Locomotor Muscle Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction

Abstract

While there is emerging evidence of peripheral microvascular dysfunction in patients with heart failure with preserved ejection fraction (HFpEF) that may be related to systemic inflammation and redox imbalance, disease-related changes in locomotor muscle microvascular responsiveness have not been determined. This study combined passive leg movement and biomarker assessments of inflammation and oxidative damage to determine the magnitude and mechanisms of lower limb microvascular function in patients with HFpEF (71±1 years; n=44) compared with healthy, similarly aged controls (68±2 years; n=39). Leg blood flow, heart rate, mean arterial pressure, and stroke volume were assessed, and plasma biomarkers of inflammation and oxidative damage were also determined. A significantly attenuated passive leg movement–induced peak change in leg blood flow (263±25 versus 371±31 mL/min, HFpEF versus control) and leg vascular conductance (2.99±0.32 versus 3.88±0.34 mL/min per mm Hg, HFpEF versus control) was observed in patients compared with controls. Similarly, the total hyperemic response to passive leg movement, expressed as leg blood flow AUC and leg vascular conductance AUC , was ≈40% less in patients with HFpEF versus control. Significantly greater C-reactive protein, IL-6 (interleukin-6), and malondialdehyde were observed in patients with HFpEF but were not correlated with passive leg movement responses. These data provide new evidence of a decline in lower limb microvascular function within a milieu of vascular inflammation that may contribute to locomotor muscle dysfunction in patients with HFpEF.