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Factors Associated with Serum B-Type Natriuretic Peptide in Infants with Single Ventricles

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Abstract

Data regarding the value of B-type natriuretic peptide (BNP) measurements in infants with a single-ventricle (SV) physiology are lacking. This analysis aimed to describe the BNP level changes in infants with an SV physiology before and after superior cavopulmonary connection (SCPC) surgery. Levels of BNP were measured by a core laboratory before SCPC (at 5.0 ± 1.6 months) and at the age of 14 months during a multicenter trial of angiotensin-converting enzyme inhibition therapy for infants with SV. Multivariable longitudinal analysis was used to model the associations between BNP levels and three sets of grouped variables (echocardiography, catheterization, growth). Multivariable analysis was performed to assess associations with patient characteristics at both visits. Associations between BNP levels and neurodevelopmental variables were investigated at the 14 month visit because neurodevelopmental assessment was performed only at this visit. The BNP level was significantly higher before SCPC (n = 173) than at the age of 14 months (n = 134). The respective median levels were 80.8 pg/ml (interquartile range [IQR], 35–187 pg/ml) and 34.5 pg/ml (IQR, 17–67 pg/ml) (p < 0.01). A BNP level higher than 100 pg/ml was present in 72 subjects (42 %) before SCPC and in 21 subjects (16 %) at the age of 14 months. In the 117 patients who had BNP measurements at both visits, the median BNP level decreased 32 pg/ml (IQR, 1–79 pg/ml) (p < 0.01). In the longitudinal multivariable analysis, higher BNP levels were associated with a higher end-systolic volume z-score (p = 0.01), a greater degree of atrioventricular (AV) valve regurgitation (p < 0.01), a lower weight z-score (p < 0.01), and a lower length z-score (p = 0.02). In multivariable analyses, a higher BNP level at the age of 14 months was associated with arrhythmia after SCPC surgery (p < 0.01), a prior Norwood procedure (p < 0.01), a longer hospital stay after SCPC surgery (p = 0.04), and a lower Bayley psychomotor developmental index (p = 0.02). The levels of BNP decreases in infants with SV from the pre-SCPC visit to the age of 14 months. A higher BNP level is associated with increased ventricular dilation in systole, increased AV valve regurgitation, impaired growth, and poorer neurodevelopmental outcomes. Therefore, BNP level may be a useful seromarker for identifying infants with SV at risk for worse outcomes.

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Acknowledgments

This study was supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057) and from the FDA Office of Orphan Products Development. It also was supported by a T32 grant from the National Heart, Lung and Blood Institute (5T32 HL007710). The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of NHLBI or NIH.

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Authors and Affiliations

  1. Department of Pediatrics, Medical University of South Carolina, 165 Ashley Avenue, Charleston, SC, 29424, USA

    Ryan J. Butts & Andrew M. Atz

  2. New England Research Institutes, Watertown, MA, USA

    Victor Zak

  3. Division of Cardiology, Children’s Hospital at Montefiore, Bronx, NY, USA

    Daphne Hsu

  4. Department of Cardiology, Cincinnati Children’s Hospital, Cincinnati, OH, USA

    James Cnota

  5. Department of Cardiology, Boston Children’s Hospital, Boston, MA, USA

    Steven D. Colan, Jami C. Levine & Renee Margossian

  6. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    David Hehir

  7. Department of Cardiology, Hospital for Sick Children, Toronto, ON, Canada

    Paul Kantor

  8. Department of Cardiology, Children’s Hospital of New York, New York, NY, USA

    Marc Richmond

  9. Department of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Anita Szwast

  10. Department of Cardiology, Brenner Children’s Hospital, Winston-Salem, NC, USA

    Derek Williams

  11. Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

    Richard Williams

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  1. Ryan J. Butts
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For the Pediatric Heart Network Investigators.

Appendix

Appendix

National Heart, Lung, and Blood Institute: Gail Pearson, Victoria Pemberton, Mario Stylianou, Marsha Mathis*

Network Chair: Lynn Mahony (University of Texas Southwestern Medical Center)

Data Coordinating Center: Lynn Sleeper (PI), Steven Colan, Lisa Virzi,* Lisa Wruck,* Victor Zak, David F. Teitel (New England Research Institutes)

Core Clinical Site Investigators: Jane W. Newburger (PI), Roger Breitbart, Jami Levine, Ellen McGrath,* Carolyn Dunbar-Masterson (Children’s Hospital Boston); Daphne Hsu* (Study Chair), William Hellenbrand (PI),* Ashwin Prakash,* Seema Mital,* Darlene Servedio* (Children’s Hospital of New York); Victoria L. Vetter (PI), Chitra Ravishankar, Sarah Tabbutt,* Meryl Cohen, Katherine Lee, Marisa Nolan, Stephanie Piacentino, Michelle Toms (Children’s Hospital of Philadelphia); D. Woodrow Benson (PI), Catherine Dent Krawczeski, Lois Bogenschutz, Teresa Barnard, Steven Schwartz,* David Nelson (Cincinnati Children’s Medical Center); Page A. W. Anderson (PI)–deceased, Jennifer Li (PI), Wesley Covitz, Kari Crawford,* Michael Hines,* James Jaggers,* Theodore Koutlas, Charlie Sang Jr, Lori Jo Sutton, Mingfen Xu (North Carolina Consortium: Duke University, East Carolina University, Wake Forest University); J. Philip Saul (PI), Andrew Atz, Girish Shirali,* Eric M. Graham, Teresa Atz (Medical University of South Carolina); L. LuAnn Minich (PI), John A. Hawkins–deceased, Richard V. Williams, Linda M. Lambert, Marian E. Shearrow (Primary Children’s Medical Center and the University of Utah, Salt Lake City, Utah); Brian McCrindle (PI), Elizabeth Radojewski, Nancy Slater, Svetlana Khaikin, Susan McIntyre (Hospital for Sick Children, Toronto)

Auxiliary Sites: Nancy Ghanayem, Kathy Mussatto, Michele Frommelt, Lisa Young-Borkowski (Children’s Hospital of Wisconsin); Albert Rocchini, Laurie Rodgers-Augustyniak (University of Michigan)

Echocardiography Core Laboratory: Steven Colan, Renee Margossian (Children’s Hospital Boston)

Genetics Core Laboratory: Wendy Chung, Liyong Deng, Patricia Lanzano (Children’s Hospital of New York)

Protocol Review Committee: Michael Artman (Chair), Judith Massicot-Fisher (Executive Secretary), Timothy Feltes, Julie Johnson, Thomas Klitzner, Jeffrey Krischer, G. Paul Matherne

Data and Safety Monitoring Board: John Kugler, Chair; Rae-Ellen Kavey (Executive Secretary), David J. Driscoll, Mark Galantowicz, Sally A. Hunsberger, Thomas J. Knight, Holly Taylor, Catherine L. Webb

*No longer at the institution listed

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Butts, R.J., Zak, V., Hsu, D. et al. Factors Associated with Serum B-Type Natriuretic Peptide in Infants with Single Ventricles. Pediatr Cardiol 35, 879–887 (2014). https://doi.org/10.1007/s00246-014-0872-z

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