AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Cardiomyopathy Masquerading as Cancer Therapy Related Cardiac Toxicity: A Multi-Hit Phenomenon?
By Parvathala N, Bloom M
Intro: Myocardial dysfunction is a recognized but uncommon manifestation of cancer therapy related cardiac toxicity (CTRCT) associated with cisplatin. While CTRCT should always be considered in patients with cancer who develop new cardiomyopathy (CM), anchoring on chemotherapy as the default etiology might confound alternate diagnoses. We present a case in which genetic predisposition and high premature ventricular contraction (PVC) burden were more likely drivers of acute decompensated heart failure (ADHF) and CM. This illustrates the consideration of a "multi-hit hypothesis" for CM in patients with cancer. Patient Information: A 65-year-old male with HPV-positive tonsillar squamous cell carcinoma, and past medical history of hyperlipidemia, nonobstructive CAD, and CKD presented with new-onset ADHF. Timeline: The patient completed 4 cycles of cisplatin and 70Gy chemoradiation, achieving remission. Six months after chemotherapy discontinuation, he was hospitalized for ADHF with LVEF 20%, LVIDd 5.60 cm, and angiogram revealed nonobstructive coronary disease. Holter monitoring revealed 25% multifocal PVC burden and a 7-beat run of NSVT. Cardiac MRI revealed LVEF 29%, RVEF 45%, minimal midwall LGE in the basal anteroseptum, and no T2 signal abnormality. Genetic testing identified a pathogenic TTN truncating variant p. Q23904* (c.71710C>T). Diagnostic Assessment: Initial attribution to cisplatin cardiotoxicity was challenged by 3 findings: (1) 6-month lag between last cisplatin exposure and ADHF, atypical for acute cisplatin toxicity; (2) 25% PVC burden sufficient to independently induce CM; (3) pathogenic TTN variant. MRI without myocardial edema/inflammation argued against acute toxic etiology. We propose a multi-hit mechanism: TTN-related myocardial vulnerability compounded by high PVC burden, with cisplatin as an unlikely primary etiology, but possible contributor. Intervention: Guideline directed medical therapy (GDMT) was initiated including sacubitril/valsartan, metoprolol, spironolactone, and dapagliflozin. The patient declined PVC ablation and ICD implantation after shared decision-making. OutcomesSeven months after GDMT initiation, LVEF remained reduced (30%, LVIDd 6.2 cm), although the patient remains asymptomatic, NYHA Class I, with unlimited exercise tolerance. Discussion: This case highlights the risk of anchoring bias in cardio-oncology. TTN truncating variants are the most common genetic cause of dilated CM, and PVC burden >20% can lead to myocardial dysfunction. CTRCT secondary to cisplatin includes a spectrum of supraventricular and ventricular arrhythmias, myocardial infarction, and thromboembolic events, albeit CM is rare. A broad diagnostic evaluation, including assessment of genetic susceptibility, is essential when evaluating CM in patients with cancer.