The prognostic impact of exercise right heart catheterization in patients with precapillary pulmonary hypertension on transplant-free survival

Background:

Pulmonary vascular diseases primary manifest with impaired exercise tolerance. We hypothesized that exercise pulmonary hemodynamics would predict outcome in arterial and inoperable chronic thromboembolic pulmonary hypertension (PAH, CTEPH).

Methods:

Right heart catheterizations from PAH and CTEPH with hemodynamic assessment during supine step-wise cycle exercise (10 Watt/3 min) were analyzed. Patients were closely followed and time of death or transplantation noted. Transplant-free survival and predictive value of hemodynamics were assessed by Cox regression and Kaplan Meier analysis.

Results:

70 patients (43 female, age 61 ± 15y, 54PAH, 16CTEPH, mean 6 minute walk distance (6MWD) 444 ± 130 m, mean pulmonary artery pressure (mPAP) 37 ± 10 mmHg, cardiac output (CO) 5.5 ± 1.8 l/min were followed 18 – 3489 d (median 610 d). 1, 3, 5, 7 year survival was 89, 80, 71, 59%. Age, NYHA functional class, 6MWD, mixed venous oxygen saturation but not resting hemodynamics predicted transplant-free survival. Power output and cardiac index at maximal exercise achieved (p-value; HR (95% CI): 0.027; 0.94 (0.89 – 0.99) and 0.034; 0.51 (0.27 – 0.95)), change in cardiac index (0.040; 0.25 (06 – 0.94)) such as multipoint ΔmPAP/ΔCO and mPAP-increase/Watt were predictive variables of transplant-free survival (0.003; 1.02 (1.01 – 1.03) and 0.038; 3.47 (1.07 – 11.25)). Kaplan-Meier survival analysis revealed a significantly better transplant-free survival for patients with a 6MWD ≥445 m (log rank p = 0.018), CI-increase ≥0.55 l/min/m² (p = 0.009) and a ΔmPAP/ΔCO slope < 14 in multipoint pressure-flow regression (p = 0.020). The CI-increase best predicted 6MWD in a multivariate stepwise regression model including age, mPAP and SmvO₂ at rest (p = 0.000, B = 112, CI 76 – 148, Coefficient 0.602). Exercise hemodynamics differed regarding NYHA functional classes but were similar in pretreated compared to treatment-naïve patients.

Conclusion: In PAH and inoperable CTEPH, cardiac index increase and multipoint pressure-flow relationship during exercise were predictive for transplant-free survival. Exercise hemodynamics correlated with established markers of disease severity and risk determinants for PH. RHC performed in the diagnosis and management of pulmonary hypertension should include measurements during both rest and exercise.