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Long-Term Enalapril Therapy for Left Ventricular Dysfunction in Doxorubicin-Treated Survivors of Childhood Cancer

From the Division of Pediatric Cardiology, University of Rochester Medical Center and Golisano Children’s Hospital at Strong, James P. Wilmot Cancer Center, and Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY; Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, SC; and Departments of Pediatric Oncology and Biostatistics, Dana-Farber Cancer Institute, Division of Hematology/Oncology and Department of Cardiology, Children’s Hospital, Department of Pediatrics, Harvard Medical School, and Department of Biostatistics, Harvard School of Public Health, Boston, MA.

Address reprint requests to Steven E. Lipshultz, MD, Division of Pediatric Cardiology, University of Rochester Medical Center, 601 Elmwood Ave, Box 631, Rochester, NY 14642; email: steve_lipshultz{at}urmc.rochester.edu

PURPOSE: A common late effect of doxorubicin therapy for childhood cancer is reduced left-ventricular (LV) wall thickness resulting in elevated LV afterload and depressed LV function. Many children are given angiotensin-converting enzyme inhibitors, which have been studied primarily in adults. We document the long-term effects of angiotensin-converting enzyme inhibitors in doxorubicin-treated survivors of childhood cancer.

PATIENTS AND METHODS: In this retrospective study, we reviewed records of 18 children who had regular echocardiographic examinations during enalapril therapy (mean age at cancer diagnosis, 8 years; mean time between completion of doxorubicin therapy and start of enalapril, 7 years; median follow-up since the start of enalapril, 10 years).

RESULTS: Over the first 6 years of enalapril therapy, there was progressive improvement toward normal values in LV dimension, afterload, fractional shortening, and mass, but all these parameters deteriorated between 6 and 10 years. LV wall thickness deteriorated throughout the study period, as did LV contractility and systolic blood pressure. Diastolic blood pressure fell slightly. By 6 years on enalapril, all six patients who had had congestive heart failure at the start of enalapril therapy had either died or undergone cardiac transplantation, compared with three of the 12 asymptomatic patients.

CONCLUSION: In doxorubicin-treated long-term survivors of childhood cancer, enalapril-induced improvement in LV structure and function is transient. The primary defect, which is LV wall thinning, continues to deteriorate, and thus the short-term improvement was mostly related to lowered diastolic blood pressure.

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