Abstract 17833: Characterization of Central versus Peripheral Predominance of Exercise Limitation in Patients With Heart Failure and Preserved Ejection Fraction

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous disorder in which abnormalities in both cardiac output (CO) and peripheral oxygen extraction (CavO ₂ ) contribute to impaired oxygen uptake (VO ₂ ). We investigated the predominant limitation to VO ₂ , according to distinct HFpEF criteria, by examining the CO vs. VO ₂ relationship during incremental exercise.

Methods: Participants underwent Cardiopulmonary Exercise Testing (CPET) with invasive hemodynamic assessment and were diagnosed with HFpEF based on characteristic symptoms and NTproBNP ≥125pg/mL, Supine PCWP ≥15mmHg, PCWP/CO ≥2mmHg/L/min or Peak PCWP ≥25mmHg. Calculated direct Fick CO versus VO ₂ slope and peak exercise data were stratified by the expected relationship of CO(L/min) = 5хVO ₂ (L/min) +5. The Mann Whitney U Test and t-test characterized those limited by cardiac output (Slope <5L/min) vs. peripheral extraction (Slope >5L/min). Results: In 425 dyspneic individuals meeting biomarker and/or hemodynamic criteria for HFpEF, 36% had predominantly peripheral limitation (Measured Peak CO > Expected). Among those with NTpro-BNP ≥125pg/mL or resting PCWP ≥15mmHg, or both (N=220) , 31% were peripherally limited. 41% of those with a PCWP/CO ≥2mmHg/mL/min or Peak PCWP ≥25mmHg, or both (N=205) , were peripherally limited. Among all peripherally limited patients (N=151), the percentage of females, NTpro-BNP levels, Hb levels, rest and peak Ca-vO ₂ , and rest and peak PVR were significantly lower compared to the cardiac limited group (Table, N=274), while resting PCWP, LVEF and HR were similar (Table).

Conclusion: Despite meeting concurrent biomarker and/or hemodynamic criteria for HFpEF, peripheral-predominant limitation to exercise capacity is common which merits consideration when deploying interventions to augment exercise capacity in HFpEF.