Similar effects of exercise training on exercise test duration and clinical outcomes in HFrEF regardless of baseline physical activity
Influence of Baseline Physical Activity Level on Exercise Training Response and Clinical Outcomes in Heart Failure: The HF-ACTION Trial
Introduction and methods
Although aerobic exercise training has been shown to improve functional capacity and to possibly reduce clinical events in patients with chronic heart failure (HF), its influence on mortality reduction remains controversial [1-3]. These controversial observations may be explained partly by differences in baseline physical activity (PA) levels since PA levels are important predictors for clinical and mortality outcomes in HF patients [4-6]. However, the influence of baseline PA levels on the response to exercise training among patients with HF is unclear. This secondary analysis of the Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) trial therefore evaluated the influence of baseline PA on exercise training-induced response and clinical events in outpatients with HFrEF.
The multicenter, international, randomized HF-ACTION trial included 2331 stable outpatients from the United States, Canada, and France with LVEF <35% and NYHA functional classes II to IV symptoms despite optimal HF treatment, who did not report to exercise more than once per week at a moderate-to-vigorous intensity at any time during the previous six weeks. Eligible patients (n=1494) were randomized assigned to either an exercise training (50.3%) or usual care (49.7%). Exercise training consisted of three sessions per week of supervised treadmill walking or stationary cycling, followed by concomitant home-based exercise twice per week during the first 36 sessions, and participants were then fully transitioned to a 5-day-per-week home-based exercise program for two to four years. Participants were further divided in tertiles based on self-reported baseline PA using the International Physical Activity Questionnaire–Short Form (IPAQ-SF). The median follow-up duration was 30.5 months.
In this secondary analysis, endpoints consisted of primary (all-cause mortality or all-cause hospitalization), and secondary (CV mortality or CV hospitalization and the composite of CV mortality or HF hospitalization) outcomes of the HF-ACTION trial, and changes in exercise capacity during the follow-up (3 and 12 months) as measured by peak oxygen uptake (VO2), cardiopulmonary exercise test (CPET) duration, and a 6-min walk test (6MWT) distance.
Baseline PA and effect of exercise training on exercise capacity
- A trend was observed towards beneficial effects of exercise training within all baseline PA tertiles, however, only CPET duration was significantly improved within all three tertiles, compared to usual care.
- There were no differences in exercise training response between baseline PA tertiles, except for peak VO2 in the middle versus lowest baseline PA tertiles at 3 months, compared to usual care, however, this was no longer significant after multivariable adjustment.
Baseline PA and effect of exercise training on mortality/hospitalization
- In both the middle and highest baseline PA tertile, lower rates of mortality and hospitalization outcomes were found, compared to the lowest tertile. However, after multivariable adjustments, only significantly lower CV mortality or CV hospitalization rates (HR: 0.82, 95%CI: 0.68-0.99) were observed in the middle baseline PA tertile, compared to the lowest tertile.
- Within tertiles, there were no significant differences in clinical event outcomes between the exercise and usual care groups. In the lowest PA tertile there was a lower risk for CV mortality or HF hospitalization, but this was no longer significant after multivariable adjustment.
In the ACTION-HF trial, higher PA baseline was associated with a more favorable clinical profile in stable outpatients with HFrEF. A program of supervised and home-based exercise training significantly improved exercise test duration similarly across baseline PA tertiles, but no significant differences in clinical outcome rates within each PA tertile were observed between subgroups randomized to exercise training versus usual care.