Not All PVR Reductions Are Created Equal: Lessons From the CADENCE Trial

The CADENCE trial evaluated sotatercept in combined post- and pre-capillary pulmonary hypertension associated with heart failure with preserved ejection fraction (CpcPH-HFpEF). We analyzed the pathophysiological implications of the observed pulmonary vascular resistance (PVR) reduction.A hemodynamic comparison was conducted contrasting the mechanistic effects of sotaercept with conventional pulmonary vasodilators.In CADENCE, PVR and pressure reductions occurred without marked cardiac output augmentation, contrasting with flow-mediated recruitment typical of traditional vasodilators. Sotatercept-induced PVR reduction may reflect true vascular reverse remodeling rather than vasodilation, underscoring the need to discriminate resistance reduction mechanisms in CpcPHHFpEF.