Screening Of Pulmonary Arterial Hypertension In Bmpr2 Mutation Carriers

Introduction: Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene (encoding Bone Morphogenetic Protein Receptor type II). Despite the lack of clear evidence, asymptomatic BMPR2 mutation carriers are recommended to undergo annual screening echocardiography for early detection of PAH. Objectives: To evaluate the utility of a comprehensive multimodal PAH screening program in asymptomatic adult BMPR2 mutation carriers. Methods: Asymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of two years (DELPHI-2 study, NCT01600898). Annual screening included clinical assessment, electrocardiogram, pulmonary function tests, 6-minute walk distance, cardiopulmonary exercise test (CPET), chest x-ray, echocardiography and N-terminal pro-brain natriuretic peptide level. Right heart catheterization (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline. Results: Fifty-five subjects (26 males, median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT pro-BNP levels. All subjects accepted RHC at inclusion which identified two mild PAH cases (3.6%) and 12 subjects with exercise pulmonary hypertension of unknown significance (21.8%). At long term follow-up, three additional PAH cases were diagnosed, yielding a PAH incidence of 2.3%/year. All detected cases have remained at low risk status on oral PAH therapy at last follow-up. Conclusion: In adult BMPR2 mutation carriers, a multimodal screening program with regular follow-up allows early detection of PAH.