Phenotyping Exercise Intolerance in HFpEF: Which Muscle is Limiting Aerobic Performance?

Background: Low aerobic power (peak VO 2 ) is common in patients with Heart Failure with preserved Ejection Fraction (HFpEF). Mechanisms for low VO 2 are diverse and vary between patients. We used the cardiac output (Qc) response to VO 2 during exercise to characterize patients with HFpEF into those with primary cardiac or peripheral defects in oxygen uptake. Methods: Patients with HFpEF (n =15, age 69±6 years) underwent invasive cardiopulmonary exercise testing with measures taken at rest, 20W, and peak exercise. A right heart catheter was used to measure end-expiratory PCWP and cardiac output (Qc, direct Fick). Oxygen uptake (VO 2 ) was measured using Douglas bags. Patients were “cardiac limited” if their ΔQc/ΔVO 2 relationship was blunted (<5) or “peripherally limited” if ΔQc/ΔVO 2 was normal or high (≥5). Effect size between groups was determined with Cohen’s d . Results: Seven patients were cardiac limited and eight were peripherally limited. ΔQc/ΔVO 2 slope was lower in cardiac limited patients (4.2±0.7 vs 6.6±1.3, Cohen’s d = 1.52). Cardiac limited patients were younger and more often female (Values and Cohen’s d shown in Table ). Peak PCWP was similar between the groups (C: 34±8 vs P: 33±7 mm Hg, d = 0.09). Peak VO 2 was higher in cardiac limited patients (C: 12.7±4.3 vs P 9.8±1.3 ml/min/kg, d = 0.85). Stroke volume reserve was lower in the cardiac limited patients (C: 9±18% vs P: 37±20%, d = 0.77). Peripheral oxygen extraction (ΔAVO 2 ) during exercise was lower in the peripherally limited patients (C: 13.2±1.7% vs P: 10.8±1.4%, d =1.24). Conclusions: Phenotyping exercise intolerance using the Fick equation can identify HFpEF patients with primary cardiac and peripheral limitations causing low aerobic power. Cardiac limited patients were unable to augment stroke volume, while peripherally limited patients were unable to augment the oxygen extraction from skeletal muscles. Exercise based phenotyping may be a useful strategy to match therapies to patient specific physiology.