Anthracycline Treatment and Ventricular Remodeling in Left Ventricular Assist Device Patients

Abstract

Nonischemic cardiomyopathy can complicate antineoplastic therapy and lead to irreversible heart failure. We evaluated structural changes at the time of left ventricular assist device implantation in heart failure patients who had been exposed to anthracycline, and we correlated those changes with clinical presentation. We retrospectively studied left ventricular core samples taken at implantation of the HeartMate II left ventricular assist device in 12 heart failure patients (mean age, 46 ± 16 yr) who had histories of anthracycline exposure. We evaluated those samples for hypertrophy, myocytolysis, and fibrosis. Histopathologic findings showed moderate-to-severe myocyte hypertrophy, moderate myocytolysis, and perivascular and interstitial fibrosis with areas of replacement fibrosis. Ultrastructural studies revealed marked decreases in myofibrils, diffuse mitochondrial swelling, and disorganization of the sarcoplasmic reticulum. The interval between anthracycline therapy and heart failure was a mean of 6.8 ± 5.7 years; duration of heart failure symptoms, 38 ± 47 months; and duration of device support, 414 ± 266 days. Four patients are continuing on device support, 3 have undergone transplantation, 3 have undergone device explantation, and 2 have died. The time of heart failure onset and the duration of symptoms did not correlate with the severity and extent of the histopathologic changes. The histopathologic findings and the clinical course varied in heart failure patients with anthracycline exposure. No correlation was observed between anthracycline therapy and the development or duration of heart failure symptoms, severity of histopathologic changes, or outcomes.