PT - JOURNAL ARTICLE AU - Cubero Salazar, Ilton M. AU - Lancaster, Andrew C. AU - Jani, Vivek P. AU - Montovano, Margaret J. AU - Kauffman, Matthew AU - Weller, Alexandra AU - Ambale-Venkatesh, Bharath AU - Zimmerman, Stefan L. AU - Simpson, Catherine E. AU - Kolb, Todd M. AU - Damico, Rachel L. AU - Mathai, Stephen C. AU - Mukherjee, Monica AU - Tedford, Ryan J. AU - Hassoun, Paul M. AU - Hsu, Steven TI - Poor Cardiac Output Reserve in Pulmonary Arterial Hypertension is Associated With Right Ventricular Stiffness and Impaired Interventricular Dependence AID - 10.1183/13993003.00420-2024 DP - 2024 Jan 01 TA - European Respiratory Journal PG - 2400420 4099 - https://publications.ersnet.org//content/early/2024/05/23/13993003.00420-2024.short 4100 - https://publications.ersnet.org//content/early/2024/05/23/13993003.00420-2024.full AB - Background Pulmonary arterial hypertension is characterized 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 characterize 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 during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance, Eed) 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 (Ea 1.76 versus 0.90 mmHg·mL−1, p<0.0001), RV stiffness (Eed 0.68 versus 0.26 mmHg·mL−1, p=0.003), and right-sided pressures (RA 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 pathophysiologic PAH differences unapparent at rest.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. 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 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. Dr. Tedford serves on steering committee for Merck, Edwards, and Abbott as well as a research advisory board for ​Abiomed. He also does haemodynamic core lab work for Merck.Conflict of interest: Dr. Hassoun serves on a scientific steering committee for MSD and on a scientific advisory board for ARIA-CV, activities unrelated to the current work.Conflict of interest: Dr. Kolb serves a fiduciary role for Oxywear, Inc., activities unrelated to the current work.Conflict of interest: All other authors have no relevant financial disclosures.