The primary aim of this project is to determine whether the chronic administration of enalapril, an inhibitor of angiotensin converting enzyme (ACE), will reduce the progression of cardiac dysfunction in pediatric oncology patients who have received anthracyclines, and who are not currently on digoxin, diuretics or vasodilators for congestive heart failure (CHF). The project includes a randomized, double blind trial of enalapril versus placebo in approximately 168 patients at least two years off treatment with some cardiac dysfunction (without CHF) after receiving anthracyclines. Randomization will be stratified by total anthracycline dose, follow-up time from treatment, and age at the time of treatment. We define cardiac dysfunction to include a fall in left ventricular shortening factor (LVSF) as measured by echocardiagram, a moderate or severe abnormality of maximal cardiac index as measured on cycle ergometry testing, an abnormal LV ejection fraction (LVEF) by gated nuclear angiography, a prolonged QT on ECG or a history of exercise intolerance. All patients receive the same baseline tests. Patients are randomized to either enalapril or placebo. Follow-up visits to ensure compliance and screen for side effects are conducted. The primary outcome variables are the rate of decline in Maximal Cardiac Index and the rate of increase in Echocardiagram/Doppler determined left ventricular end systolic wall stress. Secondary outcomes are the change in LVEF and the incidence of arrhythmias.
The second aim i s to develop an algorithm to determine indications for enalapril use, should we succeed in showing a treatment effect. This will require modeling the probability of cardiac dysfunction given patient characteristics at treatment, treatment type, cardiac status during treatment and follow-up, and the development of cost effectiveness and medical decision making models testing the algorithm.
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