Congestive Heart Failure due to Adriamycin Cardiotoxicity: Its Natural History in Children zyx ALLEN M. GOORIN, MD, KENNETH M. BOROW, MD. ANNE GOLDMAN, MD, ROBERTA G. WILLIAMS, MD, zy I. CRAIG HENDERSON, MD, STEPHEN E. SALLAN, MD, HARVEY COHEN, PHD, MD, AND NORMAN JAFFE, MB, BCH, DIP PAED. The congestive heart failure (CHF) associated with Adriamycin cardiotoxicity is frequently fatal. To investigate the course of Adriamycin-induced congestive heart failure, all Adriamycin-treated children who developed congestive heart failure at the Children's Hospital Medical Center and Sidney Farber Cancer Institute were studied. Criteria for Adriamycin-induced congestive heart failure included clinical evidence of left ventricular zyxwvutsr (LV) failure and echocardiographic evidence of abnormal left ventricular function. Fifteen children fulfilled these criteria. Eleven patients received between zyxw 400 and 500 rng/m2 of Adriamycin; four patients received cumulative doses over 500 mp/m'. Twelve of 15 (80%) children survived their acute episode of congestive heart failure. At follow-up, three patients had normalized their echocardiographic parameters of left ventricular function, three had died of their malignancies with compensated cardiac function until death, and six were clinically asymptomatic despite persistence of abnormal LV function on echocardiogram. Only three patients died of Adriamycin cardiomyopathy. In children treated with aggressive medical therapy, congestive heart failure secondary to Adriamycin cardiotoxicity may be reversible in certain cases. zyxwvu Cancer 47:2810-2816, 1981. DRIAMYCIN, A CYTOTOXIC anthracycline anti- A tumor antibiotic, has gained widespread use in the treatment of childhood leukemia and solid tumors.'.","' The major limitation to the use of this drug is its cardio- toxicity. Acute cardiac effects such as supraventricular arrhythmias, premature ventricular beats, and diffuse nonspecific ST-T wave abnormalities on electrocardio- gram are common, but rarely have clinical sig- nificance.!J.14.1i Clinically, the most important side ef- fect is a dose-related cardiomyopathy which may occur weeks to months after the cessation of drug therapy.".'"." From the Divisions of Hematology-Oncology and Cardiology, Children's Hospital Medical Center, the Division of Pediatric and Medical Oncology, Sidney Farber Cancer Institute, and the De- partment of Pediatrics, Harvard Medical School, Boston. Massa- c hu sett s. Supported in part by Grant RR-128 from the General Clinical Research Center Program of the Division of Research Resources, National Institutes of Health; the USPHS Grant-Hematology Train- ing Grant HL07146; and N.H.L.B.I. Young Investigator Research Award R 23 H L 24356-01. These data were reported in part in abstract form in zyxwvuts Proc Address for reprints: Allen M. Goorin, MD, Sidney Farber The authors thank Dr. David G. Nathan for reviewing the Accepted for publication June 4, 1980. Altf SOC c/ill ollCO/ 1979; 20:328. Cancer Institute, 44 Binney Street, Boston, MA 02115. manuscript. Once congestive heart failure has occurred, full clinical recovery is uncommon. IJL!'.I'+'~ During the past eight years, we have treated 389 children with Adriamycin. of whom 15 developed congestive heart failure secondary to Adriamycin cardiotoxicity. In our experience, the natural history of this cardiomyopathy has been more favorable than previously reported. Materials and Methods The clinical records of all patients who received Adriamycin and developed congestive heart failure at the Sidney Farber Cancer Institute or the Children's Hospital Medical Center from 1971 to April 1979 were reviewed. For each patient, symptomatic cardiac status was assessed and cardiac medications re- corded. The study population consisted of those patients who developed clinical evidence of left ven- tricular (LV) decompensation such as tachypnea, tachycardia, dyspnea and pulmonary rales, and cardio- megaly on the chest roentgenograph. All patients were treated with digoxin and diuretic therapy. The hos- pital charts were reviewed to exclude patients in whom congestive heart failure was of another etiology. An Irex ContinuTrace Systems 1 recorder and ultra- 0008-543X/81i0h15/2810 $0.90 zyxwvut 0 American Cancer Society 28 10