Case Presentation: An 82-year-old male with a history of coronary artery disease, type 2 diabetes mellitus, and cholangiocarcinoma presented with palpitations. Elevated troponin levels were noted at an outside hospital, he left against medical advice and present to UCLA for further evaluation. He presented with fatigue since his recent first cycle of treatment (cisplatin, gemcitabine, and durvalumab) and new symptom of palpitations without chest pain or shortness of breath. Vital signs and exam were unremarkable other than bradycardia to 50 bpm. His high sensitivity troponin peaked at 7,000 ng/L and his echocardiogram revealed normal left ventricular systolic function. He received aspirin, Plavix, an unfractionated heparin drip, and solumedrol for coronary angiogram given a listed iodine allergy. The patient underwent percutaneous intervention for severe coronary disease given significant left circumflex and RCA occlusions, and received temporary pacemaker, followed by a dual-chamber permanent pacemaker for persistent high-grade AV block. The day after he noted mild difficulty talking and swallowing. He passed a speech and language swallow evaluation, CT of the brain without contrast was unremarkable, and Myasthenia gravis labs returned negative. He was discharged with a neurology appointment. Over a week, he developed new neurologic symptoms of increasing dysphagia, dysarthria, and difficulty speaking. A laryngoscopic evaluation and MRI of the brain were unremarkable, and repeat swallow evaluation showed frank aspiration. His condition deteriorated, with proximal upper extremity weakness, recurrent pneumonias, leading to respiratory failure. Elevated creatinine kinase level and abnormal nerve conduction study suggested myositis. A cardiac MRI showed subendocardial hyper-enhancement, supporting myocarditis.The patient was diagnosed with an immune-mediated myocarditis-myositis-myasthenia gravis overlap syndrome, also known as “Triple-M syndrome,” likely triggered by immunotherapy. He received three days of 1g of methylprednisolone, followed by a steroid taper, IVIG, and pyridostigmine. He showed improvement in strength and a reduced need for ventilatory support; however, his respiratory failure remained severe. After a period of comfort-oriented care, he passed away peacefully.
Discussion: This case emphasizes the importance of broadening the differential diagnosis for elevated troponin, particularly in the absence of chest pain to include non-ischemic causes, such as myocarditis. Clinicians should always consider a patient’s oncologic history and review all medications, especially emerging therapies like immunotherapy, which may not be on the active medication list. Immunotherapy complications can have diverse manifestations and should be considered as potential causes of new symptoms, almost regardless of when the medication was administered. This syndrome is a particularly severe example of immunotherapy-related adverse effects.
Conclusions: This case highlights the complex intersection of cancer treatment, cardiac, and neuromuscular complications. The combination of chemotherapy, immunotherapy, and ischemic heart disease led to a multifaceted clinical presentation. This vignette underscores the importance of recognizing rare, but potentially life-threatening complications in patients undergoing cancer treatment, including immune-mediated myocarditis and myositis, and the need for a multidisciplinary approach to diagnosis and management.
