Aerobic exercise (AEX) has been shown to be beneficial for most HF patients by altering the deleterious peripheral and central mechanisms, such as inflammatory cytokines, that contribute to HF exacerbations, worsened symptom severity, and poor clinical outcomes. In addition, AEX reduces vascular resistance and improves endothelial function as well as the oxidative capacity of peripheral muscles, without worsening left ventricular remodeling. Lower rates of hospitalization, improved physical function and enhanced health-related quality of life are reported in HF patients who routinely exercise; other studies suggest AEX in HF leads to lower mortality.
The HF-ACTION trial established the safety and efficacy of moderate intensity aerobic exercise in patients with stable HF. Participants in the exercise arm completing 4 to 6 metabolic equivalents (MET) hours or more of exercise per week experienced an 18% to 26% reduction in risk, respectively, for the combined end point of all-cause mortality and hospitalization. A recent meta-analyses also showed significant reductions in brain natriuretic peptide (BNP), a strong prognostic indicator in HF, when weekly energy expenditure exceeded 400 kilocalories (kcals). AEX reduces inflammatory cytokines, including TNF-a, but the effect of aerobic exercise on ASC methylation and IL-18 in persons with HF has not been previously examined.
Persons with HF often have reduced aerobic capacity and low ventilatory efficiency, leading to poor quality of life. Clinical evaluation of aerobic capacity is measured by peak VO2, a measure of oxygen consumption during effort in a treadmill exercise test, and is a prognostic indicator of decompensation and mortality in HF. Cardiac rehabilitation exercise training has been shown to increase peak VO2; this increase in aerobic capacity is significantly related to decreased BNP and decreased oxidative stress. A two-week treatment with anakinra, an IL-1 receptor antagonist, improved peak VO2 in persons with HF in the absence of an exercise intervention. Thus, aerobic capacity in HF may be related to increased circulating inflammatory cytokines. AEX-induced ASC methylation may be a non-pharmacologic method of inflammasome modulation leading to decreased inflammation and improved aerobic capacity in HF; however, models of inflammasome modulation related to aerobic capacity have not been reported to date.