Patients with HFpEF who exhibit impaired sympathetic vasoconstrictor responsiveness have a blunted exercise hyperemia

Background: Previous studies have shown a reduced blood flow response to exercise in patients with heart failure with preserved ejection fraction (HFpEF). This research has primarily focused on an impairment in the capacity to vasodilate during exercise. However, the ability to vasoconstrict is also vital for blood flow redistribution during exercise. This is important because patients with HFpEF have been shown to exhibit reduced alpha-adrenergic responsiveness. Notably, there is considerable heterogeneity in the level to which peripheral vasodilation and vasoconstriction are blunted among patients with HFpEF. Herein, we tested the hypothesis that those patients with HFpEF who are unable to vasoconstrict to sympatho-excitation (i.e., a cold pressor test, CPT) would have a reduced leg blood flow response to single leg knee extensor (SLKE) exercise than those patients with HFpEF who are able to vasoconstrict. Methods: Forty-three patients diagnosed with HFpEF (29 females; Age: 70 ± 7 years; body mass index: 39 ± 7 kg/m 2 ) were instrumented to measure heart rate (ECG), beat-to-beat blood pressure (BP; finger photoplethysmography), common femoral artery blood flow (duplex Doppler ultrasound), and brachial BP (sphygmomanometry). Participants sat upright on a SLKE ergometer while data were recorded during 3 minutes of quiet rest, followed by a 2-minute CPT. Next, after a 15-minute break, 3 minutes of SLKE exercise was performed at 46 ± 13% of peak SLKE watts (i.e., 7 ± 1 watts). Leg blood flow was calculated (LBF = common femoral artery radius 2 X mean blood velocity X 60) and used to determine leg vascular conductance (LVC; LBF/mean arterial BP). Patients with HFpEF were divided into those who didn’t have a decrease in LVC (non-constrictors: +26 ± 24 %ΔLVC; n = 22) and those who did have a decrease in LVC (constrictors: -15 ± 14 %ΔLVC; n = 21; P < 0.001) in response to the CPT. Results: Resting heart rate, resting BP, peak SLKE watts and lean thigh mass (DEXA) were not different between groups (all P > 0.48). The change in heart rate and BP during the CPT and SLKE exercise was also not different between groups (all P > 0.20). Non-constrictors had lower resting LBF (non-constrictors: 276 ± 128 ml/min; constrictors: 421 ± 200 ml/min; P = 0.006) and LVC (non-constrictors: 3.1 ± 1.5 ml/min/mmHg; constrictors: 4.7 ± 2.3 ml/min/mmHg; P = 0.008) compared to constrictors. In response to the SLKE exercise non-constrictors had a smaller increase in LBF (non-constrictors: Δ 1139 ± 425 ml/min; constrictors: Δ 1497 ± 454 ml/min; P = 0.011) and LVC (non-constrictors: Δ 9.8 ± 3.4 ml/min/mmHg; constrictors: Δ 13.3 ± 4.5 ml/min/mmHg; P = 0.007) compared to constrictors. Conclusion: In summary, patients with HFpEF who are not able to mount a vasoconstrictor response to a CPT present with a reduced blood flow response to exercise. This work was supported by the National Institutes of Health (1P01HL137630). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.