Pathology of late-onset anthracycline cardiomyopathy

Introduction: Anthracyclines are known to have acute cardiotoxicity. Anthracycline-induced dilated cardiomyopathy may have late onset and present years after administration of the drug. Several studies have described the clinical findings in patients with late-onset cardiomyopathy, including electrocardiography, exercise testing, echocardiography, and histological findings in endomyocardial biopsies; however, there is little information on the pathological changes that are found in explanted or autopsy hearts.

Methods: We reviewed the medical records and microscopic slides of heart tissue from one patient who had an autopsy and from nine patients who had cardiac transplants between 2001 and 2008. Heart weights were compared to historic controls (heart weights normalized for the patient's heights). Hematoxylin and eosin (H&E)-stained slides were semiquantitated for evidence of necrosis, myocytolysis, interstitial fibrosis, replacement fibrosis, and the presence of inflammation.

Results: The average heart weight ranged from 231 to 470 g (mean=317 ± 65 g, median=303 g). Review of the histological sections revealed no evidence of significant necrosis or myocytolysis. Interstitial fibrosis was identified in all 10 patients, with six patients showing multifocal fibrosis, three patients showing diffuse fibrosis, and only one patient showing focal fibrosis. Replacement fibrosis was identified in six patients, with two patients displaying multifocal and four patients displaying focal replacement fibrosis.

Conclusion: Late-onset cardiomyopathy is a serious consequence of anthracycline therapy resulting in death or the need for cardiac transplantation in some patients. Unlike most other forms of dilated cardiomyopathy, the major pathological changes appear to be interstitial and/or replacement fibrosis without significant cardiac hypertrophy.