Enalapril in infants with single ventricle: results of a multicenter randomized trial.
BACKGROUND
Angiotensin-converting enzyme inhibitor therapy improves clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology have poor growth and are at risk for abnormalities in ventricular systolic and diastolic function. The ability of angiotensin-converting enzyme inhibitor therapy to preserve ventricular function and improve somatic growth and outcomes in these infants is unknown.


RESULTS
The Pediatric Heart Network conducted a double-blind trial involving 230 infants with single-ventricle physiology randomized to receive enalapril (target dose 0.4 mg . kg(-1) . d(-1)) or placebo who were followed up until 14 months of age. The primary end point was weight-for-age z score at 14 months. The primary analysis was intention to treat. A total of 185 infants completed the study. There were 24 and 21 withdrawals or deaths in the enalapril and placebo groups, respectively (P=0.74). Weight-for-age z score was not different between the enalapril and placebo groups (mean+/-SE -0.62+/-0.13 versus -0.42+/-0.13, P=0.28). There were no significant group differences in height-for-age z score, Ross heart failure class, brain natriuretic peptide concentration, Bayley scores of infant development, or ventricular ejection fraction. The incidence of death or transplantation was 13% and did not differ between groups. Serious adverse events occurred in 88 patients in the enalapril group and 87 in the placebo group.


CONCLUSIONS
Administration of enalapril to infants with single-ventricle physiology in the first year of life did not improve somatic growth, ventricular function, or heart failure severity. The results of this randomized trial do not support the routine use of enalapril in this population.
Hsu
Daphne T
DT
Division of Pediatric Cardiology, Children's Hospital at Montefiore, 3415 Bainbridge Ave., Bronx, NY 10457, USA. dhsu@montefiore.org
Zak
Victor
V
Mahony
Lynn
L
Sleeper
Lynn A
LA
Atz
Andrew M
AM
Levine
Jami C
JC
Barker
Piers C
PC
Ravishankar
Chitra
C
McCrindle
Brian W
BW
Williams
Richard V
RV
Altmann
Karen
K
Ghanayem
Nancy S
NS
Margossian
Renee
R
Chung
Wendy K
WK
Border
William L
WL
Pearson
Gail D
GD
Stylianou
Mario P
MP
Mital
Seema
S
D000450:Aldosterone / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005919:Glomerular Filtration Rate / Q000502:physiology; D006333:Heart Failure / Q000453:epidemiology*; D006352:Heart Ventricles / Q000002:abnormalities*; D006801:Humans; D007223:Infant; D013318:Stroke Volume
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000450:Aldosterone; D004656:Enalapril