Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation.

Background Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomatic BMPR2 mutation carriers. The main objectives of this study were to evaluate characteristics of asymptomatic BMPR2 mutation carriers, assess their risk of occurrence of PAH, and detect PAH at an early stage in this high-risk population. Methods Asymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of 2 years (DELPHI-2 study, NCT01600898). Annual screening included clinical assessment, electrocardiogram, pulmonary function tests, 6-minute walk distance, cardiopulmonary exercise test, chest X-ray, echocardiography, and NT pro-BNP level. Right heart catheterisation (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 (21·8%). At long term follow-up (118·8 patients.year follow-up), three additional cases were diagnosed, yielding a PAH incidence of 2·3%/year (0·99%/year in men and 3·5%/year in women). All PAH cases have remained at low-risk status on oral therapy at last follow-up. Conclusions Asymptomatic BMPR2 mutation carriers have a significant risk of developing incident PAH. International multicenter studies are needed to confirm that refined multimodal screening programs with regular follow-up allow early detection of PAH.