Abstract 1817: Enalapril Does Not Improve Growth or Ventricular Function in Infants With Single Ventricle: A Multicenter Clinical Trial
Systemic ventricular dysfunction and growth failure are common in infants with single ventricle physiology (ISV). We hypothesized that angiotensin converting enzyme inhibitor therapy would improve growth and preserve ventricular function in ISV.
Methods: A multicenter, randomized, double-blind study of enalapril (E) versus placebo (P) in ISV was performed by the Pediatric Heart Network. Subjects were randomized at < 45 days old. Target E dose was 0.4 mg/kg/day. The primary endpoint was weight-for-age Z-score (WgtZ) at 14 months (mo) of age. Secondary endpoints obtained before the superior cavo-pulmonary connection (SCPC) and at 14 mo included Ross heart failure (HF) score, B-type natriuretic peptide level (BNP), adverse events (AE), ejection fraction (EF), and Z-scores for height (HgtZ), head circumference (HCZ), ventricular mass (VMZ) and volume (VVZ). Groups were compared with intention-to-treat analysis by using longitudinal modeling (with adjustment for baseline values) for growth z-scores and by t-test or Wilcoxon rank sum test at 14 mo for all other outcomes.
Results: 230 infants (age 20±9 days) were randomized. Hypoplastic left heart was present in 63%. Gestational age was older in E vs. P group (median 39 vs. 38 wk, p=.01). Overall incidence of death or transplant was 14% (31/230) and did not differ between groups. 185 subjects completed 14 mo follow-up. We observed no benefit of E before SCPC except for lower VMZ:VVZ ratio. At 14 mo VMZ:VVZ was not different between groups and HCZ was significantly smaller in the E group (Table⇓). Prespecified subgroups are under investigation. Serious AE occurred in 88 E and 87 P subjects (p=1.0) and serious cardiac AE occurred in 29 E and 19 P subjects (p=0.19)
Conclusions: Administration of enalapril in ISV did not improve somatic growth, ventricular function, or HF severity and was associated with smaller head size. This study does not support the routine use of enalapril in this population.