Abstract 4144797: Interaction of Multiorgan Reserve Components Contributing to Exercise Intolerance in Heart Failure Patients: A Clinical Profiling Study

Background: In heart failure patients, the multiorgan system reserve capacity required to meet physiologic demands of exercise can be impaired at multiple levels. Cardiopulmonary exercise testing (CPET) with invasive hemodynamics can help dissect contributions of different organ systems to exercise intolerance. Aims: To map exercise limitations in patients with exertional dyspnea, comparing reserve capacities between HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF). Methods: From a cohort of patients undergoing invasive CPET, we included an “overt” HFpEF group defined by hemodynamic criteria (LVEF≥0.5 and PCWP rest supine≥15 mmHg) and a HFrEF group (LVEF≤0.4). We defined 7 exercise performance limitations: pulmonary mechanical impairment (VE/MVV>80% with FEV1<80% predicted [pred.]); exercise-induced steep elevation in cardiac filling pressures (PCWP/CO slope>2 mmHg/L/min); chronotropic incompetence (<80% pred. peak heart rate); reduced peak Fick stroke volume (<80% pred.); abnormal pulmonary vascular response (PVR>1.5WU at peak exercise); peripheral impairment (arteriovenous oxygen content difference<80% pred.); high metabolic cost of initiating exercise observed with excess body weight (internal work>30 watts). Results: Among 1,207 patients undergoing invasive CPET, 351 met criteria for "overt" HFpEF (mean age 60.0±14.5 years, 190 female [54%]) and 92 for HFrEF (mean age 57.9±12.9 years, 15 female [16%]). Compared to HFpEF, patients with HFrEF had more prevalent exercise-induced steep elevation in cardiac filling pressures (70% in HFrEF vs. 49% in HFpEF), chronotropic incompetence (74 vs. 48%), and deficient peak exercise stroke volume (49 vs. 12%) ( Figure ). Conversely, HFpEF patients exhibited higher peripheral impairment contributing to exercise limitation, with 45% of patients vs. 24% in HFrEF. Conclusions: This study highlights the distribution of physiologic deficits contributing to exercise intolerance in HFpEF and HFrEF patients that frequently extend beyond elevation in cardiac filling pressure and cardiac output reduction, especially in HFpEF. Mapping abnormal physiologic responses to exercise and their rank order may inform strategies to optimize functional capacity in HF.