Poor cardiac output reserve in pulmonary arterial hypertension is associated with right ventricular stiffness and impaired interventricular dependence

Background Pulmonary arterial hypertension (PAH) is characterised by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume - volume (P-V) - V) loop analysis to characterise the impact of RV diastology on poor flow augmentation during exercise in PAH. Methods RV P-V - V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index (CI) during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance (Eed)) e d )) and ventricular interdependence (left ventricular transmural pressure (LVTMP)) were compared at matched exercise stages. Results Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 mL m-2; - 2 ; p=0.0001), with higher associated exercise afterload (effective arterial elastance (Ea) a ) 1.76 versus 0.90 mmHg mL-1; - 1 ; p<0.0001), RV stiffness (Eed ed 0.68 versus 0.26 mmHg mL-1; - 1 ; p=0.003) and right-sided pressures (right atrial pressure 14 versus 8 mmHg; p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP - 4.6 versus 3.2 mmHg; p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA - PA coupling. Conclusions Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness and right- sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiological PAH differences unapparent at rest.