Author + information
- Rainer Hambrecht, MD∗ ( )( and )
- Harm Wienbergen, MD
- Bremer Institute for Heart and Circulation Research at the Klinikum Links der Weser, Bremen, Germany
- ↵∗Address for correspondence:
Prof. Dr. Rainer Hambrecht, Bremer Institute for Heart and Circulation Research at the Klinikum Links der Weser Senator-Weßling-Strasse 1, 28277 Bremen, Germany.
Exercise training (ET) is a nonpharmacological treatment option in heart failure (HF) patients with proven beneficial effects on many pathophysiological mechanisms.
ET reduces neuroendocrine activation, sympathicotone hyperactivity, and catecholamine levels in HF patients. Randomized trials have demonstrated positive hemodynamic effects of ET in patients with HF resulting in improved left ventricular function and diameters as well as reduction of peripheral resistance (1). It has been proven that ET corrects endothelial dysfunction and impaired vasomotion in HF patients. In the skeletal muscle, oxidative stress and inflammatory processes are lowered, indicated by reduced levels of inflammatory cytokines (e.g., TNF-alpha, IL-1-beta, and IL-6) and reactive oxygen species. Therefore, oxidative capacity of the skeletal muscle increases, and exercise capacity of patients with HF who perform ET is improved. Numerous studies have shown that, due to the above-mentioned mechanisms, ET is associated with an improvement of symptoms in patients with HF. Regarding prognostic effects, ET in stable patients with HF resulted in a nonsignificant trend to reduced all-cause mortality and hospitalizations in the large randomized HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise TraiNing) (hazard ratio [HR]: 0.93; 95% confidence interval [CI]: 0.84 to 1.02; p = 0.13). After adjustment for highly prognostic predictors of the primary endpoint, ET was associated with significant reductions in both all-cause mortality and hospitalizations (HR: 0.89; 95% CI: 0.81 to 0.99; p = 0.03) and cardiovascular mortality and HF hospitalization (HR: 0.85; 95% CI: 0.74 to 0.99; p = 0.03) (2). It should be noted that suboptimal adherence to ET in the training group of the HF-ACTION trial likely blunted differences between the groups during study follow-up (2).
It seems reasonable to identify patient characteristics associated with different responses to ET in order to develop tailored treatment strategies. One such characteristic is the habitual baseline level of physical activity (PA) that may predict benefits from ET programs.
Prior studies in healthy participants have suggested greater effects from ET in patients with low baseline PA levels and greater health gains from an increase in PA among people who are more sedentary (3). In a study of habitual PA levels and outcomes in patients with stable coronary artery disease, Stewart et al. (4) observed that more PA was associated with lower mortality and that the largest benefits occurred between sedentary patient groups and between those with the highest mortality risk.
In the study by Mediano et al. (3) in this issue of JACC: Heart Failure, the impact of baseline PA levels on responses to ET and on clinical events in stable patients with HF was evaluated. The authors analyzed 1,494 study participants in the HF-ACTION trial with complete baseline PA data assessed using the International Physical Activity Questionnaire (IPAQ). Changes in exercise capacity (peak Vo2, cardiopulmonary exercise test duration, 6-min walk test distance) and in prognostic endpoints (all-cause mortality and hospitalizations, cardiovascular mortality and hospitalizations, cardiovascular mortality and HF hospitalizations) were investigated, and patients undergoing HF-ACTION exercise intervention were compared with those receiving usual care. Patients randomly assigned to the exercise intervention arm were scheduled to participate in supervised walking or stationary cycling 3 days per week. After patients completed 18 supervised sessions, they were asked to add a 2-day-per-week home-based exercise program. They were fully transitioned to a 5-day-per-week home-based training program (consisting of 40 min per session at 60% to 70% of heart rate reserve) after completing 36 supervised sessions.
In the results, Mediano et al. (3) report that higher self-reported baseline PA levels, assessed by IPAQ, correlated with a favorable clinical profile (lower New York Heart Association functional class, lower Beck depression score, less atrial fibrillation), higher exercise capacity (peak Vo2, cardiopulmonary exercise test duration, 6-min walk test distance), and better clinical outcomes during long-term follow-up (23% lower rate of cardiovascular death and HF hospitalization in an adjusted model).
A major study result was that responses to ET were similar in all tertiles of self-reported PA. In the training group, significant benefits for cardiopulmonary exercise test duration after 3 and 12 months were observed in all tertiles of baseline PA. Further parameters of exercise capacity (Vo2 peak, 6-min walk test distance) and clinical outcome responses to training were similar and largely nonsignificant across baseline PA tertiles. No significant differences in event rates (all-cause mortality and hospitalizations, cardiovascular mortality and hospitalizations, cardiovascular mortality and HF hospitalization) within each PA tertile were observed among subgroups randomized to ET versus those who received usual care; although most HRs were in the direction of benefit. This means that safety of ET in HF patients was not different between baseline PA tertiles.
The authors conclude that the beneficial effects of ET in patients with chronic systolic HF are similar regardless of habitual PA level.
There are some limitations to the study. Results using questionnaires rather than direct measurements to evaluate PA levels depend on the subjective assessment of the study participants. Individuals who reported regular moderate or vigorous PA in the 6 weeks prior study enrollment were excluded, and this might have reduced the likelihood of observing positive effects of greater PA.
However, the main study result communicates a very important clinical message: all stable patients with chronic HF should be motivated to participate in ET programs, regardless of their habitual PA level.
The differences observed between the results of the present study and those with healthy participants or patients with coronary artery disease (4) may be attributed to differences in the clinical profile and PA levels of HF patients. PA in patients with HF is limited by symptoms, reduced ejection fraction, and comorbidities; therefore, habitual PA levels in HF patients are lower than in patients without HF. In patients with HF, the highest tertile of habitual PA means less metabolic equivalents × min/week than the highest tertile of habitual PA in patients without HF. In conclusion, studies of baseline PA levels in patients with HF are not directly comparable with studies of patients without HF.
It is a challenge to introduce ET programs that achieve long-term effects into clinical practice. In the HF-ACTION trial, adherence to ET in the training group was suboptimal during a long-term course. Prevention studies focusing on ET have shown that the effects of short-term education programs during rehabilitation after cardiac events are soon diminished after a few months. Modern strategies, such as telemetric control of PA by step counters and accelerometers (wearable devices) and repeated personal contacts during a long-term course, can help to achieve better long-term results from ET programs. In the recently published IPP (Intensive Prevention Program) trial (5), a 12-month prevention program, including telemetric control of PA and repetitive personal teaching by nonphysician medical assistants, resulted in highly significant improvements of PA levels in patients after myocardial infarction.
Such programs should be provided to all stable patients with HF, those who are sedentary as well as those who are already active in daily life.
The present study by Mediano et al. (3) increases evidence for the concept that every HF patient, regardless of habitual PA level, profits from structured exercise interventions. This message should be communicated to the patients to enhance motivation and increase adherence to ET programs.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Mediano M.F.F.,
- Leifer E.S.,
- Cooper L.S.,
- et al.
- Stewart R.A.H.,
- Held C.,
- Hadziosmanovic N.,
- et al.
- Wienbergen H.,
- Fach A.,
- Meyer S.,
- et al.