Souza R, Humbert M, Sztrymf B, Jaïs X, Yaïci A, Le Pavec J, Parent F, Hervé P, Soubrier F, Sitbon O, Simonneau G
Université Pains-Sud, UPRES-EA 2705 Pneumology Dept and French National Reference Centre for Pulmonary Hypertension, Antoine Béclère Hospital, Clamart, Paris, France.
Eur Respir J. 2008 Feb;31(2):343-8. doi: 10.1183/09031936.00104807. Epub 2007 Oct 24.
The aim of the present study was to describe a large cohort of fenfluramine-associated pulmonary arterial hypertension (fen-PAH) and its possible prognostic markers. The records of all patients with a diagnosis of fen-PAH evaluated at the present authors' centre from 1986-2004 were retrospectively studied. Baseline clinical and haemodynamic data were collected, as well as survival times. The median duration of fenfluramine exposure was 6 months, with a median of 4.5 yrs between exposure and onset of symptoms. Nine (22.5%) out of 40 patients evaluated resulted positive for the presence of germline bone morphogenetic protein receptor (BMPR) type 2 mutations. In these patients, the duration of exposure to fenfluramine was significantly lower than in patients without mutation. The median survival was 6.4 yrs, without significant difference between fen-PAH and a control group of idiopathic and familial pulmonary arterial hypertension patients referred to the present authors' centre during the same time frame and treated identically. Duration of fenfluramine exposure showed no relation to survival, while cardiac index was the only independent predictor of multivariate analysis. Fenfluramine-associated pulmonary arterial hypertension shares clinical, functional, haemodynamic and genetic features with idiopathic pulmonary arterial hypertension, as well as overall survival rates. Therefore, the present authors conclude that fenfluramine exposure characterises a potent trigger for pulmonary arterial hypertension without influencing its clinical course.
本研究的目的是描述一大群与芬氟拉明相关的肺动脉高压（fen-PAH）患者及其可能的预后标志物。对1986年至2004年在本研究作者所在中心接受评估的所有诊断为fen-PAH的患者记录进行了回顾性研究。收集了基线临床和血流动力学数据以及生存时间。芬氟拉明暴露的中位持续时间为6个月，暴露与症状出现之间的中位时间为4.5年。在评估的40例患者中，有9例（22.5%）种系骨形态发生蛋白受体（BMPR）2型突变检测呈阳性。在这些患者中，芬氟拉明的暴露持续时间显著低于未发生突变的患者。中位生存期为6.4年，fen-PAH与在同一时间段转诊至本研究作者所在中心并接受相同治疗的特发性和家族性肺动脉高压患者对照组之间无显著差异。芬氟拉明暴露持续时间与生存无关，而心脏指数是多变量分析的唯一独立预测因素。芬氟拉明相关的肺动脉高压与特发性肺动脉高压在临床、功能、血流动力学和基因特征以及总生存率方面具有相似之处。因此，本研究作者得出结论，芬氟拉明暴露是肺动脉高压的一个有力触发因素，但不影响其临床病程。
