This Article Full Text Full Text (PDF) All Versions of this Article: 119/13/1747    most recent CIRCULATIONAHA.108.800938v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grünig, E. Articles by Seeger, W. Search for Related Content PubMed PubMed Citation Articles by Grünig, E. Articles by Seeger, W. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Genetics Home Reference Medline Plus Health Information Pulmonary Hypertension Related Collections Clinical genetics Pulmonary circulation and disease Echocardiography Related Article

(Circulation. 2009;119:1747-1757.)
© 2009 American Heart Association, Inc.

Imaging

Stress Doppler Echocardiography in Relatives of Patients With Idiopathic and Familial Pulmonary Arterial Hypertension

Results of a Multicenter European Analysis of Pulmonary Artery Pressure Response to Exercise and Hypoxia

Ekkehard Grünig, MD; Sylvia Weissmann, PhD; Nicola Ehlken, BSc; Anna Fijalkowska, MD; Christine Fischer, PhD; Thierry Fourme, MD; Nazzareno Galié, MD; Ardeschir Ghofrani, MD; Rachel E. Harrison, MRCPCH; Sandrine Huez, MD; Marc Humbert, MD; Bart Janssen, PhD; Jaroslaw Kober, MD; Rolf Koehler, PhD; Rajiv D. Machado, PhD; Derliz Mereles, MD; Robert Naeije, MD; Horst Olschewski, MD; Steeve Provencher, MD; Frank Reichenberger, MD; Kathleen Retailleau, MD; Guido Rocchi, MD; Gérald Simonneau, MD; Adam Torbicki, MD; Richard Trembath, FRCP; Werner Seeger, MD

From Thoraxclinic (E.G., N.E.), Department of Cardiology (D.M.), and Institute of Human Genetics (C.F., B.J., R.K.), University of Heidelberg, Heidelberg, Germany; University of Giessen Lung Center (S.W., A.G., F.R., W.S.), Giessen, Germany; Université Paris-Sud 11, Hôpital Antoine Béclère (T.F., M.H., S.P., G.S.), Clamart, France; Department of Physiology (S.H., R.N., K.R.), University of Brussels, Brussels, Belgium; National Institute of Tuberculosis and Lung Diseases (A.F., J.K., A.T.), Warsaw, Poland; Department of Cardiology (N.G., G.R.), Università di Bologna, Bologna, Italy; Institute of Human Genetics (R.E.H., R.D.M., R.T.), King’s College, London, UK; Institut de Cardiologie et de Pneumologie de l’Université Laval (S.P.), Québec, Ontario, Canada; and Department of Pulmonology (H.O.), University of Graz, Graz, Austria.

Correspondence to Ekkehard Grünig, MD, Department of Pneumology Thoraxclinic, University Hospital Heidelberg, Amalienstrasse 5, D-69126 Heidelberg, Germany. E-mail ekkehard.gruenig{at}thoraxklinik-heidelberg.de

Received June 26, 2008; accepted January 23, 2009.

Background— This large, prospective, multicentric study was performed to analyze the distribution of tricuspid regurgitation velocity (TRV) values during exercise and hypoxia in relatives of patients with idiopathic and familial pulmonary arterial hypertension (PAH) and in healthy control subjects. We tested the hypothesis that relatives of idiopathic/familial PAH patients display an enhanced frequency of hypertensive TRV response to stress and that this response is associated with mutations in the bone morphogenetic protein receptor II (BMPR2) gene.

Methods and Results— TRV was estimated by Doppler echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (FIO₂=12%; 4500 m) in 291 relatives of 109 PAH patients and in 191 age-matched control subjects. Mean maximal TRVs were significantly higher in PAH relatives during both exercise and hypoxia. During exercise, 10% of control subjects but 31.6% of relatives (P<0.0001) exceeded the 90% quantile of mean maximal TRV seen in control subjects. Hypoxia revealed hypertensive TRV in 26% of relatives (P=0.0029). Among control subjects, TRV at rest was not related to age, sex, body mass index, systemic blood pressure, smoking status, or heart rate. Within kindreds identified as harboring deleterious mutations of the BMPR2 gene, a hypertensive TRV response occurred significantly more often compared with those without detected mutations.

Conclusions— Pulmonary hypertensive response to exercise and hypoxia in idiopathic/familial PAH relatives appears as a genetic trait with familial clustering, being correlated to but not caused by a BMPR2 mutation. The suitability of this trait to predict manifest PAH development should be addressed in long-term follow-up studies.

---

 

CLINICAL PERSPECTIVE

Related Article:

Clinical Summaries
Circulation 2009 119: 1691-1693. [Extract] [Full Text]

This article has been cited by other articles:

				The Task Force for the Diagnosis and Treatment of, N. Galie, M. M. Hoeper, M. Humbert, A. Torbicki, J-L. Vachiery, J. A. Barbera, M. Beghetti, P. Corris, S. Gaine, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension Eur. Respir. J., December 1, 2009; 34(6): 1219 - 1263. [Full Text] [PDF]

				Authors/Task Force Members, N. Galie, M. M. Hoeper, M. Humbert, A. Torbicki, J.-L. Vachiery, J. A. Barbera, M. Beghetti, P. Corris, S. Gaine, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension: The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS), endorsed by the International Society of Heart and Lung Transplantation (ISHLT) Eur. Heart J., October 2, 2009; 30(20): 2493 - 2537. [Full Text] [PDF]

				D. B. Badesch, H. C. Champion, M. A. Gomez Sanchez, M. M. Hoeper, J. E. Loyd, A. Manes, M. McGoon, R. Naeije, H. Olschewski, R. J. Oudiz, et al. Diagnosis and assessment of pulmonary arterial hypertension. J. Am. Coll. Cardiol., June 30, 2009; 54(1 Suppl): S55 - S66. [Abstract] [Full Text] [PDF]