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Original Research: PULMONARY HYPERTENSION |

Endothelin-1/Endothelin-3 Ratio*: A Potential Prognostic Factor of Pulmonary Arterial Hypertension

David Montani, MD; Rogerio Souza, PhD; Christoph Binkert, MS; Walter Fischli, PhD; Gerald Simonneau, PhD; Martine Clozel, PhD; Marc Humbert, PhD
Author and Funding Information

*From the Centre des Maladies Vasculaires Pulmonaires (Drs. Montani, Souza, Humbert, and Simonneau), UPRES EA2705, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, Université Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France; and Actelion Pharmaceuticals Ltd (Drs. Fischli and Clozel, and Mr. Binkert), Allschwil, Switzerland.

Correspondence to: Marc Humbert, PhD, Centre des Maladies Vasculaires Pulmonaires, UPRES EA 2705, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud. 157 rue de la Porte de Trivaux, 92140 Clamart, France; e-mail: marc.humbert@abc.aphp.fr



Chest. 2007;131(1):101-108. doi:10.1378/chest.06-0682
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Background: Pulmonary arterial hypertension (PAH) is a rare condition characterized by elevated pulmonary artery pressure leading to right-heart failure and death. Endothelin (ET)-1 has been shown to play a significant pathogenic role in PAH. ET-3 has not yet been investigated in PAH.

Methods: ET-1 and ET-3 plasma concentrations were measured in 33 PAH patients prior to any specific PAH therapy and in 9 control subjects. In PAH patients, hemodynamic parameters measured by right-heart catheterization, 6-min walk distance (6MWD), New York Heart Association (NYHA) functional class, and time until lung transplantation or death were recorded.

Results: In patients with PAH, levels of ET-1 were increased while those of ET-3 were decreased, as compared to control subjects (p < 0.005 for both comparisons). ET-1/ET-3 ratio varied little in control subjects, while it increased threefold in PAH patients (p < 0.0001). ET-1 correlated positively with right atrial pressure (RAP), indexed total pulmonary resistance, and negatively with cardiac index and venous saturation of oxygen (Svo2). ET-3 correlated positively with 6MWD. ET-1/ET-3 ratio correlated positively with RAP, negatively with Svo2 and 6MWD, and was also associated with NYHA functional class. ET-1/ET-3 ratio was associated with prognosis in this sample of PAH patients treated with specific therapies.

Conclusions: PAH is characterized by elevated ET-1 and ET-1/ET-3 ratio and decreased ET-3 plasma concentrations. All of them correlate with hemodynamic and clinical markers of disease severity. ET-1/ET-3 ratio might be a novel prognostic factor in PAH. These preliminary data should be validated in a large prospective multicenter cohort of PAH patients.

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