A prospective study comparing the repeatability and sensitivity to change of non-invasive endpoints in pulmonary arterial hypertension: the RESPIRE study

Abstract

Introduction: For clinical trials it is important to know the repeatability and sensitivity to change of study end-points. The aim of this study was to compare non-invasive candidate end-points in patients with pulmonary arterial hypertension (PAH). Methods: We examined 2 field walking tests: the six minute walk test (6MWT) and the incremental shuttle walking test (ISWT) and 2 tests of RV function: NT-proBNP and cardiac magnetic resonance imaging (cMRI). Patients with PAH underwent 6MWT, ISWT, NT-proBNP and cMRI (visit 1). At follow-up at around 6 months the investigations were repeated x2 within 24 hours (visits 2 and 3). Test-retest repeatability (visits 2 vs 3) and change with therapy (visit 2 minus visit 1) were assessed by the intraclass correlation coefficient (ICC) and a paired t-test respectively. Results: Of 44 patients, 40 completed the study; 27 patients underwent initiation or escalation of PAH therapy and 13 were stable on therapy. For all patients the ICC for the ISWT was 0.99, 6MWT 0.99, NT-proBNP 0.72, right ventricular end-systolic volume (RVESV) 0.98 and right ventricular ejection fraction (RVEF) 0.83. Following initiation or escalation of therapy there was an increase in ISWT, mean difference +40m (standard deviation (SD) 79), p=0.02 and 6MWT distance, +35m (SD 79) p=0.04, a reduction in RVESV -20ml (SD 30) p=0.002, and an increase in RVEF, +4% (SD 9), p=0.04 respectively. There was no significant change in NT-proBNP, -206 pg/m (SD 684), p=0.15. Conclusion: ISWT and 6MWT had excellent repeatability and are sensitive to change in PAH. CMRI but not NT-proBNP has excellent repeatability and is sensitive to change.