Exercise Rehabilitation as Therapy for HF

Cardiac/exercise rehabilitation offers a potential therapeutic approach in the management of patients with HF. The HF-ACTION trial (A Controlled Trial Investigating Outcomes of Exercise Training), a large, multicenter, randomized controlled study, failed to show significant improvement in all-cause mortality or all-cause hospitalization in patients who received a 12-week (3 times/week) exercise training program followed by 25-30 minute, 5 days/week home-based, self-monitored exercise workouts on a treadmill or stationary bicycle.63 However, after controlling for HF etiology, atrial fibrillation, exercise duration and depression, patients who exercised had an 11% risk reduction in the primary endpoint (P=0.03). Additionally, cardiovascular mortality or HF hospitalization was reduced by 15% after adjustment (P=0.03), and at three months after enrolment, quality of life was significantly improved in the exercise group.64 In HF-ACTION, exercise was safe and may be effective in improving clinical outcomes in patients not at highest prognostic risk. Additionally, functional status was significantly improved in patients receiving usual care plus exercise training in HF-ACTION. Distance walked at 3 months was higher and cardiopulmonary exercise time and peak oxygen consumption were improved at both 3 and 12 months in the exercise training group.63

HF-ACTION investigators found that many participants were non-adherent to the prescribed exercise program. In the first three months after enrolment, about 40% of patients fully adhered to the exercise duration goal and an additional 15% partially adhered, but in the last year of enrollment, less than 30% of participants were fully adherent and overall adherence had dropped below 45%.65 In a sub-analysis of HF-ACTION, researchers found that participants in the exercise training group with a higher volume of exercise per week had a reduction in all cause death or hospitalization, cardiovascular death or cardiovascular hospitalization and cardiovascular death or HF hospitalization at 90 days. Moreover, peak oxygen consumption, six-minute walk distance and quality of life all significantly improved in participants who exercised at a higher volume.65 HF-ACTION results provide further evidence beyond the many single center, short-term studies that showed that supervised exercise training improved quality of life and exercise capacity in patients with HF.66-78

Exercise training was found to have physiological benefits in patients with HF. Exercise training improved autonomic dysfunction and heart rate variability and was associated with a fall in resting plasma norepinephrine levels.67,79-82 It was found to improve exercise cardiac output, decrease peripheral vascular tolerance, and produce favorable changes in skeletal muscle metabolism and structure.83,84 Exercise training has been demonstrated to improve endothelium-dependent vasodilatation and coronary blood flow reserve in epicardial coronary vessels of patients with coronary artery disease, which may account for the observation that exercise training improves myocardial perfusion without reducing coronary obstruction or enhancement of collateral blood flow.85-89 Despite the favorable mechanistic studies, HF-ACTION is the only definitive study conducted to test whether exercise training for patients with HF can improve survival or reduce risk of hospitalization. The available trial data, from studies underpowered to provide definitive results had mixed results.89,90

Exercise Intolerance in HF. Exercise intolerance is an important adverse effect of HF and contributes significantly to the poor quality of life experienced by patients suffering from this syndrome. Impaired exercise capacity is an independent predictor of survival, and progressive loss of functional capacity is characteristic as HF worsens clinically.91-94 Intense investigation has focused for the past 2 decades on the potential mechanisms responsible for exercise intolerance in patients with HF. Interestingly, the degree of LV systolic dysfunction has been found to be poorly correlated with the degree of exercise intolerance.95-97 In contrast, the importance of reduced blood flow to exercising muscle is apparent from the closer relationship between exercise capacity and exercise cardiac output.98-111

Summary. Clinical studies support the concept that exercise training is safe and may be beneficial in patients with HF from LV systolic dysfunction. Evidence for benefit is derived both from mechanistic studies, short-term clinical trials that show physiologic improvement and benefits on exercise capacity following exercise training, and a large, multicenter study of long term benefits.63,64,112 The possibility exists that exercise training could be harmful to patients with HF, especially if it is applied in a population not consistent with those participating in completed studies. At present, exercise training cannot be recommended in patients with LV systolic dysfunction who had a major cardiovascular event or procedure within the last six weeks, in patients receiving cardiac devices that limit the ability to achieve target heart rates, and in patients with significant arrhythmia or ischemia during baseline cardiopulmonary exercise testing.