Abstract 13454: Relationship Between Brain-type Natriuretic Peptide and Serum Growth Factors in Infants With Single Ventricle Heart Disease and Shunt- or Ductal-dependent Pulmonary Blood Flow

Abstract

Introduction: For infants with shunt- or ductal-dependent single-ventricle heart disease (SD-SVHD), poor growth is common and associated with morbidity and impaired neurodevelopmental outcome. While attention has focused on nutrition to promote weight gain, little is known about the contribution of heart failure to diminished growth. Methods: A prospective observational pilot study was performed to assess the relationship between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors [insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3)] at 4 visits: 1) prior to discharge from neonatal intervention, 2) immediately prior to stage 2 palliation, 3) prior to discharge after stage 2 palliation, and 4) 3-6 months after stage 2 discharge. IGF-1 Z-scores were generated by the analysis lab using reference data. The relationship between log-transformed BNP and growth factors was analyzed using pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered statistically significant using a p-value <0.10, given the exploratory nature of the study. Results: The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at Visit 1 and decreased over time [287 pg/dL (IQR 147, 794), 85 pg/dL (52, 183), 90 pg/dL (70, 138), and 47 pg/dL (43, 135)]. Median IGF Z-score was <0 at each visit but increased over time [-0.9 (IQR -1.1, 0.1), -0.7 (-1.2, 0.1), -0.5 (-1.2, 0), and -0.2 (-0.8, 0)]. Inverse correlations were noted between log BNP and IGF-1 Z-score at Visit 1 (r = -0.45, p=0.06) and Visit 3 (r = -0.50, p=0.02), and between log BNP and IFGBP-3 at Visit 1 (r = -0.44, p=0.06) and Visit 2 (r = -0.34, p=0.08). There was a small effect of log BNP on IGF-1 Z-score over all time periods (coefficient: -0.23, 95% CI: -0.49, 0.024, p=0.07). Conclusions: This pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth. Further work directed at therapies that target the underlying heart failure state might help to optimize the potential for growth in this vulnerable patient population.