Screening for pulmonary arterial hypertension in adults carrying a mutation.

Background: Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomatic mutation carriers. The main objectives of this study were to evaluate the characteristics of asymptomatic mutation carriers, assess their risk of occurrence of PAH and detect PAH at an early stage in this high-risk population.

Methods: Asymptomatic mutation carriers underwent screening at baseline and annually for a minimum of 2 years (DELPHI-2 study; ClinicalTrials.gov: NCT01600898). Annual screening included clinical assessment, ECG, pulmonary function tests, 6-min walk distance, cardiopulmonary exercise testing, chest radiography, echocardiography and brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP level. Right heart catheterisation (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline.

Results: 55 subjects (26 males; median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT-proBNP 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 patient-years of follow-up), three additional cases were diagnosed, yielding a PAH incidence of 2.3% per year (0.99% per year in males and 3.5% per year in females). All PAH cases remained at low-risk status on oral therapy at last follow-up.

Conclusions: Asymptomatic mutation carriers have a significant risk of developing incident PAH. International multicentre studies are needed to confirm that refined multimodal screening programmes with regular follow-up allow early detection of PAH.