The Prognostic Significance of the Alterations of Cardiovascular Hemodynamics in Patients With Pulmonary Arterial Hypertension: A Meta-regression Analysis of Randomized Controlled Trials

Abstract Background: Hemodynamic assessment in patients with pulmonary arterial hypertension (PAH) is essential for risk stratification and pharmacological management. However, the prognostic value of the hemodynamic changes after treatment is less well established. Objectives: We investigated the prognostic impacts of the changes in hemodynamic indices, including mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), right atrial pressure (RAP) and cardiac output index (CI). We conducted this systematic review with meta-regression analysis on existing clinical trials.Methods:We searched and identified all relevant randomized controlled trials from multiple databases. An analogous R2 index was used to quantify the proportion of variance explained by each predictor in the association with PAH patients’ prognosis. A total of 20 trials and 3,263 individuals were enrolled. Results:The changes in mPAP, PVR, RAP and CI were all significantly associated with the change in 6MWD (∆6MWD). The change in mPAP was with the highest explanatory power for ∆6MWD (R2 analog=0.739). Additionally, the changes in mPAP, PVR and CI were independently predictive of adverse clinical events. The change in mPAP had the highest explanatory power for the clinical events (R2 analog =0.911). Furthermore, the change in PVR was with the highest explanatory power for total mortality of PAH patients (R2 analog =0.594). Conclusion:Hemodynamic changes after treatment, including mPAP, PVR, CI and RAP, were significantly associated with adverse clinical events or mortality in treated PAH patients. It is recommended that further studies be conducted to evaluate the changes in hemodynamic indices to guide drug titration.Trial registration number: PROSPERO; No.: CRD42019125157; URL: https://www.crd.york.ac.uk/PROSPERO/ (Date of registration: 14/03/2019)