American Heart Journal
Volume 157, Issue 1 , Pages 37-45, January 2009

Rationale and design of a trial of angiotensin-converting enzyme inhibition in infants with single ventricle

  • Daphne T. Hsu, MD

      Affiliations

    • Columbia University, New York, NY
    • Corresponding Author InformationReprint requests: Daphne T. Hsu, MD, Children's Hospital at Montefiore, R3, 3415 Bainbridge Ave., Bronx, NY 10467.
    • ,
  • Seema Mital, MD

      Affiliations

    • Columbia University, New York, NY
    • ,
  • Chitra Ravishankar, MD

      Affiliations

    • Children's Hospital of Philadelphia, Philadelphia, PA
    • ,
  • Renee Margossian, MD

      Affiliations

    • Children's Hospital Boston, Boston, MA
    • ,
  • Jennifer S. Li, MD

      Affiliations

    • Duke University, Durham, NC
    • ,
  • Lynn A. Sleeper, ScD

      Affiliations

    • New England Research Institutes, Watertown, MA
    • ,
  • Richard V. Williams, MD

      Affiliations

    • Primary Children's Medical Center, Salt Lake City, UT
    • ,
  • Jami C. Levine, MD

      Affiliations

    • Children's Hospital Boston, Boston, MA
    • ,
  • Brian W. McCrindle, MD

      Affiliations

    • Hospital for Sick Children, Toronto, Ontario, Canada
    • ,
  • Andrew M. Atz, MD

      Affiliations

    • Medical University of South Carolina, Charleston, SC
    • ,
  • Darlene Servedio, RN

      Affiliations

    • Columbia University, New York, NY
    • ,
  • Lynn Mahony, MD

      Affiliations

    • University of Texas at Southwestern Medical Center, Dallas, TX
    • ,
  • for the Pediatric Heart Network Investigators

Received 18 July 2008; accepted 12 August 2008.

Background

Angiotensin converting enzyme (ACE) inhibitors are known to improve clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology show abnormalities in ventricular function as well as poor growth. The ability of an ACE inhibitor to preserve ventricular function and improve growth in these infants is unknown.

Methods

The Pediatric Heart Network designed a randomized, double-blind trial to compare outcomes in infants with single-ventricle physiology receiving enalapril or placebo. Neonates ≤45 days old were eligible. The primary outcome is weight-for-age Z-score at 14 months of age. Secondary outcomes include other measures of somatic growth, laboratory and functional measures of heart failure, developmental indices, measures of ventricular size and function, and the relationship of the renin-angiotensin-aldosterone system genotype to the response to enalapril. The incidence and spectrum of adverse events will also be compared between treatment groups.

Results

A total of 1,245 neonates were screened and 533 (43%) were eligible. The consent rate was 43%; 230 subjects were enrolled. Parental reluctance to participate was the primary reason for non-consent in 79% of the eligible nonconsenting patients. Randomized patients were older, more likely to be male, and more likely to have hypoplastic left heart syndrome than the eligible patients who did not enroll.

Conclusions

The results of this randomized trial will make an important contribution to the management of infants with single-ventricle physiology by determining whether initiation of ACE inhibition therapy in the neonatal period improves growth, clinical outcome, and ventricular function.

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 Trial Registration #: NCT00113087.

 Funded by the National Heart, Lung, and Blood Institute (Bethesda, MD), National Institutes of Health (Bethesda, MD)/Department of Health and Human Services (Washington, DC).

 Supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057).

 Dr. J. Michael DiMaio served as guest editor for this manuscript.

PII: S0002-8703(08)00804-1

doi:10.1016/j.ahj.2008.08.030

American Heart Journal
Volume 157, Issue 1 , Pages 37-45, January 2009

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