Comparison of CMR, functional and haemodynamic variables in PAH: Insights from REPAIR

Measures that can detect large treatment effects are important for monitoring therapeutic effectiveness. The 2022 ESC/ERS Guidelines highlight the importance of imaging in monitoring disease status and treatment response in pulmonary arterial hypertension (PAH). Are the standardised treatment effect sizes (STES) of cardiac magnetic resonance imaging (CMR) comparable with functional and haemodynamic variables?REPAIR (NCT02310672) was a prospective, multicentre, single-arm, open-label, 52-week Phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition (PDE-5i), on right ventricular (RV) remodelling, cardiac function, and cardiopulmonary haemodynamics. Both CMR and functional assessments were performed at screening, and at Weeks 26 and 52; haemodynamic measurements were conducted at screening and Week 26. In thispost-hocanalysis, STES was estimated using the parametric Cohen's d and non-parametric Cliff's delta tests.At Week 26, large STES (Cohen's d) were observed for 10/20 CMR variables, including the prognostic measures of RV and left ventricular stroke volume and RV ejection fraction and the haemodynamic trial endpoint, pulmonary vascular resistance; medium STES were observed for 6-minute walk distance (6MWD). The STES were consistent in treatment-naïve patients and those escalating therapy and maintained at Week 52. Similar results were obtained using the non-parametric Cliff's delta method.The treatment effect of macitentan, alone or in combination with a PDE-5i, was comparable for several CMR and haemodynamic variables with prognostic value in PAH, and greater than that of 6MWD in patients with PAH, highlighting the emerging relevance of CMR in PAH.