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

doi:10.1161/CIRCULATIONAHA.108.800938

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 Gruenig, Sylvia Weissmann, Nicola Ehlken, Anna Fijalkowska, Christine Fischer, Thierry Fourme, Nazzareno Galie, Ardeschir Ghofrani, Rachel E. Harrison, Sandrine Huez, Marc Humbert, Bart Janssen, Jaroslaw Kober, Rolf Koehler, Rajiv D. Machado, Derliz Mereles, Robert Naeije, Horst Olschewski, Steeve Provencher, Frank ReichenbergerKathleen Retailleau, Guido Rocchi, Gerald Simonneau, Adam Torbicki, Richard Trembath, Werner Seeger

Research output: Contribution to journal › Article › peer-review

193 Citations (Scopus)

Abstract

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%; approximate to 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. (Circulation. 2009; 119: 1747-1757.)

Original language	English
Pages (from-to)	1747 - 1757
Number of pages	11
Journal	Circulation (Baltimore)
Volume	119
Issue number	13
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.108.800938
Publication status	Published - 7 Apr 2009

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Gruenig, E., Weissmann, S., Ehlken, N., Fijalkowska, A., Fischer, C., Fourme, T., Galie, N., Ghofrani, A., Harrison, R. E., Huez, S., Humbert, M., Janssen, B., Kober, J., Koehler, R., Machado, R. D., Mereles, D., Naeije, R., Olschewski, H., Provencher, S., ... Seeger, W. (2009). 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. Circulation (Baltimore), 119(13), 1747 - 1757. https://doi.org/10.1161/CIRCULATIONAHA.108.800938

@article{a41ca809924d40a28ee380986a627c68,

title = "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",

abstract = "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%; approximate to 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. (Circulation. 2009; 119: 1747-1757.)",

author = "Ekkehard Gruenig and Sylvia Weissmann and Nicola Ehlken and Anna Fijalkowska and Christine Fischer and Thierry Fourme and Nazzareno Galie and Ardeschir Ghofrani and Harrison, {Rachel E.} and Sandrine Huez and Marc Humbert and Bart Janssen and Jaroslaw Kober and Rolf Koehler and Machado, {Rajiv D.} and Derliz Mereles and Robert Naeije and Horst Olschewski and Steeve Provencher and Frank Reichenberger and Kathleen Retailleau and Guido Rocchi and Gerald Simonneau and Adam Torbicki and Richard Trembath and Werner Seeger",

year = "2009",

month = apr,

day = "7",

doi = "10.1161/CIRCULATIONAHA.108.800938",

language = "English",

volume = "119",

pages = "1747 -- 1757",

journal = "Circulation (Baltimore)",

issn = "1524-4539",

publisher = "American Heart Association, Inc.",

number = "13",

}

Gruenig, E, Weissmann, S, Ehlken, N, Fijalkowska, A, Fischer, C, Fourme, T, Galie, N, Ghofrani, A, Harrison, RE, Huez, S, Humbert, M, Janssen, B, Kober, J, Koehler, R, Machado, RD, Mereles, D, Naeije, R, Olschewski, H, Provencher, S, Reichenberger, F, Retailleau, K, Rocchi, G, Simonneau, G, Torbicki, A, Trembath, R & Seeger, W 2009, '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', Circulation (Baltimore), vol. 119, no. 13, pp. 1747 - 1757. https://doi.org/10.1161/CIRCULATIONAHA.108.800938

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. / Gruenig, Ekkehard; Weissmann, Sylvia; Ehlken, Nicola et al.
In: Circulation (Baltimore), Vol. 119, No. 13, 07.04.2009, p. 1747 - 1757.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Gruenig, Ekkehard

AU - Weissmann, Sylvia

AU - Ehlken, Nicola

AU - Fijalkowska, Anna

AU - Fischer, Christine

AU - Fourme, Thierry

AU - Galie, Nazzareno

AU - Ghofrani, Ardeschir

AU - Harrison, Rachel E.

AU - Huez, Sandrine

AU - Humbert, Marc

AU - Janssen, Bart

AU - Kober, Jaroslaw

AU - Koehler, Rolf

AU - Machado, Rajiv D.

AU - Mereles, Derliz

AU - Naeije, Robert

AU - Olschewski, Horst

AU - Provencher, Steeve

AU - Reichenberger, Frank

AU - Retailleau, Kathleen

AU - Rocchi, Guido

AU - Simonneau, Gerald

AU - Torbicki, Adam

AU - Trembath, Richard

AU - Seeger, Werner

PY - 2009/4/7

Y1 - 2009/4/7

N2 - 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%; approximate to 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. (Circulation. 2009; 119: 1747-1757.)

AB - 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%; approximate to 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. (Circulation. 2009; 119: 1747-1757.)

U2 - 10.1161/CIRCULATIONAHA.108.800938

DO - 10.1161/CIRCULATIONAHA.108.800938

M3 - Article

SN - 1524-4539

VL - 119

SP - 1747

EP - 1757

JO - Circulation (Baltimore)

JF - Circulation (Baltimore)

IS - 13

ER -

Gruenig E, Weissmann S, Ehlken N, Fijalkowska A, Fischer C, Fourme T et al. 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. Circulation (Baltimore). 2009 Apr 7;119(13):1747 - 1757. doi: 10.1161/CIRCULATIONAHA.108.800938