Haemodynamics, exercise capacity and clinical events in pulmonary arterial hypertension

Abstract

The purpose of this study was to clarify whether changes in cardiopulmonary haemodynamics induced by pharmacological therapy correlate with exercise capacity and clinical events in patients with pulmonary arterial hypertension.16 randomised trials including 2353 patients, followed up for 16.4¡10.6 weeks, measuring cardiopulmonary haemodynamics by right heart catheterisation and reporting clinical events were included. Meta-analysis and meta-regression analysis were performed to assess the effects of treatments on clinical events and the relationship between haemodynamic changes (pulmonary artery pressure, pulmonary vascular resistance, cardiac index and right atrial pressure) and clinical events.Treatments significantly reduced all-cause death (OR 0.5, 95% CI 0.3-0.7; p,0.01), hospitalisation for pulmonary arterial hypertension (OR 0.4, 95% CI 0.2-0.7; p,0.01), initiation of rescue therapy (OR 0.3, 95% CI 0.2-0.6; p,0.01) and the composite outcome (OR 0.3, 95% CI 0.3-0.5; p,0.01). No relationship was found between changes of haemodynamic parameters and clinical events, whereas changes of cardiac index and pulmonary vascular resistance significantly correlated with changes in the 6-min walking distance (r50. 64, p50.03; r5 -0.55, p50.04, respectively).In patients with pulmonary arterial hypertension, improvements of cardiopulmonary haemodynamics observed in randomised clinical trials correlate with exercise capacity changes but do not predict clinical events in a short-term follow-up. @ERSpublications In PAH, cardiopulmonary haemodynamic improvements correlate with exercise capacity changes but not with clinical events

Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement

“…In PAH, 6MWD correlates with resting cardiac output and PVR [212], New York Heart Association Functional Class [212] and HRQoL [220]. Similarly, 6MWD change following PAH treatment correlated with changes in cardiac index, PVR [221] and HRQoL [220]. However, it has proven very difficult to demonstrate any prognostic power of 6MWD change with therapy.…”

The Role of Exercise Testing in the Modern Management of Pulmonary Arterial Hypertension

“…It also correlates with New York Heart Association Functional Class [127] and quality of life [129]. Similarly change in six minute walk distance (Δ6MWD) following PAH treatment correlated with changes in cardiac index, PVR [130] and quality of life [129].…”

“…Although Δ6MWD correlates with change in haemodynamics following PAH treatment [130], it has proven very difficult to demonstrate any prognostic power of Δ6MWD with therapy despite being sought by several studies and meta-analyses [17,141,142,144,147]. The mechanism of this phenomenon has been explored recently by two further studies.…”

“…The mechanism of this phenomenon has been explored recently by two further studies. In a meta-analysis of 22 PAH treatment studies, Savarese et al [130] demonstrated that the change in haemodynamics seen with PAH treatment and correlating with Δ6MWD did not predict subsequent clinical events. In a pooled analysis of ten PAH treatment studies submitted to the US Food and Drug Administration (2404 patients), Gabler et al [16] found that, despite a significant improvement in 6MWD, it accounted for only 22.1% of the treatment effect and they concluded that it was at best a modest surrogate endpoint for clinical events.…”

“…To explain this anomaly it has been hypothesised that treatment improves both right ventricular function and haemodynamics but that only the former is strongly linked to clinical outcome [65]. Consequently Δ6MWD which correlates more strongly with change in haemodynamics [130] than change in right ventricular function [148] is poorly linked to clinical outcomes.…”