ACE Inhibitors in Pediatric Patients with Heart Failure

This article reviews reports of ACE inhibitor use in pediatric heart failure and summarizes the present implications for clinical practice. Captopril, enalapril, and cilazapril are orally active ACE inhibitors, and widely used in pediatric cardiology, although more than ten other ACE inhibitors have been applied clinically in adults. Effects of ACE inhibitors on the renin-angiotensin-aldosterone system in pediatric patients are similar to those in adults. ACE inhibitors lower aortic pressure and systemic vascular resistance, do not affect pulmonary vascular resistance significantly, and lower left atrial and right atrial pressures in pediatric patients with heart failure. In infants with a large ventricular septal defect and pulmonary hypertension, ACE inhibitors decrease left-to-right shunt in those infants with elevated systemic vascular resistance. ACE inhibitors induce a small increase in left ventricular ejection fraction, left ventricular fractional shortening, and systemic blood flow in children with left ventricular dysfunction, mitral regurgitation, and aortic regurgitation. These beneficial effects usually persist long term without the development of tolerance. Therapeutic trials of ACE inhibitors have been reported in children with heart failure and divergent hemodynamics, including myocardial dysfunction, left-to-right shunt, such as large ventricular septal defect and pulmonary hypertension, aortic or mitral regurgitation, and Fontan circulation.

Hypotension and renal failure usually occur within 5 days after starting ACE inhibition or increasing the dose and, in most cases, recovery is seen after reduction or cessation of the drug. With all ACE inhibitors, smaller doses are administered initially to prevent excessive hypotension, and doses are increased gradually to the target dose. Captopril is administered orally, usually every 8 hours. Daily doses range from 0.3 to 1.5 mg/kg in children. Enalapril is administered orally, once or twice a day, and daily doses range from 0.1 to 0.5 mg/kg. Enalaprilat is administered intravenously, one to three times a day, in doses ranging from 0.01 to 0.05 mg/kg/dose.

For the treatment of chronic heart failure in children, ACE inhibitors are essential along with other medications including diuretics, digoxin, and β-blockers (β-adrenoceptor antagonists).