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 ( P - V ) loop analysis to characterise the impact of RV diastology on poor flow augmentation during exercise in PAH.
Methods: RV P - 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 ( E _ed )) 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 ; p=0.0001), with higher associated exercise afterload (effective arterial elastance ( E _a ) 1.76 versus 0.90 mmHg·mL ^-1 ; p<0.0001), RV stiffness ( E _ed 0.68 versus 0.26 mmHg·mL ^-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 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.
Competing Interests: Conflict of interest: T.M. Kolb serves a fiduciary role for Oxywear, Inc., activities unrelated to the current work. R.J. Tedford reports no direct conflicts of interest related to this manuscript. He is the co-chair of the PH due to left heart disease task force for the 7th World Symposium on Pulmonary Hypertension and Deputy Editor for the Journal of Heart and Lung Transplantation. He reports general disclosures to include consulting relationships with Abbott, Acorai, Aria CV Inc., Acceleron/Merck, Alleviant, Boston Scientific, Cytokinetics, Edwards LifeSciences, Gradient, Lexicon Pharmaceuticals, Medtronic and United Therapeutics. R.J. Tedford serves on a steering committee for Merck, Edwards and Abbott, as well as a research advisory board for Abiomed. He also does haemodynamic core laboratory work for Merck. P.M. Hassoun serves on a scientific steering committee for MSD and on a scientific advisory board for Aria CV, activities unrelated to the current work. The other authors have no relevant financial disclosures.
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