and Troponin I < 10 ng/L. No signs of increased pulmonary pressure was observed. Pulmonary embolism was treated with weight-adjusted low-molecular heparin daily. Due to deteriorating cognitive function and progression of extra-cardiac metastasis prednisolone dose was increased to 75 mg daily and the patient was referred to palliative care. Figure 3 (A) Electrocardiogram obtained 12 weeks after treatment initiation with normalization of T waves in inferior leads (II, III, and aVF). (B) Echocardiogram obtained 12 weeks after treatment initiation showing persistent reduction in cardiac metastatic size (arrows) with improvement in global longitudinal strain and normalization of contraction pattern (C).

eks after treatment initiation with normalization of T waves in inferior leads (II, III, and aVF). (B) Echocardiogram obtained 12 weeks after treatment initiation showing persistent reduction in cardiac metastatic size (arrows) with improvement in global longitudinal strain and normalization of contraction pattern (C). Discussion We present a case of symptomatic cardiac melanoma, treated with immune checkpoint inhibitors resulting in regression of cardiopulmonary symptoms and reduction in cardiac metastatic size, which persisted 6 weeks after discontinuation of therapy. To our knowledge, this is the first report of cardiac melanoma treated with both ipilimumab and nivolumab. A decade ago metastatic melanoma had a 5-year survival rate of 5–10% on standard chemotherapies but with the introduction of immunotherapies in 2011 survival rates have been increasing.10,11 Nivolumab has significantly prolonged overall survival compared with conventional chemotherapy (dacarbazine)12 and in CheckMate O67 treatment with ipilimumab and nivolumab prolonged survival compared with ipilimumab after 4 years of follow-up.13

ction of immunotherapies in 2011 survival rates have been increasing.10,11 Nivolumab has significantly prolonged overall survival compared with conventional chemotherapy (dacarbazine)12 and in CheckMate O67 treatment with ipilimumab and nivolumab prolonged survival compared with ipilimumab after 4 years of follow-up.13 When cardiac melanoma is present, the most common location is in relation to the right-sided heart chambers.14 Though melanoma in the heart has been observed in up to 47.2% of patients post-mortem, finding patients presenting with symptoms primarily relating to the cardiovascular system is rare.2,3 Patients without cardiac symptoms should therefore be offered a screening of cardiac involvement by ECG, troponins, and NT-pro-BNP and in cases of abnormalities a two- and three-dimensional echocardiography should be performed to identify conditions such as; outflow tract obstruction, pericardial effusion, or signs of pulmonary embolism. In symptomatic cases with significant obstructive tumour masses cardiac surgery might be an option, but even with early surgical intervention prognosis remain poor mainly due to diffuse myocardial infiltration and metastasis in other organ systems.4 Though the patient had extra-cardiac metastasis that progressed during immunotherapy, this case demonstrates that treatment with ipilimumab and nivolumab vary rarely affects cardiac function and provides clinical benefits in patients with cardiac melanoma.

myocardial infiltration and metastasis in other organ systems.4 Though the patient had extra-cardiac metastasis that progressed during immunotherapy, this case demonstrates that treatment with ipilimumab and nivolumab vary rarely affects cardiac function and provides clinical benefits in patients with cardiac melanoma. With the increased use of immune checkpoint inhibitors, toxicity is increasingly recognized as a clinical problem. For patients treated with ipilimumab and nivolumab, the most common symptoms are gastrointestinal. Particular diarrhoea which occurs in up to 30% of patients in clinical trials treated with ipilimumab.15 The patient discussed did develop immune checkpoint inhibitor-induced colitis and his symptoms were managed by administration of prednisolone and TNF-alpha antibody (infliximab). However, due to the severity of the colitis, the patient was not able to continue immunotherapy. A rare but serious toxic effect is immune-mediated myocarditis, which has been reported in 0.27% of patients treated with ipilimumab and nivolumab.16 This diagnosis should be considered if patients present with clinical deterioration in the weeks following treatment initiation.

t was not able to continue immunotherapy. A rare but serious toxic effect is immune-mediated myocarditis, which has been reported in 0.27% of patients treated with ipilimumab and nivolumab.16 This diagnosis should be considered if patients present with clinical deterioration in the weeks following treatment initiation. Brain metastases are common in patients with melanoma and are found in more than 75% of cases at the time of death.17 Historically prognosis has been poor with a median overall survival of 2–5 months and only 5% surviving in the long-term (>5 years). Due to its poor prognosis randomized phase III trials are warranted but data from a randomized phase II study suggest that this population might benefit from combination therapy as well.18,19 In the current case, the patient initially reported regression of cerebral symptoms but had increased cognitive problems and progression of cerebral metastasis on magnetic resonance while on combination therapy. Conclusion Despite cerebral progression of melanoma, this case demonstrates clinical benefits of treating cardiac melanoma with ipilimumab and nivolumab causing regression of cardiopulmonary symptoms and metastatic size. Lead author biography Christian B. Poulsen is a senior registrar in cardiology at the Regional Hospital West Jutland in Herning, Denmark. He has previously performed experimental studies of atherosclerosis in porcine models as part of his PhD. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online.

Lead author biography Christian B. Poulsen is a senior registrar in cardiology at the Regional Hospital West Jutland in Herning, Denmark. He has previously performed experimental studies of atherosclerosis in porcine models as part of his PhD. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytz182_Supplementary_Slide_Set Click here for additional data file.

Learning points An increasing number of transcatheter aortic valve implantation (TAVI) procedures are being performed, making it important to recognize and manage rare complications to improve patient outcomes. Vascular complications are common during TAVI; however, not all vascular complications are the same. During TAVI, when a mobile echogenic mass was found in the left ventricle and ascending aorta by echocardiogram, associated with acute aortic insufficiency, possible valve avulsion with potential embolization should be suspected. A workup should be performed to locate the embolus with interventions for embolectomy and revascularization.

a mobile echogenic mass was found in the left ventricle and ascending aorta by echocardiogram, associated with acute aortic insufficiency, possible valve avulsion with potential embolization should be suspected. A workup should be performed to locate the embolus with interventions for embolectomy and revascularization. Introduction Critical aortic stenosis affects an estimated 4.6% of individuals over 77 years of age.1 It is considered reasonable to perform valve-in-valve transcatheter aortic valve implantation (TAVI) for severely symptomatic patients with bioprosthetic valve stenosis or regurgitation who have high risk of re-operation and in whom improvement in haemodynamics is anticipated.2 Common complications during the TAVI procedure include major vascular complications, bleeding, stroke, coronary obstruction, and arrhythmias.3,4 Thus far, few cases of native or prosthetic valve leaflet avulsion without embolization during TAVI have been reported; these patients were managed conservatively.5–8 We report a case of bioprosthetic valve leaflet avulsion and embolization causing major vascular occlusion during the valve-in-valve TAVI procedure. To our knowledge, this is the first case of valve leaflet avulsion and embolization that was managed successfully by immediate diagnosis and vascular surgical intervention. Timeline Time Events 0 min Valve-in-valve transcatheter aortic valve implantation started under general anaesthesia under transoesophageal echocardiogram (TOE) guidance. 60 min Nosecone advanced across the bioprosthetic valve. Patient became hypotensive.

Introduction Critical aortic stenosis affects an estimated 4.6% of individuals over 77 years of age.1 It is considered reasonable to perform valve-in-valve transcatheter aortic valve implantation (TAVI) for severely symptomatic patients with bioprosthetic valve stenosis or regurgitation who have high risk of re-operation and in whom improvement in haemodynamics is anticipated.2 Common complications during the TAVI procedure include major vascular complications, bleeding, stroke, coronary obstruction, and arrhythmias.3,4 Thus far, few cases of native or prosthetic valve leaflet avulsion without embolization during TAVI have been reported; these patients were managed conservatively.5–8 We report a case of bioprosthetic valve leaflet avulsion and embolization causing major vascular occlusion during the valve-in-valve TAVI procedure. To our knowledge, this is the first case of valve leaflet avulsion and embolization that was managed successfully by immediate diagnosis and vascular surgical intervention. Timeline Time Events 0 min Valve-in-valve transcatheter aortic valve implantation started under general anaesthesia under transoesophageal echocardiogram (TOE) guidance. 60 min Nosecone advanced across the bioprosthetic valve. Patient became hypotensive. TOE showed a large mobile echogenic mass that appeared to be moving back and forth from the left ventricle to the aorta through the annulus. 70 min No pericardial effusion was noted on TOE. Severe intra-valvular regurgitation was noted.

Timeline Time Events 0 min Valve-in-valve transcatheter aortic valve implantation started under general anaesthesia under transoesophageal echocardiogram (TOE) guidance. 60 min Nosecone advanced across the bioprosthetic valve. Patient became hypotensive. TOE showed a large mobile echogenic mass that appeared to be moving back and forth from the left ventricle to the aorta through the annulus. 70 min No pericardial effusion was noted on TOE. Severe intra-valvular regurgitation was noted. No response was observed to intravenous vasopressors, inotropes, and rapid ventricular pacing to improve haemodynamic stability. The large mobile mass was no longer seen. Evolut R valve deployment. 90 min Absence of distal left lower extremity pulses was noted. Angiography showed a large filling defect at the level of the left common femoral artery bifurcation. 180 min Open exploration of the femoral artery and embolectomy was performed. Leaflet of previous bioprosthetic valve was removed. Left lower extremity circulation was re-established.

90 min Absence of distal left lower extremity pulses was noted. Angiography showed a large filling defect at the level of the left common femoral artery bifurcation. 180 min Open exploration of the femoral artery and embolectomy was performed. Leaflet of previous bioprosthetic valve was removed. Left lower extremity circulation was re-established. Case presentation We present the case of a 77-year-old Caucasian male with a medical history of hypertension, hyperlipidaemia, hypothyroidism, triple vessel coronary artery bypass, and surgical aortic valve replacement with a 27-mm Mosaic Ultra valve 10 years prior. He developed progressively worsening shortness of breath (New York Heart Association Class III symptoms) on mild exertion for 1 month. He denied dizziness or lightheadedness, chest pain, or palpitations. On cardiac auscultation, a Grade IV mid-systolic murmur was audible along the upper right sternal border and was further diagnosed with severe bioprosthetic valve stenosis. Transoesophageal echocardiogram (TOE) showed left ventricular ejection fraction of 35–40%, severely calcified and restricted mobility of the bioprosthetic valve leaflets (Figure 1 and Supplementary material online, Video S1). Doppler spectral profile showed low-flow, low-gradient aortic bioprosthetic stenosis with mean gradient of 34 mmHg (Figure 2 and Supplementary material online, Video S2) and valve area of 0.6 cm2. No findings consistent with endocarditis were noted. Results of blood investigations revealed, haemoglobin 11 gm/dL and otherwise normal.

al profile showed low-flow, low-gradient aortic bioprosthetic stenosis with mean gradient of 34 mmHg (Figure 2 and Supplementary material online, Video S2) and valve area of 0.6 cm2. No findings consistent with endocarditis were noted. Results of blood investigations revealed, haemoglobin 11 gm/dL and otherwise normal. Figure 1 Transoesophageal echocardiogram mid-oesophageal short-axis view showing bioprosthetic aortic valve with severe stenosis and calcification (arrow pointing). Figure 2 Transoesophageal echocardiogram mid-oesophageal long-axis view showing turbulent flow through the bioprosthetic aortic valve (arrow pointing).

al profile showed low-flow, low-gradient aortic bioprosthetic stenosis with mean gradient of 34 mmHg (Figure 2 and Supplementary material online, Video S2) and valve area of 0.6 cm2. No findings consistent with endocarditis were noted. Results of blood investigations revealed, haemoglobin 11 gm/dL and otherwise normal. Figure 1 Transoesophageal echocardiogram mid-oesophageal short-axis view showing bioprosthetic aortic valve with severe stenosis and calcification (arrow pointing). Figure 2 Transoesophageal echocardiogram mid-oesophageal long-axis view showing turbulent flow through the bioprosthetic aortic valve (arrow pointing). As a part of the workup 4 weeks prior to scheduled TAVI, the patient underwent a coronary angiogram and percutaneous intervention of the left-main/ostial circumflex with a drug-eluting stent. He was scheduled for a valve-in-valve TAVI because of his comorbid conditions including the need for re-operation and high Society of Thoracic Surgeons risk score. The use of a 26-mm Evolut R valve was recommended for the valve-in-valve TAVI. The procedure was performed under general anaesthesia under TOE guidance. An angiogram of the chest, abdomen, and pelvis confirmed the suitability of the iliofemoral vasculature for the TAVI procedure. Right femoral artery access was obtained under fluoroscopic guidance. Two Perclose devices were used to preclose the arterial access. The arterial access was upgraded to a 14-Fr cook sheath. A 6-Fr arterial sheath was placed through the left femoral artery after confirming suitability under fluoroscopy. A 6-Fr pigtail catheter was placed in the ascending aorta. The patient was heparinized to maintain activated clotting time >300 s during the procedure.

e arterial access was upgraded to a 14-Fr cook sheath. A 6-Fr arterial sheath was placed through the left femoral artery after confirming suitability under fluoroscopy. A 6-Fr pigtail catheter was placed in the ascending aorta. The patient was heparinized to maintain activated clotting time >300 s during the procedure. The bioprosthetic valve was crossed using a 4-Fr Amplatz Left 1 (AL1) catheter and a 0.035-inch straight wire. The AL1 catheter was exchanged to a 5-Fr pigtail catheter. A 0.035-inch pre-shaped Amplatz wire was introduced and positioned in the left ventricular apex. Over this wire, a 26-mm Medtronic valve was introduced. Significant resistance was encountered when advancing the nosecone across the bioprosthetic valve. After the nosecone was introduced into the left ventricle (LV) apex, the patient became hypotensive. Therefore, TOE was performed to assess for pericardial effusion. Although no pericardial effusion was noted, a large mobile echogenic mass (9 mm × 13 mm) was seen that appeared to be moving back and forth from the LV to the aorta through the annulus (Figure 3 and Supplementary material online, Video S3). Further, severe intravalvular regurgitation was noted (Figure 4 and Supplementary material online, Video S4). The patient was administered intravenous vasopressors, inotropes, and rapid ventricular pacing to improve haemodynamic stability. The large mobile mass was no longer seen across the aortic annulus. We proceeded further by deploying the Evolut R valve in a pre-selected coplanar view. Post-valve deployment, haemodynamic stability was attained. Both TOE and ascending aortogram confirmed no paravalvular leak. The delivery sheath was removed from the body and exchanged to a 14-Fr sheath. The Perclose sutures were used to close the entry site. A subsequent right iliofemoral angiogram showed no evidence of dissection at the entry site with preserved flow beyond it. The left common femoral arterial access was closed using a Perclose suture. Distal left lower extremity pulses were absent at the end of the procedure; therefore, a limited left iliofemoral angiogram was performed from the contralateral access. Angiography showed a large filling defect at the femoral bifurcation level (Figure 5 and Supplementary material online, Video S5). We suspected that the filling defect was the embolized prosthetic valve leaflet. Open exploration of the femoral artery and an embolectomy were performed.

med from the contralateral access. Angiography showed a large filling defect at the femoral bifurcation level (Figure 5 and Supplementary material online, Video S5). We suspected that the filling defect was the embolized prosthetic valve leaflet. Open exploration of the femoral artery and an embolectomy were performed. A leaflet/fragment of the previous bioprosthetic valve was removed (Figure 6). Figure 3 Arrow pointing large mobile echogenic mass (9 mm × 13 mm) seen on mid-oesophageal long-axis view. Figure 4 Mid-oesophageal long-axis view showing severe intravalvular regurgitation. Figure 5 Angiography showing a large filling defect at the femoral bifurcation level (arrow pointing). Figure 6 A leaflet/fragment of the previous bioprosthetic valve retrieved through embolectomy, measuring 1.0 cm × 1.4 cm. The post-operative course was uneventful; no neurological deficits were noted, and the patient was discharged home on post-operative Day 2. At 1-month follow-up, the patient remained without symptoms of heart failure and able to take care of daily activities of living comfortably. Discussion Vascular complications are not uncommon during a TAVI procedure.4,9,10 However, the aetiology of most of these complications is thrombotic and is related to focal vessel injury at the vessel entry site. Femoral artery embolic complications are rare during a TAVI procedure.

The post-operative course was uneventful; no neurological deficits were noted, and the patient was discharged home on post-operative Day 2. At 1-month follow-up, the patient remained without symptoms of heart failure and able to take care of daily activities of living comfortably. Discussion Vascular complications are not uncommon during a TAVI procedure.4,9,10 However, the aetiology of most of these complications is thrombotic and is related to focal vessel injury at the vessel entry site. Femoral artery embolic complications are rare during a TAVI procedure. In our case, we suspect that during the act of crossing the prosthetic stenotic valve with the nosecone, the leaflet avulsed owing to mechanical trauma/shear stress that led to severe regurgitation and severe hypotension. Over the years, the role of TOE during TAVI procedures has decreased significantly owing to factors such as the need for general anaesthesia and increased length of stay.11 However, TOE could provide invaluable information that could help determine management during a TAVI procedure. In our patient, the use of TOE helped with the prompt detection of possible causes of haemodynamic instability and an incidental finding of a large mobile echogenic mass. These findings helped us to determine the strategy for treating the acute limb ischaemia noted at the end of the procedure. Thus far, few reported cases of aortic valve leaflet avulsion without embolization during transcatheter aortic valve replacement have been managed successfully via the percutaneous snare retrieval technique5 and endovascular snare technique.8 In our case, prior to proceeding with an open surgical procedure, a multidisciplinary team had a thorough discussion regarding the open vs. endovascular management options. Based on the TOE and angiogram findings, we pursued an open approach rather than an endovascular strategy to avoid fragmentation of the embolized prosthetic valve causing further distal embolization.

al procedure, a multidisciplinary team had a thorough discussion regarding the open vs. endovascular management options. Based on the TOE and angiogram findings, we pursued an open approach rather than an endovascular strategy to avoid fragmentation of the embolized prosthetic valve causing further distal embolization. Our case also highlights the challenges faced in valve-in-valve TAVI procedures compared with native valve TAVI procedures. Bioprosthetic stenotic valves are difficult to cross compared with native valves. This could be related to several factors including the dense fibrous tissue matrix associated with stenotic prosthetic valves. To avoid avulsing the valve leaflet/tissue, valvuloplasty with an undersized balloon could be performed to decrease the resistance encountered with the crossing of prosthetic stenotic valve leaflets. The balloon-expandable Edwards S3 valve could have easier crossability through the stenotic valve, with shorter length of the nose cone and the valve which probably translate to less shearing force on the diseased valve leaflets, but it is unclear whether the use of a balloon-expandable Edwards TAVI valve would have led to a different outcome in our patient compared to a self-expanding Evolut R valve.

tenotic valve, with shorter length of the nose cone and the valve which probably translate to less shearing force on the diseased valve leaflets, but it is unclear whether the use of a balloon-expandable Edwards TAVI valve would have led to a different outcome in our patient compared to a self-expanding Evolut R valve. Vascular complications are common during a TAVI procedure. However, not all vascular complications are the same. Our case highlights an embolic vascular complication from an avulsed prosthetic material during a challenging valve-in-valve TAVI procedure. Our case also highlights the invaluable information obtained from a TOE that helped guide the strategy towards a favourable outcome for our patient. Lead author biography Sudhakar Kinthala is a diplomate of the American Board of Anesthesiology who works as an attending anaesthesiologist at Guthrie Robert Packer Hospital in Sayre, PA, USA. He has been providing clinical and academic anaesthesiology services for the past 16 years. He completed his residency in anaesthesiology from New York Presbyterian Brooklyn Methodist Hospital in collaboration with Weill Cornell Medicine. He is a fellowship trained Cardiac and neuroanaesthesiologist and board certified anaesthesiologist in India. He is actively involved in teaching residents and medical students. He has published widely in various journals. Dr Kinthala’s main areas of interest are cardiac and neuroanaesthesiology and perioperative patient safety. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online.

Lead author biography Sudhakar Kinthala is a diplomate of the American Board of Anesthesiology who works as an attending anaesthesiologist at Guthrie Robert Packer Hospital in Sayre, PA, USA. He has been providing clinical and academic anaesthesiology services for the past 16 years. He completed his residency in anaesthesiology from New York Presbyterian Brooklyn Methodist Hospital in collaboration with Weill Cornell Medicine. He is a fellowship trained Cardiac and neuroanaesthesiologist and board certified anaesthesiologist in India. He is actively involved in teaching residents and medical students. He has published widely in various journals. Dr Kinthala’s main areas of interest are cardiac and neuroanaesthesiology and perioperative patient safety. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material ytaa010_Supplementary_Data Click here for additional data file.

The case report is perhaps the oldest form of medical publication. Reports on specific patients date back at least to the 2nd millennium BCE, and until the 20th century, case reports were considered a mainstay of clinical research.1 Indeed, many diseases and syndromes still bear witness to the influence of case reports and case series on the medical lexicon. With the rise of more advanced research techniques, case reports rightly no longer exhibit the same power in guiding medical practice they once did; however, they still have an important part to play in medical practice. This issue marks the launch of European Heart Journal – Case Reports (EHJ-CR). This new open access journal joins the rest of the European Society of Cardiology (ESC) family and aims to broaden the society’s coverage of medical publishing by providing a dedicated repository for case reports, case series, cardiac images and local quality improvement projects (QIPs) of wider significance. Case reports can be submitted directly to the journal (via https://academic.oup.com/ehjcr) or transferred from one of the other members of the ESC journal family.

ishing by providing a dedicated repository for case reports, case series, cardiac images and local quality improvement projects (QIPs) of wider significance. Case reports can be submitted directly to the journal (via https://academic.oup.com/ehjcr) or transferred from one of the other members of the ESC journal family. Much of the continuing importance of case reports as a publication format comes from their role in educating junior clinicians in the technique of writing, editing, and submitting manuscripts for review and publication. Further, case reports should have a specific structure and a simple message making the review process ideal for educating more senior clinicians with limited experience of undertaking peer review. To this end, EHJ-CR has been launched with a mandate to be an education platform to help develop the skills of current and future clinician researchers. The EHJ-CR is intended to assist members of the young cardiology groups within the ESC and its associations in gaining publishing, reviewing, and editing experience.

. To this end, EHJ-CR has been launched with a mandate to be an education platform to help develop the skills of current and future clinician researchers. The EHJ-CR is intended to assist members of the young cardiology groups within the ESC and its associations in gaining publishing, reviewing, and editing experience. The junior reviewer programme developed by the EHJ-CR forms the centre point for the education efforts. Clinicians either in specialty training or within 5 years of completion with some research experience have been recruited to join this programme. Articles published within the EHJ-CR will be reviewed by both a junior reviewer from this programme and a senior experienced reviewer. This process has two main benefits. The junior reviewer will have their review scrutinized by his/her senior colleague and feedback will be provided. This provides a learning experience for the reviewer. Further, given the relatively junior authorship of many case reports, this ensures that the peer-review process is truly undertaken by close peers to the manuscript authors. Those that successfully participate as junior reviews will be accredited for their work and contribution to the journal.

erience for the reviewer. Further, given the relatively junior authorship of many case reports, this ensures that the peer-review process is truly undertaken by close peers to the manuscript authors. Those that successfully participate as junior reviews will be accredited for their work and contribution to the journal. An important feature of the EHJ-CR is the aim to publish high-quality, well-written, and researched case reports. However, truly unique, one-of-a-kind, case reports are increasingly rare. Although these remain important and interesting, this journal will not be limited to these alone. Indeed, case reports of relatively common conditions will be considered if they demonstrate beautiful instructive images or an interesting/important learning point. Other article types that are similarly undertaken in large part by more junior clinicians will also be published by the EHJ-CR. Quality improvement projects form a vital element of institutional management. Good QIPs are often a labour-intensive process, which can reveal important lessons for clinical practice. They are often undertaken by junior clinicians with limited scope to share their findings and improve outcomes outside their local institution. The EHJ-CR intends to publish high-quality QIPs with a message that may be of widespread benefit.

r-intensive process, which can reveal important lessons for clinical practice. They are often undertaken by junior clinicians with limited scope to share their findings and improve outcomes outside their local institution. The EHJ-CR intends to publish high-quality QIPs with a message that may be of widespread benefit. The EHJ-CR intends to utilize multimedia elements as a central component of the journal. Taking an experimental perspective, the journal will be a pilot vehicle for novel social media approaches to publishing for the ESC journal family. The journal will aim to publish slide shows with each case report and develop podcasts to discuss particular case reports in greater detail. Case reports involving complex multidisciplinary management will be published as ‘grand rounds’ with increase word and figure limits to allow for complete discussion of the case complexity. We continue to see the case report as an important aspect of medical publications, no longer as the driver of medical practice but as a format with significant educational promise. The EHJ-CR, as the home of the cardiology case report will help ensure the educational benefit of publishing is developed and improved for all clinicians involved in the research or management of cardiac patients and pathology. Conflict of interest: None declared.

Learning points Serious intra-aortic balloon pump (IABP) complications are rare; however, they may have major consequences. Prompt recognition of blood within the balloon pump’s helium tubing is crucial as it indicates balloon rupture. This should then prompt immediate removal to reduce the risk for entrapment. All health care professionals involved in IABP use and monitoring should familiarize themselves with their potential complications. This is even more crucial now that they are encountered less commonly. There have been a number of extrication methods described when dealing with balloon pump entrapment. Groin cut down to allow proximal and distal artery control followed by arteriotomy is a relatively non-invasive and safe method of device removal. Introduction The intra-aortic balloon pump (IABP) was first introduced in the 1960s as a means to provide extra haemodynamic support to those in cardiogenic shock.1 Over the next 40 years, the insertion of an IABP became a common occurrence in cases of cardiogenic shock not reversed with the use of pharmacological agents.2 More recent studies, however, have called into question the mortality benefit of IABP use in myocardial infarction, and this has seen a sharp decline in their use in recent years.3 Their use is still widespread, however, and the balloon pump remains a viable tool in the management of cardiogenic shock.

logical agents.2 More recent studies, however, have called into question the mortality benefit of IABP use in myocardial infarction, and this has seen a sharp decline in their use in recent years.3 Their use is still widespread, however, and the balloon pump remains a viable tool in the management of cardiogenic shock. Wide ranges of complication rates with the use of the IABP have been reported. These vary from as low as 7% up to 50%.4,5 The Japanese multi-institutional IABP Balloon Study group noted a 1.7% balloon rupture rate on the use of the IABP in 2803 patients.5 Rupture was indicated by either the presence of blood within the pump tubing or activation of the pump’s rupture alarm system. Of the 43 cases of rupture, 10 cases subsequently required surgical removal. As the use of the balloon pump continues to decline, familiarity in dealing with their rare, but serious, complications also decreases. Careful monitoring of these devices should be stressed at all times while insitu. Day Events 1 Patient presents acutely with chest pain 3 weeks post-percutaneous coronary intervention (PCI) and stenting to left anterior descending artery (LAD). Angiogram performed: stent thrombosis causing left anterior descending/first diagonal (LAD/D1) occlusion—thrombus aspirated and stenting performed—TIMI 3 flow Hypotensive: dobutamine 5 μg/kg/min infusion commenced 2 Worsening hypotension—increasing dobutamine requirements. Increased to 10 μg/kg/min. Insertion of IABP 4 (p.m.) Patient improving—reducing dobutamine requirements. Decision made to remove pump. Blood noted in tubing at the time of attempted removal—balloon entrapment 5 (a.m.) Groin cut down and surgical removal of pump

Worsening hypotension—increasing dobutamine requirements. Increased to 10 μg/kg/min. Insertion of IABP 4 (p.m.) Patient improving—reducing dobutamine requirements. Decision made to remove pump. Blood noted in tubing at the time of attempted removal—balloon entrapment 5 (a.m.) Groin cut down and surgical removal of pump Timeline Case presentation A 56-year-old woman presented with sudden onset central chest pain and shortness of breath on a background of PCI and stenting for worsening angina 3 weeks before. On examination, the patient was dyspnoeic with a heart rate of 100 beats/min and blood pressure of 110/70 mmHg. Normal S1 and S2 heart sounds were present on auscultation. An electrocardiogram was performed, which showed normal sinus rhythm with ST-elevation in leads I and aVL. The patient was haemodynamically stable on presentation; however, the condition of the patient deteriorated and a dobutamine infusion was commenced at a rate of 5 ug/kg/min. The patient was then transferred for primary PCI. The patient was on aspirin and clopidogrel 75mg along with atorvastatin 40 mg at night. The patient had a 10 pack-year smoking history; however, they had not smoked for the past 10 years. Background medical history was significant for hyper-cholesterolaemia and a spontaneous intracranial bleed 4 years previously. A coronary angiogram was performed that confirmed a LAD/D1 occlusion caused by a stent thrombosis. Thrombus aspiration and stenting was performed with good result and TIMI 3 flow. Clopidogrel was switched to ticagrelor following the procedure.

The patient had a 10 pack-year smoking history; however, they had not smoked for the past 10 years. Background medical history was significant for hyper-cholesterolaemia and a spontaneous intracranial bleed 4 years previously. A coronary angiogram was performed that confirmed a LAD/D1 occlusion caused by a stent thrombosis. Thrombus aspiration and stenting was performed with good result and TIMI 3 flow. Clopidogrel was switched to ticagrelor following the procedure. Despite successful intervention, the patient remained persistently hypotensive and an echo revealed a reduced ejection fraction of 10–15% with anterior apicoseptal hypokinesis, a dilated left atrium and moderate functional mitral regurgitation. Dobutamine requirements increased to 10 μg/kg/min, and the decision was made to insert an IABP and Swan Ganz catheter for management of the persistent hypotension in the setting of a reduced ejection fraction. This was done percutaneously via the right groin. Unfractionated heparin was commenced at 1000 IU/h. Over the next 48 h, the patient’s condition improved with a reduction in ionotropic requirements and stable renal function. Due to this marked improvement in haemodynamic parameters, the decision to remove the device was made. At the time of removal, however, it was noticed that there was blood within the helium tubing suggesting device perforation. The pump was removed without difficulty to 10 cm, at which point significant resistance was encountered suggesting balloon entrapment. Right lower limb pulses were not palpable, however, Doppler signals were present distally.

r, it was noticed that there was blood within the helium tubing suggesting device perforation. The pump was removed without difficulty to 10 cm, at which point significant resistance was encountered suggesting balloon entrapment. Right lower limb pulses were not palpable, however, Doppler signals were present distally. The vascular surgery team was contacted and a computed tomography angiogram was performed, which showed the tip of the balloon to lie within the distal right common iliac artery (Figures 1–3). Unfractionated heparin was re-commenced at 1000 IU/h. Figure 1 Axial computed tomography image showing intra-aortic balloon pump lodged within right common iliac artery. Swan Ganz catheter located in right femoral vein. Figure 2 Occlusion of right external iliac artery due to intra-aortic balloon pump entrapment. Figure 3 Tip of intra-aortic balloon pump within distal right common iliac artery. The patient was brought to the operating theatre for cut down and removal under general anaesthesia. A transverse incision was made in the right groin and extended inferiorly to form a T shape. A femoral arteriotomy was performed after achieving proximal and distal control of the common femoral artery. The existing arterial puncture site with catheter in situ was extended transversely, and the balloon was extracted without difficulty. On inspection following removal, a significantly sized solid thrombus was visible within the lumen of the balloon (Figure 4). Figure 4 Solid thrombus within balloon lumen.

A transverse incision was made in the right groin and extended inferiorly to form a T shape. A femoral arteriotomy was performed after achieving proximal and distal control of the common femoral artery. The existing arterial puncture site with catheter in situ was extended transversely, and the balloon was extracted without difficulty. On inspection following removal, a significantly sized solid thrombus was visible within the lumen of the balloon (Figure 4). Figure 4 Solid thrombus within balloon lumen. A Fogarty catheter was used to perform an iliac embolectomy, which resulted in the removal of a small clot. The arteriotomy site was closed uneventfully as was the skin. The Swan Ganz catheter was left in situ. Good distal pulses were present following the procedure. Testing of the balloon post-removal showed a number of small holes and a very solid thrombus that could not be fragmented with finger pressure (Figures 5 and 6) Figure 5 Solid intraluminal thrombus. Figure 6 Small holes visible when water is introduced under pressure. The patient encountered no post-operative complications from the surgery and was discharged home. Management of heart failure in the setting of a reduced ejection fraction is ongoing. Discussion Although their use is decreasing, IABPs are the most commonly used mechanical assist devices in the management of haemodynamic instability, which is not amenable to less invasive strategies.6 It is an effective way to increase both diastolic blood pressure and coronary perfusion while reducing afterload.6

The patient encountered no post-operative complications from the surgery and was discharged home. Management of heart failure in the setting of a reduced ejection fraction is ongoing. Discussion Although their use is decreasing, IABPs are the most commonly used mechanical assist devices in the management of haemodynamic instability, which is not amenable to less invasive strategies.6 It is an effective way to increase both diastolic blood pressure and coronary perfusion while reducing afterload.6 In general, the complication rate with the use of IABPs is low, given the cohort of patients involved. Analysis of just under 17 000 balloon pump insertions from 1996 to 2000 showed a 7% incidence of all complications with the use of an IABP.4 Major complication rates were 2.6% and a mortality rate of 0.5% as a direct result of IABP use.4 Other studies have suggested higher complication rates ranging from 20% to 50%.5 When complications arise, however, they have the potential to be extremely serious including the loss of limbs and even death. The device used in this case involved a 40 cm3 polyurethane balloon, which can be easily inflated and deflated with helium. Helium is used as it is a low-viscosity gas that facilitates its quick introduction and removal to the balloon in diastole and systole, respectively.6

In general, the complication rate with the use of IABPs is low, given the cohort of patients involved. Analysis of just under 17 000 balloon pump insertions from 1996 to 2000 showed a 7% incidence of all complications with the use of an IABP.4 Major complication rates were 2.6% and a mortality rate of 0.5% as a direct result of IABP use.4 Other studies have suggested higher complication rates ranging from 20% to 50%.5 When complications arise, however, they have the potential to be extremely serious including the loss of limbs and even death. The device used in this case involved a 40 cm3 polyurethane balloon, which can be easily inflated and deflated with helium. Helium is used as it is a low-viscosity gas that facilitates its quick introduction and removal to the balloon in diastole and systole, respectively.6 Complications associated with balloon perforation such as in this case can be catastrophic. Arterial helium embolism is a documented complication of larger perforations in the balloon membrane allowing a sudden introduction of a large volume of helium into the systemic circulation and resulting in significant neurological deficit and even death.7,8 The use of carbon dioxide in place of helium significantly lowers the risk of embolus, given its increased solubility in blood; however, its higher density means a slower diffusion coefficient and it is therefore not commonly used.9

stemic circulation and resulting in significant neurological deficit and even death.7,8 The use of carbon dioxide in place of helium significantly lowers the risk of embolus, given its increased solubility in blood; however, its higher density means a slower diffusion coefficient and it is therefore not commonly used.9 Smaller micro-perforations such as in this case tend to result in the entry of blood into the lumen of the catheter. This is because pressure inside the balloon is not sufficient enough to overcome the surface tension at the balloon—blood interface and as a result blood moves into the cavity.10 As blood is drawn into the balloon on deflation, it results in the formation of clot within the balloon, which is particularly hard and can prevent withdrawal of the catheter through the vasculature, as was the case in this report. Entrapment is seen more commonly within the female vasculature, and this is felt to be due to the narrower calibre of the female femoral artery.11 The presence of atherosclerosis is also a known risk factor for entrapment.11 As the use of balloon pump becomes less common in the era of PCI via a radial approach, this case report should serve to highlight the importance of close observation and rapid action to remove the IABP in the event of perforation.

Smaller micro-perforations such as in this case tend to result in the entry of blood into the lumen of the catheter. This is because pressure inside the balloon is not sufficient enough to overcome the surface tension at the balloon—blood interface and as a result blood moves into the cavity.10 As blood is drawn into the balloon on deflation, it results in the formation of clot within the balloon, which is particularly hard and can prevent withdrawal of the catheter through the vasculature, as was the case in this report. Entrapment is seen more commonly within the female vasculature, and this is felt to be due to the narrower calibre of the female femoral artery.11 The presence of atherosclerosis is also a known risk factor for entrapment.11 As the use of balloon pump becomes less common in the era of PCI via a radial approach, this case report should serve to highlight the importance of close observation and rapid action to remove the IABP in the event of perforation. Immediate action can result in the successful removal of the device before the development of dense clot. The use of intraluminal thrombolytic administration can be used to aid removal; however, its use in cases where the balloon thrombus has been present for a period of >1 h, such as in this case, is debatable, given the solid consistency of the clot.12–15

essful removal of the device before the development of dense clot. The use of intraluminal thrombolytic administration can be used to aid removal; however, its use in cases where the balloon thrombus has been present for a period of >1 h, such as in this case, is debatable, given the solid consistency of the clot.12–15 The optimal removal strategy of an entrapped IABP is still unclear, given its rarity. A number of different approaches have been referenced in the literature with varying degrees of success. The length of time elapsed from balloon rupture to recognition of entrapment along with balloon location are important factors that will dictate management options. Millham et al.15 reported two cases of entrapment in 1991 at the end of which they concluded that the abdominal aorta should be controlled proximally in cases where the catheter tip resides above the inguinal ligament. Fukushima et al.13 describe a case of entrapment within the aorta of a 68-year-old gentleman, where removal was carried out using a guidewire with fluoroscopy via the axillary artery.

Millham et al.15 reported two cases of entrapment in 1991 at the end of which they concluded that the abdominal aorta should be controlled proximally in cases where the catheter tip resides above the inguinal ligament. Fukushima et al.13 describe a case of entrapment within the aorta of a 68-year-old gentleman, where removal was carried out using a guidewire with fluoroscopy via the axillary artery. As is evident from this, there have been numerous techniques used since the late 1980s for the removal of entrapped aortic balloon pumps. In the case reported herein, it was possible to gain both proximal and distal control of the involved vessels to ensure any bleeding could be controlled quickly and adequately should the need arise. The technique used here did not require the need for retro peritoneal aortic exposure, and the associated morbidity that comes with this, as suggested by Millham et al.15 Pre-operative imaging to delineate anatomy and identify the location of obstruction is vital in planning the most appropriate approach on a case-by-case basis, as it helps determine the most appropriate method for its removal.

exposure, and the associated morbidity that comes with this, as suggested by Millham et al.15 Pre-operative imaging to delineate anatomy and identify the location of obstruction is vital in planning the most appropriate approach on a case-by-case basis, as it helps determine the most appropriate method for its removal. If blood is noted within the external tubing supplying the balloon pump, it should prompt swift extraction of the balloon. Helium should be the only thing within the helium tubing and blood can only enter if the balloon surface has been damaged. Often an alarm will sound on the IABP console if blood gets in this tubing, but this is unreliable and often will not sound, as was the situation in this case. Vigilance in monitoring this tubing is therefore paramount in the overall care of patients under IABP support. If blood is noted—it should prompt the removal of the balloon within 30 min, as the longer it is left after its rupture the drier the clot becomes and the less likely it is to extract at the bedside. Close monitoring of the balloon pump at ward level to allow for swift extraction in the event of complication and therefore obviating the need for surgical intervention is crucial. This case report should serve to highlight the importance of strict vigilance of IABPs by ward staff that may be less familiar with their use and complications as balloon pump use becomes more infrequent.

wift extraction in the event of complication and therefore obviating the need for surgical intervention is crucial. This case report should serve to highlight the importance of strict vigilance of IABPs by ward staff that may be less familiar with their use and complications as balloon pump use becomes more infrequent. Author Contributions N.H. and N.S. were involved in compilation of data and writing of this piece. J.C. and P.M. were lead consultants/senior authors involved in the management of the case. Consent Informed consent was obtained from this patient for publication of this case history and associated images in line with COPE recommendations. Conflicts of interest: none declared.

Learning points A normal or pseudonormal B-type natriuretic peptide level should not exclude a cardiac cause of dyspnoea in a patient with heart failure. In the urgent care setting, cardiac tamponade is a serious cause of heart failure with normal or pseudo-normal BNP level and should not be missed. Introduction B-type natriuretic peptide (BNP) has been widely used in helping to establish the diagnosis of heart failure (HF) in the urgent care setting in a patient in whom diagnosis is uncertain and presenting with symptoms that can be similar to those found in HF.1,2 Many known conditions can falsely increase BNP level.1,2 However, very few are the causes of lower-than-expected or normal BNP.3–5 We herein report the case of a 78-year-old female patient with severe aortic stenosis and end-stage ovarian cancer presenting with dyspnoea and found to have normal BNP in the setting of cardiac tamponade.

tions can falsely increase BNP level.1,2 However, very few are the causes of lower-than-expected or normal BNP.3–5 We herein report the case of a 78-year-old female patient with severe aortic stenosis and end-stage ovarian cancer presenting with dyspnoea and found to have normal BNP in the setting of cardiac tamponade. Timeline Eight months prior to presentation Medical history significant for severe aortic stenosis. Recently diagnosed with Stage IV epithelial ovarian carcinoma with liver and bone metastases, but refused chemotherapy. Six months prior to presentation Dyspnoea, acute HF, BNP level 682 pg/mL. Bisoprolol 2.5 mg orally daily then increased to 2.5 mg orally twice daily, furosemide 40 mg orally daily and ramipril 5 mg orally daily. Upon presentation to the emergency room Hypotension and tachycardia, severe dyspnoea, lungs clear to auscultation. BNP level 278 pg/mL. Echocardiogram showed large pericardial effusion. Urgent pericardiocentesis drained haematic neoplastic fluid. Non-contrast computed tomography (CT) chest did not show consolidation or pulmonary metastases. After 10 days The patient was clinically stable. A new BNP level was 1147 pg/mL. Workup excluded idiopathic, autoimmune, infectious, traumatic and cardiac causes of tamponade. She was discharged on Day 11 of HF therapy with follow-up for a scheduled chemotherapy regimen. Case report A 78-year-old female patient with a medical history significant for severe aortic stenosis and Stage IV epithelial ovarian carcinoma with liver and right iliac bone metastases diagnosed 8 months ago but not treated was admitted to the emergency department because of severe dyspnoea at rest of same day duration. Upon arrival, she was tachypneic, respiratory rate was estimated at 24 breaths/min, blood pressure was 85/55 mmHg, and pulse rate was paradoxical 114 b.p.m. General examination was significant for a pale and cachectic woman in acute distress. Physical examination revealed distended jugular veins and hepatojugular reflux. Cardiac auscultation was remarkable for an aortic systolic murmur Grade 4/6, best heard at the second right intercostal space with a significant decrease in S2. The lungs were clear to auscultation. An electrocardiogram showed sinus tachycardia with low-voltage QRS complexes. Laboratory workup was normal, except for a haemoglobin level of 8.9 g/dL, haematocrit of 27%, blood urea nitrogen of 96 mg/dL, creatinine level of 1.9 mg/dL, and mildly elevated liver enzymes.

ease in S2. The lungs were clear to auscultation. An electrocardiogram showed sinus tachycardia with low-voltage QRS complexes. Laboratory workup was normal, except for a haemoglobin level of 8.9 g/dL, haematocrit of 27%, blood urea nitrogen of 96 mg/dL, creatinine level of 1.9 mg/dL, and mildly elevated liver enzymes. Troponin I level was 0.07 ng/mL (cut-off value 0.08) (Table 1). Table 1 Laboratory values measured at baseline and during the recent admission Normal reference values Six months prior to presentation Upon admission 10 days later WBC (4000–11 000/μL) 9300, 58% Leucocytes 8400, 54% Leucocytes 9200, 56% Leucocytes Hb (female: 12–16 g/dL) 9.5 8.9 9.3 Hct (36–48%) 29 27 28 TSH (0.5–5 μU/mL) 1.4 1.6 NA FT4 (0.8–2.3 ng/dL) 1.9 2.1 NA BUN (7–18 mg/dL) 67 96 81 Creatinine (0.6–1.2 mg/dL) 0.9 1.9 1.1 Troponin I (<0.08 ng/mL) 0.02 0.07 NA ALT (0–20 U/L) 72 83 79 ANA (<1:40 dilution) NA Requested <1:40 RF (<1:16 dilution) NA Requested <1:16 BNP (<100 pg/mL) 628 278 1147 WBC, white blood cell count; Hb, haemoglobin; Hct, haematocrit; TSH, thyroid-stimulating hormone; FT4, free tetraiodothyronine; BUN, blood urea nitrogen; ALT, alanine aminotransferase; ANA, antinuclear antibody; RF, rheumatoid factor; BNP, B-type natriuretic peptide; NA, not available.

:16 BNP (<100 pg/mL) 628 278 1147 WBC, white blood cell count; Hb, haemoglobin; Hct, haematocrit; TSH, thyroid-stimulating hormone; FT4, free tetraiodothyronine; BUN, blood urea nitrogen; ALT, alanine aminotransferase; ANA, antinuclear antibody; RF, rheumatoid factor; BNP, B-type natriuretic peptide; NA, not available. Six months ago, she presented with dyspnoea and she was diagnosed with acute HF. Her baseline BNP level was 682 pg/mL (congestive HF unlikely if BNP < 100 pg/mL and very likely if BNP > 400 pg/mL). Her medications included furosemide 40 mg orally once daily, bisoprolol 2.5 mg orally twice daily, and ramipril 5 mg orally once daily. A new BNP level to rule out decompensated HF was 278 pg/mL. A chest radiograph showed cardiomegaly with clear lungs (Figure 1). A bedside transthoracic echocardiography showed cardiac tamponade (Figure 2), in addition to severe aortic stenosis (aortic valve area 0.8 cm2, mean gradient 46 mmHg, and peak jet velocity 4.7 m/s) and left ventricular hypertrophy. The ejection fraction was calculated at 50–55%. An urgent ultrasound-guided pericardiocentesis drained 830 mL of haematic fluid, leading to significant clinical improvement without any complications. Cytological examination of the pericardial fluid did not show any malignant cell. However, analysis of a fluid sample revealed a haematocrit level of 11%, white cell count of 2805/mL with 64% lymphocytes and 12% monocytes, lactate dehydrogenase of 372 U/dL, and glucose level of 67 mg/dL. CA125 was significantly elevated with 121 U/mL (normal < 35 U/mL). A purified protein derivative skin test was negative. Gram stain and three culture bottles were also negative. A CT scan of the chest did not show pulmonary metastases or consolidation (Figure 3).

ehydrogenase of 372 U/dL, and glucose level of 67 mg/dL. CA125 was significantly elevated with 121 U/mL (normal < 35 U/mL). A purified protein derivative skin test was negative. Gram stain and three culture bottles were also negative. A CT scan of the chest did not show pulmonary metastases or consolidation (Figure 3). Figure 1 Water bottle sign on chest X-ray consistent with pericardial effusion. Figure 2 Transthoracic echocardiogram showing a large pericardial effusion with right atrial collapse (arrow) consistent with a cardiac tamponade. Figure 3 Non-contrast computed tomography scan of the chest showing resolving tamponade after insertion of a pericardial drain. The patient was admitted to the coronary care unit and, 10 days later, transthoracic echocardiography was repeated showing a normal pericardium with a residual minimal effusion. A new BNP level was therefore ordered revealing a significant increase to 1147 pg/mL. The patient was clinically stable, and her vital signs were within normal limits. Serum antinuclear antibody and rheumatoid factor came out normal. All laboratory values are shown in Table 1. She was discharged the next day with a scheduled 1 week appointment in the clinic for optimization of her medical treatment and discussion of the potential benefits of chemotherapy protocols but was lost to follow-up. This case report was approved by the ethics committee of Clemenceau Medical Center.

The patient was admitted to the coronary care unit and, 10 days later, transthoracic echocardiography was repeated showing a normal pericardium with a residual minimal effusion. A new BNP level was therefore ordered revealing a significant increase to 1147 pg/mL. The patient was clinically stable, and her vital signs were within normal limits. Serum antinuclear antibody and rheumatoid factor came out normal. All laboratory values are shown in Table 1. She was discharged the next day with a scheduled 1 week appointment in the clinic for optimization of her medical treatment and discussion of the potential benefits of chemotherapy protocols but was lost to follow-up. This case report was approved by the ethics committee of Clemenceau Medical Center. Discussion BNP has diuretic, natriuretic, and vasodilator properties. Nevertheless, BNP may reduce blood pressure, which is not its main physiological effect. Additionally, BNP is mainly released by the ventricular myocardium in response to elevations of end-diastolic pressure and volume, whereas other natriuretic peptides can be produced by the atria.6 Few conditions are associated with elevated BNP other than congestive HF and include acute myocardial infarction, atrial fibrillation, acute coronary syndrome, cardioversion, valvular heart disease, and myocarditis.1,2 Other non-cardiac causes include acute kidney injury, chronic kidney disease, hypertension, and pulmonary diseases such as pulmonary hypertension, severe chronic obstructive pulmonary disease, pneumonia, pulmonary embolism, adult respiratory distress syndrome, and older age.1,2

lvular heart disease, and myocarditis.1,2 Other non-cardiac causes include acute kidney injury, chronic kidney disease, hypertension, and pulmonary diseases such as pulmonary hypertension, severe chronic obstructive pulmonary disease, pneumonia, pulmonary embolism, adult respiratory distress syndrome, and older age.1,2 Obesity is associated with lower BNP levels in healthy individuals and patients with chronic HF. Conditions associated with lower-than-expected BNP are female gender, liver cirrhosis, hyperthyroidism, sepsis, chemotherapy, flash pulmonary oedema, and constrictive pericarditis.3–5 In case of pericardial constriction, the ventricular wall stretch is limited by the thickened stiff pericardium. These physiological differences suggest that the elevation in plasma BNP levels in constrictive pericarditis is modest and is expected to be much less than the levels measured in case of restrictive cardiomyopathy.7 In our case, the BNP level was expected to be significantly high because of the acute kidney injury and the patient’s cancer and HF history. However, it was found to be normal for her age. Based on the laboratory values, the progressive accumulation of bloody fluid in the pericardium was thought to be of malignant origin, despite the absence of malignant cells. Vaitkus et al.8 showed that cytological examination of pericardial fluid was positive for malignancy in only 65–85% of cancer patients who underwent pericardiocentesis.

values, the progressive accumulation of bloody fluid in the pericardium was thought to be of malignant origin, despite the absence of malignant cells. Vaitkus et al.8 showed that cytological examination of pericardial fluid was positive for malignancy in only 65–85% of cancer patients who underwent pericardiocentesis. Chronic tamponade resulted in a constrictive physiology leading to impaired ventricular stretching and a subsequent lower-than-expected BNP level. When tamponade resolved, BNP level was sufficiently high to explain the symptoms of HF of the patient. A study conducted by Minai et al.9 validated the importance of our observation. Patients with cardiac tamponade had a pseudonormal BNP level. When pericardiocentesis was performed, BNP level was significantly high. To our knowledge, other causes that can decrease BNP level were not present in our case (e.g. sepsis, chemotherapy, or other conditions mentioned earlier). Conclusion In the urgent care setting, patients admitted with dyspnoea and suspected to have HF despite a normal or pseudonormal BNP level should have an urgent echocardiogram to exclude any pericardial disease, especially a chronic tamponade. The clinician’s role is crucial, because a lower-than-expected BNP level can mask an underlying life-threatening condition and if diagnosed it can be lifesaving. Consent: Informed consent was obtained from this patient for publication of this case history and associated images in line with COPE recommendations. Conflict of interest: none declared.

Learning points Swallowing-induced tachycardia is a rare entity. There is a possible relationship between autonomic instability and the swallowing-induced atrial tachycardia observed in this patient with hypertrophic cardiomyopathy. Introduction Swallowing-induced tachycardia is defined as a tachyarrhythmia reproducible with deglutination, in the absence of underlying cardiac or gastrointestinal pathology. Approximately 50 cases of swallowing-induced tachycardia have been reported worldwide since 1926.1 We present a unique case of a swallowing-induced atrial tachycardia in an adolescent with hypertrophic cardiomyopathy (HCM). Hypertrophic cardiomyopathy, also referred to as hypertrophic obstructive cardiomyopathy, results from a genetic defect that causes asymmetric hypertrophy of the interventricular ventricular septum. The pathophysiology of HCM involves left ventricular outflow obstruction, mitral regurgitation, diastolic dysfunction, ischaemia, autonomic dysregulation, and arrhythmias.2–4 The clinical manifestations of this disorder range from patients who are asymptomatic to those who develop dyspnoea, chest pain, syncope, arrhythmias, and even sudden cardiac death.2 This case adds to the body of literature supporting a possible aetiologic relationship between arrhythmias and autonomic dysregulation in patients with HCM.

stations of this disorder range from patients who are asymptomatic to those who develop dyspnoea, chest pain, syncope, arrhythmias, and even sudden cardiac death.2 This case adds to the body of literature supporting a possible aetiologic relationship between arrhythmias and autonomic dysregulation in patients with HCM. Timeline 3 months prior to presentation Patient reports palpitations while eating. Holter monitor reveals paroxysms of atrial tachycardia. Near syncopal event occurs while swallowing. Inpatient hospital course (4 days) Telemetry reveals non-sustained atrial tachycardia when patient swallows. Cine esophagram is unremarkable. Radiofrequency ablation (5 hours) Activation mapping of left atrium is performed while patient swallows. Successful radiofrequency ablation of ectopic focus in right superior pulmonary vein. Case report A 17-year-old man with HCM presented to the emergency department with a 3-month history of palpitations that lasted up to 5 s and occurred multiple times throughout the day. He was found to have paroxysms of atrial tachycardia on an outpatient Holter monitor and had experienced a near syncopal episode associated with swallowing. On presentation, his examination was notable for a resting heart rate of 65 b.p.m. with a blood pressure of 125/60 mmHg. On cardiac examination, his rate and rhythm were regular without audible murmurs, rubs or gallops, or a displaced point of maximal impulse. The remainder of the physical examination was unremarkable. The patient was admitted to telemetry, which consistently demonstrated a non-sustained atrial tachycardia when the patient swallowed. A cine oesophogram was performed and was unremarkable. A timeline of the patient’s outpatient and inpatient course is outlined. A 12-lead rhythm strip of the patient’s paroxysmal atrial tachycardia can be seen in Figure 1.

y, which consistently demonstrated a non-sustained atrial tachycardia when the patient swallowed. A cine oesophogram was performed and was unremarkable. A timeline of the patient’s outpatient and inpatient course is outlined. A 12-lead rhythm strip of the patient’s paroxysmal atrial tachycardia can be seen in Figure 1. Figure 1 A 12-lead rhythm strip of the paroxysmal atrial tachycardia (red box) induced by swallowing. After obtaining consent, the patient was brought to the electrophysiology (EP) lab, where tachycardia could not be induced with programmed electrical stimulation. Activation mapping was performed using the Biosense-Carto™ system (Biosense Webster, Diamond Bar, CA, USA). By having the patient periodically swallow 10–20 cm3 of saline, non-sustained atrial tachycardia was induced (Figure 2). The Lasso catheter (Biosense Webster) was used to take multiple simultaneous activation points from a single premature atrial contraction. The earliest activity was localized to the anterior aspect of the right superior pulmonary vein (RSPV). After radiofrequency isolation of the RSPV and ablation of the right anterior ganglionated plexus, the tachycardia was non-inducible despite repeated swallowing and isoproterenol medication. The patient remained asymptomatic, without any further palpitations, in the 12 months of follow-up after the ablation.

in (RSPV). After radiofrequency isolation of the RSPV and ablation of the right anterior ganglionated plexus, the tachycardia was non-inducible despite repeated swallowing and isoproterenol medication. The patient remained asymptomatic, without any further palpitations, in the 12 months of follow-up after the ablation. Figure 2 Surface and intracardiac electrograms of swallowing-induced arrhythmia. Top 4 leads (I, II, aVF, and V1) reflect surface electrocardiogram tracings. CS 1–10 and PV1–10 reflect intracardiac electrograms originating from coronary sinus and right superior pulmonary vein, respectively. The patient is in normal sinus rhythm until swallowing water (longitudinal black line), followed by three beats of non-sustained atrial tachycardia (black arrows) with earliest activation in the Lasso catheter located in the right superior pulmonary vein. CS, coronary sinus; PV, pulmonary vein. Discussion Deglutition-induced atrial tachycardia is a rare phenomenon that has never been documented in adolescents and in the setting of HCM. Previous cases have documented swallowing as a trigger for both bradyarrhythmias and a wide range of supraventricular tachyarrhythmias. In a similar case to our patient, Engel et al.5 reported an autonomic focus in the left atrium as a trigger for a swallowing-induced tachyarrhythmia.

escents and in the setting of HCM. Previous cases have documented swallowing as a trigger for both bradyarrhythmias and a wide range of supraventricular tachyarrhythmias. In a similar case to our patient, Engel et al.5 reported an autonomic focus in the left atrium as a trigger for a swallowing-induced tachyarrhythmia. Reports have raised the possibility of autonomic dysregulation as a mechanism for atrial arrhythmias in patients with HCM.3,4,6 Exaggerated sympathetic activity, manifesting as hyper-responsiveness of the myocardium to catecholamines has been described in swallowing-induced atrial fibrillation.6 The relationship between increased sympathetic activity and swallowing-induced tachyarrhythmias is supported by Tandeter et al.7 in their report of a swallowing-induced atrial tachyarrhythmia that was also initiated by the β-agonist salbutamol. In our case, it is possible that autonomic changes associated with the patient’s HCM may have played a role in the patient’s swallowing-induced atrial tachycardia.

ythmias is supported by Tandeter et al.7 in their report of a swallowing-induced atrial tachyarrhythmia that was also initiated by the β-agonist salbutamol. In our case, it is possible that autonomic changes associated with the patient’s HCM may have played a role in the patient’s swallowing-induced atrial tachycardia. Successful radiofrequency ablations of swallowing-induced atrial arrhythmias targeting the pulmonary vein ostia or the posterior walls of the left or right atria have been performed. Although pulmonary vein isolation is the standard target for atrial fibrillation ablation, another strategy involves targeting the parasympathetic input to the heart. Thus, the ability to cure swallowing-induced atrial tachycardia with pulmonary vein isolation may be related either to isolation of the culprit vein or denervation of the ganglionated plexus. In our patient, both isolation of the RSPV and ablation of the right anterior ganglionated plexus, might have contributed to the successful long-term cure. Consent: Informed consent was obtained from this patient for publication of this case history and associated images in line with COPE recommendations. Conflict of interest: none declared.

Learning points Takotsubo syndrome (TTS) complicated by cardiogenic shock is a challenging clinical problem, as treatment with inotropic agents and/or vasopressors is contraindicated. Mechanical circulatory support for TTS-induced cardiogenic shock is a reasonable treatment option and has acceptable outcomes.

Learning points Takotsubo syndrome (TTS) complicated by cardiogenic shock is a challenging clinical problem, as treatment with inotropic agents and/or vasopressors is contraindicated. Mechanical circulatory support for TTS-induced cardiogenic shock is a reasonable treatment option and has acceptable outcomes. Introduction Takotsubo syndrome (TTS) is an acute and usually reversible heart failure syndrome with an estimated prevalence of 1–2% in patients suspected of an acute coronary syndrome.1 Several diagnostic criteria have been proposed, and we support the criteria suggested by the Heart Failure Association of the European Society of Cardiology.2 Takotsubo syndrome is characterized by regional wall abnormalities of the myocardium (no culprit of atherosclerotic coronary artery disease), frequently preceded by a stressful trigger (emotional of physical). The classical pattern of regional wall abnormalities is apical and circumferential mid-ventricular hypokinesia and basal hypercontractility; however, anatomical variants exist.1,2 In the classical pattern, end-systolic the left ventricle resembles a Takotsubo, which is a Japanese word for an octopus trap with a narrow neck and globular lower portion. Excessive catecholamine release caused by the stressful trigger are believed to play a crucial role in the pathophysiology of TTS.2 Complications that can occur include mitral regurgitation, arrhythmias, thrombus formation, pericardial effusion, ventricular wall rupture, cardiogenic shock, and death.2 Treatment of refractory cardiogenic shock in TTS is particularly challenging, as catecholamines are contraindicated and mechanical circulatory support (MCS) may be the only option left. We present here such a patient and review the literature reporting on the treatment of TTS with MCS.

e, cardiogenic shock, and death.2 Treatment of refractory cardiogenic shock in TTS is particularly challenging, as catecholamines are contraindicated and mechanical circulatory support (MCS) may be the only option left. We present here such a patient and review the literature reporting on the treatment of TTS with MCS. Patient information A 67-year-old woman discovered that there had been a burglary in her daughter’s house. Immediately she developed severe chest pain combined with shortness of breath and her husband called the emergency services. Her medical history consisted of type 2 diabetes mellitus controlled by oral drugs and chronic obstructive pulmonary disease (COPD). During transport to the hospital, an electrocardiogram (ECG) was taken, and ST-elevation myocardial infarction was suspected. Physical examination On arrival at the catheterization laboratory, the patient was in severe distress, heart rate was 107 b.p.m., and blood pressure was 88/64 mmHg. Central capillary refill time was 6 s. Cardiac and pulmonary auscultation revealed no abnormalities.

Immediately she developed severe chest pain combined with shortness of breath and her husband called the emergency services. Her medical history consisted of type 2 diabetes mellitus controlled by oral drugs and chronic obstructive pulmonary disease (COPD). During transport to the hospital, an electrocardiogram (ECG) was taken, and ST-elevation myocardial infarction was suspected. Physical examination On arrival at the catheterization laboratory, the patient was in severe distress, heart rate was 107 b.p.m., and blood pressure was 88/64 mmHg. Central capillary refill time was 6 s. Cardiac and pulmonary auscultation revealed no abnormalities. Diagnostic assessment An ECG (Figure 1) was obtained showing sinus rhythm of 108 b.p.m.; intermediate heart axis and normal conduction times; 1 mm concave ST-segment elevations in leads V4 through V6; 1 mm PT-a segment depression in lead II, to a lesser extent also in leads aVF, V5, and V6; and PT-a segment elevation in lead aVR. The differential diagnosis included pericarditis, acute coronary syndrome, or TTS. It was decided to continue with a coronary angiogram to exclude or treat significant obstructive coronary artery disease. Coronary angiography did not show obstructive coronary artery disease, and a left ventriculogram (Figure 2A and B, see Supplementary material online, Video S1) showed apical and mid-ventricular akinesia and basal hypercontractility supporting a diagnosis of TTS.

or treat significant obstructive coronary artery disease. Coronary angiography did not show obstructive coronary artery disease, and a left ventriculogram (Figure 2A and B, see Supplementary material online, Video S1) showed apical and mid-ventricular akinesia and basal hypercontractility supporting a diagnosis of TTS. Figure 1 ECG taken in the catheterization laboratory: sinus rhythm 108 b.p.m., intermediate heart axis, and normal conduction times; 1 mm concave ST-segment elevations in leads V4 through V6; 1 mm PT-a segment depression in lead II, to a lesser extent also in leads aVF, V5, and V6; and PT-a segment elevation in aVR. Figure 2 (A) Left ventriculogram in diastole. (B) Left ventriculogram in systole demonstrating apical and mid-ventricular akinesia and basal hypercontractility (arrows). Figure 3 Flow diagram of systematic search of literature (performed 18 June 2017). Search terms: (Takotsubo) AND (Extracorporeal Circulation or Heart-Assist Devices).

Figure 2 (A) Left ventriculogram in diastole. (B) Left ventriculogram in systole demonstrating apical and mid-ventricular akinesia and basal hypercontractility (arrows). Figure 3 Flow diagram of systematic search of literature (performed 18 June 2017). Search terms: (Takotsubo) AND (Extracorporeal Circulation or Heart-Assist Devices). Interventions Already shortly after arrival at the catheterization laboratory, it was concluded that the patient was in shock and a fluid challenge was initiated. During diagnostic evaluation at the catheterization laboratory, the patient received 2 L of sodium chloride (0.9%) for 45 min. In addition, phenylephrine (0.05 mg/min) was added; however, the patient continued to deteriorate due to cardiogenic shock. The cardiothoracic surgeon was consulted to perform emergency implantation of central extracorporeal life support (ECLS). To relieve the left ventricle, a cannula was inserted in the left atrium, and a return cannula was inserted in the ascending aorta (output 3.8 L/min). The haemodynamic parameters stabilized, and the patient was transferred to the intensive care unit (ICU). Timeline Time Events Start of episode 67-year old woman presenting with chest pain and shortness of breath. Prehospital ECG suggests ST-elevation myocardial infarction Accepted for STEMI-protocol and straight transport to catheterization laboratory Physical examination: severe distress, heartrate 107 bpm, RR 88/63 mmHg, no signs of decompensation: Shock Fluid challenge: 2 L NaCl 0.9% in 45 minutes Phenylephrine (0.05 mg/minute) started as vasopressor

Timeline Time Events Start of episode 67-year old woman presenting with chest pain and shortness of breath. Prehospital ECG suggests ST-elevation myocardial infarction Accepted for STEMI-protocol and straight transport to catheterization laboratory Physical examination: severe distress, heartrate 107 bpm, RR 88/63 mmHg, no signs of decompensation: Shock Fluid challenge: 2 L NaCl 0.9% in 45 minutes Phenylephrine (0.05 mg/minute) started as vasopressor LV-angiogram: Takotsubo syndrome Cardiogenic shock Central ECLS implanted 24 hours later Cardiac tamponade Tamponade surgically relieved Echocardiography: complete recovery of left ventricular function ECLS weaned and removed

Physical examination: severe distress, heartrate 107 bpm, RR 88/63 mmHg, no signs of decompensation: Shock Fluid challenge: 2 L NaCl 0.9% in 45 minutes Phenylephrine (0.05 mg/minute) started as vasopressor LV-angiogram: Takotsubo syndrome Cardiogenic shock Central ECLS implanted 24 hours later Cardiac tamponade Tamponade surgically relieved Echocardiography: complete recovery of left ventricular function ECLS weaned and removed 7 weeks later Fully recovered at the outpatient clinic Follow-up and outcomes About 24 h later, the patient deteriorated. A high central venous pressure together with collapse of the right atrium on transoesophageal echocardiography (TOE) led to the diagnosis of cardiac tamponade as a bleeding complication of ECLS. A repeat sternotomy was performed, and once the tamponade was relieved, direct visual inspection as well as TOE (see Supplementary material online, Video S2) demonstrated that the left ventricular function was completely recovered and no regional wall abnormalities were present. The patient was successfully weaned from the ECLS in the same session. The further course of the patient on the ICU was complicated by atrial fibrillation, prolonged mechanical ventilation due to COPD exacerbation and a delirium. The patient was discharged from the hospital 30 days after admission. Seven weeks after discharge the patient was seen in the outpatient clinic and was doing well.

e further course of the patient on the ICU was complicated by atrial fibrillation, prolonged mechanical ventilation due to COPD exacerbation and a delirium. The patient was discharged from the hospital 30 days after admission. Seven weeks after discharge the patient was seen in the outpatient clinic and was doing well. Discussion Cardiogenic shock caused by TTS, as was the case in the patient we reported here, is a difficult entity to treat. In retrospect, the initial treatment with an aggressive fluid challenge and phenylephrine seems inappropriate. It is, however, important to keep in mind that a final diagnosis had not yet been made, and the patient was in shock (‘dry and cold’). At first, after 1 L of sodium chloride (0.9%), the patient was responsive to this treatment. Therefore, it was decided to continue fluid infusion until a final diagnosis had been made. Phenylephrine was added when the shock was progressive, which we believe was a reasonable choice as it is a vasopressor primarily affecting the peripheral vasculature. In hindsight, it would have been more appropriate to discontinue the fluid challenge after 0.5–1 L of sodium chloride (0.9%) and start an inotropic agent and/or vasopressor when the patient further deteriorated in shock. Yet, given the final diagnosis of TTS, there was no perfect treatment strategy to follow. Inotropic agents and/or vasopressors (e.g. dobutamine, dopamine, norepinephrine, epinephrine, and milrinone) are considered contraindicated in TTS as they might worsen the clinical situation and prognosis by further activation of catecholamine-related pathways.2 Mechanical circulatory support might be the only remaining viable treatment option, which led to the decision of treatment by ECLS in our patient.

ine, and milrinone) are considered contraindicated in TTS as they might worsen the clinical situation and prognosis by further activation of catecholamine-related pathways.2 Mechanical circulatory support might be the only remaining viable treatment option, which led to the decision of treatment by ECLS in our patient. Mechanical circulatory support The choice for the type of MCS in cardiogenic shock depends on several factors, including institutional availability and experience. Evidence is lacking to recommend a specific type. An intra-aortic balloon pump (IABP) has been used during cardiogenic shock in TTS. However, haemodynamic support by an IABP is usually inadequate, and the results of the IABP-SHOCK II trial, although a different patient category than patients with TTS, do not provide evidence for the use of an IABP.3 Femoral venoarterial ECLS has several theoretical advantages: quick and relatively easy insertion, circulatory support up to >4.5 L/min (depending on the cannula size) and extracorporeal membrane oxygenation improves tissue oxygenation in case of pulmonary oedema. However, afterload reduction in TTS is desirable and femoral venoarterial ECLS may, in the contrary, increase afterload. In theory, central MCS would therefore be preferable, being neutral on afterload. However, there are no randomized trials comparing the outcome of these devices in cardiogenic shock, let alone in TTS-induced cardiogenic shock. We chose central ECLS with venous return from the left atrium and a return cannula in the ascending aorta, because this creates reduction of preload, is neutral on afterload, and provides adequate haemodynamic support.

paring the outcome of these devices in cardiogenic shock, let alone in TTS-induced cardiogenic shock. We chose central ECLS with venous return from the left atrium and a return cannula in the ascending aorta, because this creates reduction of preload, is neutral on afterload, and provides adequate haemodynamic support. Systematic review of the literature To gain insight in the use of MCS for TTS-induced cardiogenic shock, we performed a PubMed search (Figure 3) using the following search terms: (Takotsubo) AND (Extracorporeal Circulation or Heart-Assist Devices). Including our patient, 17 cases of TTS-induced cardiogenic shock requiring MCS have been reported in the literature (Table 1). The age of the patients ranged from 16 years to 74 years, and 71% of the patients were female. Table 1 List of all case reports of mechanical circulatory support in TTS-induced cardiogenic shock

ncluding our patient, 17 cases of TTS-induced cardiogenic shock requiring MCS have been reported in the literature (Table 1). The age of the patients ranged from 16 years to 74 years, and 71% of the patients were female. Table 1 List of all case reports of mechanical circulatory support in TTS-induced cardiogenic shock Study (year) Age (years) Sex Cause of TTSb Inotropic agents/vasopressors before MCS MCS type Survival Follow-up Aa (2017) 67 F Stress Phenylephrine Central ECLS left atrium–aorta Yes 7 weeks B4 (2016) 27 F Pheochromocytoma (Nor)epinephrine ECLS V–A Yes 1 month C5 (2016) 56 M Post-liver transplantation Not Reported TandemHeart® Yes 25 days B6 (2015) 65 F Stress Norepinephrine, dobutamine, dopamine Impella® 2.5 Yes 6 days C7 (2015) 16 M Poly-trauma Not reported ECLS V–A Yes 22 days 30 M Poly-trauma Not reported ECLS V–A Yes 46 M Poly-trauma Not reported ECLS V–A Noc 19 F Poly-trauma Not reported ECLS V–A Noc D8 (2015) 46 F Pheochromocytoma Norepinephrine, dobutamine ECLS V–A Yes 77 days E9 (2015) 31 F Medication Norepinephrine, epinephrine ECLS V–A Yes 8 days F10 (2014) 37 F Post-cardiac surgery Epinephrine, vasopressin ECLS V–A Yes 2 months G11 (2013) 74 F Unknown Not reported ECLS V–A Yes In-hospital H12 (2012) 45 F Stress Dobutamine, noradrenaline ECLS V–A Yes 16 days I13 (2012) 19 M Stress and B-cell lymphoma Not reported Extracorporeal temporally central LVAD Yes 6 months J14 (2011) 37 F Post-Caesarean section Norepinephrine, dobutamine, dopamine ECLS V–A Yes 6 months K15 (2009) 74 F Stress Norepinephrine, epinephrine ECLS V–A Yes 6 months L16 (2008) 51 F Pheochromocytoma Dobutamine, epinephrine ECLS V–A Yes 8 days ECLS, extracorporeal life support; F, female; LVAD, left ventricular assist device; M, male; MCS, mechanical circulatory support; V–A, venoarterial; TTS, Takotsubo syndrome.

(2009) 74 F Stress Norepinephrine, epinephrine ECLS V–A Yes 6 months L16 (2008) 51 F Pheochromocytoma Dobutamine, epinephrine ECLS V–A Yes 8 days ECLS, extracorporeal life support; F, female; LVAD, left ventricular assist device; M, male; MCS, mechanical circulatory support; V–A, venoarterial; TTS, Takotsubo syndrome. a Patient described in this article. b Cause or circumstances in which TTS occurred. c Death not related to ECLS (traumatic brain injury). ECLS was the most used type of MCS (82% of the cases). In-hospital survival was 88%, and the two deaths were not to related to the device or TTS but were considered to result from traumatic brain injury.7 Although there might be a publication bias, complications were rare in the reported cases. In one patient, femoral venoarterial ECLS was complicated by leg ischaemia, which resolved without permanent injury. In our case, MCS was complicated by cardiac tamponade. Bleeding complications occur frequently in patients with MCS and is related to the use of anticoagulation. Conclusion Inotropic agents and/or vasopressors are contraindicated in TTS-induced refractory cardiogenic shock, making MCS a reasonable treatment option in this situation, and this has acceptable outcomes. Devices that reduce pre-load and do not increase afterload are preferable on theoretical grounds. Prospectively designed studies with sufficient number of patients are needed to further investigate the role of MCS in TTS-induced refractory cardiogenic shock. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online.

Conclusion Inotropic agents and/or vasopressors are contraindicated in TTS-induced refractory cardiogenic shock, making MCS a reasonable treatment option in this situation, and this has acceptable outcomes. Devices that reduce pre-load and do not increase afterload are preferable on theoretical grounds. Prospectively designed studies with sufficient number of patients are needed to further investigate the role of MCS in TTS-induced refractory cardiogenic shock. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Consent: Informed consent was obtained from this patient for publication of this case history and associated images in line with COPE recommendations. Conflict of interest: none declared. Supplementary Material Supplementary Video S1 Click here for additional data file. Supplementary Video S2 Click here for additional data file.

Learning points Pacemaker-lead thrombosis, mainly asymptomatic, may be detected by echocardiography a long time after implantation of a permanent pacemaker. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography is a useful technique to confirm or exclude the inflammatory cause of a mass attached to the pacemaker lead. Introduction Pacemaker-lead thrombosis is considered uncommon. The differential diagnosis from lead infection (vegetation) is challenging. Echocardiography cannot reliably differentiate the thrombotic or infective origin of the masses.1,2 The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has emerged as a valuable imaging technique to confirm or exclude intracardiac infection in patients with implanted cardiac electronic devices.3

cannot reliably differentiate the thrombotic or infective origin of the masses.1,2 The 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has emerged as a valuable imaging technique to confirm or exclude intracardiac infection in patients with implanted cardiac electronic devices.3 Timeline 25 years earlier Initial pacemaker implantation (DDDR) 6 months before 1st hospitalization Uncomplicated generator replacement 1st hospitalization Vegetation-like masses on the atrial portion of the ventricular lead (finding in routine echo). Endocarditis criteria not fulfilled. Patient discharged on acenocoumarol 1 month after 1st hospitalization Masses not present on follow-up echo 2nd hospitalization (over 2 years later) Fever, reappearance of the vegetation-like masses at the same site. Endocarditis criteria not clearly fulfilled. 18F-fluorodeoxyglucose positron emission tomography/computed tomography excluded the inflammatory origin of the masses. Patient discharged on acenocoumarol 1 month after 2nd hospitalization Masses not present on follow-up echo 6 months after 2nd hospitalization Masses not present on follow-up echo Case presentation An 85-year-old man with a permanent DDDR pacemaker (implantation 25 years ago due to complete heart block) was admitted for differential diagnosis and treatment of a right atrial mass, revealed in a routine transthoracic echocardiogram (TTE), which was performed on an outpatient basis, for the evaluation of dyspnoea on exertion (New York Heart Association III stage). The patient had a prior medical history of arterial hypertension and three-vessel coronary artery disease under medical treatment. Coronary angiography was performed 2 years ago. Percutaneous coronary artery angioplasty was not feasible due to the complexity of the atheromatic lesions and the patient refused any surgical treatment. Six months prior to this hospitalization, he had undergone uncomplicated generator replacement due to battery depletion. On admission, the patient was afebrile with a heart rate of 60 b.p.m. and blood pressure 120/65 mmHg. The ECG showed pacing rhythm, and he was pacemaker-dependent. Physical examination of the heart, lung, and abdomen revealed no abnormalities and there were no signs of localized infection at the pacemaker pocket site.

On admission, the patient was afebrile with a heart rate of 60 b.p.m. and blood pressure 120/65 mmHg. The ECG showed pacing rhythm, and he was pacemaker-dependent. Physical examination of the heart, lung, and abdomen revealed no abnormalities and there were no signs of localized infection at the pacemaker pocket site. Biochemical examinations (red and white blood cells count, C-reactive protein and erythrocyte sedimentation rate, liver function tests, thyroid function tests, urine analysis, and plasma markers of coagulation) were within normal range. The interrogation of the device revealed normal findings. The TTE showed the left and right ventricle within normal size and contractility range. The apical four chamber view (Figure 1A and B) revealed clearly two mobile masses (32 mm and 19 mm long) with a common stem, of low echogenicity and elliptic shape, attached to the ventricular lead of the pacemaker, prolapsing through the tricuspid valve in systole (ventricular lead type: Medtronic 4043–58, passive fixation, bipolar). Contrast-enhanced chest and computed tomography showed a pulmonary infarct in the right upper lobe. A Doppler study of the upper and lower extremity veins did not show any thrombi. Figure 1 First hospitalization: transthoracic echocardiogram apical four-chambers view: (A) two masses with a common stem (arrows) attached to the pacemaker lead, (B) prolapsing through tricuspid valve at systole, and (C) 1 month after 1st hospitalization, no mass was detected.

The TTE showed the left and right ventricle within normal size and contractility range. The apical four chamber view (Figure 1A and B) revealed clearly two mobile masses (32 mm and 19 mm long) with a common stem, of low echogenicity and elliptic shape, attached to the ventricular lead of the pacemaker, prolapsing through the tricuspid valve in systole (ventricular lead type: Medtronic 4043–58, passive fixation, bipolar). Contrast-enhanced chest and computed tomography showed a pulmonary infarct in the right upper lobe. A Doppler study of the upper and lower extremity veins did not show any thrombi. Figure 1 First hospitalization: transthoracic echocardiogram apical four-chambers view: (A) two masses with a common stem (arrows) attached to the pacemaker lead, (B) prolapsing through tricuspid valve at systole, and (C) 1 month after 1st hospitalization, no mass was detected. The patient was held on low molecular heparin (LMWH). Three sets of blood cultures and urine culture were negative. The patient remained in-hospital for a close echocardiographic follow-up and for the final identification of all blood cultures. Ten days after his admission, he presented low grade fever up to 37.5°C, normal white blood cell count and C-reactive protein at 70 mg/L (normal range <3 mg/L). A positive urine culture of Escherichia coli was detected. After 2 weeks of antimicrobial treatment (ciprofloxacin 200 mg bid) and under LMWH the patient was afebrile, with normal inflammatory markers and small decrease of the size of the cardiac masses in the TTE.

C-reactive protein at 70 mg/L (normal range <3 mg/L). A positive urine culture of Escherichia coli was detected. After 2 weeks of antimicrobial treatment (ciprofloxacin 200 mg bid) and under LMWH the patient was afebrile, with normal inflammatory markers and small decrease of the size of the cardiac masses in the TTE. The patient was discharged on acenocoumarol. A TTE after 1 month did not visualize the cardiac masses (Figure 1C). Acenocoumarol with a goal INR of 2.0–2.5 was recommended to be continued for an additional 3 month period. After discontinuation of acenocoumarol, the patient received aspirin 100 mg daily, due to the coexisting coronary artery disease. The patient did not receive any other anticoagulant or antiplatelet therapy and did not attend any other scheduled follow-up appointments. Over 2 years after his 1st admission, the patient, without anticoaguland therapy anymore, was readmitted to our clinic due to a 7-day history of fever up to 38.5°C. Once more, physical examination revealed no signs of localized infection.

The patient did not receive any other anticoagulant or antiplatelet therapy and did not attend any other scheduled follow-up appointments. Over 2 years after his 1st admission, the patient, without anticoaguland therapy anymore, was readmitted to our clinic due to a 7-day history of fever up to 38.5°C. Once more, physical examination revealed no signs of localized infection. The TTE revealed two new vegetation-like masses, possibly attached to the same site of the ventricular lead. Transoesophageal echocardiogram (TOE) confirmed clearly the existence of the masses approximately of the same size as in the 1st hospitalization and their attachment to the pacemaker lead (Figure 2). Once more, most of the biochemical examinations (red blood cells count, erythrocyte sedimentation rate, liver function tests, thyroid function tests, urine analysis, and plasma markers of coagulation) were within normal range, with only slight elevation of white blood cells count [11 000/μL (normal range 4000–9000/μL), 76% PMN (normal range 50–80%), and C-reactive protein (23 mg/L)]. Two out of five blood cultures yielded Staphylococcus epidermidis. Contrast-enhanced chest computed tomography showed no pulmonary infarcts. The patient was held on vancomycin 2 g daily and meropenem 1 g daily, combined with LMWH (enoxaparin 60 mg bid). Differential diagnosis between contaminated thrombus and vegetation was challenging. However, 18F-FDG PET/CT scan, which was performed 2 days after admission, demonstrated increased uptake of 18F-FDG in the outer part of the middle pulmonary lobe and in the sigmoid colon (Figure 3). The diagnosis of vegetation was excluded and lead thrombosis was confirmed once more (relapse). Antibiotics were discontinued. A sigmoidoscopy was performed, which revealed polyposis of the sigmoid colon. Endoscopic polypectomy was performed one month afterwards. At that time, the TOE echocardiogram revealed total resolution of the masses (Figure 2B).

xcluded and lead thrombosis was confirmed once more (relapse). Antibiotics were discontinued. A sigmoidoscopy was performed, which revealed polyposis of the sigmoid colon. Endoscopic polypectomy was performed one month afterwards. At that time, the TOE echocardiogram revealed total resolution of the masses (Figure 2B). Figure 2 Second hospitalization: transoesophageal echocardiogram: (A) mid-oesophageal five-chamber view showing the masses attached to the ventricular lead (arrow) prolapsing in the right atrium at systole, (B1) modified mid-oesophageal short-axis view showing the two leads (arrows) and the masses attached to the ventricular lead, (B2) modified mid-oesophageal bicaval view showing the lead through superior vena cava and the two masses with a common stem (wide arrow) in the right atrium, and (C) transthoracic echocardiogram apical four-chambers view showing the ventricular lead without the masses (arrows) after anticoagulant treatment. Figure 3 Second hospitalization: Single – Photon Emission Computed Tomography (SPECT) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography showing increase uptake (A) in the outer part of the middle pulmonary lobe and (B) in sigmoid colon. Since then, the patient remains asymptomatic on acenocoumarol therapy with a goal INR of 2.0 – 2.5, with no detectable intracardiac masses in a follow-up TTE, 6 months after his 2nd hospitalization. Repeated device interrogation did not detect any dysfunction. Of note, no atrial tachyarrhythmia was ever detected.

Figure 3 Second hospitalization: Single – Photon Emission Computed Tomography (SPECT) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography showing increase uptake (A) in the outer part of the middle pulmonary lobe and (B) in sigmoid colon. Since then, the patient remains asymptomatic on acenocoumarol therapy with a goal INR of 2.0 – 2.5, with no detectable intracardiac masses in a follow-up TTE, 6 months after his 2nd hospitalization. Repeated device interrogation did not detect any dysfunction. Of note, no atrial tachyarrhythmia was ever detected. Discussion Lead-associated thrombosis in patients with cardiac implantable devices is considered uncommon. In a recent study, the incidence was 1, 4% among 1086 such patients, who underwent TTE.4 The TOE can visualize better the route of the leads in the right atrium and the superior vena cava.

Since then, the patient remains asymptomatic on acenocoumarol therapy with a goal INR of 2.0 – 2.5, with no detectable intracardiac masses in a follow-up TTE, 6 months after his 2nd hospitalization. Repeated device interrogation did not detect any dysfunction. Of note, no atrial tachyarrhythmia was ever detected. Discussion Lead-associated thrombosis in patients with cardiac implantable devices is considered uncommon. In a recent study, the incidence was 1, 4% among 1086 such patients, who underwent TTE.4 The TOE can visualize better the route of the leads in the right atrium and the superior vena cava. The aetiology of lead thrombosis is still ambiguous. Thrombus formation on the intra-vein course of pacemaker leads may be based on a foreign-body type reaction, followed by inflammation and fibrosis.5 Several thrombus formation risk-factors have been reported, such as heart failure, atrial fibrillation, coagulopathies, thrombocytopenia, polycythaemia, and silicone pacemaker leads.6–9 Thrombus attached to pacemaker leads maybe asymptomatic or presented with various symptoms such as acute congestive heart failure, shock, chest pain, malaise, cyanosis, and fever.10–13 In several studies, the incidence of symptomatic pulmonary embolism in patients with lead thrombosis was quite low (0–5%), while asymptomatic or subclinical PE was found up to 48%.14 In our patient, lead masses were detected in both cases by TTE, due to their large size and the limited shadowing artefact of the pacemaker leads.

The aetiology of lead thrombosis is still ambiguous. Thrombus formation on the intra-vein course of pacemaker leads may be based on a foreign-body type reaction, followed by inflammation and fibrosis.5 Several thrombus formation risk-factors have been reported, such as heart failure, atrial fibrillation, coagulopathies, thrombocytopenia, polycythaemia, and silicone pacemaker leads.6–9 Thrombus attached to pacemaker leads maybe asymptomatic or presented with various symptoms such as acute congestive heart failure, shock, chest pain, malaise, cyanosis, and fever.10–13 In several studies, the incidence of symptomatic pulmonary embolism in patients with lead thrombosis was quite low (0–5%), while asymptomatic or subclinical PE was found up to 48%.14 In our patient, lead masses were detected in both cases by TTE, due to their large size and the limited shadowing artefact of the pacemaker leads. Transoesophageal echocardiogram did not contribute further to differential diagnosis. The clinical course under anticoagulation provided the definite diagnosis of lead thrombosis (mass disintegration without complications—therapeutic criterion). The re-detection of similar lead-attached masses after 2 years, is quite remarkable (reformation may have occurred quite earlier than detection time). During 2nd hospitalization the clinical suspicion for pacemaker-lead infection was high. Diagnosis was challenging once more.

thout complications—therapeutic criterion). The re-detection of similar lead-attached masses after 2 years, is quite remarkable (reformation may have occurred quite earlier than detection time). During 2nd hospitalization the clinical suspicion for pacemaker-lead infection was high. Diagnosis was challenging once more. Meanwhile, revised ESC guidelines of infective endocarditis15 demonstrated that 18F-FDG PET/CT is a strong additive diagnostic tool in cases of <possible> endocarditis of prosthetic valves. Regarding IE of pacemaker and defibrillation leads, 18F-FDG PET/CT was not included in the diagnostic criteria due to insufficient data. In our patient, 18F-FDG PET/CT was the only remained diagnostic tool and successfully excluded the presence of inflammatory lead vegetation. The administration of antibiotics for only 2 days before PET should not reduce the diagnostic accuracy of 18F-FDG PET/CT scan, as it is well known that infective endocarditis with large vegetations is a severe infection, requiring a quite long period of treatment with antibiotics (or even surgical treatment). In agreement with the above point of view, the benign clinical course of the 2nd hospitalization totally excludes the possibility of a false negative 18F-FDG PET/CT scan. Nevertheless, the finding of lung uptake for FDG cannot be interpreted reliably. Except advanced age, there were no other apparent provocable cause of that recurrent thrombosis.

Regarding IE of pacemaker and defibrillation leads, 18F-FDG PET/CT was not included in the diagnostic criteria due to insufficient data. In our patient, 18F-FDG PET/CT was the only remained diagnostic tool and successfully excluded the presence of inflammatory lead vegetation. The administration of antibiotics for only 2 days before PET should not reduce the diagnostic accuracy of 18F-FDG PET/CT scan, as it is well known that infective endocarditis with large vegetations is a severe infection, requiring a quite long period of treatment with antibiotics (or even surgical treatment). In agreement with the above point of view, the benign clinical course of the 2nd hospitalization totally excludes the possibility of a false negative 18F-FDG PET/CT scan. Nevertheless, the finding of lung uptake for FDG cannot be interpreted reliably. Except advanced age, there were no other apparent provocable cause of that recurrent thrombosis. In conclusion, this report shows that (i) pacemaker-lead thrombosis, mainly asymptomatic, may be detected by echocardiography a long time after implantation of a permanent pacemaker, (ii) lead thrombosis may also relapse, after initial but no continued anticoagulant therapy, and (iii) The 18F-FDG PET/CT is a useful technique to confirm or exclude the inflammatory cause of a mass attached to the pacemaker lead. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online.

In conclusion, this report shows that (i) pacemaker-lead thrombosis, mainly asymptomatic, may be detected by echocardiography a long time after implantation of a permanent pacemaker, (ii) lead thrombosis may also relapse, after initial but no continued anticoagulant therapy, and (iii) The 18F-FDG PET/CT is a useful technique to confirm or exclude the inflammatory cause of a mass attached to the pacemaker lead. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material Supplementary Video S1 Click here for additional data file.

Learning points Cardiac Sarcoidosis caused non-ischaemic tethering mitral regurgitation (MR). Endocardial linear infarct exclusion technique (ELIET) is useful for treating tethering MR. Endocardial linear infarct exclusion technique shortens the papillary muscle length, which improved tethering of the mitral leaflet. Beyond resolving left ventricle enlargement between the papillary muscles that was caused by the aneurysm of the posterior wall. Introduction Cardiac sarcoidosis involves focal myocardial injury.1 When it develops in the posterolateral wall of the heart, the patient often presents with severe tethering mitral regurgitation (MR).1 Herein, we report the case of a patient with cardiac sarcoidosis with severe functional MR and dyskinesis of the posterior wall that was treated successfully using the endocardial linear infarct exclusion technique (ELIET).

wall of the heart, the patient often presents with severe tethering mitral regurgitation (MR).1 Herein, we report the case of a patient with cardiac sarcoidosis with severe functional MR and dyskinesis of the posterior wall that was treated successfully using the endocardial linear infarct exclusion technique (ELIET). Timeline 12/10/2016 Patient became aware of dyspnoea 1/30/2017 Patient became aware of pretibial pitting oedema 2/1/2017 Patient was admitted to our hospital and diagnosed with congestive heart failure (B-type natriuretic peptide (BNP): 1141 pg/mL) 3/10/2017 Patient’s condition worsened (BNP: 2601 pg/mL) and patient was hospitalized. 4/18/2017 We performed precise examinations and diagnosed with cardiac sarcoidosis 4/24/2017 Operation was performed 5/11/2017 Discharge 12/8/2017 Latest follow-up echocardiography (BNP: 291 pg/mL) Case presentation A 63-year-old woman with a history of hypertension, hyperuricaemia, and uveitis presented to our hospital complaining of dyspnoea upon exertion (NYHA Class II). We heard coarse crackling in both lungs, and systolic murmur of the Levine IV/VI within the apex. Mild pitting oedema was detected on both legs. Laboratory tests indicated an elevated B-type natriuretic peptide (BNP) value of 2601 pg/mL (normal < 18.4 pg/mL). A chest X-ray showed a 62% increase in the cardiothoracic ratio (normal < 50%).

ckling in both lungs, and systolic murmur of the Levine IV/VI within the apex. Mild pitting oedema was detected on both legs. Laboratory tests indicated an elevated B-type natriuretic peptide (BNP) value of 2601 pg/mL (normal < 18.4 pg/mL). A chest X-ray showed a 62% increase in the cardiothoracic ratio (normal < 50%). Transthoracic echocardiography showed dyskinesis of the posterior wall of the left ventricle (LV) accompanied by thinning. The left chamber diameter was increased [LV diastolic diameter (normal 30–50 mm), 66 mm; LV systolic diameter (normal 20–30 mm), 51 mm] and the LV ejection fraction (LVEF) (normal 55–80%) was reduced to 33.5%. A transoesophageal echocardiogram (TOE) revealed that contraction of the posterior wall caused significant tethering of P2, thereby resulting in severe functional MR. (Figure 1D). The regurgitate volume was 92 mL (severe: >60 mL) (Figure 1A–C). Figure 1 Echocardiac data; (A, B) Transthoracic echocardiography showed dyskinesis of the posterior wall of the left ventricle accompanied by thinning. (C) The expansion of the annulus caused by the enlargement of the left ventricle, also merged the effective regurgitant orifice of 0.71 cm2. (D) Transoesophageal echocardiogram revealed that contraction of the posterior wall caused significant tethering of P2, resulting in severe functional mitral regurgitation. (D) The regurgitant volume was 92 mL.

s caused by the enlargement of the left ventricle, also merged the effective regurgitant orifice of 0.71 cm2. (D) Transoesophageal echocardiogram revealed that contraction of the posterior wall caused significant tethering of P2, resulting in severe functional mitral regurgitation. (D) The regurgitant volume was 92 mL. Computed tomography (CT) and magnetic resonance imaging with late gadolinium enhancement revealed contrast effect and thinning of the posterior wall (Figure 2), thereby suggesting that it was not viable. The abnormal accumulation was also observed on fluorodeoxyglucose-positron emission tomography (Figure 2B). We suspected cardiac sarcoidosis due to the presence of wall motion abnormalities that were confined to portions of the LV. The patient’s uveitis was confirmed to be iris adhesions, which is the characteristic ocular lesion of sarcoidosis. Coronary angiography was performed to exclude ischaemic heart disease, and no significant stenosis was detected. The patient experienced a period of heart failure, during which her BNP increased to 2601 pg/mL (normal < 18.4 pg/mL). This patient had moderate TR (TR pressure gradient 49 mmHg) associated with mild right heart failure [TAPSE (normal > 16 mm): 14 mm; FAC (normal > 35%): 32% with accompanying tricuspid valve annulus expansion (47 mm)], such that intervention was necessary. Pre-operative cardiac catheter data after heart failure treatment using a diuretic was as follows: Pulmonary artery (PA) (normal 15–30/3–12 mmHg): 33/12 (20) mmHg; Right ventricle (RV) (normal 15–30/2–8 mmHg): 34/1 (3) mmHg; Right Atrium (RA) (normal 2–8 mmHg): 5/2 (2) mmHg; pulmonary capillary wedge pressure (normal 2–15 mmHg): 6/6 (5) mmHg.

theter data after heart failure treatment using a diuretic was as follows: Pulmonary artery (PA) (normal 15–30/3–12 mmHg): 33/12 (20) mmHg; Right ventricle (RV) (normal 15–30/2–8 mmHg): 34/1 (3) mmHg; Right Atrium (RA) (normal 2–8 mmHg): 5/2 (2) mmHg; pulmonary capillary wedge pressure (normal 2–15 mmHg): 6/6 (5) mmHg. Figure 2 Computed tomography and magnetic resonance imaging. (A) Revealed contrast effect and thinning of the posterior wall. (B) The abnormal accumulation was also observed on fluorodeoxyglucose-positron emission tomography. (C) Computed tomography after endocardial linear infarct exclusion technique; post-operative computed tomography scans can indicate the efficacy of linear aneurysm resection compared to Dor-plasty, since the sphericity index was decreased from 0.75 to 0.61. (D) Magnetic resonance imaging with late gadolinium enhancement revealed contrast effect and thinning of the posterior wall suggesting it was not viable. The surgery was performed using ELIET, mitral annuloplasty, tricuspid annuloplasty, and the MAZE procedure. Initially, an incision was made in the LV at the centre of the scar area along the coronary artery. The first layer was linearly closed with 3-0 polypropylene continuous sutures to approximate the border between the normal and infarcted myocardium. The second layer was closed with a combination of interrupted and continuous sutures (Figure 3). The cardiopulmonary bypass time was 273 min, and the aortic cross clamp time was 132 min.

was linearly closed with 3-0 polypropylene continuous sutures to approximate the border between the normal and infarcted myocardium. The second layer was closed with a combination of interrupted and continuous sutures (Figure 3). The cardiopulmonary bypass time was 273 min, and the aortic cross clamp time was 132 min. Figure 3 Surgical procedure of endocardial linear infarct exclusion technique; (A, B) Initially, an incision was made in the left ventricle at the centre of the scar area along the coronary artery. (C) The first layer was linearly closed with 3-0 polypropylene continuous sutures to approximate the border between the normal and infarcted myocardium. (D) The second layer was closed with a combination of interrupted and continuous sutures. (E) Schematic diagram of endocardial linear infarct exclusion technique seen in left ventricular short axis cross section. Histopathological analysis of the resected posterior wall myocardium revealed thinning of the endocardium, replacement fibrosis, lymphocyte infiltration, and epithelialization (Figure 4A). CD68 staining was positive (Figure 4B). Together, these findings are consistent with sarcoidosis. An echocardiogram taken 6 months after surgery revealed reversal of remodelling and a disappearance of the tethering. There was no recurrence of MR and no signs of heart failure.

tration, and epithelialization (Figure 4A). CD68 staining was positive (Figure 4B). Together, these findings are consistent with sarcoidosis. An echocardiogram taken 6 months after surgery revealed reversal of remodelling and a disappearance of the tethering. There was no recurrence of MR and no signs of heart failure. Figure 4 Histopathological analysis of the resected posterior wall myocardium revealed thinning of the endocardium, replacement fibrosis, lymphocyte infiltration, and epithelialization (haematoxylin and eosin staining) ×40 (A). CD68 staining was positive ×400 (B). In the TOE, the pre-tenting height/PL angle was 13 mm/56°, which was reduced to 10.2 mm/23° post-operatively. These data showed improvements in tethering. Additionally, MR had not recurred during the 6 months of follow-up. Additionally, post-operative CT scans can indicate the efficacy of linear aneurysm resection compared to Dor-plasty, since the sphericity index was decreased from 0.75 to 0.61 (normal 0.45–0.62) (Figure 2C). There were no post-operative complications or symptoms of heart failure. Since this patient did not have a diagnosis of sarcoidosis before being admitted to our hospital, there was no history of relevant medical treatment before surgery. Corticosteroid treatment has been used as a therapeutic option for patients with cardiac sarcoidosis, and the initiation of corticosteroid therapy before systolic dysfunction develops produces excellent clinical outcomes.1 Thus, prednisolone therapy was performed post-operatively in this case.

treatment before surgery. Corticosteroid treatment has been used as a therapeutic option for patients with cardiac sarcoidosis, and the initiation of corticosteroid therapy before systolic dysfunction develops produces excellent clinical outcomes.1 Thus, prednisolone therapy was performed post-operatively in this case. Discussion In functional MR, there is no conclusive evidence that mitral valve intervention was associated with a survival benefit.2 When mitral annuloplasty with downsizing was performed, it was reported that tethering of the posterior leaflet was reinforced and MR recurred.3,4 Therefore, in the American Heart Association guidelines, chordal-sparing mitral valve replacement (MVR) is recommended for patients with severe disease (NYHA Class III or above). However, valve replacement carries the risk of rupturing the LV when its myocardium is thin.5 Moreover, this does not indicate that MVR is more suitable than the subvalvular procedure for repairing mitral valve prolapse. Several studies describing the use of the subvalvular procedure with good results have been described.6 Myocardial infarction of the posterior wall of the LV causes the myocardium between the mitral valve annulus and papillary muscle attachment on the posterior wall of the LV to become thin and expand, thereby resulting in ischaemic MR, for which left surgical ventricular reconstruction (SVR) of the LV posterior wall is the most effective treatment.7 Yaku et al.8 developed a novel method of surgical ventricular restoration for an infarcted posterolateral wall. The left ventricular lumen morphology affects wall stress (i.e. wall stress decreases as the lumen elongates and becomes larger, thereby closely approximating a spherical shape).9,10 A study of dilated cardiomyopathy, which is essentially an enlarged lumen, demonstrated that the left ventricular cavity also becomes spherical in shape. It has been reported that contractility decreases with such changes to lumen morphology, as lumen morphology is related to wall stress and cardiac function.11–13

9,10 A study of dilated cardiomyopathy, which is essentially an enlarged lumen, demonstrated that the left ventricular cavity also becomes spherical in shape. It has been reported that contractility decreases with such changes to lumen morphology, as lumen morphology is related to wall stress and cardiac function.11–13 During Dor-plasty, which is as commonly performed as left ventriculoplasty, the infarct part is incised, and a tobacco suture is constructed on the side of the left ventricular lumen. Once this area is stitched, the left ventricular long axis is shortened after the operation, which decreases the tendency of the ventricle to develop into a spheroid. Table 1 Pre and post-operative echocardiac data Variable Pre- operative Post- operative LVDd (mm) 68.4 55 LVDs (mm) 53.4 40 LVEDVI (mL/m2) 128.4 87.2 LVESVI (mL/m2) 99.2 46.3 Ejection fraction (%) 33.5 54.7 Severity of mitral regurgitation IV I Tethering angle of the posterior leaflet 56 23 Tenting height (mm) 13 10 LV, left ventricular; Dd, end-diastolic diameter; Ds, end-systolic diameter; EDVI, end-diastolic volume index; ESVI, end-systolic volume index; BNP, B-type natriuretic peptide. During the ELIET, which we used in this case, the LV was shortened along the short axis rather than along the long axis by cutting the infarcted part longitudinally and suturing circumferentially. In the original report describing this procedure, the sphericity index increased in both groups, but the rate of increase tended to be larger in the Dor-plasty group than in the ELIET group.14

ong the short axis rather than along the long axis by cutting the infarcted part longitudinally and suturing circumferentially. In the original report describing this procedure, the sphericity index increased in both groups, but the rate of increase tended to be larger in the Dor-plasty group than in the ELIET group.14 In this patient, we speculated that cardiac sarcoidosis caused the LV posterior wall to form an aneurysm, thereby resulting in advanced tethering at the posterior mitral valve cusp and severe functional MR.1 One advantage of ELIET for the posterior all is that it shortens the papillary muscle length, which leads to improved tethering of the mitral leaflet. Beyond resolving LV enlargement between the papillary muscles that was caused by the aneurysm of the posterior wall, the greatest benefit of the ELIET is that the SVR can restore the left ventricular volume and improve tethering. Additionally, by using the ELIET, the LV is incised, but not excised. Therefore, the coronary artery is less likely to be sacrificed. The risk of bleeding is low because ventriculotomy is closed with two layers. Consequently, we can control severe MR with ELIET and mitral annuloplasty with no severe complications. As described herein, the procedure can promote good LV reverse remodelling without the recurrence of heart failure.

kely to be sacrificed. The risk of bleeding is low because ventriculotomy is closed with two layers. Consequently, we can control severe MR with ELIET and mitral annuloplasty with no severe complications. As described herein, the procedure can promote good LV reverse remodelling without the recurrence of heart failure. We successfully treated a case of cardiac sarcoidosis combined with severe functional MR. There are several valuable take-away from this case, including: (i) two key procedures in this operation (i.e. surgical ventricular restoration and the repair of tethering of posterior leaflet); (ii) applying the ELIET to the posterior wall shortens the papillary muscle length, thereby improving tethering of the mitral leaflet; and (iii) SVR and mitral valve plasty are still feasibly and the preferred treatment method, even in challenging and complex cases. Patient perspective The patient was satisfied with her treatment and her only concern was regarding the recurrence of sarcoidosis, for which we prescribed prednisolone. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Takayasu arteritis (TA) has been found to be a more common aetiology for ischaemic heart disease in young patients than other more frequently suspected diagnosis and cardiovascular death secondary to coronary involvement in patients with TA is not rare. Suspicion and stepwise work up allow its diagnosis and proper management. Introduction Large vessel vasculitis (LVV) includes multiple conditions causing inflammation of large arteries, especially the aortic arch and its branches. The two characteristic entities are giant cell arteritis and Takayasu arteritis (TA).1–3 Coronary involvement in LVV can occur in a quarter of patients, and the transmural compromise of the ostia and proximal segments is the most common alteration.2,4–7 Although ischaemic cardiomyopathy is the most common cause of death in the presence of coronary involvement of LVV, acute myocardial infarction is also observed.1,8 However, ischaemic causes of cardiogenic shock tend to be overlooked in younger patients due to the lower incidence of myocardial infarction.9 This report illustrates the case of a young woman that developed cardiogenic shock secondary to coronary involvement of TA. It demonstrates how a thorough approach can help elucidate uncommon causes for cardiogenic shock in young patients. Timeline

Introduction Large vessel vasculitis (LVV) includes multiple conditions causing inflammation of large arteries, especially the aortic arch and its branches. The two characteristic entities are giant cell arteritis and Takayasu arteritis (TA).1–3 Coronary involvement in LVV can occur in a quarter of patients, and the transmural compromise of the ostia and proximal segments is the most common alteration.2,4–7 Although ischaemic cardiomyopathy is the most common cause of death in the presence of coronary involvement of LVV, acute myocardial infarction is also observed.1,8 However, ischaemic causes of cardiogenic shock tend to be overlooked in younger patients due to the lower incidence of myocardial infarction.9 This report illustrates the case of a young woman that developed cardiogenic shock secondary to coronary involvement of TA. It demonstrates how a thorough approach can help elucidate uncommon causes for cardiogenic shock in young patients. Timeline Day Event Day 1 Patient consulted the first time the Emergency Department (ED) for cough and chest pain and was discharged with a diagnosis of acute bronchitis Day 4 Patient consulted the second time to the ED and developed symptoms of cardiogenic shock. Laboratory tests, echocardiography, and chest X-ray were obtained. Transferred to the Coronary Care Unit Day 5 Cardiac magnetic resonance was performed—differential diagnoses of acute myocarditis and takotsubo cardiomyopathy Day 6 (AM) Coronary angiography to confirm the diagnosis showed a critical lesion on the left main coronary artery Day 6 (PM) Surgical pericardial patch graft to restore flow in the left coronary artery Day 10 Repeat echocardiography was performed to assess left ventricular function

arditis and takotsubo cardiomyopathy Day 6 (AM) Coronary angiography to confirm the diagnosis showed a critical lesion on the left main coronary artery Day 6 (PM) Surgical pericardial patch graft to restore flow in the left coronary artery Day 10 Repeat echocardiography was performed to assess left ventricular function Case summary A 33-year-old woman presented to the emergency department with 1 month of asthenia, non-productive bouts of cough, and associated chest pain. She was discharged with no further work up and a diagnosis of acute bronchitis. Three days later she returned with worsening stabbing, non-radiated chest pain described as pleuritic, however, exacerbated on exertion and improved at rest, and associated to exertional and paroxysmal nocturnal dyspnoea. Physical examination revealed blood pressure of 112/64 mmHg, heart rate of 116 b.p.m., respiratory rate of 19 breaths/min, oxygen saturation of 98% on room air, no murmurs, fine bilateral crackles in the lung bases, no abdominal abnormalities, and no lower extremity oedema.

Case summary A 33-year-old woman presented to the emergency department with 1 month of asthenia, non-productive bouts of cough, and associated chest pain. She was discharged with no further work up and a diagnosis of acute bronchitis. Three days later she returned with worsening stabbing, non-radiated chest pain described as pleuritic, however, exacerbated on exertion and improved at rest, and associated to exertional and paroxysmal nocturnal dyspnoea. Physical examination revealed blood pressure of 112/64 mmHg, heart rate of 116 b.p.m., respiratory rate of 19 breaths/min, oxygen saturation of 98% on room air, no murmurs, fine bilateral crackles in the lung bases, no abdominal abnormalities, and no lower extremity oedema. A D-dimer and chest X-ray were normal but the electrocardiogram showed 2-mm ST depression in precordial leads, and a positive delta troponin I-hs increasing from 0.06 to 2.25 ng/mL (0–0.026 ng/mL). Other laboratory results such as C-reactive protein and the erythrocyte sedimentation rate were within normal limits. Transthoracic echocardiography revealed a severely dilated left ventricle (LV) with mid-ventricular, apical dyskinesia, severe compromise of the systolic function, left ventricular ejection fraction (LVEF) of 20%, diastolic dysfunction, severe functional mitral regurgitation, moderate functional tricuspid regurgitation, and an estimated pulmonary systolic arterial pressure of at least 80 mmHg (Figure 1, Supplementary material online, Video S1).

ompromise of the systolic function, left ventricular ejection fraction (LVEF) of 20%, diastolic dysfunction, severe functional mitral regurgitation, moderate functional tricuspid regurgitation, and an estimated pulmonary systolic arterial pressure of at least 80 mmHg (Figure 1, Supplementary material online, Video S1). Figure 1 Transthoracic echocardiography: (A) apical two-chamber during diastole and (B) apical two-chamber during systole. On admission to the Coronary Care Unit, blood pressure was 86/54 mmHg and heart rate was 124 b.p.m., findings consistent with cardiogenic shock. IV norepinephrine was administered for 8 h and then successfully weaned off. The initial work up diagnoses were takotsubo cardiomyopathy (TCM) or acute myocarditis. Therefore, optimal medical therapy was initiated with Enalapril 2.5 mg b.i.d., Spironolactone 25 mg daily (QD), Carvedilol 3.125 mg b.i.d., IV Furosemide 5 mg, and low molecular weight heparin (LMWH). Despite the positive delta troponin, no antiplatelet therapy was initiated due to the non-coronary distribution of the wall motion abnormalities found on echocardiography that led to suspicion of the aforementioned differential diagnoses. The next day a cardiac magnetic resonance (cMRI) revealed mild LV dilatation, and LVEF of 45%, severe segmental contractility abnormalities in the apical and mid-ventricular walls, with normal basal contractility, which resembled the pattern seen in TCM (Figure 2, Supplementary material online, Video S2). However, no myocardial oedema, fibrosis, or scarring was observed.

aled mild LV dilatation, and LVEF of 45%, severe segmental contractility abnormalities in the apical and mid-ventricular walls, with normal basal contractility, which resembled the pattern seen in TCM (Figure 2, Supplementary material online, Video S2). However, no myocardial oedema, fibrosis, or scarring was observed. Figure 2 Cardiac magnetic resonance: (A) two-chamber during diastole and (B) two-chamber during systole. Angiography had not been performed because the troponin elevation was considered to be a leak from the myocarditis, TCM, or heart failure. However, it became necessary to fulfil the diagnostic criteria for TCM and due to the inconclusive results of the cMRI. Results revealed a 99% ostial obstruction in the left main coronary artery with no additional findings (Figure 3). Figure 3 Coronary angiography: right anterior oblique caudal view of left main coronary artery. Red arrow showing critical lesion in the proximal left main coronary artery.

Angiography had not been performed because the troponin elevation was considered to be a leak from the myocarditis, TCM, or heart failure. However, it became necessary to fulfil the diagnostic criteria for TCM and due to the inconclusive results of the cMRI. Results revealed a 99% ostial obstruction in the left main coronary artery with no additional findings (Figure 3). Figure 3 Coronary angiography: right anterior oblique caudal view of left main coronary artery. Red arrow showing critical lesion in the proximal left main coronary artery. After the coronary angiogram, the patient was emergently transferred to the operating room were severe left coronary ostium stenosis without atheroma plaques was encountered. A pericardium patch was used to widen the ostium of the left main coronary artery. Although arterial grafts were a possible treatment approach, the patch was chosen because of the high long-term risk of occlusion and narrowing with venous or arterial grafts due to the patients’ young age. Additionally, a review of the literature suggested the possibility of further inflammation and stenosis at the proximal anastomotic sites of grafts, in the brachiocephalic, subclavian, or internal mammary arteries.10–12 Surgical specimens were analysed by the pathology laboratory and reported vascular wall architecture distorted by fibrosis, lymphoplasmacytic inflammatory infiltrates, and obliterative vasculopathy, compatible with LVV (Figure 4). These findings along with the type of vessels involved and the clinical characteristics of the patient led to a diagnosis of TA.

pathology laboratory and reported vascular wall architecture distorted by fibrosis, lymphoplasmacytic inflammatory infiltrates, and obliterative vasculopathy, compatible with LVV (Figure 4). These findings along with the type of vessels involved and the clinical characteristics of the patient led to a diagnosis of TA. Figure 4 Pathology specimen: vascular wall architecture distorted by fibrosis, lymphoplasmacytic inflammatory infiltrates, and obliterative vasculopahty, with no granulomas, compatible with large vessel vasculitis. After 4 days in the hospital wards receiving prednisone 50 mg QD as primary treatment for TA, and Carvedilol 6.25 mg b.i.d., Enalapril 5 mg b.i.d., Spironolactone 25 mg QD, and dual antiplatelet therapy, she was discharged with complete LV function recovery, and no valvular alterations as shown by transthoracic echocardiography. It was a notable recovery thought to be secondary to ischaemia resolution in the setting of myocardial stunning and lack of scar tissue. Follow-up 2 weeks later with neck, chest, and abdominal computed tomography angiography failed to reveal further vessel compromise, and she denied having chest pain and an improved functional class.

e recovery thought to be secondary to ischaemia resolution in the setting of myocardial stunning and lack of scar tissue. Follow-up 2 weeks later with neck, chest, and abdominal computed tomography angiography failed to reveal further vessel compromise, and she denied having chest pain and an improved functional class. Discussion In TA, the aortic branches are usually compromised in a transmural manner with subsequent stenosis, or obstruction due to thrombus formation, or aneurysmal thrombosis or rupture.8 Symptoms relate to end organ hypo-perfusion, hypertension secondary to renal artery stenosis, pulselessness in upper extremities, and neurological symptoms such as postural dizziness and seizures are common.3,8 Even though the development of cardiogenic shock follows the same principle of end organ hypo-perfusion, its diagnosis is challenging as clinicians are not frequently exposed to it. Additionally, the clinical diagnosis of TA requires further manifestations of symptomatic ischaemia in other vessel groups apart from the arteriographic evidence of narrowing of the aorta or its primary branches.13 Therefore, in a patient with few symptoms, the diagnosis is furthermore complicated as it would require pathologic corroboration of the inflammatory vessel compromise. On the other hand, it is easy to mistakenly minimize symptoms of chest pain in young patients and discharge them without further evaluation. In this case, an ischaemic cause was not initially suspected, and work up was more compatible with myocarditis or TCM.

Discussion In TA, the aortic branches are usually compromised in a transmural manner with subsequent stenosis, or obstruction due to thrombus formation, or aneurysmal thrombosis or rupture.8 Symptoms relate to end organ hypo-perfusion, hypertension secondary to renal artery stenosis, pulselessness in upper extremities, and neurological symptoms such as postural dizziness and seizures are common.3,8 Even though the development of cardiogenic shock follows the same principle of end organ hypo-perfusion, its diagnosis is challenging as clinicians are not frequently exposed to it. Additionally, the clinical diagnosis of TA requires further manifestations of symptomatic ischaemia in other vessel groups apart from the arteriographic evidence of narrowing of the aorta or its primary branches.13 Therefore, in a patient with few symptoms, the diagnosis is furthermore complicated as it would require pathologic corroboration of the inflammatory vessel compromise. On the other hand, it is easy to mistakenly minimize symptoms of chest pain in young patients and discharge them without further evaluation. In this case, an ischaemic cause was not initially suspected, and work up was more compatible with myocarditis or TCM. Nonetheless, a study of 40 young female patients presenting with ischaemic heart disease, revealed that 10% were diagnosed with TA.14 This proportion was higher than that of other diagnoses such as vasospastic angina, drug abuse, aortic dissection, and TCM. This finding brings attention to TA as a differential diagnosis of ischaemic heart disease, that is easily overlooked as the other aetiologies are thought to be more common.

e diagnosed with TA.14 This proportion was higher than that of other diagnoses such as vasospastic angina, drug abuse, aortic dissection, and TCM. This finding brings attention to TA as a differential diagnosis of ischaemic heart disease, that is easily overlooked as the other aetiologies are thought to be more common. Furthermore, a series in China revealed that 7.7% of the patients with TA had coronary involvement, concluding that cardiovascular death secondary to coronary involvement is not rare.15 Taking this into account, clinicians should keep TA as a possible differential diagnosis in young women presenting with chest pain. The approach to these patients requires a stepwise work up with different imaging modalities, coronary, and aortic angiography. Following these steps allowed the team to diagnose a non-suspected aetiology of a severe left main coronary artery lesion in a young patient. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material Supplementary Video 1 Click here for additional data file. Supplementary Video 2 Click here for additional data file.

Learning points Expert radiographic review of patients with implanted cardiac devices is important. The lateral chest radiograph is especially informative on the course of the leads. In this case, if the lateral film was done earlier, it would have led to the earlier discovery of lead misplacement. Expert electrocardiographic review of patients with supposed bi-ventricular pacing is important to identify any cardiac device problems. In this case, the initial telemetry review identified an unusual bi-ventricular paced QRS morphology, which eventually led to the discovery of the left ventricular lead misplacement. Introduction Cardiac resynchronization therapy (CRT) is an integral part of heart failure management in the appropriate setting.1 Left ventricular (LV) lead placement into the coronary sinus (CS) is generally considered to be safe, with a high success rate at first procedural attempt. Chronic lead misplacement is rare.2 Timeline

The following day, a CS venogram revealed a CS that was intact and confirmed that the LV lead did not pass through any part of the coronary venous system (Figure 3). Figure 3 A coronary sinus venogram using AL2 diagnostic catheter via right femoral vein. The coronary sinus is intact with good lateral branches and confirms that the ‘left ventricular lead’ is not in the coronary sinus but embedded in the RV myocardium. A review of a computerized tomography performed 3 years earlier (for a non-cardiac indication) showed that the lead was embedded in the right ventricular myocardium, breaching into the pericardium (Figure 4), an abnormality that had not been recognized by the reporting radiologist. It is possible then, that the misplaced LV lead is the cause of the chronic pericardial effusion. On serial echocardiographic imaging, the pericardial effusion had never been significant enough to require pericardiocentesis; it measured 0.9 cm anteriorly around the RV and 1.3 cm posteriorly. Figure 4 Reconstructed computed tomography images revealing coronary sinus lead partial perforation into the pericardial layers and consequential chronic pericardial effusion (0.8 cm anteriorly and 1.3 cm posteriorly). The original implantation report revealed that the procedure was undertaken in an elective surrounding and no particular difficulty was documented. The LV lead was a Guidant 4555 Acuity Spiral® IS1 BI (Boston Scientific).

Introduction Cardiac resynchronization therapy (CRT) is an integral part of heart failure management in the appropriate setting.1 Left ventricular (LV) lead placement into the coronary sinus (CS) is generally considered to be safe, with a high success rate at first procedural attempt. Chronic lead misplacement is rare.2 Timeline Time Events 2008 Elective implantation of cardiac resynchronization therapy-defibrillator at another cardiac centre for non-ischaemic dilated cardiomyopathy and left bundle branch block. Current admission Day 1 Acute admission to the heart failure unit with decompensated heart failure. Day 2 Pacing check 97% ‘bi-ventricular’ pacing. Day 4 Consultant electrophysiologist review of patient case, following observation of the unusual BiV-paced QRS morphology on patient telemetry. Chest radiograph review in AP and lateral views: the lateral film showed the left ventricular (LV) lead not going into the coronary sinus (CS). CT thorax from a few years earlier was reviewed which seemed to also show abnormal course of the CS lead, into the RV myocardium. Day 5 A CS venogram confirming misplacement of the LV lead. (episode of pyrexia delayed plans for new LV lead placement). Day 20 Further deterioration continued despite treatment. The deterioration was gradual prior to rapid development of cardiogenic shock and multi-organ failure. The patient was also being treated for Gram negative cocci bacteraemia. Day 21 Admission to the intensive care unit for inotropic support and haemofiltration for related acute renal failure with hyperkalaemia. Day 28 RIP.

deterioration was gradual prior to rapid development of cardiogenic shock and multi-organ failure. The patient was also being treated for Gram negative cocci bacteraemia. Day 21 Admission to the intensive care unit for inotropic support and haemofiltration for related acute renal failure with hyperkalaemia. Day 28 RIP. Case summary A 73-year-old lady was admitted from home directly to the heart failure unit with symptoms of gradually worsening breathlessness, over a duration of 4 weeks. The patient had a background of non-ischaemic dilated cardiomyopathy, chronic pericardial effusion of unknown aetiology, severe LV systolic impairment (ejection fraction <35%), and left bundle branch block. She had CRT-defibrillator implantation at another cardiac centre in 2008. Regular medications included Bumetanide, Carvedilol, and weekly Metolazone. Prior to admission, there had been unsuccessful attempts at offloading by the Community Heart Failure Team.

irment (ejection fraction <35%), and left bundle branch block. She had CRT-defibrillator implantation at another cardiac centre in 2008. Regular medications included Bumetanide, Carvedilol, and weekly Metolazone. Prior to admission, there had been unsuccessful attempts at offloading by the Community Heart Failure Team. Clinical examination revealed tachypnoea at rest and coarse crepitations. On auscultation of the heart sounds there were pansystolic murmurs audible at both the lower left sternal edge and at the apex in keeping with tricuspid and mitral regurgitation. The jugular venous pulse was raised at >5 cmH20 and there was bilateral pitting oedema above the knee levels. Vital signs were measured: Blood pressure 101/67 mmHg, heart rate 80 b.p.m. and oxygen saturations at 97% on room air. Acute management of heart failure was initially with administration of intravenous furosemide (240 mg/24 h infusion). Over time, there was clear resistance to treatment despite escalation in management. A transthoracic echocardiogram showed that the LV systolic function had further deteriorated, with an ejection fraction of 10–15%, with no change in the size of the pericardial effusion (0.8–1.3 cm, anteriorly and posteriorly) and no associated haemodynamic impact. There was severe tricuspid and mitral regurgitation; this was a longstanding finding.

showed that the LV systolic function had further deteriorated, with an ejection fraction of 10–15%, with no change in the size of the pericardial effusion (0.8–1.3 cm, anteriorly and posteriorly) and no associated haemodynamic impact. There was severe tricuspid and mitral regurgitation; this was a longstanding finding. A device check showed apparent 97% bi-ventricular pacing with satisfactory parameters. The device was Boston Scientific, set at VVIR at base rate of 80. The right atrial lead sensing was at 0.3 mV and impedance was at 513 Ohms. There was underlying atrial fibrillation. The right ventricle (RV) lead sensing was at 14.1 mV, impedance at 884 Ohms, and the threshold was 1.3 V at 0.4 ms. The LV lead sensing was at 16.4 mV, impedance was 884 Ohms, and the threshold was 2.2 V at 1 ms. During the electrophysiology team ward round, a telemetry review led to focus on this particular patient. The paced QRS morphology was atypical for bi-ventricular pacing. Electrocardiogram (ECG) during supposed bi-ventricular pacing showed a QRS duration of 174 ms in a right bundle branch block pattern. The intrinsic QRS duration was 196 ms (Figure 1). A postero-anterior chest radiograph was compatible with a satisfactory LV lead position but the lateral film showed clear malposition (Figure 2). Figure 1 Rhythm strip comparing QRS pattern and duration during bi-ventricular pacing and with intrinsic rhythm. Figure 2 AP and lateral chest radiographs. The ‘left ventricular lead’ is situated, coiled into RV myocardium, close to the epicardial surface.

During the electrophysiology team ward round, a telemetry review led to focus on this particular patient. The paced QRS morphology was atypical for bi-ventricular pacing. Electrocardiogram (ECG) during supposed bi-ventricular pacing showed a QRS duration of 174 ms in a right bundle branch block pattern. The intrinsic QRS duration was 196 ms (Figure 1). A postero-anterior chest radiograph was compatible with a satisfactory LV lead position but the lateral film showed clear malposition (Figure 2). Figure 1 Rhythm strip comparing QRS pattern and duration during bi-ventricular pacing and with intrinsic rhythm. Figure 2 AP and lateral chest radiographs. The ‘left ventricular lead’ is situated, coiled into RV myocardium, close to the epicardial surface. The following day, a CS venogram revealed a CS that was intact and confirmed that the LV lead did not pass through any part of the coronary venous system (Figure 3). Figure 3 A coronary sinus venogram using AL2 diagnostic catheter via right femoral vein. The coronary sinus is intact with good lateral branches and confirms that the ‘left ventricular lead’ is not in the coronary sinus but embedded in the RV myocardium.

Figure 4 Reconstructed computed tomography images revealing coronary sinus lead partial perforation into the pericardial layers and consequential chronic pericardial effusion (0.8 cm anteriorly and 1.3 cm posteriorly). The original implantation report revealed that the procedure was undertaken in an elective surrounding and no particular difficulty was documented. The LV lead was a Guidant 4555 Acuity Spiral® IS1 BI (Boston Scientific). The patient was scheduled for placement of a new LV lead but the procedure was delayed due to an episode of pyrexia. The plan was to leave the chronically misplaced LV lead in situ as the risk of cardiac perforation and death, with attempted extraction would be extremely high. The patient gradually further deteriorated before a rapid descent into cardiogenic shock. Inotropic support and haemofiltration was given in an intensive care setting. She was also treated for Gram negative cocci bacteraemia. The patient was eventually palliated before her unfortunate but expected death.

The patient was scheduled for placement of a new LV lead but the procedure was delayed due to an episode of pyrexia. The plan was to leave the chronically misplaced LV lead in situ as the risk of cardiac perforation and death, with attempted extraction would be extremely high. The patient gradually further deteriorated before a rapid descent into cardiogenic shock. Inotropic support and haemofiltration was given in an intensive care setting. She was also treated for Gram negative cocci bacteraemia. The patient was eventually palliated before her unfortunate but expected death. Discussion Satisfactory LV lead positions can be obtained via the coronary venous system in >99.8% of patients.3 It is not clear why the mal-positioning occurred or why it was not recognized and corrected. The original device implantation report did not reveal any unusually challenging circumstances. A CS venogram had been undertaken at the time of implant, and it was believed that the LV lead was deployed into a branch of the CS. It is most likely that the lead was misplaced and was somehow not recognized. The AP fluoroscopy projection, alongside a dilated and rotated cardiomyopathic heart would certainly give the false impression that there was satisfactory LV lead placement. In addition, the LV lead parameters have always been satisfactory, giving no cause for a review into the LV lead integrity or position. The other possibility is that the lead had completely displaced later on after implant but this reason is less plausible, given the position of the lead and no recorded interval change in lead appearance from historical imaging.

ays been satisfactory, giving no cause for a review into the LV lead integrity or position. The other possibility is that the lead had completely displaced later on after implant but this reason is less plausible, given the position of the lead and no recorded interval change in lead appearance from historical imaging. The LV lead used was a Guidant 4555 Acuity Spiral®. This lead is not known to be problematic at implant or during follow-up, when compared with similar generation modern LV leads. Steffel et al.,4 conducted a retrospective study of long-term performance of modern CS leads (a range of leads, with implant dates from 2003–10) and found there was macro-displacement in 3.6% of 193 patients, across a median of 111 days. There were no cases of misplacement. Overall, modern leads tend to have a good stability profile at follow-up with low rates of macro or micro displacements.5,6

odern CS leads (a range of leads, with implant dates from 2003–10) and found there was macro-displacement in 3.6% of 193 patients, across a median of 111 days. There were no cases of misplacement. Overall, modern leads tend to have a good stability profile at follow-up with low rates of macro or micro displacements.5,6 It cannot be objectively proven if dual right ventricular pacing actively accelerated the progression of this patient’s heart failure. However, given our knowledge of the potential harm of chronic right ventricular pacing7,8 and the fact that this patient had underlying severe non-ischaemic dilated cardiomyopathy, it is likely that dual right ventricular pacing had contributed to her chronically sub-optimal functional status in addition to worsening cardiac function. Providencia et al.9 recently published a study looking at the possibility of dual-site right ventricular pacing for patients with heart failure, after failure to deliver a CS lead. Earlier reports suggested this alternative possibility.10 The dual RV group had worse clinical outcomes compared to the matched control group with higher rates of all-cause mortality and heart transplantation.

ity of dual-site right ventricular pacing for patients with heart failure, after failure to deliver a CS lead. Earlier reports suggested this alternative possibility.10 The dual RV group had worse clinical outcomes compared to the matched control group with higher rates of all-cause mortality and heart transplantation. In the 10 years that passed, it is only with retrospective review of patient ECG and imaging that we have found that the evidence of LV lead misplacement was there all along but not previously recognized. This patient only had a lateral chest radiograph after we requested this, to confirm the suspicion. Her previous films in the AP or PA projection may have given the false impression of a satisfactory lead position. Cardiac resynchronization therapy optimization clinic assessments did not identify the problem with the LV lead. Conclusion A review of the patient telemetry eventually led to the unexpected discovery of chronic LV lead misplacement. This case illustrated the importance of expert review of radiographic and electrocardiographic data in patients with implanted cardiac devices.11,12 Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the next of kin of the deceased patient has given consent for this anonymised case report to be written and published. Conflict of interest: none declared.

Learning points ICD conductor extrusion can be associated with an increased risk of intracavitary thrombus formation. In such situation, systemic oral anticoagulation can be helpful for both the diagnostic and treatment of the patient. Individual patient profile and wishes should guide the long-term therapy. Introduction Narrow calibre ICD leads have been recalled due to increased risk of insulation failure and cable extrusions.1 Regular fluoroscopic screening of these leads is recommended. But, as long as they remain electrically functional, no prophylactic replacement or extraction is advised.2 However, when an intracavitar thrombus involving externalized conductors is identified, the safest therapeutic approach remains undetermined.

usions.1 Regular fluoroscopic screening of these leads is recommended. But, as long as they remain electrically functional, no prophylactic replacement or extraction is advised.2 However, when an intracavitar thrombus involving externalized conductors is identified, the safest therapeutic approach remains undetermined. Timeline Events 2008 Reanimated of sudden cardiac arrest— diagnostic: VT/VF Primary cardiac disease: Arrhythmogenic right ventricular dysplasia Implantation of SJM Riata lead 2015 Several appropriate ICD therapy Generator change due to battery depletion November 2016 Conductor externalization identified during routine ICD follow-up January 2017 Appropriate ICD therapy for VT TEE/TEO identify a large intracavitary mass where the conductors are externalized Oral AC is started May 2017 TEE check: atrial thrombus has disappeared September 2017 Recurrence of VT appropriately treated Patient under OAC No thrombus recurrence Case presentation A 45-year-old Caucasian man suffering from arythmogenic right ventricular dysplasia, and implanted 8 years earlier with a Saint Jude Medical Riata lead, presented to our emergency department after he received an appropriate therapy for a prolonged episode of slow VT. During his last follow-up (3 months before), an externalization of the conductors at the distal part of the ICD lead was diagnosed, but, the ICD lead remaining electrically functional, the patient was reassured.1 During his stay at the emergency, the physical exam was normal but a transthoracic echocardiography was performed and identified an endocavitary mass appended to the ICD lead. A 3-dimensional transoesophageal echocardiography confirmed the presence of a large irregular right atrial mass (3 × 2 cm) attached to the ICD lead in the right atrium (Figure 1 and Supplementary material online, Video S1), precisely where the fluoroscopic investigation identified the conductor externalization (Figure 2, arrows). The CRP being normal, the primary hypothesis was an endocavitary thrombus and the patient was therefore anticoagulated. After 2 months of treatment with acenocoumarol (Target INR = 3), the atrial mass had completely disappeared, confirming thus the suspected diagnosis. At this stage, the patient was proposed for a transvenous lead extraction with reimplantation of a new high voltage lead. However, he declined and opted for a prolonged anticoagulation.

of treatment with acenocoumarol (Target INR = 3), the atrial mass had completely disappeared, confirming thus the suspected diagnosis. At this stage, the patient was proposed for a transvenous lead extraction with reimplantation of a new high voltage lead. However, he declined and opted for a prolonged anticoagulation. At his last follow-up, 9 months after discharge, an echocardiography was performed, confirming the absence of thrombus recurrence. Figure 1 A 3-dimensional transoesophageal echocardiography showing a large thrombus attached along the ICD lead in the right atrium, precisely where fluoroscopic investigation identified the conductor externalization (see Figure 2). Figure 2 Antero-posterior fluoroscopic examination of the riata lead demonstrating a clear conductor externalization (arrows) in the right atrium.

Figure 1 A 3-dimensional transoesophageal echocardiography showing a large thrombus attached along the ICD lead in the right atrium, precisely where fluoroscopic investigation identified the conductor externalization (see Figure 2). Figure 2 Antero-posterior fluoroscopic examination of the riata lead demonstrating a clear conductor externalization (arrows) in the right atrium. Discussion Although narrow calibre ICD leads with insulation defects and conductor externalization are presumed to increase the thrombogenic risk, very few reports were published to document this specific problem.3,4 In our opinion, this risk should be taken into account in the clinical decision making process to explant or abandon ICD leads with insulation failure. In this case, the ICD lead remaining electrically functional, our patient opted for a long-term anticoagulation. Although it might be suggested that a lead extraction would have been a more definite solution with only a limited risk if performed in experienced centres,5 the risk of thrombus still exists, even with non-advisory leads. Therefore, we believe that individual patient profile and wishes should guide the therapy. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material Supplementary Video S1 Click here for additional data file.

Learning points Myocardial ischaemia due to subclavian artery stenosis is an important alternative diagnosis to coronary artery disease after coronary artery bypass graft. A history of peripheral vascular disease and a blood pressure difference between the upper extremities >15 mmHg are clinical predictors of subclavian artery stenosis. First-line treatment for subclavian stenosis is percutaneous revascularization.

olving mitral valves are often more mobile and found at the leaflet closure line.15 Cardiac masses due to papillary fibroelastomas may mimick vegetations, but they are typically located on the LV side of the valve. In contrast, LSE lesions are more echogenic and can affect any part of the leaflet, predominantly base.13 Figure 3 (A) Mitral valve infectious vegetation most commonly located on atrial coaptation side. (B) Cardiac masses such as papillary fibroelastoma may mimic vegetation, but they are typically located on the left ventricular side of mitral valve. (C) Non-infectious mitral valve vegetations can be variable in shape and size typically smaller than infectious and can affect any part of the leaflets, but with tendency to occur more often near the leaflet base. The incidence of thromboembolic cerebrovascular events in patients with LSE has been reported as 10–20% and a cardio embolic origin was assumed in most cases.12 Roland et al.1 presented the first fully integrated study linking Libman–Sacks vegetations with cerebromicroembolism, cerebral hypoperfusion, ischaemic brain injury, stroke/TIA, neurocognitive dysfunction, and death.

Learning points Myocardial ischaemia due to subclavian artery stenosis is an important alternative diagnosis to coronary artery disease after coronary artery bypass graft. A history of peripheral vascular disease and a blood pressure difference between the upper extremities >15 mmHg are clinical predictors of subclavian artery stenosis. First-line treatment for subclavian stenosis is percutaneous revascularization. Introduction Subclavian artery stenosis occurs up to 4.6% in patients who are referred for a coronary artery bypass graft (CABG).1,2 Subclavian artery stenosis can cause lower pressure distal from the stenosis, compromising blood flow in the ipsilateral mammary artery. In severe left subclavian artery stenosis, upper extremity exertion can result in a coronary subclavian steal syndrome (CSSS) due to retrograde blood flow up the left internal mammary artery (LIMA). After CABG, this condition may result in myocardial ischaemia despite patency of the grafted vessels. Common risk factor for subclavian stenosis is atherosclerosis, while less common causes are large vessel arteritis (i.e. Takayasu disease, giant cell arteritis), fibromuscular dysplasia, radiotherapy, thoracic outlet syndromes, or congenital malformations of the right aortic arch.3–5 We report a case of a patient with previous history of a LIMA to left anterior descending artery (LAD) bypass graft who reported angina. After detection of severe ischaemia on Rubidium-82 positron emission tomography (Rb-82-PET), coronary angiography revealed subclavian artery stenosis as the cause of myocardial ischaemia. Soon afterwards an out-of-hospital cardiac arrest occurred and an emergency coronary angiography was performed.

who reported angina. After detection of severe ischaemia on Rubidium-82 positron emission tomography (Rb-82-PET), coronary angiography revealed subclavian artery stenosis as the cause of myocardial ischaemia. Soon afterwards an out-of-hospital cardiac arrest occurred and an emergency coronary angiography was performed. Timeline Day 1 Patient experiences stable angina, exertional dyspnoea ECG shows signs of left ventricle hypertrophy with strain and ST segment elevation Day 2 Echocardiography revealed dilated left ventricle with hypokinesia of the anterior wall, left ventricular ejection fraction (LVEF) 25% Day 5 Myocardial perfusion [Rubidium-82 positron emission tomography (Rb-82-PET)] revealed anterior wall ischaemia and decreased LVEF 23–20% Day 7 Out-of-hospital cardiac arrest Coronary angiography with ipsilateral (left) subclavian artery stenosis. Percutaneous intervention of subclavian artery Case report A 68-year-old man with a history of coronary artery disease reported stable angina and exertional dyspnoea. Medical history revealed hypertension, endovascular treatment of lower extremity peripheral vascular disease (percutaneous transluminal angioplasty of the left superficial femoral artery), and a two-vessel CABG including a LIMA to the LAD and venous graft aorta-obtuse marginal (aorta-OM) and a percutaneous coronary intervention (PCI) of the left main stem. No hyperlipidaemia, diabetes, or smoking was reported. On physical examination blood pressure was 166/85 mmHg (no bilateral arm measurement was performed), heart rate 90/min. Resting ECG shows signs of left ventricle hypertrophy with strain and increased elevation in V1–V3. Echocardiography showed dilated left ventricle with hypokinesia of the anterior wall, with a decreased left ventricular ejection fraction (LVEF) of 25%. To determine myocardial perfusion, non-invasive imaging using Rb-82 PET was performed, demonstrating extensive ischaemia in the anterior wall (myocardial territory supplied by the LAD) (Figure 1) and decreased LVEF (20% after Regadenoson and 23% in rest). Following the results of the Rb-82 PET, the patient was scheduled for a coronary angiography. An emergency coronary angiography was performed after the patient presented with an out-of-hospital cardiac arrest. Coronary angiography via the right femoral artery was performed showing no stenosis in the LIMA or other coronary arteries (Figure 2).

the Rb-82 PET, the patient was scheduled for a coronary angiography. An emergency coronary angiography was performed after the patient presented with an out-of-hospital cardiac arrest. Coronary angiography via the right femoral artery was performed showing no stenosis in the LIMA or other coronary arteries (Figure 2). However, selective arteriography of the left subclavian artery demonstrated (Figure 3) a plaque that is hazy, ulcerated, and causes a severe stenosis of the proximal part of left subclavian artery. Percutaneous revascularization was performed successfully using an 8.0×39 mm self-expandable bare metal stent (Figure 4). Predilatation was performed using serial balloon inflations of 10 mm and 12 mm. Treatment of the subclavian artery stenosis was enough to restore antegrade perfusion of the LAD territory via the LIMA graft. Figure 1 Rubidium-82 positron emission tomography. The stress study demonstrates a decreased perfusion of the anterior wall, while the rest study showed normal perfusion, indicative of myocardial ischaemia of the left anterior descending artery territory. Figure 2 Angiography demonstrates normal patent grafts (left internal mammary artery-left anterior descending artery, aorta-obtuse marginal). Figure 3 Angiography demonstrates a plaque that is hazy, ulcerated and causes a stenosis of the proximal left subclavian artery (white arrow). Figure 4 Angiography after revascularization with bare metal stent showing restoration of normal flow in the subclavian artery.

Figure 2 Angiography demonstrates normal patent grafts (left internal mammary artery-left anterior descending artery, aorta-obtuse marginal). Figure 3 Angiography demonstrates a plaque that is hazy, ulcerated and causes a stenosis of the proximal left subclavian artery (white arrow). Figure 4 Angiography after revascularization with bare metal stent showing restoration of normal flow in the subclavian artery. After 2-years’ follow-up, patient reported again atypical chest pain and fatigue. Follow-up Rb-82 PET was performed (2 years after percutaneous intervention of the left subclavian artery) showing no myocardial ischaemia (Figure 5) and normalization of left ventricle systolic function (57% after Regadenoson and 52% in rest). Figure 5 Rubidium-82 positron emission tomography. Two-years after bare metal stent of subclavian stenosis demonstrating no myocardial ischaemia.

olysis and valve thrombosis rates were reported as low as 0.10% and 0.06% per patient years, respectively.6 We report a case of a 67-year-old patient who was recently reoperated on for rheumatic mitral and tricuspid valve disease and had a Starr–Edwards aortic valve implanted 51 years earlier with no valve dysfunction. Timeline Year Event 1965 Aortic valve replacement with a Magovern mechanical prosthesis for rheumatic valve disease 1966 Second cardiac procedure: aortic valve replacement with a Starr–Edwards 8A caged-ball prosthesis for Magovern valve dehiscence 1969 Third cardiac procedure: reinsertion of the Starr–Edwards aortic valve for partial prosthesis dehiscence and systematic ball replacement 2009 Atrial fibrillation and ischaemic stroke with aphasia. Complete clinical recovery within 3 months 2016 Hospitalization for pulmonary oedema revealing severe rheumatic mitral valve insufficiency 2017 Fourth cardiac procedure: mitral valve replacement with a Carbomedics mechanical prosthesis associated with tricuspid valve annuloplasty. The 51-year-old Starr–Edwards aortic valve was let intact.

After 2-years’ follow-up, patient reported again atypical chest pain and fatigue. Follow-up Rb-82 PET was performed (2 years after percutaneous intervention of the left subclavian artery) showing no myocardial ischaemia (Figure 5) and normalization of left ventricle systolic function (57% after Regadenoson and 52% in rest). Figure 5 Rubidium-82 positron emission tomography. Two-years after bare metal stent of subclavian stenosis demonstrating no myocardial ischaemia. Discussion We described a case of angina in a post-CABG patient with symptomatic subclavian artery occlusive disease. Although the most common cause of angina in a post-CABG patient is progression of native vessel coronary atherosclerosis and disease in the grafts, a subclavian stenosis should be considered. Patients with atherosclerotic occlusive plaques in the subclavian artery are usually asymptomatic because of the abundant collateral blood supply in the head, neck, and shoulder. Coronary subclavian steal syndrome has a reported incidence of approximately 2.5%.6 The classical presentation of CSSS is angina induced by left upper extremity activity. A severe stenosis can also result in reversal of blood flow in the vertebral artery causing posterior circulation vertebro-basilar symptoms (like dizziness or syncope) also known as subclavian vertebral steal syndrome. The case presented here issues two clinically important points. Firstly, we did not determine the pressure difference between the right and left arm in follow-up. Secondly, identifying the risk of subclavian stenosis was important, especially in a patient with a history of peripheral vascular disease. A history of peripheral vascular disease and a blood pressure difference between the upper extremities greater than 15 mmHg are clinical predictors of subclavian artery stenosis.7,8 However, bilateral blood pressure measurement can still miss patients who have equal bilateral subclavian artery stenosis. The benefits of routine screening before CABG are not known. Radionuclide imaging is included in the follow-up strategies after PCI and CABG in patients with symptoms. In our case, we showed ischaemia in the anterior wall on Rb-82 PET (indicating decreased flow in the LIMA-LAD); however, the true mechanism of this decreased coronary blood flow in stress is not visualized using this imaging technique. Selective arteriography of the left subclavian artery demonstrated a plaque that is hazy, ulcerated, and causes a severe stenosis of the proximal part of left subclavian artery.

in the LIMA-LAD); however, the true mechanism of this decreased coronary blood flow in stress is not visualized using this imaging technique. Selective arteriography of the left subclavian artery demonstrated a plaque that is hazy, ulcerated, and causes a severe stenosis of the proximal part of left subclavian artery. Other non-invasive imaging modalities, such as Doppler ultrasound, computed tomography, and magnetic resonance angiography could be performed to identify a subclavian artery stenosis.9 Current treatment options include a surgical bypass, percutaneous angioplasty, and stenting. Percutaneous angioplasty with stent support is considered the first-line treatment for subclavian artery stenosis.6,10–12 A surgical method should be considered after failure of endovascular treatment in low-surgical-risk patients.13 The patency rates of subclavian arteries after percutaneous revascularization are high (75%) at 10 years’ follow-up.14 Conclusion Coronary ischaemia due to subclavian artery stenosis is an important alternative diagnosis to coronary artery disease after CABG. Stenosis of the left subclavian artery can result in decreased flow in the ipsilateral internal mammary artery, compromising coronary circulation supplied by a LIMA graft. Consent: The authors confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Libman–Sacks lesions have a tendency to cause thromboembolic events. Cryptogenic strokes with high suspicion of underlying autoimmune disease should be worked up thoroughly for underlying valvular heart disease. Transoesophageal images should be implemented in patients presenting with thromboembolic phenomena. Background Libman–Sacks endocarditis (LSE), characterized by non-infective inflammatory and/or thrombotic vegetations, may be a common and under-recognized pathogenesis of cerebral macroemboli or microemboli.1 It was first described in patients with lupus by Libman and Sacks.2 It can be associated with antiphospholipid antibody syndrome (APLS).3 Positive antiphospholipid antibodies on two or more occasions at least 12 weeks apart, along with the clinical criteria of vascular thrombosis or foetal loss during pregnancy are used for the diagnosis of APLS.4 Antiphospholipid antibody syndrome can occur as a primary disorder or secondary to an underlying disease such as lupus or other systemic autoimmune diseases.5 Between 20% and 30% of patients with SLE have persistent moderate-to-high-risk antiphospholipid-antibody profiles.6 These patients tend to have higher prevalence of thrombotic events, obstetric complications, valve disease, pulmonary hypertension, haematological and renal complications, along with moderate or severe cognitive impairment than the patients who are negative for such antibodies.6

isk antiphospholipid-antibody profiles.6 These patients tend to have higher prevalence of thrombotic events, obstetric complications, valve disease, pulmonary hypertension, haematological and renal complications, along with moderate or severe cognitive impairment than the patients who are negative for such antibodies.6 Autoimmune disease associated valvulopathy is initially asymptomatic and often underdiagnosed.5 Patients with vegetations tend to have poor outcomes, with reduced event-free time to cerebrovascular events, cognitive disability, or death.1 Transoesophageal echocardiography (TOE), a method with higher sensitivity and specificity than transthoracic echocardiography (TTE), is the best antemortum diagnostic modality for LSE established so far.7,8 It should be implemented when there is a high suspicion for an underlying rheumatological disorder, especially in patients presenting with thromboembolic phenomena. Timeline

Transoesophageal echocardiography (TOE), a method with higher sensitivity and specificity than transthoracic echocardiography (TTE), is the best antemortum diagnostic modality for LSE established so far.7,8 It should be implemented when there is a high suspicion for an underlying rheumatological disorder, especially in patients presenting with thromboembolic phenomena. Timeline 1996 Diagnosed with systemic lupus erythematosus Hydroxychloroquine sulfate initiated 2007 Stopped taking hydroxychloroquine sulfate September 2017 Intermittent double vision November 2017 Internal medicine office visit 11 November 2017 Urgent magnetic resonance imaging brain suggestive of multiple ischaemic strokes 12 November 2017 Hospitalization 13 November 2017 Transthoracic echocardiogram with no abnormalities. Continued to have symptoms. Autoimmune work up concerning for antiphospholipid syndrome 16 November 2017 Transoesophageal echocardiogram significant for mitral valve vegetation. Systemic anticoagulation initiated along with Hydroxychloroquine sulfate 18 November 2017 Discharged home with no neurological deficits with uneventful outpatient follow-up 2 weeks later 3 January 2017 Repeat transoesophageal echocardiography showed complete resolution of previously described mitral vegetation

etation. Systemic anticoagulation initiated along with Hydroxychloroquine sulfate 18 November 2017 Discharged home with no neurological deficits with uneventful outpatient follow-up 2 weeks later 3 January 2017 Repeat transoesophageal echocardiography showed complete resolution of previously described mitral vegetation Case summary A 49-year-old Caucasian female saw a primary care physician complaining of intermittent double vision of 2 months duration. The double vision came and went, sometimes vertical and sometimes horizontal. Each episode lasted for a few hours to several hours. She was sent to see a neurologist, who urgently sent her for a magnetic resonance imaging (MRI) of the head, which revealed multiple embolic infarcts of the brain stem. Thus, she was advised for urgent admission to a hospital. She is a previously generally healthy woman who takes non-steroidal agents for arthritis, but otherwise she takes no other regular medications and works as a child care provider at home. She is married and has two healthy children, and she denies any previous miscarriage or spontaneous abortion. She denies fever, chills, headache, night sweats, weight loss, nausea, or vomiting.

eroidal agents for arthritis, but otherwise she takes no other regular medications and works as a child care provider at home. She is married and has two healthy children, and she denies any previous miscarriage or spontaneous abortion. She denies fever, chills, headache, night sweats, weight loss, nausea, or vomiting. On further questioning, she stated that 21 years ago, she had inflammatory arthropathy, and was diagnosed with lupus by a rheumatologist. Hydroxychloroquine sulfate (unknown dose) treatment was implemented and it was continued for several years. However, she stopped taking it 10 years ago of her own decision as she had no symptoms other than mild chronic arthritic pain, for which she continued to take non-steroidal agents over the counter. She denies history of rash, photosensitivity, renal problems, seizures, pleurisy, pericarditis, or anaemia. She admits occasional canker sores sometimes and mild thinning of the hair.

on as she had no symptoms other than mild chronic arthritic pain, for which she continued to take non-steroidal agents over the counter. She denies history of rash, photosensitivity, renal problems, seizures, pleurisy, pericarditis, or anaemia. She admits occasional canker sores sometimes and mild thinning of the hair. On arrival, the patient was haemodynamically stable. Cardiovascular examination was unremarkable with an undisplaced point of maximum impulse, normal S1 and S2, no murmurs or friction rub, and normal breath sounds on auscultation. Pertinent neurological examination findings include a mild weakness in adduction of the left eye with no nystagmus. Finger-to-nose testing however, revealed mild dysmetria on past-pointing on the right side only. She also demonstrated a mild dysmetria on heel-to-shin testing on the right. Gait assessment revealed mild truncal ataxia with difficulty walking and tandem gait without assistance. Deep tendon reflexes were symmetrical 1+/5 in biceps, triceps, 1/5 ankle jerks. Outpatient MRI, reviewed by a neurologist, was significant for multiple subacute ischaemic strokes in the brain stem area. Normal intracranial branching pattern without aneurysm or vasculitis was demonstrated on MRA. Carotid Doppler ultrasound showed no significant atherosclerotic lesions.

On arrival, the patient was haemodynamically stable. Cardiovascular examination was unremarkable with an undisplaced point of maximum impulse, normal S1 and S2, no murmurs or friction rub, and normal breath sounds on auscultation. Pertinent neurological examination findings include a mild weakness in adduction of the left eye with no nystagmus. Finger-to-nose testing however, revealed mild dysmetria on past-pointing on the right side only. She also demonstrated a mild dysmetria on heel-to-shin testing on the right. Gait assessment revealed mild truncal ataxia with difficulty walking and tandem gait without assistance. Deep tendon reflexes were symmetrical 1+/5 in biceps, triceps, 1/5 ankle jerks. Outpatient MRI, reviewed by a neurologist, was significant for multiple subacute ischaemic strokes in the brain stem area. Normal intracranial branching pattern without aneurysm or vasculitis was demonstrated on MRA. Carotid Doppler ultrasound showed no significant atherosclerotic lesions. Initial transthoracic echocardiogram showed preserved ejection fraction and no significant abnormalities. However, because of cryptogenic stroke at a young age, transoesophageal echocardiogram was recommended, which demonstrated no intracardiac shunt, but it did show mildly thickened mitral valve leaflets with several fixed vegetations and moderate eccentric regurgitation (Figure 1). Figure 1 Initial transoesophageal two-chamber view demonstrating several small sessile, loosely organized, fixed mitral vegetations with moderate regurgitation directed eccentrically.

Initial transthoracic echocardiogram showed preserved ejection fraction and no significant abnormalities. However, because of cryptogenic stroke at a young age, transoesophageal echocardiogram was recommended, which demonstrated no intracardiac shunt, but it did show mildly thickened mitral valve leaflets with several fixed vegetations and moderate eccentric regurgitation (Figure 1). Figure 1 Initial transoesophageal two-chamber view demonstrating several small sessile, loosely organized, fixed mitral vegetations with moderate regurgitation directed eccentrically. Inflammatory parameters were not suggestive of infection, white blood cell count 7.7 × 109/L (4.0–11.0 × 109/L), C-reactive protein 7.5 mg/dL (0.0–10.0 mg/dL) and erythrocyte sedimentation rate 64 mm/h (0.0–20.0 mm/h). Blood cultures showed no growth. C3 was normal and C4 level 14 mg/dL (16–38 mg/dL) was mildly decreased. C and S protein levels were normal. Rheumatological evaluation yielded elevated double-stranded DNA, anticardiolipin antibody IgG >112 m GPL-U/m, IgM 50.9 MPL-U/mL (0.0–19.9 MPL-U/mL), and a positive lupus anticoagulant test, elevated beta 2 glycoprotein Ab IgG> 112.0 unit/mL, IgM 34.9 unit/mL (0.0–9.9 unit/mL), high RNP of 2.4 AI (0.0–0.9 AI), and SSA of greater than 8.0 AI (0.0–0.9 AI) and normal SSB. All of the above are suggestive as significant for lupus, with secondary APLS. We assumed a diagnosis of LSE and the patient started anticoagulation therapy (enoxaparin to warfarin bridging) along with appropriate rheumatological therapy for lupus using hydroxychloroquine 200 mg twice a day.

Inflammatory parameters were not suggestive of infection, white blood cell count 7.7 × 109/L (4.0–11.0 × 109/L), C-reactive protein 7.5 mg/dL (0.0–10.0 mg/dL) and erythrocyte sedimentation rate 64 mm/h (0.0–20.0 mm/h). Blood cultures showed no growth. C3 was normal and C4 level 14 mg/dL (16–38 mg/dL) was mildly decreased. C and S protein levels were normal. Rheumatological evaluation yielded elevated double-stranded DNA, anticardiolipin antibody IgG >112 m GPL-U/m, IgM 50.9 MPL-U/mL (0.0–19.9 MPL-U/mL), and a positive lupus anticoagulant test, elevated beta 2 glycoprotein Ab IgG> 112.0 unit/mL, IgM 34.9 unit/mL (0.0–9.9 unit/mL), high RNP of 2.4 AI (0.0–0.9 AI), and SSA of greater than 8.0 AI (0.0–0.9 AI) and normal SSB. All of the above are suggestive as significant for lupus, with secondary APLS. We assumed a diagnosis of LSE and the patient started anticoagulation therapy (enoxaparin to warfarin bridging) along with appropriate rheumatological therapy for lupus using hydroxychloroquine 200 mg twice a day. A follow-up transoesophageal echocardiogram showed complete resolution of the previously described vegetation (Figure 2). The patient has had several multidisciplinary follow-up visits since discharge with most recent one being 6 months from hospitalization with no clinical recurrence of thromboembolic events. Figure 2 Follow-up transoesophageal two-chamber view shows resolution of previous mitral valve vegetation and regurgitation.

A follow-up transoesophageal echocardiogram showed complete resolution of the previously described vegetation (Figure 2). The patient has had several multidisciplinary follow-up visits since discharge with most recent one being 6 months from hospitalization with no clinical recurrence of thromboembolic events. Figure 2 Follow-up transoesophageal two-chamber view shows resolution of previous mitral valve vegetation and regurgitation. Discussion This case describes a patient with multiple brainstem strokes with what appears to be mitral LSE associated with history of mild lupus, positive anticardiolipin antibody, and positive lupus anticoagulant. Libman–Sacks vegetations develop mainly on the mitral valve and the aortic valve, but may affect any other valves, or even subvalvular apparatus. Isolated tricuspid valve endocarditis is rarely reported.9 Libman–Sacks endocarditis presentation can range from asymptomatic valvular thickening to heart failure from valvular dysfunction along with generalized symptoms of fatigue, fevers, night sweats, and weight loss. As demonstrated in our case, a stroke in ‘silent’ autoimmune disorder is certainly possible and APLS should be ruled out. Catastrophic APLS is most feared and often fatal complication. The diagnosis is challenging especially if there is no history of APLS and should be suspected in patients presenting with acute renal failure and the respiratory distress syndrome, diffuse alveolar haemorrhage, encephalopathy, and adrenal haemorrhage syndrome.10

rophic APLS is most feared and often fatal complication. The diagnosis is challenging especially if there is no history of APLS and should be suspected in patients presenting with acute renal failure and the respiratory distress syndrome, diffuse alveolar haemorrhage, encephalopathy, and adrenal haemorrhage syndrome.10 Secondary infective endocarditis should be considered in lupus patients with acute refractory heart failure and fever of unknown origin.11 A significant proportion of patients with lupus have LSE detected in autopsy studies (30–50%). Nevertheless, the real prevalence of LSE remains unknown since most patients with Libman–Sacks vegetations have asymptomatic valve abnormalities.12 Moyssakis et al.12 described 11% incidence of LSE by TTE and an association with lupus duration, cerebrovascular events, disease activity, presence of anticardiolipin antibody, and manifestations of antiphospholipid syndrome over a 4-year period in 342 patients. Roldan et al.13 studied 69 patients with lupus by TOE and found a 43% incidence of LSE, which suggests a possibility of higher prevalence of undiagnosed LSE in patients with lupus. It is of paramount importance to integrate clinical findings with those of TOE, transcranial Doppler, and brain MRI in patients with acute, recent (within 2–4 weeks), or recurrent stroke or transient ischaemic attack (TIA); cognitive dysfunction, or seizures, focal brain abnormalities as it should lead to a prompt and accurate diagnosis and treatment of LSE.1

e clinical findings with those of TOE, transcranial Doppler, and brain MRI in patients with acute, recent (within 2–4 weeks), or recurrent stroke or transient ischaemic attack (TIA); cognitive dysfunction, or seizures, focal brain abnormalities as it should lead to a prompt and accurate diagnosis and treatment of LSE.1 The pathogenesis of valve lesions in LSE involves endothelial damage by autoimmune activity on the valvular surface that leads to fibrin-platelet formation. Further deposition of immunoglobulins and complement components leads to cusp fibrosis, thickening, and scarring, and ultimately to valvular vegetation, deformation, or dysfunction. Regurgitant jet effects are more pronounced and prevalent in the left-sided heart valves. Valvular pathological conditions tend to be more severe in patients with both lupus and APLS.14 Although often challenging, it is important to distinguish between infectious and non-infectious vegetations as treatment differs significantly. Certain subtle echocardiographic findings can be utilized along with clinical/infectious correlation to achieve correct diagnosis (Figure 3). Infective endocarditis lesions involving mitral valves are often more mobile and found at the leaflet closure line.15 Cardiac masses due to papillary fibroelastomas may mimick vegetations, but they are typically located on the LV side of the valve. In contrast, LSE lesions are more echogenic and can affect any part of the leaflet, predominantly base.13

patients with LSE has been reported as 10–20% and a cardio embolic origin was assumed in most cases.12 Roland et al.1 presented the first fully integrated study linking Libman–Sacks vegetations with cerebromicroembolism, cerebral hypoperfusion, ischaemic brain injury, stroke/TIA, neurocognitive dysfunction, and death. Patients who present with mild valvular thickening and vegetations can be successfully treated with anticoagulation therapy along with appropriate lupus therapy as demonstrated in our case.16 There is experimental and clinical evidence that hydroxychloroquine may reduce the risk of thrombosis in patients with SLE,17,18 a trial of steroids in addition to standard lupus therapy medication may be given. However, steroids themselves may lead to fibrosis later.19 It is important to note that recurrent venous thrombosis despite warfarin use is a well-recognized complication of the antiphospholipid syndrome.20 When warfarin therapy fails despite a therapeutic INR, options include higher-intensity warfarin therapy (target INR, 3–4); the addition of low-dose aspirin, hydroxychloroquine, or a statin; use of low-molecular-weight heparin; and a combination of these approaches. In addition, antiphospholipid antibodies can cause artifactual prolongation of the prothrombin time, leading to falsely elevated INR results and a subtherapeutic warfarin dose which is typically seen with point-of-care devices21; For now, there is insufficient evidence to determine the relative efficacy and safety of direct oral anticoagulants in this patient population.22

factual prolongation of the prothrombin time, leading to falsely elevated INR results and a subtherapeutic warfarin dose which is typically seen with point-of-care devices21; For now, there is insufficient evidence to determine the relative efficacy and safety of direct oral anticoagulants in this patient population.22 However, haemodynamically significant valvular lesions or thromboembolic phenomena are indications for consideration of the surgery similar to that for infective endocarditis.23 In a prospective clinical and echocardiographic study, approximately 10% of SLE patients developed severe valvular regurgitation associated with high levels of anticardiolipin antibody.24 Vianna et al. reported that valve lesions in LSE are more severe in patients with secondary APLS than in patients with APLS alone. Patients with secondary APLS needed surgery more often, and they had a higher perioperative risk. They also had a higher incidence of autoimmune haemolytic anaemia, neutropenia, low-complement component four levels, thrombocytopenia, and antiphospholipid manifestations.25 There are some recent case reports indicating need for redo bioprostetic mitral valve replacement secondary to underlying APLS with LSE. It is concerning that some of these patients already had undiagnosed APLS prior to surgery.26,27 Improvement with current therapy of Libman–Sacks vegetations, cerebromicroembolism, brain perfusion and injury, and neurocognitive dysfunction further support a causal association of LSE and cerebrovascular disease.1

However, haemodynamically significant valvular lesions or thromboembolic phenomena are indications for consideration of the surgery similar to that for infective endocarditis.23 In a prospective clinical and echocardiographic study, approximately 10% of SLE patients developed severe valvular regurgitation associated with high levels of anticardiolipin antibody.24 Vianna et al. reported that valve lesions in LSE are more severe in patients with secondary APLS than in patients with APLS alone. Patients with secondary APLS needed surgery more often, and they had a higher perioperative risk. They also had a higher incidence of autoimmune haemolytic anaemia, neutropenia, low-complement component four levels, thrombocytopenia, and antiphospholipid manifestations.25 There are some recent case reports indicating need for redo bioprostetic mitral valve replacement secondary to underlying APLS with LSE. It is concerning that some of these patients already had undiagnosed APLS prior to surgery.26,27 Improvement with current therapy of Libman–Sacks vegetations, cerebromicroembolism, brain perfusion and injury, and neurocognitive dysfunction further support a causal association of LSE and cerebrovascular disease.1 Even though anticoagulation is still the cornerstone of treatment in these cases, it is usually not effective for non-thrombotic manifestations of antiphospholipid antibodies, nephropathy, and microthrombosis. Thus, immunomodulatory treatment strategies targeting these additional targets have been used and increasingly investigated (new). Finally, addressing traditional risk factors for cardiovascular disease, as well as active systemic autoimmune diseases, is not to be forgotten.10

ibodies, nephropathy, and microthrombosis. Thus, immunomodulatory treatment strategies targeting these additional targets have been used and increasingly investigated (new). Finally, addressing traditional risk factors for cardiovascular disease, as well as active systemic autoimmune diseases, is not to be forgotten.10 Conclusion Cryptogenic stroke patients with high suspicion of underlying autoimmune disease should be worked up thoroughly for possible valvular heart disease associated with lupus, APLS, or both. Acquisition of transoesophageal images should be implemented in these subsets of patients because transthoracic echocardiogram alone may miss the diagnosis of LSE as shown in our case. Early recognition of cardiac manifestation, timely management, amelioration of risk factors, as well as close follow-up of lupus or APLS patients, can reduce their mortality and provide adequate prevention of recurrence and progression of cerebrovascular disease. Patient perspective Patient was satisfied with her treatment. Acknowledgements The authors thank Dr Tara Deryavoush, DO for her illustration. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points In surgically corrected tetralogy of Fallot patients with fever of unknown origin, prosthetic pulmonary valve endocarditis needs to be adequately investigated. As echocardiography of the pulmonary valve is technically difficult, a high clinical suspicion is needed and signs of right heart failure should always be searched for. General guidelines do not address this issue; we recommend early surgical intervention when large vegetations, sustained fever, and clinical signs of haemodynamic impact are present.

As echocardiography of the pulmonary valve is technically difficult, a high clinical suspicion is needed and signs of right heart failure should always be searched for. General guidelines do not address this issue; we recommend early surgical intervention when large vegetations, sustained fever, and clinical signs of haemodynamic impact are present. Introduction Prosthetic valve endocarditis is a rare complication of valve replacement surgery with an incidence of 0.3–4.2% per patient-year,1,2 and accounts for approximately 20% of all cases of infective endocarditis (IE).3 Most cases of prosthetic valve endocarditis regard adults with prosthetic aortic or mitral valve infections; reports of prosthetic pulmonary valve endocarditis (PVE) are rarely described outside major cohort reviews that usually focus on left-sided heart valves.4 PVE has about 50 descriptions in worldwide literature,4 but due to the increasing number of surgically corrected tetralogy of Fallot (TOF) patients (that often include pulmonary valve implantation) this scenario is likely to become more frequent, and the number of PVE has been rising, especially in percutaneously treated patients.2 It is associated with high morbidity and mortality,5 and its diagnosis is challenging. Due to the anterior position and variable fibrosis of the pulmonary valve (PV), transoesophageal echocardiography (TOE) use is technically difficult.6 A high clinical suspicion is needed and thus reporting PVE presentation and imaging features is essential.

gh morbidity and mortality,5 and its diagnosis is challenging. Due to the anterior position and variable fibrosis of the pulmonary valve (PV), transoesophageal echocardiography (TOE) use is technically difficult.6 A high clinical suspicion is needed and thus reporting PVE presentation and imaging features is essential. Timeline Day 1 Hospital admission: fever >72 h of unknown origin + signs of right heart failure Day 3 Positive blood cultures for relatively resistant to penicillin Streptococcus mitis Transthoracic echocardiogram (TTE) suggestive of pulmonary valve endocarditis (PVE) Started on iv amoxicillin 200 mg/kg/day plus iv gentamicin 3 mg/kg/day Day 4 Transoesophageal echocardiography confirmed diagnosis of PVE with right ventricular outflow tract obstruction Day 5 Patient was transferred to the surgical centre Day 7 Sustained fever. Repeated blood cultures—identical result Antibiotic treatment was empirically changed to iv Vancomicin 30 mg/kg/day plus iv gentamicin 3 mg/kg/day

Day 4 Transoesophageal echocardiography confirmed diagnosis of PVE with right ventricular outflow tract obstruction Day 5 Patient was transferred to the surgical centre Day 7 Sustained fever. Repeated blood cultures—identical result Antibiotic treatment was empirically changed to iv Vancomicin 30 mg/kg/day plus iv gentamicin 3 mg/kg/day Day 10 Sustained fever. Repeat TTE—identical to previous exams Day 12 Surgical valve replacement with a Freestyle valve n° 25 implantation Week 6 Hospital discharge Case presentation A 37-year-old man came to the emergency department with complaints of orthopnoea, non-productive cough and fever >38.5°C for over 72 h. Physical examination showed a lower limb oedema, positive hepatojugular reflux, and a cardiac systolic murmur. His blood analysis showed leucocitosis of 11.67 × 109 cells/L (4.5–11) with neutrofilia of 9.37 × 109 cells/L (2.0–8.5) and an elevated C-reactive protein of 198 mg/L (<5 mg/L). His chest X-ray had no signs of pulmonary congestion. His previous medical history included a TOF that was corrected in 1999, with a pulmonary biologic valve replacement 2 years later (with a Carpentier-Edwards Perimount® bioprosthesis), secondary to major pulmonary regurgitation.

eactive protein of 198 mg/L (<5 mg/L). His chest X-ray had no signs of pulmonary congestion. His previous medical history included a TOF that was corrected in 1999, with a pulmonary biologic valve replacement 2 years later (with a Carpentier-Edwards Perimount® bioprosthesis), secondary to major pulmonary regurgitation. After hospital admission, blood cultures were positive for relatively resistant to penicillin Streptococcus mitis, and directed intravenous antibiotics (amoxicillin plus gentamicin) were given. The transthoracic echocardiogram (TTE) showed a mobile mass arising from the pulmonary prosthesis (Figure 1, red arrow). In order to better define this finding, a TOE was performed, showing the presence of multiple mobile structures arising from the arterial surface of the prosthesis and also from the pulmonary trunk (PT), extending into the right pulmonary artery and causing right ventricular obstruction, with a mean and max right ventricular outflow tract (RVOT)-PT gradient of 35 and 52 mmHg, respectively (Figures 2–4). Figure 1 Transthoracic echocardiogram. Ao, aortic valve; PT, pulmonary trunk; RVOT, right ventricular outflow tract. Figure 2 Transoesophageal echocardiogram. Red arrow pointing to a mobile mass arising from the arterial side of the pulmonary prosthesis, extending into the right pulmonary artery and causing right ventricle obstruction; PT, pulmonary trunk; RVOT, right ventricular outflow tract.

Figure 1 Transthoracic echocardiogram. Ao, aortic valve; PT, pulmonary trunk; RVOT, right ventricular outflow tract. Figure 2 Transoesophageal echocardiogram. Red arrow pointing to a mobile mass arising from the arterial side of the pulmonary prosthesis, extending into the right pulmonary artery and causing right ventricle obstruction; PT, pulmonary trunk; RVOT, right ventricular outflow tract. Figure 3 Transoesophageal echocardiogram. Red arrow-head pointing to a filamentous structure arising from the PT and red arrow pointing to the mobile mass arising from the pulmonary prosthesis. PT, pulmonary trunk; RPA, right pulmonary artery. Figure 4 3D reconstruction from the transoesophageal echocardiogram. Red arrow pointing to the mass arising from the pulmonary prosthesis. The information obtained through both echocardiography techniques allowed for the definitive diagnosis of pulmonary prosthesis endocarditis. Due to sustained fever and positive blood cultures despite directed IV-therapy, cardiac surgery was performed with PT opening during cardiopulmonary bypass to allow the removal of a 9 cm vegetation and a Freestyle valve n° 25 implantation. The patient was discharged after 6 weeks course of antibiotics and, after 1 year follow-up, is currently well. He was advised to perform prophylaxis according to current guidelines.1

rformed with PT opening during cardiopulmonary bypass to allow the removal of a 9 cm vegetation and a Freestyle valve n° 25 implantation. The patient was discharged after 6 weeks course of antibiotics and, after 1 year follow-up, is currently well. He was advised to perform prophylaxis according to current guidelines.1 Discussion We report a case of a pulmonary prosthesis endocarditis causing RVOT obstruction and right heart failure. At admission, the patient had fever of unknown origin and signs of right heart failure. After appropriate investigation, definitive diagnosis was obtained according to the modified Duke criteria for the diagnosis of IE, with two major and two minor criteria.7 After an early surgical correction, the patient recovered well. To recognize prosthetic PVE implies a high clinical suspicion, since imaging of the right side of the heart is difficult and many times incorrectly disregarded. The biggest case series published to date concluded that TTE and TOE should complement each other in the evaluation of patients with suspected PVE, but still fail to diagnose more than 10% of cases.6

gh clinical suspicion, since imaging of the right side of the heart is difficult and many times incorrectly disregarded. The biggest case series published to date concluded that TTE and TOE should complement each other in the evaluation of patients with suspected PVE, but still fail to diagnose more than 10% of cases.6 In this case, the identified microorganism was a gram positive bacterium: S. mitis. The most commonly identified organisms in previously described cases were Staphylococcus aureus, coagulase-negative staphylococcus and streptococcal species.3,4,6 An upper respiratory tract infection (RTI) might have been the underlying cause for bacteraemia in this case, since S. mitis is an uncommon but known cause for RTI8,9 and the patient later referred a short period of fever, with hoarseness and cough 1 month previous to the hospital admission. In current literature, right-sided endocarditis surgical indications and timing are not clear.1 The majority of published cases refer to sustained fever and signs of haemodynamic impact as major indications for a surgical treatment,4,6 but no major consensus have been published.

In this case, the identified microorganism was a gram positive bacterium: S. mitis. The most commonly identified organisms in previously described cases were Staphylococcus aureus, coagulase-negative staphylococcus and streptococcal species.3,4,6 An upper respiratory tract infection (RTI) might have been the underlying cause for bacteraemia in this case, since S. mitis is an uncommon but known cause for RTI8,9 and the patient later referred a short period of fever, with hoarseness and cough 1 month previous to the hospital admission. In current literature, right-sided endocarditis surgical indications and timing are not clear.1 The majority of published cases refer to sustained fever and signs of haemodynamic impact as major indications for a surgical treatment,4,6 but no major consensus have been published. In conclusion, this case represents the importance of searching for clinical signs of right heart failure as well as the relevance of an adequate right heart imaging, especially when clinical suspicion of PVE is present. As general guidelines do not address this issue, determining surgical indications and timing is a challenge. Transthoracic and TOE combination, despite technically difficult, allowed a correct diagnosis and a timely treatment. According to our case and to available literature, we recommend considering surgical treatment when large vegetations, sustained fever and clinical signs of haemodynamic impact are present. Acknowledgement The authors thank to Ana Agapito for her time and support in obtaining patient follow-up data.

In conclusion, this case represents the importance of searching for clinical signs of right heart failure as well as the relevance of an adequate right heart imaging, especially when clinical suspicion of PVE is present. As general guidelines do not address this issue, determining surgical indications and timing is a challenge. Transthoracic and TOE combination, despite technically difficult, allowed a correct diagnosis and a timely treatment. According to our case and to available literature, we recommend considering surgical treatment when large vegetations, sustained fever and clinical signs of haemodynamic impact are present. Acknowledgement The authors thank to Ana Agapito for her time and support in obtaining patient follow-up data. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Introduction Learning points Prosthetic valve thrombosis (PVT) is a life-threatening condition, made even rarer due to the contemporary pure carbon bileaflet metallic valve, owing to its smoother surface and improved haemodynamics. History of subtherapeutic anticoagulation, rapid onset of symptom and short time interval from surgery, raises the clinical suspicion of PVT. Transoesophageal echocardiogram and cine-fluoroscopy offer complementary information in determining disc mobility. Thrombolysis is an effective treatment but carries risks of bleeding and peripheral systemic thromboembolism. Recurrent thrombosis should prompt the clinician to investigate for other rare causes of hypercoagulability. Despite overcoming the morbidity associated with severe native valve disease, prosthetic metallic valve replacement is not without its inherent morbidity, in particular from prosthetic valve thrombosis (PVT).

Thrombolysis is an effective treatment but carries risks of bleeding and peripheral systemic thromboembolism. Recurrent thrombosis should prompt the clinician to investigate for other rare causes of hypercoagulability. Despite overcoming the morbidity associated with severe native valve disease, prosthetic metallic valve replacement is not without its inherent morbidity, in particular from prosthetic valve thrombosis (PVT). Although rare, with an incidence of 0.2–6% per patient-year, PVT remains a serious and potentially fatal complication.1,2 This is strongly influenced by various interacting factors such as prosthetic valve location, type of prosthesis, presence of low cardiac state, and the adequacy of anticoagulation.3 Metallic mitral valve prostheses confer higher PVT risk compared with those in the aortic position, owing to lower flow rates. Furthermore, the type of prosthesis, in particular the out-dated caged ball valve conferred the highest PVT risk, compared with the bileaflet or tilting disc valves.3 Technological advances in valve design, composition and improved haemodynamics have led to favourable safety profiles.4,5 Herein, we describe a rare case of PVT presenting with cardiogenic shock, on a background of the contemporary On-X valve, which confers a favourable thrombogenicity profile. It highlights the importance of thorough clinical examination and prompt use of echocardiography in differentiating potential causes in mechanical valve patients. Timeline

Herein, we describe a rare case of PVT presenting with cardiogenic shock, on a background of the contemporary On-X valve, which confers a favourable thrombogenicity profile. It highlights the importance of thorough clinical examination and prompt use of echocardiography in differentiating potential causes in mechanical valve patients. Timeline 6 months prior to presentation Patient with severe rheumatic mitral stenosis undergoes mitral valve replacement with 27/29 mm On-X valve 14 days prior to presentation Subtherapeutic international normalized ratio (INR) of 1.8 10 days prior to presentation Patient experiences dyspnoea and reduced exercise tolerance Day 1 Patient presented with cardiogenic shock. INR 6.1. Transthoracic echocardiography showed severe mitral stenosis. Treated with IV furosemide and low dose GTN infusion. Warfarin withheld and IV unfractionated heparin commenced once INR <3.5 Day 3 Transoesophageal echocardiogram (TOE) confirmed the antero-lateral disc to be fixed with no flow across the disc and the postero-medial disc to have restricted movement, with a mean transmitral gradient of 22 mmHg Day 4 Patient thrombolysed with Alteplase Day 5 Normalization of transmitral gradient Day 10 Patient discharged with higher target INR 3.5–4.5 and aspirin 6 weeks after presentation TOE revealed disc hypomobilty with a large adherent clot. Patient was admitted immediately back to cardiac care unit (CCU) 7 days after TOE Patient underwent emergency redo-mitral bioprosthetic valve surgery 10 weeks after redo surgery Patient was followed-up with cardiac surgeons and made good recovery without any complications

ed disc hypomobilty with a large adherent clot. Patient was admitted immediately back to cardiac care unit (CCU) 7 days after TOE Patient underwent emergency redo-mitral bioprosthetic valve surgery 10 weeks after redo surgery Patient was followed-up with cardiac surgeons and made good recovery without any complications Case summary A 45-year-old woman was admitted to directly to our cardiology department, with a 10-day history of dyspnoea, reduced exercise tolerance, paroxysmal nocturnal dyspnoea, and haemoptysis, whilst on vacation abroad. She had a background of pure carbon bileaflet metallic mitral valve (27/29 mm On X) for severe rheumatic mitral stenosis, operated on 6 months previously, with no other comorbidities or prior history of thrombosis. Her medication comprised only of warfarin and bisoprolol 2.5 mg once daily. Her trip was abandoned prematurely due to a deterioration in her symptoms. Prior to her trip her international normalized ratio (INR) was subtherapeutic at 1.8. Clinical examination revealed a normal jugular venous pulse (JVP), soft mechanical first heart sound, widespread bilateral pulmonary crepitations, with no peripheral oedema. Her blood pressure was 91/56 mmHg with a heart rate of 85 b.p.m. Clinical impression was acute left ventricular failure secondary to valve obstruction.

cal examination revealed a normal jugular venous pulse (JVP), soft mechanical first heart sound, widespread bilateral pulmonary crepitations, with no peripheral oedema. Her blood pressure was 91/56 mmHg with a heart rate of 85 b.p.m. Clinical impression was acute left ventricular failure secondary to valve obstruction. Her electrocardiogram showed sinus rhythm. Arterial blood gas sampling revealed a type 1 respiratory failure with partial pressures of oxygen of 7.9 kPa (NR >10.5 kPa) and carbon dioxide of 4.1 kPa (NR 4.5–6.0 kPa) on room air. Her chest radiograph confirmed pulmonary oedema. Blood tests were unremarkable except for an INR of 6.1 (target INR 2–3) and D Dimer of 0.48 µg/mL (NR <0.50 µg/mL). Bedside transthoracic echocardiography showed restricted metallic mitral disc mobility with a mean transmitral gradient of 25 mmHg, indicating severe mitral stenosis with preserved left ventricular function (Figure 1). Fluoroscopy was performed to further delineate the disc motion, which revealed severely reduced mobility. An urgent transoesophageal echocardiogram (TOE) confirmed the antero-lateral disc to be fixed with no flow across the disc and the postero-medial disc to have restricted movement, with a mean transmitral gradient of 22 mmHg (Figure 2). Three-dimensional (3D) TOE of the prosthetic mitral valve was performed for better visualization and to distinguish between thrombus and pannus (Figure 3). Three-dimensional TOE demonstrated the antero-lateral disc to be fixed with surrounding thrombus.

movement, with a mean transmitral gradient of 22 mmHg (Figure 2). Three-dimensional (3D) TOE of the prosthetic mitral valve was performed for better visualization and to distinguish between thrombus and pannus (Figure 3). Three-dimensional TOE demonstrated the antero-lateral disc to be fixed with surrounding thrombus. Figure 1 Continuous wave Doppler through the mitral valve on admission (transthoracic echocardiogram), showing a raised mean transmitral gradient of 25 mmHg. Figure 2 Continuous wave Doppler through the mitral valve (transoesophageal echocardiogram), showing a raised mean transmitral gradient of 22 mmHg. Figure 3 Still frame of three-dimensional rendered image from transoesophageal echocardiogram of the mitral valve. Arrow indicates the fixed antero-lateral disc of the mitral valve. She was commenced on diuretics and a low dose of GTN infusion for pulmonary venodilatation. Her warfarin was withheld and she was commenced on intravenous (IV) unfractionated heparin once her INR was below 3.5.

Figure 3 Still frame of three-dimensional rendered image from transoesophageal echocardiogram of the mitral valve. Arrow indicates the fixed antero-lateral disc of the mitral valve. She was commenced on diuretics and a low dose of GTN infusion for pulmonary venodilatation. Her warfarin was withheld and she was commenced on intravenous (IV) unfractionated heparin once her INR was below 3.5. Urgent cardiac surgical review was sought. After close discussion between the cardiologists, cardiac surgeons and the patient, it was decided that further surgery on the valve carried an excess mortality risk. Thrombolysis was therefore offered to the patient. On Day 4 of admission, following written informed consent, a bolus of 10 mg of alteplase was administered followed by 80 mg infusion over 3 h. IV unfractionated heparin was re-instituted following completion of thrombolysis. Within 24 h of the infusion the metallic first heart sound became audible. Repeat transthoracic echocardiogram revealed normalization of mean transmitral gradients of 3 mmHg (Figure 4). Fluoroscopy showed normalization of one of the discs with improved mobility of the other disc. The patient was discharged with a higher therapeutic INR range of 3.5–4.5 and aspirin 75 mg, with weekly INR monitoring. Figure 4 Continuous wave Doppler through the mitral valve (transthoracic echocardiogram) post-thrombolysis, showing normalization with a mean transmitral gradient of 3.4 mmHg.

Urgent cardiac surgical review was sought. After close discussion between the cardiologists, cardiac surgeons and the patient, it was decided that further surgery on the valve carried an excess mortality risk. Thrombolysis was therefore offered to the patient. On Day 4 of admission, following written informed consent, a bolus of 10 mg of alteplase was administered followed by 80 mg infusion over 3 h. IV unfractionated heparin was re-instituted following completion of thrombolysis. Within 24 h of the infusion the metallic first heart sound became audible. Repeat transthoracic echocardiogram revealed normalization of mean transmitral gradients of 3 mmHg (Figure 4). Fluoroscopy showed normalization of one of the discs with improved mobility of the other disc. The patient was discharged with a higher therapeutic INR range of 3.5–4.5 and aspirin 75 mg, with weekly INR monitoring. Figure 4 Continuous wave Doppler through the mitral valve (transthoracic echocardiogram) post-thrombolysis, showing normalization with a mean transmitral gradient of 3.4 mmHg. Unfortunately, despite being asymptomatic, her repeat TOE 6 weeks post-thrombolysis, revealed an elevated mean transmitral gradient of 10 mmHg with an immobile antero-lateral disc and a mobile postero-medial disc (Figure 5). A mobile 10 mm × 7 mm structure was attached to the postero-medial disc causing intermittent severe mitral stenosis. It transpired that despite the patient’s best efforts, her INR on one occasion dropped below two. The patient was admitted immediately back to coronary care unit, further thrombolysis was considered, but the risk of peripheral embolization from the large thrombus was deemed too high. Emergency valve replacement with a bioprosthetic valve was chosen as the best strategy, to avoid further morbidity from prosthetic valve thrombosis and negate the need for anticoagulation. Seven days after the TOE, the patient underwent redo mitral valve surgery. She made a good recovery without any complications and was followed up with the cardiac surgeons 10 weeks later.

as chosen as the best strategy, to avoid further morbidity from prosthetic valve thrombosis and negate the need for anticoagulation. Seven days after the TOE, the patient underwent redo mitral valve surgery. She made a good recovery without any complications and was followed up with the cardiac surgeons 10 weeks later. Figure 5 Continuous wave Doppler through the mitral valve (transoesophageal echocardiogram) 6 weeks post-thrombolysis, showing a raised mean transmitral gradient of 10 mmHg. In view of recurrent thrombosis, the patient was tested for rare causes of hypercoagulability. The JAK-2 (V617F) mutation is linked with the myeloproliferative neoplasias, polycythaemia rubra vera and essential thrombocythemia, both of which confer increased arterial and venous thrombotic risk, tested negative in this patient. In addition, anti-cardiolipin antibody and IgM and IgG β2-glycoprotein I antibodies, specific for antiphospholipid syndrome, also tested negative in this patient. Discussion The prospect of prosthetic valve thrombosis is a feared complication, due to its significant impact on mortality. This patient presented with symptoms of acute left ventricular failure due to left side valve obstruction from mitral valve thrombosis. In this case, a history of subtherapeutic anticoagulation, the subsequent rapid development of symptoms and the short time interval from surgery, strongly supported prosthetic valve thrombosis.6

nt presented with symptoms of acute left ventricular failure due to left side valve obstruction from mitral valve thrombosis. In this case, a history of subtherapeutic anticoagulation, the subsequent rapid development of symptoms and the short time interval from surgery, strongly supported prosthetic valve thrombosis.6 Unexpectedly, this prosthetic valve thrombosis occurred in a patient with the contemporary On-X valve, which has a favourable safety profile.4 It has a flared inlet which reduces flow turbulence and a long exit point which aligns flow, both of which contribute to better haemodynamics across the valve.5 Furthermore, the pure pyrolytic carbon design confers a smoother surface reducing thrombogenicity. A study by Chambers et al.4 revealed that in 407 patients with On-X mitral valve, only two cases (0.1% per patient-year) developed valve thrombosis, over a mean follow-up of 5 years. A previous study by Williams et al.,7 reported that in a poorly anticoagulated population of 242 patients with the On-X mitral valve, only one case (0.2% patient-year) developed valve thrombosis. This emphasises the true rarity of such a case presentation. Bedside transthoracic echocardiography was performed in this patient. The demonstration of an elevated mean transmitral Doppler gradient confirmed valve obstruction. TOE offers better visualization of the valve and enabled the distinction between thrombus and pannus; the later tends to occur around the sewing ring, develops over a period longer than 6 months post-surgery and has a more insidious symptom onset. A study by Barbetseas et al.6 reported that valve hypomobility was observed in all patients with PVT compared with 60% in those with pannus. Furthermore, the 3D functionality conferred by TOE was particularly useful. Cine-fluoroscopy has a valuable role in determining leaflet mobility, with a very high negative predictive value of 91% compared with 78% for TOE as shown by Montorsi et al.8

rved in all patients with PVT compared with 60% in those with pannus. Furthermore, the 3D functionality conferred by TOE was particularly useful. Cine-fluoroscopy has a valuable role in determining leaflet mobility, with a very high negative predictive value of 91% compared with 78% for TOE as shown by Montorsi et al.8 The management of such patients necessitates the expertise of both cardiologists and cardiac surgeons in agreeing the best treatment strategy for the patient. The surgical risk from reoperation can be up to 30%, which for this case on initial presentation was deemed too high.9 Thrombolysis has been shown to be a feasible strategy especially in cases of cardiogenic shock with New York Heart Association (NYHA) 4 (4). However, thrombolysis is not without its inherent risks, with systemic embolism occurring in 10%, re-thrombosis in 20% and mortality risk in 10%.10,11 The improvement in patient symptoms and transmitral gradient, despite restricted disc mobility on fluoroscopy, prompted the adoption of a higher target INR and aspirin. A study by Laffort et al.12 showed that patients on both aspirin and oral anticoagulants had lower incidence of non-obstructive periprosthetic valve thrombi compared with those on oral anticoagulation alone. Further admission with recurrent valve thrombosis led to the decision for replacement of the valve with a bioprosthetic valve, to negate the risk of future valve thrombosis.

rin and oral anticoagulants had lower incidence of non-obstructive periprosthetic valve thrombi compared with those on oral anticoagulation alone. Further admission with recurrent valve thrombosis led to the decision for replacement of the valve with a bioprosthetic valve, to negate the risk of future valve thrombosis. In patients with recurrent thrombosis, attention should be given to the possibility of an underlying pro-thrombotic state. This may be influenced by an underlying myeloproliferative neoplasia, which are strongly associated with thrombosis in unusual sites (cerebral, hepatic). This patient tested negative for the JAK2 (V617F) mutation, which is present in 97% of patients with polycythaemia rubra vera and 60% of patients with essential thrombocythemia.13 A potential systemic condition contributing to a prothrombotic milieu is anti-phospholipid syndrome. This is characterized by a history of recurrent miscarriages, arterial and venous thrombosis of unusual sites, livedo reticularis and the presence of lupus anticoagulant, anticardiolipin and anti-β2 glycoprotein I antibodies.14 This patient had no history of recurrent foetal loss and tested negative for the auto-antibodies. In this case, the repeated interruption in therapeutic anticoagulation albeit brief was the strongest culprit for repeated PVT.

the presence of lupus anticoagulant, anticardiolipin and anti-β2 glycoprotein I antibodies.14 This patient had no history of recurrent foetal loss and tested negative for the auto-antibodies. In this case, the repeated interruption in therapeutic anticoagulation albeit brief was the strongest culprit for repeated PVT. Conclusion A history of subtherapeutic anticoagulation and the rapid development of dyspnoea, should prompt the clinician to suspect PVT. Thorough clinical examination and immediate bedside echocardiography are critical for assessing prosthetic valve patients in cardiogenic shock. The treatment of PVT is complex, with considerable risks to the patient, irrespective of the strategy (thrombolysis/emergency valve replacement), necessitating the expertise of cardiologists and cardiac surgeons.15 Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Implantation of implantable cardioverter-defibrillator (ICD) with optimal medical therapy is an appropriate therapeutic option for coronary artery spasm patients with aborted sudden cardiac death (SCD). Most coronary artery spasm patients with aborted SCD have normal left ventricular ejection fraction and do not have arrhythmogenic substrates, so they may be good candidates for the implantation of subcutaneous ICD. Introduction Coronary artery spasm is more common in Japanese and Koreans than in Caucasians.1 Its clinical presentation varies widely from stable angina to sudden cardiac death (SCD).1,2 For those who have experienced aborted SCD (ASCD), implantable cardioverter-defibrillator (ICD) implantation in addition to optimal medical therapy is a therapeutic option.3 However, transvenous ICD implantation comes with risk of complications, associated with morbidity and financial cost.4 Subcutaneous ICD systems have become readily available as an alternative to conventional transvenous ICD systems in select clinical settings.5 To our knowledge, there have not been any published reports discussing implantation of subcutaneous ICD for lethal arrhythmia due to coronary artery spasm. We, therefore, present for the first time, the case of a coronary artery spasm patient with ASCD who was treated with implantation of subcutaneous ICD for secondary prevention of SCD. Timeline

Introduction Coronary artery spasm is more common in Japanese and Koreans than in Caucasians.1 Its clinical presentation varies widely from stable angina to sudden cardiac death (SCD).1,2 For those who have experienced aborted SCD (ASCD), implantable cardioverter-defibrillator (ICD) implantation in addition to optimal medical therapy is a therapeutic option.3 However, transvenous ICD implantation comes with risk of complications, associated with morbidity and financial cost.4 Subcutaneous ICD systems have become readily available as an alternative to conventional transvenous ICD systems in select clinical settings.5 To our knowledge, there have not been any published reports discussing implantation of subcutaneous ICD for lethal arrhythmia due to coronary artery spasm. We, therefore, present for the first time, the case of a coronary artery spasm patient with ASCD who was treated with implantation of subcutaneous ICD for secondary prevention of SCD. Timeline Time Events Day 0 A 50-year-old man collapsed on his way to work at 8 AM. After chest compression, an automated external defibrillator detected ventricular fibrillation (VF). Six electrical shocks were required to terminate VF. He was intubated and started on mechanical ventilation management at the emergency room. Emergency cardiac catheterization showed normal coronary artery and left ventricular contraction. Targeted temperature management and intravenous injection of nicorandil was started in the intensive care unit setting. Day 2 He was withdrawn from mechanical ventilation management. Day 13 Acetylcholine provocation test: positive Day 15 Cardiac electrophysiological study: negative Day 26 Subcutaneous implantable cardioverter-defibrillator implantation Day 33 Discharge from hospital with no residual neurological deficits

e unit setting. Day 2 He was withdrawn from mechanical ventilation management. Day 13 Acetylcholine provocation test: positive Day 15 Cardiac electrophysiological study: negative Day 26 Subcutaneous implantable cardioverter-defibrillator implantation Day 33 Discharge from hospital with no residual neurological deficits Case report A 50-year-old Japanese male with a medical history of thoracic haemangioma who was taking no medications and was regularly followed by computed tomography suddenly collapsed on his way to work at 8 AM. He had no history of angina and no risk factors for arteriosclerosis, such as hypertension, diabetes mellitus, or smoking. He had no prior history of syncope or a family history of syncope or juvenile SCD. Chest compression was immediately performed by bystanders. After several minutes’ resuscitation effort, he was connected to an automated external defibrillator (AED). The AED detected ventricular fibrillation (VF) and delivered the appropriate electrical shock, but VF continued. On the fourth electrical shock delivery, VF was terminated transiently, but recurred immediately (Figure 1A). Two additional shocks finally terminated the VF, and the ECG recorded by the AED showed ST-segment elevation (Figure 1B). After return of spontaneous circulation, the patient was brought to the emergency room. At presentation to the emergency room, he was unconscious with Glasgow coma scale score of 5/15 (e1, v1, and m3). His heart rate was 136 b.p.m., blood pressure was 157/110 mmHg, and there was no cardiac murmur or extra sound. He arrived ventilated by a laryngeal tube which we removed so he could be intubated, and placed on mechanical ventilation. His ECG showed ST-segment elevation in the lateral leads and ST-segment depression in the inferior leads (Figure 1C). Laboratory analysis revealed normal values for complete blood cell count, electrolytes, and cardiac enzymes. As for electrolytes, he had a potassium level of 3.9 mEq/L (normal: 3.6–5.0 mEq/L), sodium of 139 mEq/L (136–147 mEq/L), calcium of 10.0 mg/dL (8.7–10.1 mg/dL), and magnesium of 2.0 mg/dL (1.8–2.6 mg/dL). As for cardiac enzymes, CK was 177 U/L (57–197 U/L), CK-MB was 77 U/L (0–25U/L), and troponin I was 0.0070 ng/mL (<0.040 ng/mL). We immediately performed emergency cardiac catheterization, which showed normal left ventricular contraction and no significant stenosis or thrombosis of the coronary arteries.

.8–2.6 mg/dL). As for cardiac enzymes, CK was 177 U/L (57–197 U/L), CK-MB was 77 U/L (0–25U/L), and troponin I was 0.0070 ng/mL (<0.040 ng/mL). We immediately performed emergency cardiac catheterization, which showed normal left ventricular contraction and no significant stenosis or thrombosis of the coronary arteries. After the acute phase passed, his ECG was completely normal, it displayed; normal QT interval, and lacked T-wave alternans, notched T-wave, and early repolarization including a J-wave (Figure 1D). Therefore, this patient did not satisfy any of the diagnostic criteria for long QT syndrome.6 Based on these ECG and catheterization results, we gave a tentative diagnosis of coronary artery spasm. He was admitted to the intensive care unit and treated with targeted temperature management (target temperature of 34°C for 24 h) for the neurological defects under sedation with fentanyl, propofol, and dexmedetomidine. Intravenous injection of nicorandil (2 mg/h) was used for the prevention of coronary artery spasm. Figure 1 (A) After appropriate electrical cardioversion was delivered four times, transient sinus rhythm was obtained but ventricular fibrillation returned. (B) After two more shocks, the automated external defibrillator ECG showed termination of ventricular fibrillation and ST-segment elevation. (C) After termination of ventricular fibrillation, 12 lead ECG showed ST-segment elevation in the lateral leads and ST-segment depression in the inferior leads. (D) After the acute phase passed, his ECG was completely normal.

nal defibrillator ECG showed termination of ventricular fibrillation and ST-segment elevation. (C) After termination of ventricular fibrillation, 12 lead ECG showed ST-segment elevation in the lateral leads and ST-segment depression in the inferior leads. (D) After the acute phase passed, his ECG was completely normal. His ECG monitor during hospitalization showed no ventricular premature beats. Transthoracic echo cardiogram and contrast enhancement magnetic resonance imaging (MRI) did not detect any structural heart disease. Two days after admission, sedative drugs were interrupted, and he was able to be weaned from mechanical ventilation. At that point, although his consciousness was completely clear with Glasgow coma scale score of 15/15 (e4, v5, and m6), he had a slight disturbance of short-term memory. A brain MRI conducted 5 days after admission, revealed no abnormalities. Thirteen days after admission, we performed acetylcholine provocation test after >24 h discontinuation of calcium channel blocker (CCB) and nicorandil.7 Intracoronary injection of 20 μg of acetylcholine into the left coronary artery induced coronary artery spasm of the distal portion of the left anterior descending coronary artery (Figure 2, black arrows). Fifteen days after his event, we performed cardiac electrophysiological study, while he was on nifedipine (20 mg/day) and nicorandil (15 mg/day).7 Programmed stimulation with triple extra-stimuli at the right ventricular apex and outflow did not induce any lethal ventricular arrhythmia. A drug challenge with intravenous pilsicainide did not show any ECG indications of Brugada syndrome. The patient’s neurological status gradually improved and by discharge, he had no residual neurological deficits.

extra-stimuli at the right ventricular apex and outflow did not induce any lethal ventricular arrhythmia. A drug challenge with intravenous pilsicainide did not show any ECG indications of Brugada syndrome. The patient’s neurological status gradually improved and by discharge, he had no residual neurological deficits. Figure 2 (A) LAO cranial view of the left coronary artery at baseline. (B) LAO cranial view of the left coronary artery after intracoronary injection of 20 μg of acetylcholine into it. It induced spasm of the distal portion of the left anterior descending artery (black arrows). Taking all of the findings together, we attributed the patient's ASCD to coronary artery spasm and implanted a subcutaneous ICD under general anaesthesia for secondary prevention of SCD (Figure 3). The patient was discharged on nifedipine and nicorandil. During the 1 year of follow-up, the patient has been free of angina. Implantable cardioverter-defibrillator interrogation revealed no ventricular arrhythmias and appropriate ICD therapy. Figure 3 The chest X-ray after implantation of the subcutaneous implantable cardioverter-defibrillator.

Taking all of the findings together, we attributed the patient's ASCD to coronary artery spasm and implanted a subcutaneous ICD under general anaesthesia for secondary prevention of SCD (Figure 3). The patient was discharged on nifedipine and nicorandil. During the 1 year of follow-up, the patient has been free of angina. Implantable cardioverter-defibrillator interrogation revealed no ventricular arrhythmias and appropriate ICD therapy. Figure 3 The chest X-ray after implantation of the subcutaneous implantable cardioverter-defibrillator. Discussion Recent studies report that appropriate medical treatment including prescription of CCB and smoking cessation can achieve good long-term outcomes for coronary artery spasm patients,1 even those who have suffered ASCD.8 However, it is also true that in three recent large scale observational studies, lethal ventricular arrhythmic events were found to recur in about one in four cases of coronary artery spasm patients with ASCD.9–11 The first of these found a non-significant trend towards fewer cardiac deaths in the patients who had received an ICD as opposed to those who had not (4% vs. 19%, P = 0.15).9 Nevertheless, the authors concluded that ICDs were likely beneficial, and that the P-value did not reach significance due to small sample size. Another study found that coronary artery spasm patients with lethal ventricular arrhythmia were not always saved by appropriate cardioversion,12 especially those who were current smokers or who discontinued medication.13 We ourselves believe that based on the high recurrence rate of ventricular tachyarrhythmias, implantation of ICD with optimal medical therapy is an appropriate therapeutic option for coronary artery spasm patients with ASCD, especially if the less invasive subcutaneous ICD is deployed.

or who discontinued medication.13 We ourselves believe that based on the high recurrence rate of ventricular tachyarrhythmias, implantation of ICD with optimal medical therapy is an appropriate therapeutic option for coronary artery spasm patients with ASCD, especially if the less invasive subcutaneous ICD is deployed. A recent research study reported that the rate of all complications from implantation of transvenous dual chamber ICD was 14.1% and the rate of major complications requiring re-intervention was 6.7%.5 Another study reported that subcutaneous ICD had less frequent lead complications and longer lead survival than transvenous ICD, whereas there was no significant difference in the rate of appropriate shock between transvenous ICD and subcutaneous ICD.14 Subcutaneous ICD is indicated for prevention of SCD in patients who have no need for concomitant bradycardia therapy, cardiac resynchronization therapy, or anti-tachycardia pacing therapy.5 Unlike patients with prior myocardial infarction or cardiomyopathy, most coronary artery spasm patients with ASCD have normal left ventricular ejection fraction and do not have arrhythmogenic substrates. Therefore, they may be good candidates for the implantation of subcutaneous ICD. Conclusion We reported the first case of a coronary artery spasm patient without structural heart disease who underwent implantation of a subcutaneous ICD after surviving VF. Coronary artery spasm patients may be good candidates for implantation of subcutaneous ICD.

A recent research study reported that the rate of all complications from implantation of transvenous dual chamber ICD was 14.1% and the rate of major complications requiring re-intervention was 6.7%.5 Another study reported that subcutaneous ICD had less frequent lead complications and longer lead survival than transvenous ICD, whereas there was no significant difference in the rate of appropriate shock between transvenous ICD and subcutaneous ICD.14 Subcutaneous ICD is indicated for prevention of SCD in patients who have no need for concomitant bradycardia therapy, cardiac resynchronization therapy, or anti-tachycardia pacing therapy.5 Unlike patients with prior myocardial infarction or cardiomyopathy, most coronary artery spasm patients with ASCD have normal left ventricular ejection fraction and do not have arrhythmogenic substrates. Therefore, they may be good candidates for the implantation of subcutaneous ICD. Conclusion We reported the first case of a coronary artery spasm patient without structural heart disease who underwent implantation of a subcutaneous ICD after surviving VF. Coronary artery spasm patients may be good candidates for implantation of subcutaneous ICD. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points A new longevity record beyond 50 years for valve prostheses has been set by the caged-ball mechanical Starr–Edwards aortic valve. This landmark should contribute to reassure physicians and patients on the excellent performance of this valve. Systematic replacement of Starr–Edwards aortic valve when reoperating patients on mitral and/or tricuspid valve is not mandatory.

A new longevity record beyond 50 years for valve prostheses has been set by the caged-ball mechanical Starr–Edwards aortic valve. This landmark should contribute to reassure physicians and patients on the excellent performance of this valve. Systematic replacement of Starr–Edwards aortic valve when reoperating patients on mitral and/or tricuspid valve is not mandatory. Introduction The caged-ball valve created by Albert Starr and Lowell Edwards was implanted for the first time in September 1960 in the mitral position.1 It was the first valvular prosthesis produced and marketed on a large scale. Its long-term results up to 40 years have made the Starr–Edwards prosthetic valve a benchmark in the field of valvular surgery.2,3 However, if reoperation rates were reported similar to those of other more recent mechanical valves with regard to infection and prosthetic valve dehiscence,4 it has been frequently stated that the Starr–Edwards valves had a higher risk of thrombo-embolic events and of valve dysfunction. In fact, freedom from thrombo-embolic events after the implantation of Starr–Edwards valve in the aortic position varied from 74% to 87% at 10 years depending mainly on the time frame of the studies, which likely reflected evolutions in anticoagulation protocols.4,5 Furthermore, in the most recent series, haemolysis and valve thrombosis rates were reported as low as 0.10% and 0.06% per patient years, respectively.6 We report a case of a 67-year-old patient who was recently reoperated on for rheumatic mitral and tricuspid valve disease and had a Starr–Edwards aortic valve implanted 51 years earlier with no valve dysfunction.

covery within 3 months 2016 Hospitalization for pulmonary oedema revealing severe rheumatic mitral valve insufficiency 2017 Fourth cardiac procedure: mitral valve replacement with a Carbomedics mechanical prosthesis associated with tricuspid valve annuloplasty. The 51-year-old Starr–Edwards aortic valve was let intact. Case report In 1966, a 17-year-old patient underwent reoperation at Broussais hospital for dehiscence and dysfunction of a Magovern valve prosthesis implanted a year earlier for rheumatic aortic valvular disease. A Starr–Edwards Model 1200 prosthesis Size 8A was then implanted. Two years later, this patient had to be reoperated on for valve reinsertion and the silastic ball of the Starr–Edwards valve was also preventively changed. Over the following 50 years, she was maintained under Coumadin, had regular check-ups, and did not present any noticeable medical problems except for a permanent atrial fibrillation (AF) and an ischaemic stroke event in 2009 although the international normalized ratio (INR) was within the therapeutic window between 2.5 and 3.5. She completely recovered from the latter event within 3 days. Recently, at age 67, she became symptomatic with dyspnoea New York Heart Association (NYHA) Class III. Auscultation revealed a systolic murmur at the mitral area. Transthoracic echocardiography showed severe mitral insufficiency associated with increased left ventricular (LV) dysfunction (LV ejection fraction 42% and LV end-systolic diameter 48 mm). The mitral valve was extremely remodelled; the chordae were short and thickened, responsible for a Type IIIa posterior leaflet dysfunction. The anterior leaflet was severely retracted (height 22 mm) but also prolapsing at the level of A2 by lateral displacement of marginal chordae. On the other hand, the Starr–Edwards aortic valve prosthesis was found to function well with a mean transaortic gradient at 16.8 mmHg, peak velocity of 267 cm/s, effective orifice Area of 1.33 cm2, and no significant regurgitation (Figure 1). Moderate tricuspid insufficiency (regurgitant orifice area 25 mm2) and mild pulmonary arterial hypertension (systolic pulmonary arterial pressure 48 mmHg) were also noted. Finally, on preoperative computed tomography scan assessment (Figure 2), an anomalous aortic origin of the circumflex artery originating from the right coronary sinus was detected.

(regurgitant orifice area 25 mm2) and mild pulmonary arterial hypertension (systolic pulmonary arterial pressure 48 mmHg) were also noted. Finally, on preoperative computed tomography scan assessment (Figure 2), an anomalous aortic origin of the circumflex artery originating from the right coronary sinus was detected. Figure 1 Preoperative Transthoracic Echocardiography: continuous-wave Doppler evaluation of the Starr–Edwards aortic prosthesis. Figure 2 3D Computed Tomography imaging volume rendering reconstruction of a three-chamber view showing the normal functioning of the Starr–Edwards valve in the aortic position.

(regurgitant orifice area 25 mm2) and mild pulmonary arterial hypertension (systolic pulmonary arterial pressure 48 mmHg) were also noted. Finally, on preoperative computed tomography scan assessment (Figure 2), an anomalous aortic origin of the circumflex artery originating from the right coronary sinus was detected. Figure 1 Preoperative Transthoracic Echocardiography: continuous-wave Doppler evaluation of the Starr–Edwards aortic prosthesis. Figure 2 3D Computed Tomography imaging volume rendering reconstruction of a three-chamber view showing the normal functioning of the Starr–Edwards valve in the aortic position. The decision was made to operate on her mitral valve. Oral anticoagulation was discontinued 5 days before surgery and relayed by non-fractioned heparin when the INR was below 2.5. The intervention was performed by median sternotomy with the complete release of LV adhesions. Transoesophageal echocardiography in the operating room confirmed that the Starr valve was functioning normally and reinforced our idea of preserving this valve (see Supplementary material online, Video S1 and S2). The extracorporeal circulation was carried out by central canulation under moderate hypothermia. After aortic clamping and anterograde cold blood cardioplegia, the mitral valve was approached via the Sondergaard groove. Analysis of the mitral lesions showed that the valve vas not amenable to a repair procedure. A mitral valve replacement was then performed with a Carbomedics N°29 mechanical prosthesis combined with a tricuspid annuloplasty by a Carpentier-Edwards Physio prosthetic ring N°30. The duration of the aortic cross-clamping was 90 min. The postoperative care was uneventful, except for an episode of transient oliguria and pulmonary congestion which was favourably treated by diuretics and non-invasive ventilation.

ned with a tricuspid annuloplasty by a Carpentier-Edwards Physio prosthetic ring N°30. The duration of the aortic cross-clamping was 90 min. The postoperative care was uneventful, except for an episode of transient oliguria and pulmonary congestion which was favourably treated by diuretics and non-invasive ventilation. The patient was put back on oral anticoagulation with a new targeted INR between 3 and 4. Postoperative echocardiographic assessment of the Starr–Edwards aortic prosthesis showed no functional modification compared with preoperative evaluation (see Supplementary material online, Video S3). The patient was able to leave the hospital quickly and is still doing well 5 months after the intervention.

en 3 and 4. Postoperative echocardiographic assessment of the Starr–Edwards aortic prosthesis showed no functional modification compared with preoperative evaluation (see Supplementary material online, Video S3). The patient was able to leave the hospital quickly and is still doing well 5 months after the intervention. Discussion Since its introduction in 1960, more than 175 000 patients have received the Starr–Edwards valve in the mitral, aortic, or tricuspid position.7 The case of our patient is, to the best of our knowledge, the first reported observation of a Starr–Edwards prosthetic valve still functioning after 50 years. Only two valve-related complications occurred during the follow-up. The first was a reintervention for valve dehiscence 2 years after its implantation. One can assume that this complication was due to a technical cause and not to the Starr–Edwards valve itself, because the native annulus had suffered previous damage from the dehiscence of the initial Magovern prosthesis. The change of the silastic ball had been carried out systematically, but the replaced ball did not present an abnormal infiltration pattern as described for the model 1000.8 The second was an ischaemic stroke that occurred 43 years after implantation without any additional image seen on the cardiac echography. Although thrombus from the valve prosthesis cannot be definitively excluded as the cause of stroke, the patient was also in AF. Contrary to a widely disseminated belief, the rate of thrombo-embolic events in patients with Starr–Edwards valves is not higher than that of patients with the latest generation of valves regardless of the position.9 Fortunately, this event did not have any long-term neurological consequences for our patient who fully recovered. The excellent haemodynamic stability of this valve reported in the literature10 as well as the aortic valve echocardiographic parameters led us to adopt a conservative attitude on this aortic valve. Moreover, mitral valve exposure via the Sondergaard groove was not limited by the aortic valve prosthesis protrusion towards the left atrium. This allowed us to limit the surgical time in a patient with an already significant ventricular dysfunction and thus to reduce the risk of excess mortality and complications inherent in double mitral and aortic valve replacements.11 In view of the need for anticoagulation treatment, we chose to implant a bileaflet mechanical valve in the mitral position.

l time in a patient with an already significant ventricular dysfunction and thus to reduce the risk of excess mortality and complications inherent in double mitral and aortic valve replacements.11 In view of the need for anticoagulation treatment, we chose to implant a bileaflet mechanical valve in the mitral position. Preservation of the posterior subvalvular apparatus during mitral valve replacement was performed in a systematic manner for contributing to late improvement of ventricular function as recommended by many authors and European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines.12,13 Conclusion The excellent durability of the Starr valve is further demonstrated by this observation. This might allow having a conservative attitude regarding these valves, which, in this case, has shortened the operative time, thereby contributing to a good operative outcome. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Supplementary Material Supplementary Video S1 Click here for additional data file. Supplementary Video S2a Click here for additional data file. Supplementary Video S2b Click here for additional data file. Acknowledgements The authors are grateful to Dr Philippe Menasché and Dr Wasseem Borik for their editing contribution. Consent: The authors confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance.

Supplementary Video S2b Click here for additional data file. Acknowledgements The authors are grateful to Dr Philippe Menasché and Dr Wasseem Borik for their editing contribution. Consent: The authors confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: A.C. is a scientific advisor at Edwards Lifesciences R&D. Author Contributions: M.A. compiled data and was involved in writing the article. G.S. helped in editing figures. A.C. was involved in clinical and surgical management and article reviewing. J.J. contributed to clinical and surgical management, article writing, reviewing, and editing.

An 81-year-old man with previous coronary artery bypass grafting was admitted to our hospital for non-ST-segment elevation myocardial infarction, and he was transferred to the cathlab to perform urgent coronary catheterization. Radial access was not considered because of unknown grafts number and anatomy. After a straightforward 6 Fr femoral artery access, it was not possible to advance the 0.035″ J wire in the descending aorta. Even attempts with 0.035″ hydrophilic Terumo® Radifocus® Guidewire M were ineffective, and the angiography showed a severe stenosis of the ipsilateral iliac artery (Figure 1A). After several efforts, we advanced a 0.014″ Terumo® Runthrough® NS floppy coronary wire beyond the stenosis but gentle attempts to advance the diagnostic catheter failed. After positioning the floppy guide wire in the descending aorta, a 1.5 × 20 mm balloon was inflated at 8 atm partially out from the tip of the diagnostic catheter. Then, the diagnostic catheter was advanced beyond the stenosis (balloon-assisted tracking technique1; Figure 1B, Supplementary material online, Video S1). After that, percutaneous coronary intervention was performed on degenerate venous free graft for left coronary circumflex artery (Figure 2). Finally, aortography confirmed an abdominal aortic aneurism with a tight stenosis of proximal right iliac artery (Figure 1C, Supplementary material online, Video S2). The balloon-assisted tracking (BAT) technique was developed to overcome difficulties of transradial access, where arterial spasm and tortuosity may play a major role, rather than tight focal atherosclerotic disease. The application of BAT technique in the femoral setting could be a useful technique to increase support of the 0.014-inch wire allowing a safer catheter advancement, so minimizing risk of vascular damage and reducing the need of an alternative arterial access. Its use should be limited to extreme conditions, when a more supportive guide cannot be positioned beyond a stenotic or tortuous arterial segment. To our knowledge, this is the first report of useful BAT in districts others than arteries of the arm.

scular damage and reducing the need of an alternative arterial access. Its use should be limited to extreme conditions, when a more supportive guide cannot be positioned beyond a stenotic or tortuous arterial segment. To our knowledge, this is the first report of useful BAT in districts others than arteries of the arm. Figure 1 Balloon-assisted tracking of tight stenosis of right iliac artery. (A) Severe stenosis of proximal right iliac artery. (B) Balloon-assisted tracking through right iliac artery. (C) Abdominal aortic aneurism with tight stenosis of proximal right iliac artery. (D) Schematic representation of femoral balloon-assisted tracking. Figure 2 Percutaneous coronary intervention at culprit lesion on degenerate free graft. (A) Degenerate venous free graft for left coronary circumflex artery. (B) Final result after stent implantation. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Supplementary Material Supplementary Data Click here for additional data file. Acknowledgements The authors would like to thank Mr Salvatore Spanu for his graphical support. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.

Learning points Treatment of pulmonary arterial hypertension (PAH)-specific drugs in patients with PAH who have an impossible-to-close ventricular septal defect (VSD) can decrease pulmonary vascular resistance and provide vascular reactivity with oxygen, which then enables VSD closure. However, lifelong follow-up is essential, as long-term studies are lacking. Although VSD closure was associated with further reduction in pulmonary artery pressure, PAH-specific drugs were still required after the closure. Introduction Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and remodelling of pulmonary arteries, leading to elevated pulmonary artery pressure and right heart failure. Congenital shunt disease is one of the causes of PAH.1 High flow by systemic-to-pulmonary (S/P) shunting through a cardiac defect increases shear stress of the pulmonary artery wall and can ultimately remodel pulmonary arteries.2 In an animal study, the disappearance of shunt flow caused pulmonary arterial vasculopathy to regress after flow correction.3,4 Regression of shunt flow by cardiac defect closure can stop progression of PAH and might reverse remodelling of pulmonary arteries.

artery wall and can ultimately remodel pulmonary arteries.2 In an animal study, the disappearance of shunt flow caused pulmonary arterial vasculopathy to regress after flow correction.3,4 Regression of shunt flow by cardiac defect closure can stop progression of PAH and might reverse remodelling of pulmonary arteries. In the 2015 European Society of Cardiology guidelines, PAH associated with congenital heart diseases (CHD) is divided into four clinical groups: (i) Eisenmenger syndrome; (ii) PAH associated with a prevalent S/P shunt; (iii) PAH with small/coincidental defects; and (iv) PAH after defect correction.1 Defect closure is a contraindication in those with Eisenmenger syndrome or PAH with small/coincidental defects. The feasibility of defect closure based on pulmonary vascular resistance (PVR) was studied in patients with PAH associated with a prevalent S/P shunt. Defect closure is possible in patients with PAH associated with an S/P shunt who have low PVR.5 Recently, a ‘treat-and-repair’ strategy has been considered in patients who have S/P shunting but high PVR initially.6 A cardiac defect can be closed in patients whose PVR decreases after treatment with PAH-specific drugs. It remains unknown; however, which patients would benefit from a treat-and-repair strategy, what sort of anti-PAH treatment is effective, and when to perform surgical closure. We report three adult patients with PAH associated with a ventricular septal defect (VSD) in whom a treat-and-repair strategy was used.

c drugs. It remains unknown; however, which patients would benefit from a treat-and-repair strategy, what sort of anti-PAH treatment is effective, and when to perform surgical closure. We report three adult patients with PAH associated with a ventricular septal defect (VSD) in whom a treat-and-repair strategy was used. Patient 1 A 49-year-old woman was diagnosed with VSD at birth and underwent pulmonary artery banding during infancy. She was recently diagnosed with severe PAH and was referred to our hospital for treatment. The patient had dyspnoea. Her heart rate was 111 b.p.m., blood pressure 126/94 mmHg, and SpO2 92% with oxygen administration at 2 L/min. Cardiovascular examination revealed increased intensity of P2 and pansystolic murmur at the third right intercostal space on auscultation and parasternal heave. The lung field were clear. The remainder of the physical examination was unremarkable. Transthoracic echocardiography showed perimembranous-type VSD (34 × 34 mm) with a bidirectional shunt, a dilated right ventricle, and an estimated right ventricular systolic pressure of 108 mmHg (Figure 1A–C; see also Supplementary material online, Video S1). Right heart catheterization (RHC) revealed a mean pulmonary artery pressure (mPAP) of 76 mmHg, PVR index (PVRi) of 15.8 Wood units/m2, pulmonary blood flow-to-systemic blood flow ratio (Qp/Qs) of 1.68, and PVRi systemic vascular resistance index ratio (Rp/Rs) of 0.4 (Table 1). Vasoreactivity testing with the patient breathing 100% oxygen for 10 min showed the following decreases: mPAP 73 mmHg, PVRi 12.5 Wood units/m2, Rp/Rs 0.34. There was also an increase in Qp/Qs of 2.34. Table 1 Haemodynamic change in Patient 1

8, and PVRi systemic vascular resistance index ratio (Rp/Rs) of 0.4 (Table 1). Vasoreactivity testing with the patient breathing 100% oxygen for 10 min showed the following decreases: mPAP 73 mmHg, PVRi 12.5 Wood units/m2, Rp/Rs 0.34. There was also an increase in Qp/Qs of 2.34. Table 1 Haemodynamic change in Patient 1 First evaluation Post-treatment Post-operation Baseline Oxygen Baseline Oxygen Baseline mPAP (mmHg) 76 73 58 72 42 mSAP (mmHg) 94 87 69 70 80 PAWP (mmHg) 11 9 9 11 9 Qp (L/min/m2) 4.11 5.11 5.54 8.53 2.86 Qs (L/min/m2) 2.44 2.18 2.51 2.62 2.86 Qp/Qs 1.68 2.34 2.20 3.26 1 PVRi (WU m2) 15.8 12.5 8.8 7.2 11.5 PVRi reduction rate (%) — −21 — −18 — SVRi (WU m2) 39.3 37.2 25.1 23.3 26.6 Rp/Rs 0.40 0.33 0.35 0.31 0.43 Rp/Rs reduction rate (%) — −18 — −11 — SaO2 97 99 92 99 98 mPAP, mean pulmonary artery pressure; mSAP, mean systemic arterial pressure; PAWP, pulmonary artery wedge pressure; Qp, body surface area (BSA) indexed pulmonary blood flow; Qs, BSA indexed systemic blood flow (cardiac index); PVRi, BSA indexed pulmonary vascular resistance; SVRi, BSA indexed systemic vascular resistance; WU, wood unit; SaO2, arterial oxygen saturation.

temic arterial pressure; PAWP, pulmonary artery wedge pressure; Qp, body surface area (BSA) indexed pulmonary blood flow; Qs, BSA indexed systemic blood flow (cardiac index); PVRi, BSA indexed pulmonary vascular resistance; SVRi, BSA indexed systemic vascular resistance; WU, wood unit; SaO2, arterial oxygen saturation. Figure 1 Patient 1: transthoracic echocardiography. Top panels (A–C) represent the initial evaluation. (A) Parasternal long-axis view. (B) Apical four-chamber view. Arrows identify the ventricular septal defect. (C) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 108 mmHg. Bottom panels (D–F) represent the post-operative evaluation. (D) Parasternal long-axis view. (E) Apical four-chamber view. (F) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 50 mmHg.

er evaluation of tricuspid regurgitation shows the peak pressure gradient at 108 mmHg. Bottom panels (D–F) represent the post-operative evaluation. (D) Parasternal long-axis view. (E) Apical four-chamber view. (F) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 50 mmHg. Because surgical closure of the VSD would be difficult, we started combination therapy with sildenafil 60 mg/day and ambrisentan 5 mg/day. Right heart catheterization performed 3 months after treatment showed mPAP 68 mmHg, PVRi 11.4 Wood units/m2, Qp/Qs 2.13, and Rp/Rs 0.35. We added epoprostenol and gradually increased the dose. Right heart catheterization at 1 year after treatment showed mPAP 58 mmHg, PVRi 8.8 Wood units/m2, Qp/Qs 2.2, and Rp/Rs 0.35. Vasoreactivity testing with 100% oxygen for 10 min showed mPAP 72 mmHg, PVRi 7.2 Wood units/m2, Qp/Qs 3.26, and Rp/Rs 0.31 (with the patient on sildenafil at 60 mg/day, ambrisentan at 5 mg/day, and epoprostenol at 30 ng/kg/min). The patient underwent surgery for the VSD with a patch and a flap valve. Transthoracic echocardiography 10 months post-operatively showed an estimated right ventricular systolic pressure of 50 mmHg (Figure 1D–F; see also Supplementary material online, Video S2). Right heart catheterization performed 10 months post-operatively showed mPAP 42 mmHg, PVRi 11.5 Wood units/m2 (with the patient on sildenafil 60 mg/day, ambrisentan 5 mg/day, epoprostenol 24 ng/kg/min).

mated right ventricular systolic pressure of 50 mmHg (Figure 1D–F; see also Supplementary material online, Video S2). Right heart catheterization performed 10 months post-operatively showed mPAP 42 mmHg, PVRi 11.5 Wood units/m2 (with the patient on sildenafil 60 mg/day, ambrisentan 5 mg/day, epoprostenol 24 ng/kg/min). Patient 2 A 20-year-old man had been diagnosed with VSD and PAH at birth in another hospital. Treatment with sildenafil 60 mg and ambrisentan 10 mg was started at age 5 years. The patient was referred to our hospital at age 20 years. The patient had slight dyspnoea. His heart rate was 58 b.p.m., blood pressure 97/52 mmHg, and SpO2 94% in room air. Cardiovascular examination revealed increased intensity of P2 and pansystolic murmur at the third right intercostal space on auscultation and parasternal heave. The lung field were clear. The remainder of the physical examination was unremarkable. Transthoracic echocardiography showed perimembranous-type VSD (18 × 18 mm) with left-to-right shunt, dilated right ventricle, and estimated right ventricular systolic pressure of 91 mmHg (Figure 2A–C; see also Supplementary material online, Video S3). Right heart catheterization showed mPAP 71 mmHg, PVRi 9.0 Wood units/m2, Qp/Qs 1.59, and Rp/Rs 0.41 (Table 2). Vasoreactivity testing breathing 100% oxygen for 10 min showed no change in mPAP 73 mmHg but decreases in PVRi of 7.8 Wood units/m2, Qp/Qs 2.37, and Rp/Rs 0.30. We initiated administration of beraprost and changed sildenafil to tadarafil. Right heart catheterization performed 1 year later showed mPAP 76 mmHg, PVRi 11.8 Wood units/m2, Qp/Qs 1.34, and Rp/Rs of 0.61. Vasoreactivity testing breathing 100% oxygen for 10 min showed mPAP 72 mmHg, PVRi 7.7 Wood units/m2, Qp/Qs 2.05, and Rp/Rs 0.36 (with the patient on tadarafil at 20 mg/day, ambrisentan at 10 mg/day, and beraprost at 240 µg/day). The patient underwent surgery for patch closure of the VSD and small atrial septal fenestration. Transthoracic echocardiography 2 years later showed estimated right ventricular systolic pressure of 48 mmHg (Figure 2D–F; see also Supplementary material online, Video S4). Right heart catheterization performed 2 years post-operatively showed mPAP 48 mmHg and PVRi 9.1 Wood units/m2 (with the patient on riociguat 7.5 mg/day, macitentan 5 mg/day, and treprostinil 15 ng/kg/min). Table 2 Haemodynamic change in Patient 2

48 mmHg (Figure 2D–F; see also Supplementary material online, Video S4). Right heart catheterization performed 2 years post-operatively showed mPAP 48 mmHg and PVRi 9.1 Wood units/m2 (with the patient on riociguat 7.5 mg/day, macitentan 5 mg/day, and treprostinil 15 ng/kg/min). Table 2 Haemodynamic change in Patient 2 First evaluation Post-treatment Post-operation Baseline Oxygen Baseline Oxygen Baseline mPAP (mmHg) 71 73 76 72 48 mSAP (mmHg) 92 87 86 84 80 PAWP (mmHg) 18 20 12 16 18 Qp (L/min/m2) 5.87 6.8 5.44 7.27 4.5 Qs (L/min/m2) 3.69 2.87 4.06 3.55 3.3 Qp/Qs 1.59 2.37 1.34 2.05 – PVRi (WU m2) 9.0 7.8 11.8 7.7 9.1 PVRi reduction rate (%) — −13 — −35 — SVRi (WU m2) 22.2 26.1 19.5 21.4 21.8 Rp/Rs 0.41 0.30 0.61 0.36 0.42 Rp/Rs reduction rate (%) — −27 — −49 — SaO2 94 99 94 99 99 mPAP, mean pulmonary artery pressure; mSAP, mean systemic arterial pressure; PAWP, pulmonary artery wedge pressure; Qp, body surface area (BSA) indexed pulmonary blood flow; Qs, BSA indexed systemic blood flow (cardiac index); PVRi, BSA indexed pulmonary vascular resistance; SVRi, BSA indexed systemic vascular resistance; WU, wood unit; SaO2, arterial oxygen saturation.

temic arterial pressure; PAWP, pulmonary artery wedge pressure; Qp, body surface area (BSA) indexed pulmonary blood flow; Qs, BSA indexed systemic blood flow (cardiac index); PVRi, BSA indexed pulmonary vascular resistance; SVRi, BSA indexed systemic vascular resistance; WU, wood unit; SaO2, arterial oxygen saturation. Figure 2 Patient 2: transthoracic echocardiography. Top panels (A–C) represent the initial evaluation. (A) Parasternal short-axis view, (B) Apical four-chamber view. Arrows identify the ventricular septal defect. (C) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 91 mmHg. Bottom panels (D–F) represent the post-operative evaluation. (D) Parasternal short-axis view. (E) Apical four-chamber view. (E) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 48 mmHg.

er evaluation of tricuspid regurgitation shows the peak pressure gradient at 91 mmHg. Bottom panels (D–F) represent the post-operative evaluation. (D) Parasternal short-axis view. (E) Apical four-chamber view. (E) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 48 mmHg. Timeline Time Events Case 1 At birth Diagnosis of ventricular septal defect (VSD) 49 years of age Diagnosis of pulmonary arterial hypertension (PAH). Mean pulmonary artery pressure (PAP) of 76 mmHg and indexed pulmonary vascular resistance (PVRi) of 15.8 Wood units/m2. Started treatment with sildenafil (60 mg/day) and ambrisentan (5 mg/day) 3 months later Addition of epoprostenol and titration of the dose 12 months later Mean PAP of 58 mmHg, PVRi of 8.8 Wood units/m2. Repair of VSD 22 months later Mean PAP of 42 mmHg and PVRi of 11.5 Wood units/m2 (sildenafil at 60 mg/day, ambrisentan at 5 mg/day, and epoprostenol at 24 ng/kg/min) Case 2 At birth Diagnosis of VSD and PAH 5 years of age Started treatment with sildenafil (60 mg/day) and ambrisentan (10 mg/day) 20 years of age Addition of beraprost (240 µg/day) and change from sildenafil to tadarafil (20 mg/day). 12 months later Mean PAP of 76 mmHg and PVRi of 11.8 Wood units/m2. Repair of VSD 36 months later Mean PAP of 48 mmHg and PVRi of 9.1 Wood units/m2 (riociguat at 7.5 mg/day, macitentan at 5 mg/day, and treprostinil at 15 ng/kg/min) Case 3 2 years of age Diagnosis of VSD and PAH 4 years of age Left pulmonary artery banding 18 years of age Started treatment with ambrisentan (10 mg/day) 49 years old of age Mean PAP of 60 mmHg and PVRi of 12 Wood units/m2. Addition of main pulmonary artery banding 12 months later Mean PAP of 38 mmHg and PVRi of 6.5 Wood units/m2. Repair of VSD 18 months later Mean PAP of 15 mmHg and PVRi of 4 Wood units/m2 (ambrisentan at 10 mg/day) Patient 3 A 49-year-old woman was diagnosed with VSD and PAH at 2 years of age in another hospital. Left pulmonary artery banding was performed at age 4 years. Treatment with ambrisentan and warfarin was started at age 18 years. At age 49 years, the patient was referred to our hospital for possible VSD closure. The patient had slight dyspnoea. Her heart rate was 76 b.p.m., blood pressure 95/46 mmHg, and SpO2 95% breathing room air. Cardiovascular examination revealed pansystolic murmur at the third right intercostal space on auscultation. The lung field were clear. The remainder of the physical examination was unremarkable.

. The patient had slight dyspnoea. Her heart rate was 76 b.p.m., blood pressure 95/46 mmHg, and SpO2 95% breathing room air. Cardiovascular examination revealed pansystolic murmur at the third right intercostal space on auscultation. The lung field were clear. The remainder of the physical examination was unremarkable. Transthoracic echocardiography showed a perimembranous, muscular-type VSD (18 × 19 mm) with a bidirectional shunt, dilated right ventricle, and estimated right ventricular systolic pressure of 56 mmHg (Figure 3A–C; see also Supplementary material online, Video S5). Right heart catheterization showed mPAP 60 mmHg, PVRi 12 Wood units/m2, Qp/Qs 2.54, and Rp/Rs 0.29 (Table 3). Vasoreactivity testing with the patient breathing 100% oxygen for 10 min did show decreased mPAP (at 60 mmHg) but was associated with decreased PVRi of 6.0 Wood units/m2 and Rp/Rs of 0.2 and increased Qp/Qs of 4.42. The initial strategy was to band the main pulmonary artery. Right heart catheterization performed 1 year after banding showed decreases in mPAP of 38 mmHg, PVRi of 6.5 Wood units/m2, and Rp/Rs of 0.21. Qp/Qs was increased by 2.87. Vasoreactivity testing breathing 100% oxygen for 10 min showed mPAP 43 mmHg, PVRi 5.8 Wood units/m2, Qp/Qs 3.72, and Rp/Rs 0.14 (with the patient on ambrisentan 10 mg/day). The patient underwent surgery for patch closure of the VSD and debanding of the main and left pulmonary arteries. Transthoracic echocardiography 6 months later showed an estimated right ventricular systolic pressure of 29 mmHg (Figure 3D–F; see also Supplementary material online, Video S6). Right heart catheterization performed 6 months after surgery showed mPAP 15 mmHg and PVRi 4 Wood units/m2 (with the patient on ambrisentan at 10 mg/day). Table 3 Haemodynamic change in Patient 3

an estimated right ventricular systolic pressure of 29 mmHg (Figure 3D–F; see also Supplementary material online, Video S6). Right heart catheterization performed 6 months after surgery showed mPAP 15 mmHg and PVRi 4 Wood units/m2 (with the patient on ambrisentan at 10 mg/day). Table 3 Haemodynamic change in Patient 3 First evaluation Post-treatment Post-operation Baseline Oxygen Baseline Oxygen Baseline mPAP (mmHg) 60 60 38 43 15 mSAP (mmHg) 73 62 60 70 52 PAWP (mmHg) 13 14 6 9 7 Qp (L/min/m2) 3.92 7.69 4.91 5.88 2.26 Qs (L/min/m2) 1.54 1.74 1.71 1.58 2.26 Qp/Qs 2.54 4.42 2.87 3.72 1 PVRi (WU m2) 12.0 6 6.5 5.8 4.0 PVRi reduction rate (%) — −50 — −11 — SVRi (WU m2) 41.6 30.5 32.2 40.5 21.7 Rp/Rs 0.29 0.20 0.21 0.14 0.18 Rp/Rs reduction rate (%) — −31 — −33 — SaO2 96 99 92 99 95 mPAP, mean pulmonary artery pressure; mSAP, mean systemic arterial pressure; PAWP, pulmonary artery wedge pressure; Qp, body surface area (BSA) indexed pulmonary blood flow; Qs, BSA indexed systemic blood flow (cardiac index); PVRi, BSA indexed pulmonary vascular resistance; SVRi, BSA indexed systemic vascular resistance; WU, wood unit; SaO2, arterial oxygen saturation.

temic arterial pressure; PAWP, pulmonary artery wedge pressure; Qp, body surface area (BSA) indexed pulmonary blood flow; Qs, BSA indexed systemic blood flow (cardiac index); PVRi, BSA indexed pulmonary vascular resistance; SVRi, BSA indexed systemic vascular resistance; WU, wood unit; SaO2, arterial oxygen saturation. Figure 3 Patient 3: Transthoracic echocardiography. Top panels (A–C) represent the initial evaluation. (A) Parasternal long-axis view. (B) Apical four-chamber view. Arrows identify the ventricular septal defect. (C) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 56 mmHg. Bottom panels (D–F) represent the post-operative evaluation. (C) Parasternal long-axis view. (D) Apical four-chamber view. (C) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 29 mmHg.

ler evaluation of tricuspid regurgitation shows the peak pressure gradient at 56 mmHg. Bottom panels (D–F) represent the post-operative evaluation. (C) Parasternal long-axis view. (D) Apical four-chamber view. (C) Continuous-wave Doppler evaluation of tricuspid regurgitation shows the peak pressure gradient at 29 mmHg. Discussion During the natural history of PAH associated with VSD in adult patients, PAH and right heart failure develop, ultimately leading to a change from left-to-right shunting to right-to-left shunting (i.e. Eisenmenger syndrome). This condition then leads to severe hypoxia, cyanosis, and death. Recent advances in PAH-specific drugs have dramatically changed the treatment for PAH to a treatment-and-repair strategy.7 Treatment with PAH-specific drugs initially and then repair by cardiac defect closure has thus been attempted in patients with PAH associated with a cardiac defect. Our experience of three cases of PAH associated with VSD revealed three important points: (i) all three patients showed a response to vasoactive testing with oxygen breathing (decreased PVRi and Rp/Rs without reducing the decreased mPAP because of increased Qp/Qs); (ii) reduced PVRi 12 months after starting treatment with a combination of PAH-specific drugs; (iii) VSD closure was associated with further reduction in mPAP, although PAH-specific drugs were still required.

ith oxygen breathing (decreased PVRi and Rp/Rs without reducing the decreased mPAP because of increased Qp/Qs); (ii) reduced PVRi 12 months after starting treatment with a combination of PAH-specific drugs; (iii) VSD closure was associated with further reduction in mPAP, although PAH-specific drugs were still required. A treat-and-repair strategy has three merits for patients with PAH associated with a cardiac defect. First, closing the defect can prevent the progression of Eisenmenger syndrome. Although the short-term outcome in these patients is good (5-year survival 88%),8 their survival rate reportedly declined annually after age 40 years.8 Second, further reduction in mPAP is obtained by shunt closure because the high flow due to S/P shunting is diminished. Third, PAH-specific drugs are easy to use after shunt closure. Pulmonary arterial hypertension-specific drugs increase left-to-right shunting and can promote pulmonary artery remodelling by increasing shear stress under cardiac shunt. A treat-and-repair strategy is thought to be more difficult in patients with PAH associated with VSD than in those with PAH associated with an atrial septal defect which is a pretricuspid valve cardiac defect associated with volume overload in the right ventricle. In contrast, VSD is a post-tricuspid valve cardiac defect associated with both volume and pressure overload. Therefore, PAH-specific drugs in patients with VSD could easily cause right heart failure. Hence, care must be taken when using PAH-specific drugs in these patients.

with volume overload in the right ventricle. In contrast, VSD is a post-tricuspid valve cardiac defect associated with both volume and pressure overload. Therefore, PAH-specific drugs in patients with VSD could easily cause right heart failure. Hence, care must be taken when using PAH-specific drugs in these patients. The indication for defect closure is important for a successful treat-and-repair strategy. Defect closure in patients with high PVR could cause pulmonary hypertension crisis and death because shunting partially acts as a safety valve in PAH patients with CHD.9 It was reported that defect closure in patients with high PVR associated with VSD caused immediate post-operative death.10 Achieving low PVR is therefore desirable before defect closure. Criteria for shunt closure in the 2015 European Society of Cardiology guidelines were based on baseline PVR data from the most recent literature.1 Shunt closure is contraindicated when the PVRi is >8 Wood units/m2. When PVRi is 4–8 Wood units/m2, patients should be referred to a centre with expertise in evaluating patients’ operability via vasoreactivity testing.

an Society of Cardiology guidelines were based on baseline PVR data from the most recent literature.1 Shunt closure is contraindicated when the PVRi is >8 Wood units/m2. When PVRi is 4–8 Wood units/m2, patients should be referred to a centre with expertise in evaluating patients’ operability via vasoreactivity testing. Vasoreactivity testing is important for evaluating operability because the criteria for shunt closure based on the results of vasoreactivity testing have been proposed. Lopes et al.11 recommended that a baseline PVRi < 6 Wood units/m2 and Rp/Rs < 0.3 be used as favourable criteria for defect closure. Vasoreactivity testing should be performed if the baseline PVRi is 6–9 Wood units/m2 and the Rp/Rs is 0.3–0.5. Here, a decrease in PVRi of 20%, a decrease in Rp/Rs of 20%, a final PVRi of <6 Wood units/m2, and a final Rp/Rs < 0.3 indicates that it is possible to close the cardiac defect. In our case series, all three patients showed a response to vasoactive testing with oxygen breathing. These criteria were fully met in Patients 2 and 3 and were almost met in patient 1. None of our three patients had post-operative complications. Hu et al.12 reported results of a treat-and-repair strategy for 39 adult patients with PAH associated with VSD and high PVR. Six patients (15%) experienced pulmonary hypertension crises, and two patients (5%) died post-operatively. These patients did not meet the aforementioned criteria preoperatively. Sufficient reduction of the PVR or Rp/Rs by PAH-specific drugs could contribute to successful defect closure.

sociated with VSD and high PVR. Six patients (15%) experienced pulmonary hypertension crises, and two patients (5%) died post-operatively. These patients did not meet the aforementioned criteria preoperatively. Sufficient reduction of the PVR or Rp/Rs by PAH-specific drugs could contribute to successful defect closure. The anti-PAH treatment chosen is important. We chose anti-PAH treatment according to the baseline PVRi and PVRi and Qp/Qs responses during vasoreactivity testing. If the responses of PVRi and Qp/Qs during vasoreactivity testing were good, regardless of the baseline PVRi, we chose pulmonary artery binding because we thought that high flow was related to this state. If the baseline PVRi was high and the PVRi and/or Qp/Qs response during vasoreactivity testing was weak, we administered PAH-specific drugs. Treatment with an endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) has been shown to produce favourable functional and haemodynamic results in patients with PAH associated with CHD.13–16 Therefore, our first choice of PAH-specific drugs were an ERA and a PDE5i. When the PVRi remained high and the response of the PVRi and/or Qp/Qs during vasoreactivity testing was weak after treatment with the ERA and PDE5i, we chose epoprostenol. If the PVRi remained moderate and the response of the PVRi and/or Qp/Qs during vasoreactivity testing was weak after treatment with the ERA and PDE5i, we changed the drug and/or used triple oral combination therapy. Hence, further accumulation of cases is needed to establish an effective strategy for anti-PAH treatment before VSD closure.

moderate and the response of the PVRi and/or Qp/Qs during vasoreactivity testing was weak after treatment with the ERA and PDE5i, we changed the drug and/or used triple oral combination therapy. Hence, further accumulation of cases is needed to establish an effective strategy for anti-PAH treatment before VSD closure. We performed vasoreactivity testing with 100% oxygen breathing to predict operability. This effectiveness of this method, however, is controversial. The use of 100% oxygen may decrease the accuracy of flow calculations by the Fick method because a small arteriovenous oxygen difference magnifies any saturation error, which would cause lower resistance. Nitric oxide is also used for vasoreactivity testing and perhaps should be considered for predicting operability. A fenestrated VSD patch was used in Patient 1. A fenestrated VSD patch converts a large VSD into a small VSD. This fenestration allows for a right-to-left shunt when the PAP remains high post-operatively, which could prevent pulmonary hypertensive crises,17 although a right-to-left shunt through a fenestrated VSD patch might lead to systemic desaturation and prolonged intubation. The remaining shunting is associated with infective endocarditis and systemic embolism.18 A pop-off valve in the VSD patch should be used in selected cases. Conclusion We successfully adopted a treat-and-repair strategy in adult patients with severe PAH associated with VSD. Our case series suggests that this strategy is a promising approach for adult patients with severe PAH associated with VSD. Supplementary material

A fenestrated VSD patch was used in Patient 1. A fenestrated VSD patch converts a large VSD into a small VSD. This fenestration allows for a right-to-left shunt when the PAP remains high post-operatively, which could prevent pulmonary hypertensive crises,17 although a right-to-left shunt through a fenestrated VSD patch might lead to systemic desaturation and prolonged intubation. The remaining shunting is associated with infective endocarditis and systemic embolism.18 A pop-off valve in the VSD patch should be used in selected cases. Conclusion We successfully adopted a treat-and-repair strategy in adult patients with severe PAH associated with VSD. Our case series suggests that this strategy is a promising approach for adult patients with severe PAH associated with VSD. Supplementary material Supplementary material is available at European Heart Journal - Case Reports online. Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared. Supplementary Material Supplementary Data Click here for additional data file.

Case description A 34-year-old man presented with drug refractory symptomatic atrial tachycardia (AT) a month after bicaval orthotopic heart transplantation due to dilated cardiomyopathy. An electrophysiological study was performed after transplant rejection was ruled out. The activation map in the right atrium (RA) during the AT showed a centrifugal activation from the high atrial septum. Atrial tachycardia was terminated due to a mechanical bump of catheter manoeuvre (Pentaray NAV) and was never induced thereafter. Atrial tachycardia was assumed to be originated from the left atrium (LA). Following a trans-septal puncture, the local potential in the LA during sinus rhythm was evaluated. Automatic electrical activities of the recipient heart were observed in the LA posterior wall and four pulmonary veins, which were dissociated from the donor rhythm. A line of sites with the dissociated two rhythms revealed the anastomosis line between the donor and the recipient heart. The anastomosis line in the LA could be projected in an electroanatomical mapping system by tagging these sites (Figure 1). In atrial pace mapping,1 the LA anteroseptal wall in the donor site adjacent to the anastomosis showed the best pace map that approximated the configuration of P wave and intracardiac electrograms of the clinical AT. This site was just opposite to the earliest activation site in the RA. We identified this site as the origin of the AT, and radiofrequency (RF) catheter ablation was performed (Figure 2). The AT did not recur during 1 year of follow-up. Previous studies reported focal ATs arising from a low-voltage area in the RA adjacent to the anastomosis line2 and ATs from a recipient LA conducting to the donor atria.3 To the best of our knowledge, this is the first report of focal AT originated from the donor LA after heart transplantation and treated with catheter ablation.

udies reported focal ATs arising from a low-voltage area in the RA adjacent to the anastomosis line2 and ATs from a recipient LA conducting to the donor atria.3 To the best of our knowledge, this is the first report of focal AT originated from the donor LA after heart transplantation and treated with catheter ablation. Figure 1 Electrophysiological identification of the anastomosis line. (A) Local electrograms on the anastomosis line during sinus rhythm. White arrowheads and black arrowheads indicate donor rhythm and recipient rhythm, respectively. (B) The line of light blue dots represents the anastomosis line. CS, coronary sinus; HRA, high right atrium; RV, right ventricle. Figure 2 Origin of the focal atrial tachycardia in the left atrium. (A) Intracardiac electrograms and the configuration of P wave at the best pace mapping site (left atrium anteroseptum). (B) The dark blue dot in the left atrium represents the best pace mapping site. The activation map in the right atrium was performed during the atrial tachycardia. CS, coronary sinus; HRA, high right atrium; RV, right ventricle. Conflict of interest: none declared. Author contributions: S.K. and Y.M conceived, designed, analysed, and interpreted data; S.K., Y.M., A.C drafted the manuscript and revised it critically for important intellectual content; and H.T approved the final manuscript submitted.

Patient information Learning point Ventricular tachycardia is not always due to a primary cardiac pathology, a wide array of other causes especially endocrinal causes should be entertained. A 35-year-old female presented to the emergency department of a nearby hospital with nausea, vomiting, and giddiness since 3 days. She was dry and cold to touch and the pulse and blood pressure were not measurable. Initial assessment was remarkable for gross clinical features of hypothyroidism with hoarse voice and myxoedema. A rhythm strip (long lead II) ECG (Figure 1) revealed broad complex polymorphic ventricular tachycardia (PMVT). Successful cardioversion was performed with 150 J asynchronous DC shock. Baseline sinus rhythm showed a prolonged corrected QT interval (QTc) of 760 ms with T-wave inversion in V1–V6, I, avl, II, III, and avf (Figure 2). Post-cardioversion she had normal pulse of good volume, force, and tension with BP of 110/70 mmHg. On auscultation she had normal S1S2 with no added sounds. Figure 1 Long lead II (rhythm strip) showing Broad complex polymorphic ventricular tachycardia (PMVT). Figure 2 Baseline 12-lead ECG showing sinus rhythm with prolonged QT interval (QTc) of 760 ms with T-wave inversion in V1–V6, avl, II, III, and avf.