The prognostic significance of the alterations of pulmonary hemodynamics in patients with pulmonary arterial hypertension: a meta-regression analysis of randomized controlled trials

Shih-Hsien Sung,Chen-Huan Chen,Chi-Jung Huang,Wan-Yu Yeh,Hao-Min Cheng,Wei-Ming Huang,Chern-En Chiang

doi:10.1186/s13643-021-01816-0

Abstract

BackgroundHemodynamic 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.ObjectivesWe 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.MethodsWe 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 21 trials and 3306 individuals were enrolled.ResultsThe 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 = 0.740). 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 = 0.612).ConclusionHemodynamic 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.Systematic review registrationPROSPERO CRD42019125157

Highlights

There have been significant advances in pharmacological therapies in the past decade, pulmonary arterial hypertension (PAH) remains a progressive and fatal disease
Patients with increasing mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and right atrial pressure (RAP) were independently associated with less improvement of 6MWD (β = −7.1067, −0.1046, and −10.6923, respectively), and increasing change in cardiac index (CI) was independently related to better improvement of 6MWD (β = 42.4492)
Progression of PAH is usually characterized by increasing mPAP, PVR, and RAP, and decreasing CI, and this study aggregates the evidence of existing randomized controlled trials (RCTs) for verification

Summary

Introduction

There have been significant advances in pharmacological therapies in the past decade, pulmonary arterial hypertension (PAH) remains a progressive and fatal disease. Given the variable long-term survival rates between patients, risk stratification has been endorsed in the clinical management of PAH. While the European guideline has proposed a risk prediction algorithm, comprising 9 measures [1], Benza et al computed a risk score calculator for 1-year survival in 504 individuals from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) [2]. Despite the existing prediction models, the prognostic significance of the changes of these parameters during treatment for patients with PAH has not been systematically examined. Hemodynamic assessment in patients with pulmonary arterial hypertension (PAH) is essential for risk stratification and pharmacological management. The prognostic value of the hemodynamic changes after treatment is less well established

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