Abstract 11853: Serum Matrix Metalloproteinase 2 is Associated With Lower Ventricular Stiffness and Suboptimal Outcomes in Children With Single Right Ventricle Physiology Who Are Under Consideration for Stage 3 Palliation

Abstract

Background: Increased extracellular matrix (ECM) metabolism is associated with poor outcomes in numerous cardiovascular diseases. However, its relationship to outcomes in patients with single right ventricle physiology (SRV) is unknown. The objective of this study was to investigate the association of measures of ECM metabolism to outcomes in SRV patients under consideration for stage 3 palliation (S3P). Methods: SRV patients undergoing routine pre-S3P catheterization were prospectively enrolled. Serum matrix metalloproteinase 2 (MMP-2), cardiac magnetic resonance T1 mapping derived extracellular volume (ECV), and pressure-volume loop derived ventricular stiffness (β) by micro-conductance catheter were collected. Controls were age-matched children undergoing closure of clinically insignificant patent ductus arteriosus. SRV were divided into those who had an optimal outcome or suboptimal outcome (hemodynamic concern causing delay in S3P, length of stay ≥ 14 days, heart transplant or death in first year after S3P). Results: Of 30 patients, 15 had SRV and 15 were controls; 7 SRV patients had suboptimal outcome. Mean age was 4.2 ± 0.7 years. SRV patients with suboptimal outcome had lower β (p = 0.05) and ECV (p = 0.04) than patients with optimal outcome (Figure A and B, respectively). MMP-2 was lower in SRV patients with suboptimal outcome compared to SRV patients with optimal outcome and controls (Figure C) (p = 0.05). In SRV patients, MMP-2 correlated with β (r = 0.56, p = 0.03). Conclusion: In biventricular heart disease characterized by chronically increased afterload, MMP-2, ECV, and ventricular stiffness are elevated. In contrast, this study shows that SRV patients with lower MMP-2, ECV, and ventricular stiffness have worse outcomes at the time of S3P; this suggests immature ECM metabolism leads to poor outcomes in SRV patients. Future studies exploring the mechanism by which immature ECM and dysregulated ECM metabolism influence SRV outcomes are warranted.