Enalapril in infants with single ventricle: results of a multicenter randomized trial
Daphne T Hsu, Victor Zak, Lynn Mahony, Lynn A Sleeper, Andrew M Atz, Jami C Levine, Piers C Barker, Chitra Ravishankar, Brian W McCrindle, Richard V Williams, Karen Altmann, Nancy S Ghanayem, Renee Margossian, Wendy K Chung, William L Border, Gail D Pearson, Mario P Stylianou, Seema Mital, Pediatric Heart Network Investigators, Gail Pearson, Victoria Pemberton, Mario Stylianou, Marsha Mathis, Lynn Mahony, Lynn Sleeper, Steven Colan, Lisa Virzi, Lisa Wruck, Victor Zak, David F Teitel, Leslie Kalish, Patty Connell, Jane W Newburger, Roger Breitbart, Jami Levine, Ellen McGrath, Carolyn Dunbar-Masterson, Daphne Hsu, William Hellenbrand, Ashwin Prakash, Seema Mital, Darlene Servedio, Victoria L Vetter, Chitra Ravishankar, Sarah Tabbutt, Meryl Cohen, Katherine Lee, Marisa Nolan, Stephanie Piacentino, Michelle Toms, D Woodrow Benson, Catherine Dent Krawczeski, Lois Bogenschutz, Teresa Barnard, Steven Schwartz, David Nelson, Page A W Anderson, Jennifer Li, Wesley Covitz, Kari Crawford, Michael Hines, James Jaggers, Theodore Koutlas, Charlie Sang Jr, Lori Jo Sutton, Mingfen Xu, J Philip Saul, Andrew Atz, Girish Shirali, Eric M Graham, Teresa Atz, LuAnn Minich, John A Hawkins, Richard V Williams, Linda M Lambert, Marian E Shearrow, Brian McCrindle, Elizabeth Radojewski, Nancy Slater, Svetlana Khaikin, Susan McIntyre, Nancy Ghanayem, Kathy Mussatto, Michele Frommelt, Lisa Young-Borkowski, Albert Rocchini, Laurie Rodgers-Augustyniak, Steven Colan, Renee Margossian, Wendy Chung, Liyong Deng, Patricia Lanzano, Michael Artman, Judith Massicot-Fisher, Timothy Feltes, Julie Johnson, Thomas Klitzner, Jeffrey Krischer, G Paul Matherne, John Kugler, Rae-Ellen Kavey, David J Driscoll, Mark Galantowicz, Sally A Hunsberger, Thomas J Knight, Holly Taylor, Catherine L Webb, Daphne T Hsu, Victor Zak, Lynn Mahony, Lynn A Sleeper, Andrew M Atz, Jami C Levine, Piers C Barker, Chitra Ravishankar, Brian W McCrindle, Richard V Williams, Karen Altmann, Nancy S Ghanayem, Renee Margossian, Wendy K Chung, William L Border, Gail D Pearson, Mario P Stylianou, Seema Mital, Pediatric Heart Network Investigators, Gail Pearson, Victoria Pemberton, Mario Stylianou, Marsha Mathis, Lynn Mahony, Lynn Sleeper, Steven Colan, Lisa Virzi, Lisa Wruck, Victor Zak, David F Teitel, Leslie Kalish, Patty Connell, Jane W Newburger, Roger Breitbart, Jami Levine, Ellen McGrath, Carolyn Dunbar-Masterson, Daphne Hsu, William Hellenbrand, Ashwin Prakash, Seema Mital, Darlene Servedio, Victoria L Vetter, Chitra Ravishankar, Sarah Tabbutt, Meryl Cohen, Katherine Lee, Marisa Nolan, Stephanie Piacentino, Michelle Toms, D Woodrow Benson, Catherine Dent Krawczeski, Lois Bogenschutz, Teresa Barnard, Steven Schwartz, David Nelson, Page A W Anderson, Jennifer Li, Wesley Covitz, Kari Crawford, Michael Hines, James Jaggers, Theodore Koutlas, Charlie Sang Jr, Lori Jo Sutton, Mingfen Xu, J Philip Saul, Andrew Atz, Girish Shirali, Eric M Graham, Teresa Atz, LuAnn Minich, John A Hawkins, Richard V Williams, Linda M Lambert, Marian E Shearrow, Brian McCrindle, Elizabeth Radojewski, Nancy Slater, Svetlana Khaikin, Susan McIntyre, Nancy Ghanayem, Kathy Mussatto, Michele Frommelt, Lisa Young-Borkowski, Albert Rocchini, Laurie Rodgers-Augustyniak, Steven Colan, Renee Margossian, Wendy Chung, Liyong Deng, Patricia Lanzano, Michael Artman, Judith Massicot-Fisher, Timothy Feltes, Julie Johnson, Thomas Klitzner, Jeffrey Krischer, G Paul Matherne, John Kugler, Rae-Ellen Kavey, David J Driscoll, Mark Galantowicz, Sally A Hunsberger, Thomas J Knight, Holly Taylor, Catherine L Webb
Abstract
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.
Methods and 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.
Trial registration: ClinicalTrials.gov NCT00113087.
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Source: PubMed