Abstract Body (Do not enter title and authors here): Introduction: Anemia (males: [Hb] <13.5 g/dL, females: <12 g/dL) is common in heart failure with preserved ejection fraction (HFpEF) and associated with exercise intolerance. The hemodynamic effect of anemia and the mechanism by which anemia impairs exercise capacity in patients with HFpEF are unclear. We investigated the effects of anemia on exercise hemodynamics and oxygen transport and utilization (VO₂) during a cardiopulmonary exercise test (CPET) and single leg knee extension exercise (SLKE) in patients with HFpEF.

Methods: Patients with HFpEF (n=57) classified as non-anemic (n=33, 67% female, age: 70±7 y, BMI: 39.3±5.8 kg/m², [Hb]: 13.7±1.5 g/dL) or anemic (63% female, age: 71±7 y, BMI: 34.7±5.9 kg/m², [Hb]: 11.2±0.9 g/dL) completed CPET on a seated upright cycle ergometer. A subgroup (n=20 non-anemic; 14 anemic) also completed SLKE to exhaustion. During CPET we measured VO₂ (indirect calorimetry), arterio-venous O₂ difference (Δa-vO₂; arterial and right heart catheters) and cardiac output (Qc; Direct Fick). During SLKE we measured femoral artery blood flow (LBF; Doppler ultrasound), Δa-vO₂ (pulse oximetry and femoral venous catheter) and leg VO₂. We also measured total hemoglobin mass (tHbmass; carbon monoxide rebreathing) and plasma volume. Data were compared via independent samples t-tests.

Results: The anemic group had lower relative tHbmass (g/kg lean mass; Figure 1A) compared to non-anemic, with no difference in plasma volume (Figure 1B). Peak VO₂ during CPET was similar between groups (non-anemic: 1.32±0.39 vs anemic: 1.24±0.44 L/min, P=0.269), but the anemic group had a higher Q_c-VO₂ slope (Figure 1C & D) and a lower Δa-vO₂ (non-anemic: 12.6±1.8; anemic: 10.7±1.4 mL/dL, P<0.001). During SLKE, no difference was detected in peak leg VO₂, LBF, Δa-vO₂, or diffusive capacity (all, P>0.175); however, the anemic group had a significantly greater LBF-VO₂ slope (Figure 1D).

Conclusion: Patients with HFpEF and anemia present with a hyperdynamic circulation during exercise despite similar peak VO₂ to non-anemic peers. [Hb] modifies the coupling of oxygen delivery and demand and may be a key mechanism responsible for hyperdynamic circulatory responses to exercise in patients with HFpEF and anemia.