Abstract
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.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Schweitzer has nothing to disclose.
Conflict of interest: Dr. MONTANI reports grants and personal fees from Actelion, grants and personal fees from Bayer, personal fees from GSK, personal fees from Pfizer, grants, personal fees and non-financial support from MSD, personal fees from Chiesi, personal fees from Boerhinger, non-financial support from Acceleron, personal fees from Incyte Biosciences France, outside the submitted work.
Conflict of interest: Dr. Girerd has nothing to disclose.
Conflict of interest: Dr. JAIS reports grants from Bayer, grants and personal fees from MSD, grants, personal fees and non-financial support from Actelion/Janssen, outside the submitted work.
Conflict of interest: Dr. Laveneziana reports personal fees from NOVARTIS FRANCE, personal fees from CHIESI FRANCE, outside the submitted work.
Conflict of interest: Dr. Lau reports grants and personal fees from Actelion, grants and personal fees from GSK, outside the submitted work.
Conflict of interest: Dr. Bouchachi has nothing to disclose.
Conflict of interest: Dr. Hascoet reports grants and personal fees from Abbott, outside the submitted work.
Conflict of interest: Dr. Gunther has nothing to disclose.
Conflict of interest: Dr. Godinas has nothing to disclose.
Conflict of interest: Dr. Parent has nothing to disclose.
Conflict of interest: Dr. Guignabert has nothing to disclose.
Conflict of interest: Dr. Beurnier has nothing to disclose.
Conflict of interest: Dr. CHEMLA has nothing to disclose.
Conflict of interest: Dr. Hervé has nothing to disclose.
Conflict of interest: Dr. EYRIES has nothing to disclose.
Conflict of interest: Dr. Soubrier has nothing to disclose.
Conflict of interest: Dr. SIMONNEAU reports personal fees from Bayer, personal fees and non-financial support from MSD, personal fees from Acceleron, outside the submitted work.
Conflict of interest: Dr. SITBON reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, personal fees from Acceleron Pharmaceuticals, personal fees from AOP Orphan, grants and personal fees from Bayer HealthCare, grants and personal fees from MSD, personal fees from Ferrer, personal fees from Gossamer Bio, grants from GSK, outside the submitted work.
Conflict of interest: Dr. Savale reports personal fees and non-financial support from Actelion, grants, personal fees and non-financial support from GSK, non-financial support from MSD, personal fees and non-financial support from Bayer, outside the submitted work.
Conflict of interest: Dr. Humbert reports grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from Astrazeneca, personal fees from Novartis, personal fees from Roche, personal fees from Sanofi, personal fees from Teva, grants and personal fees from Acceleron, grants and personal fees from Actelion, grants and personal fees from Bayer, personal fees from Merck, outside the submitted work.
This is a PDF-only article. Please click on the PDF link above to read it.
- Received November 18, 2020.
- Accepted December 17, 2020.
- Copyright ©ERS 2020
