Anthracycline-induced cardiomyopathy: long-term effects on myocardial cellintegrity, cardiac adrenergic innervation and fatty acid uptake

Cardiotoxicity of anthracyclines is a clinical challenge in cancer chemothe rapy. Limited data is available on the physiological mechanisms responsible for anthracycline-induced heart failure or its recovery. We studied four p atients with a history of severe anthracycline-induced heart failure manife sted 2-116 months earlier by using radionuclide ventriculography for the me asurement of left ventricular function, indium-111-antimyosin scintigraphy for the detection of myocardial cell injury and iodine-123-metaiodobenzylgu anidine (MIBG) scintigraphy for the assessment of cardiac adrenergic innerv ation. Myocardial perfusion and fatty acid utilization were assessed with i odine-123-paraphenyl pentadecanoid acid (pPPA) and single photon emission c omputed tomography (SPECT). Symptoms of congestive heart failure (CHF) were still present in two patients whereas the others were asymptomatic at the time of the study. The patients who showed complete clinical recovery had n ormal or near normal left ventricular ejection fraction (LVEF) (47 and 52%) , whereas the patients with symptoms of heart failure had low ejection frac tions (21 and 31%). All patients presented with abnormal antimyosin uptake and decreased myocardial MIBG uptake. Patients with low ejection fraction t ended to have higher antimyosin uptake suggesting more severe, persistent m yocyte injury. All but one patient showed normal fatty acid utilization. Th ese data suggest that patients with a history of severe anthracycline-induc ed cardiomyopathy have persistent myocardial cell injury and adrenergic dys function up to 10 years after the development of heart failure. These findi ngs seem to be present regardless of recovery of left ventricular function.