Prognostic relevance of Exercise Pulmonary Hypertension: Results of the multi-center PEX-NET Clinical Research Collaboration

Background Exercise pulmonary hypertension (exercise PH) was defined by a mean pulmonary arterial pressure (mPAP)/cardiac output (CO) slope >3 mmHg·L −1 ·min −1 between rest and exercise in the 2022 ESC/ERS PH guidelines. However, large, multi-center studies on the prognostic relevance of exercise hemodynamics and its added value to resting hemodynamics are missing. Patients and Methods The PEX-NET (Pulmonary Hemodynamics during Exercise Network) registry enrolled patients who underwent clinically indicated right heart catheterizations both at rest and ergometer exercise from 23 PH-centers worldwide. In this retrospective analysis we included subjects with resting mPAP<25 mmHg and complete hemodynamic data at rest and exercise in the same body position. Mixed effects Cox proportional hazard models with random effect center were applied to identify independent markers of prognosis among the hemodynamic parameters. Results We included n=764 patients (64% females, age: 59yrs (IQR:46–69), mPAP: 17 mmHg (IQR:14–20)). Median observation time was 6.8yrs (range:0.1–15.9) and 87 patients (11%) died during follow-up. After adjustment for age, sex, hemoglobin level, and resting hemodynamics, CO (p=0.001; HR: 0.85 (95%CI:0.77–0.93)) and trans-pulmonary gradient (p=0.044; HR: 1.04 (95%CI:1.00–1.08)) at peak exercise and the mPAP/CO slope (p<0.001; HR: 1.12 (95%CI:1.06–1.18)) were the only independent predictors of prognosis. Patients with mPAP/CO slope >3 mmHg·L −1 ·min −1 had significantly worse survival compared to those with ≤3 mmHg·L −1 ·min −1 (p=0.013; HR: 2.04 (95%CI:1.16–3.58)). Conclusion The mPAP/CO slope is a robust and independent predictor of prognosis in patients with normal or mildly elevated resting pulmonary arterial pressure that provides prognostic information beyond resting hemodynamics and appears suitable to define exercise PH.