Angiotensin Converting Enzyme Inhibition in Children With Mitral Regurgitation (AceiMR)

This study will evaluate the efficacy and safety of angiotensin converting enzyme inhibition (ACE-I) therapy for the treatment of mitral regurgitation (MR).

BACKGROUND: MR causes volume overload and hemodynamic burden on the left ventricle. Initial compensatory mechanisms may fail, leading to increased severity. Patients who have had repair of an atrioventricular septal defect (AVSD) are selected for this study as they have a relatively high incidence of moderate MR and their regurgitant orifice is mobile and dynamic, contributing to the likelihood that they might respond to medical therapy. DESIGN NARRATIVE: This is a randomized, double-blind, placebo-controlled trial of ACE-I therapy in children less than 18 years of age with at least moderate MR who are at least 6 months postoperative from repair of an AVSD. A non-randomized Observational Phase enrolled 181 children who were less than 6 months postoperative from repair of an AVSD, who were then evaluated at 6 months for trial eligibility.

Comparison of the effect of ACE-I therapy with placebo on MR severity, left ventricular geometry, hemodynamics, and signs and symptoms of congestive heart failure

Comparison of the incidence of adverse events occurring in subjects treated with ACE-I therapy to that in subjects receiving placebo (measured after six months of therapy)

Inclusion Criteria: Children less than 18 years of age and at least 6 months post AVSD repair or reoperation At least moderate MR Asymptomatic or minimally symptomatic, defined by Ross Heart Failure Class I or II Atrioventricular synchrony (paced or intrinsic) Exclusion Criteria: Tetrology of Fallot, total or partial anomalous venous connection More than trivial MS or outflow obstruction Other sources of LV volume overload Hypertrophic obstructive cardiomyopathy Significant residual coarctation

Li JS, Colan SD, Sleeper LA, Newburger JW, Pemberton VL, Atz AM, Cohen MS, Golding F, Klein GL, Lacro RV, Radojewski E, Richmond ME, Minich LL. Lessons learned from a pediatric clinical trial: the Pediatric Heart Network angiotensin-converting enzyme inhibition in mitral regurgitation study. Am Heart J. 2011 Feb;161(2):233-40. doi: 10.1016/j.ahj.2010.10.030.

Atz AM, Hawkins JA, Lu M, Cohen MS, Colan SD, Jaggers J, Lacro RV, McCrindle BW, Margossian R, Mosca RS, Sleeper LA, Minich LL; Pediatric Heart Network Investigators. Surgical management of complete atrioventricular septal defect: associations with surgical technique, age, and trisomy 21. J Thorac Cardiovasc Surg. 2011 Jun;141(6):1371-9. doi: 10.1016/j.jtcvs.2010.08.093. Epub 2010 Dec 15.