Right ventricular myocarditis and rapid fibrosis induced by pazopanib.

Abstract

A 56-year-old woman with metastatic chondrosarcoma visited our emergency department because of chest discomfort. Treatment with oral pazopanib, a multi-targeted tyrosine kinase inhibitor that targets angiogenesis growth factor receptors, fibroblast growth factor receptors, platelet-derived growth factor receptors, and vascular endothelial growth factor receptors, was initiated 26 days previously. Electrocardiography showed new-onset significant ST elevation in the precordial leads V1–V3 and pathologic Q-waves in leads III and aVF (Panel A). The cardiac and inflammatory biomarker levels were elevated as follows: creatine kinase (CK), 705 (reference range, 32–135 IU/L); CK-myocardial band (MB) fraction, 12.5 (reference range, 0–5 ng/mL); troponin-T, 402 (reference range, 0–14 pg/mL); NT-proBNP, 11 230 (reference range, 0–287 pg/mL); and C-reactive protein, 77.3 (reference range, 0–8 mg/L). Echocardiography showed newly developed akinesia with thinning in the septum and throughout the right ventricle with markedly reduced biventricular systolic dysfunction compared with echocardiography performed 1 month ago (Panel B and Supplementary data online, Video). Luminal narrowing or thrombosis in the coronary arteries was not observed on emergency coronary angiography (Panel C). Cardiac magnetic resonance imaging performed on the second day of hospitalization showed diffuse late gadolinium enhancement in the right ventricular wall and the right side of the septum (Panel D). The nails of both hands showed hyperpigmentation and onycholysis induced by taking pazopanib (Panel E). Despite the discontinuation of pazopanib and heart failure management, she developed fatal ventricular tachycardia and cardiogenic shock (Panel F). Imaging findings show pazopanib-induced right ventricular myocarditis with subsequent rapid wall thinning and fibrosis.