Chronic anthracycline cardiotoxicity: haemodynamic and histopathological manifestations suggesting a restrictive...

Of 38 patients referred with suspected cardiotoxicity after administration of antineoplastic drugs, 11 patients with signs of manifest or latent anthracycline cardiotoxicity were selected for heart catheterisation with endomyocardial biopsy. Ultrastructural abnormalities of the myocytes with myofibrillar loss and cytoplasmic vacuolation were present in most patients and these findings were more pronounced in biopsy specimens from the left ventricle. Surprisingly, light microscopy showed considerable fibrous thickening of the endocardium in 10 of 11 patients, primarily in the left ventricle. These morphological findings together with the echocardiographic and the haemodynamic data suggest that chronic anthracycline cardiotoxicity is a restrictive endomyocardial disease. The biochemical mechanisms responsible for endocardial fibrosis are unknown, but drug induced damage to the endocardium, possibly mediated via hormonal or humoral agents, may feature in the initial phase of the toxic process. The present observations contribute toward the understanding of the pathophysiology of human anthracycline cardiotoxicity.