Kovacs Gabor, Humbert Marc, Avian Alexander, Lewis Gregory D, Ulrich Silvia, Vonk Noordegraaf Anton, Souza Rogerio, Galiè Nazzareno, Malhotra Rajeev, Saxer Stephanie, Grünig Ekkehard, Egenlauf Benjamin, Ewert Ralf, Heine Alexander, Tedford Ryan J, Houston Brian A, Kasperowicz Krzysztof, Kurzyna Marcin, Rosenkranz Stephan, Herkenrath Simon, Barbera Joan Albert, Blanco Isabel, Oliveira Rudolf K F, Andersen Mads, Savale Laurent, Systrom David, Maron Bradley A, Tello Khodr, Condliffe Robin, Mak Susanna, Baratto Claudia, Hsu Steven, D'Alto Michele, McCabe Colm, Herve Philippe, Olschewski Horst
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
Ludwig Boltzmann Institute for Lung Vascular Research Graz, Graz, Austria.
Eur Respir J. 2024 Nov 27;64(6). doi: 10.1183/13993003.00698-2024. Print 2024 Dec.
Exercise pulmonary hypertension (PH) was defined by a mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope >3 mmHg·min·L between rest and exercise in the 2022 European Society of Cardiology/European Respiratory Society PH guidelines. However, large, multicentre studies on the prognostic relevance of exercise haemodynamics and its added value to resting haemodynamics are missing.
The PEX-NET (Pulmonary Haemodynamics during Exercise Network) registry enrolled patients who underwent clinically indicated right heart catheterisations both at rest and ergometer exercise from 23 PH centres worldwide. In this retrospective analysis we included subjects with resting mPAP <25 mmHg and complete haemodynamic data at rest and exercise in the same body position. Mixed effects Cox proportional hazard models with random effect centre were applied to identify independent markers of prognosis among the haemodynamic parameters.
We included 764 patients (64% females; median (interquartile range) age 59 (46-69) years and mPAP 17 (14-20) mmHg). Median (range) observation time was 6.8 (0.1-15.9) years and 87 patients (11%) died during follow-up. After adjustment for age, sex, haemoglobin level and resting haemodynamics, CO (hazard ratio (HR) 0.85, 95% CI 0.77-0.93; p=0.001) and transpulmonary gradient (HR 1.04, 95% CI 1.00-1.08; p=0.044) at peak exercise and the mPAP/CO slope (HR 1.12, 95% CI 1.06-1.18; p<0.001) were the only independent predictors of prognosis. Patients with a mPAP/CO slope >3 mmHg·min·L had significantly worse survival compared to those with a mPAP/CO slope ≤3 mmHg·min·L (HR 2.04, 95% CI 1.16-3.58; p=0.013).
The mPAP/CO slope is a robust and independent predictor of prognosis in patients with normal or mildly elevated resting PAP that provides prognostic information beyond resting haemodynamics and appears suitable to define exercise PH.
在2022年欧洲心脏病学会/欧洲呼吸学会肺动脉高压指南中，运动性肺动脉高压（PH）定义为静息和运动之间平均肺动脉压（mPAP）/心输出量（CO）斜率>3 mmHg·min·L。然而，关于运动血流动力学的预后相关性及其对静息血流动力学的附加值的大型多中心研究尚缺。
运动期间肺血流动力学网络（PEX-NET）注册研究纳入了来自全球23个肺动脉高压中心的在静息和测力计运动时均接受临床指征右心导管检查的患者。在这项回顾性分析中，我们纳入了静息mPAP<25 mmHg且在相同体位下有静息和运动时完整血流动力学数据的受试者。应用带有随机效应中心的混合效应Cox比例风险模型来确定血流动力学参数中独立的预后标志物。
我们纳入了764例患者（64%为女性；年龄中位数（四分位间距）为59（46 - 69）岁，mPAP为17（14 - 20）mmHg）。中位（范围）观察时间为6.8（0.1 - 15.9）年，87例患者（11%）在随访期间死亡。在调整年龄、性别、血红蛋白水平和静息血流动力学后，运动峰值时的CO（风险比（HR）0.85，95%置信区间0.77 - 0.93；p = 0.001）、跨肺压差（HR 1.04，95%置信区间1.00 - 1.08；p = 0.044）以及mPAP/CO斜率（HR 1.12，95%置信区间1.06 - 1.18；p<0.001）是仅有的独立预后预测因子。与mPAP/CO斜率≤3 mmHg·min·L的患者相比，mPAP/CO斜率>3 mmHg·min·L的患者生存率显著更差（HR 2.04，95%置信区间1.16 - 3.58；p = 0.013）。
mPAP/CO斜率是静息PAP正常或轻度升高患者预后的一个可靠且独立的预测因子，它能提供超越静息血流动力学的预后信息，似乎适合用于定义运动性PH。
