Pneumologie 2009; 63 - V357
DOI: 10.1055/s-0029-1213989

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

E Grünig 1, S Weissmann 2, N Ehlken 1, A Fijalkowska 3, C Fischer 4, T Fourme 5, N Galié 6, HA Ghofrani 7, R Harrison 8, S Huez 9, M Humbert 5, B Janssen 4, J Kober 3, R Koehler 4, R Machado 10, D Mereles 11, R Naije 12, H Olschewski 13, S Provencher 5, F Reichenberger 7, K Retailleau 12, G Rocchi 6, G Simonneau 5, A Torbicki 3, R Trembath 10, W Seeger 7
  • 1Thoraxklinik Heidelberg
  • 2University of Gießen
  • 3National Institue of Tuberculosis and Lung disease, Warsaw
  • 4Institute of human genetics, University of Heidelberg
  • 5Hôpital Antoine Béclère, Clamart
  • 6Department of Cardiology, University of Bologna
  • 7Lung Center, University of Gießen
  • 8Institute of Human Genetrics, University of London
  • 9Department of Physiology, University of Brussels
  • 10Institute of human genetics, University of London
  • 11Cardiology, University of Heidelberg
  • 12Department of Physiology, University of Brussels
  • 13Department of Pulmology, University of Graz

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

Methods: TRV was estimated by Doppler-echocardiography during supine bicycle exercise in normoxia and during 120 minutes of normobaric hypoxia (Fi02=12% ˜ 4.500m) in 291 relatives of 109 PAH patients and in 191 age- matched controls.

Results: Mean maximal TRVs were significantly higher in PAH relatives during both exercise and hypoxia. During exercise, 10% of controls but 31.6% (p<0.0001) of relatives exceeded the 90 percent quantile of mean maximal TRV seen in controls. Hypoxia revealed hypertensive TRV in 26% of relatives (p=0.0029). Amongst controls TRV at rest was not related to age, gender, body mass index, systemic blood pressure, smoking status or heart rate. Within kindreds identified to harbor deleterious mutations of the BMPR2 gene, a hypertensive TRV response occurred significantly more often compared to those without detected mutations.

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

The study was funded by a grant of the European Union, 5th framework program: „Disposition to PPH, QLG1-CT-2002–01116“