Cardiotoxicity associated with high-dose cyclophosphamide therapy

Abstract

The cardiac effects of chemotherapeutic regimens using high doses of cyclophosphamide (180 mg/kg over 4 days) were assessed in 32 patients with hematologic malignant neoplasms. Left ventricular systolic function, determined by the fractional shortening on echocardiogram, declined substantially 5-16 days after the initiation of cyclophosphamide therapy. Although pericardial effusion on echocardiogram occurred in 33% of the patients studied, ECG voltage decreased 5-14 days after beginning cyclophosphamide therapy even in those patients without pericardial effusion. Congestive heart failure was noted in 9 patients (28%) within 3 wk of cyclophosphamide administration. Six of these patients (19%) died of myocardial failure. Pericardial tamponade occurred in 6 patients (19%), including 5 who died of myocardial failure. Histopathologic and EM findings showed endothelial injury and a hemorrhagic myopericarditis. Cyclophosphamide in this high dose is associated with a toxic, often fatal, pericardiomyopathy. Depression of ECG voltage and systolic left ventricular function, though common, do not necessarily predict clinical cardiac deterioration.