Abstract 10300: The Effects of the Bone Morphogenetic Protein Receptor Type 2 Mutation on the Right Ventricle in Pulmonary Arterial Hypertension

Abstract

Introduction: The effects of a mutation in the bone morphogenetic protein receptor 2 gene (BMPR2) gene on right ventricular (RV)adaptation are currently unknown. Therefore, we investigated RV function in PAH patients with and without BMPR2 mutation by combining in vivo measurements with molecular and histological analysis of human RV and left ventricular (LV) tissue. Methods: 97 idiopathic or familial PH patients were genetically screened for the presence of a BMPR2 mutation. 28 patients carried a BMPR2 muation, 69 did not. In vivo measurements were assessed using right heart catheterization (RHC)and cardiac magnetic resonance imaging.To investigate the role of TGF-β and BMPRII signaling, human RV and LV tissue were studied in controls (n=6), mutation carriers (n=5) and non-carriers (n=11). Results: Despite a similar mean pulmonary artery pressure (noncarriers 54±15 vs. mutation carriers 55±9 mmHg)and pulmonary vascular resistance (755 (483-1043) vs. 931 (624-1311) dynes*s/cm 5 ), mutation carriers presented with a more severely compromised RV function (RV ejection fraction: 37.6±12.8 vs. 29.0±9 %: p<0.05, cardiac index 2.7±0.9 vs. 2.2±0.4 l/min/m 2 ). Differences continued to exist after treatment. TGF-β and BMPRII signaling, as well as hypertrophy, fibrosis, capillary density and inflammation were similar between mutation carriers and non-carriers. Conclusions: Despite a similar afterload, RV function is severely more affected in BMPR2 mutation carriers compared to non-carriers. However, these differences cannot be explained by a different TGF-B, BMPR2 signaling or cardiac adaptation.