Repeatability and sensitivity to change of non-invasive end points in PAH: the RESPIRE study

Abstract

End points that are repeatable and sensitive to change are important in pulmonary arterial hypertension (PAH) for clinical practice and trials of new therapies. In 42 patients with PAH, test-retest repeatability was assessed using the intraclass correlation coefficient and treatment effect size using Cohen's d statistic. Intraclass correlation coefficients demonstrated excellent repeatability for MRI, 6 min walk test and log to base 10 N-terminal pro-brain natriuretic peptide (log₁₀NT-proBNP). The treatment effect size for MRI-derived right ventricular ejection fraction was large (Cohen's d 0.81), whereas the effect size for the 6 min walk test (Cohen's d 0.22) and log₁₀NT-proBNP (Cohen's d 0.20) were fair. This study supports further evaluation of MRI as a non-invasive end point for clinical assessment and PAH therapy trials.Trial registration number NCT03841344.

Keywords: imaging/CT MRI etc; primary pulmonary hypertension.

Figure 1

Comparison of treatment effect size using Cohen’s d results in patients initiating and/or escalating pulmonary arterial hypertension (PAH) therapy. 6MWT, 6 min walk test; Log₁₀NT-ProBNP, log to base 10 N-terminal pro-brain natriuretic peptide; RV, right ventricular.

Figure 2

Cohen’s d versus interstudy intraclass correlation coefficient (ICC) for study measurements. DCE, dynamic contrast-enhanced imaging; Log₁₀NT-ProBNP, log to base 10 N-terminal pro-brain natriuretic peptide; PAFWHM, pulmonary arterial full width at half maximum; RVEF, right ventricular ejection fraction; RVSV, right ventricle stroke volume; 6MWT 6 min walk test. ICC >0.75=excellent repeatability. Cohen’s d value of <0.20 was considered no change, 0.20–0.49 was considered fair change, 0.50–0.79 was considered a medium change and ≥0.80 was considered a large change.