Impaired skeletal muscle vasodilation during exercise in heart failure with preserved ejection fraction

Abstract

Background Exercise intolerance is a hallmark symptom of heart failure patients with preserved ejection fraction (HFpEF), which may be related to an impaired ability to appropriately increase blood flow to the exercising muscle. Methods We evaluated leg blood flow (LBF, ultrasound Doppler), heart rate (HR), stroke volume (SV), cardiac output (CO), and mean arterial blood pressure (MAP, photoplethysmography) during dynamic, single leg knee-extensor (KE) exercise in HFpEF patients (n = 21; 68 ± 2 yrs) and healthy controls (n = 20; 71 ± 2 yrs). Results HFpEF patients exhibited a marked attrition during KE exercise, with only 60% able to complete the exercise protocol. In participants who completed all exercise intensities (0-5-10-15W; HFpEF, n = 13; Controls, n = 16), LBF was not different at 0W and 5W, but was 15-25% lower in HFpEF compared to controls at 10W and 15W (P < 0.001). Likewise, leg vascular conductance (LVC), an index of vasodilation, was not different at 0W and 5W, but was 15-20% lower in HFpEF compared to controls at 10W and 15W (P < 0.05). In contrast to these peripheral deficits, exercise-induced changes in central variables (HR, SV, CO), as well as MAP, were similar between groups. Conclusions These data reveal a marked reduction in LBF and LVC in HFpEF patients during exercise that cannot be attributed to a disease-related alteration in central hemodynamics, suggesting that impaired vasodilation in the exercising skeletal muscle vasculature may play a key role in the exercise intolerance associated with this patient population.

Effects of Endurance Training on Detrimental Structural, Cellular, and Functional Alterations in Skeletal Muscles of Heart Failure With Preserved Ejection Fraction

“…Nevertheless, the same authors haven also provided data to support that an increase in the arterial-mixed venous O 2 difference is likely the primary mechanism underlying the higher peak achieved post-training in HFpEF [26,27], which indicates a peripheral limitation is present in HFpEF. Based on these data and together with our findings, we speculate improved microvascular perfusion may be the primary mechanism leading to an improvements in peak following endurance training in HFpEF (which is known to be impaired [30,31]), as this would be predicted to elevate O 2 diffusion delivery from capillary to mitochondria (as dictated by Fick's Law) [34]. activity was assessed, which tended to be higher in HFpEF rats (E), while LC3 II/I protein levels were assessed to provide an index of autophagy and these were depressed in HFpEF compared to controls (F).…”

“…as reviewed in ref. [23]), we speculate the main mechanism responsible for the increase in peak likely resides at the peripheral vascular level [30,31]. Indeed patients with HFpEF are known to have endothelial dysfunction [32] and we have previously shown endurance training can reverse in vitro endothelial dysfunction in aortic rings isolated from hypertensive rats with HFpEF [33].…”

Skeletal Muscle Alterations Are Exacerbated in Heart Failure With Reduced Compared With Preserved Ejection Fraction

“…26 Furthermore, it is also known that HFpEF can induce endothelial dysfunction, 27 with more recent data showing limb blood flow and vasodilation are impaired during exercise. 28 Overall, therefore, although our data indicate that greater skeletal muscle alterations are induced in HFrEF compared with HFpEF, further investigations are warranted to determine whether this plays a more dominant role in limiting exercise capacity in one rather than in the other disease entity.…”

Sarcopenia and Heart Failure

“…Sustained sympathetic activity is linked with excessive oxidative stress further contributing to mitochondrial damage, muscular protein dysfunction, and degradation. Angiotensin-II, epinephrine, and norepinephrine can, moreover, cause endothelial dysfunction, heterogeneity of blood flow, and lower capillary density, all linked with sarcopenia genesis [19].…”