LAUSR

A 66-year-old man with chronic myelomonocytic leukaemia (CMML) presented with myalgias and acute-onset shortness of breath, profound orthopnoea, and bilateral pedal oedema of 1 day’s duration. He had been diagnosed with CMML a year and half before presentation, and after an inadequate response to four cycles of decitabine chemotherapy, he underwent a matched unrelated donor allogeneic haematopoietic stem cell transplant 7 months before presentation. Six months after his transplant, he developed recurrent anaemia and thrombocytopenia, and bone marrow biopsy confirmed relapsed CMML. He was enrolled in an experimental protocol of ipilimumab, a monoclonal antibody (IgG1) that blocks the checkpoint protein cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), to promote anti-tumour immunity. One week after receiving his first infusion, he was admitted to the hospital with abdominal pain and diarrhoea, and was found to have colitis involving the descending and sigmoid colon. He underwent flexible sigmoidoscopy and biopsy of the inflamed tissue showed focal active colitis and ulceration with no diagnostic features of cytomegalovirus infection or graft-vs.-host disease. A diagnosis of ipilimumab-related colitis was made, and he was treated with a 7-day taper of dexamethasone. His presenting cardiopulmonary symptoms began on the day after he completed corticosteroid treatment. At presentation, his temperature was 36.8 ∘C, pulse was 108 b.p.m., blood pressure was 116/59 mmHg, respiratory rate was 24/min, and oxygen saturation was 92% on room air. His breathing was laboured and he was unable to lie flat. His jugular venous pressure was elevated at 12 cmH2O. Auscultation of the heart and lungs revealed a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . rapid and regular heart rate, an S4 gallop, and audible crackles at the bases of both lung fields. His extremities were warm and he had 2+ bilateral symmetric pitting pedal oedema. His complete blood count was near his recent baseline with a white blood cell count of 33×103 cells/mm3 (with 44% monocytes), haematocrit was 28.9%, and platelet count was 7000/μL. Other laboratories measurements of note included a serum sodium of 132 mmol/L, alanine aminotransferase 268 U/L, aspartate aminotransferase 189 U/L, lactate 2.9 mmol/L, troponin-T 1.99 ng/mL (reference range <0.01 ng/mL), creatine kinase 1172 U/L (reference range 39–308 U/L), creatine kinase MB isoenzyme 168.5 ng/ml (reference range 0.0–7.7 mg/ml), and N-terminal-pro-B-type natriuretic peptide 2155 pg/ml (reference range <900 pg/ml). His electrocardiogram showed low voltage, sinus rhythm, and a new right bundle branch block (Figure 1), and chest radiography revealed mild interstitial oedema and small bilateral pleural effusions. Computed tomography angiography of the chest showed no evidence of pulmonary embolism. Transthoracic echocardiography demonstrated preserved left ventricular systolic function (ejection fraction 70%) with evidence of diastolic dysfunction, normal right ventricular size and function, and no significant valvular lesions. He was given intravenous furosemide for decongestion and admitted to the cardiac intensive care unit for closer monitoring. It was recommended that a pulmonary artery catheter be placed for closer haemodynamic assessment; however, the patient declined invasive monitoring. Within hours of presentation, he developed progressive hypotension requiring the initiation of dopamine as well as progressive high-grade atrioventricular block and ultimately complete heart block with a wide ventricular escape (Figure 1). He was started on empirical high-dose methylprednisolone (1000 mg daily), and was offered temporary transvenous pacing and right heart catheterization with endomyocardial biopsy, but again declined all invasive measures. Following extensive discussion between the patient, the treating oncologist, and the intensive care unit team, the patient was transitioned to comfort measures only given . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . his poor oncological prognosis. He expired within 24 h. Post-mortem examination with microscopic evaluation of skeletal muscle biopsies demonstrated inflammatory myositis, characterized by a predominantly CD3+ T-cell inflammatory infiltrate with associated myocyte necrosis (Figure 2). Microscopic evaluation of cardiac muscle was not performed because of the family’s request for a limited post-mortem examination.