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Exercise for Chronic Heart Failure: A Call to ACTION?
By Susan T. Marcolina, MD, FACP. Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA; she reports no financial relationship to this field of study.
Heart failure (HF), the end result of many cardiovascular disorders and a common disabling clinical syndrome, affects almost 6 million people in the United States.1 This growing public health problem and economic burden accounts for 12-15 million office visits and 6.5 million hospital days yearly.2 Such patients, in addition to being at increased risk for death, have important quality-of-life issues including diminished social and physical functioning due to dyspnea and fatigue. Although evidence-based pharmacologic treatments3 and device interventions4 reduce mortality, they have provided only modest improvements in quality of life (see Table 1).
Exercise in conjunction with diet and pharmacologic therapy has been an important therapeutic lifestyle intervention to reduce cardiovascular risk factors. Traditionally, physicians have recommended that HF patients limit their physical activity. This position has changed over the past 20 years, however, with the recognition that the ensuing physical deconditioning increases disability and poor outcomes despite optimal medical therapy. Inactivity also increases the risk for thromobembolic events, pulmonary infections, and depression, which increase mortality for HF and all forms of heart disease.5
Risk Factors for Heart Failure
Risk factors for developing heart failure are listed in Table 2. Regular aerobic exercise is an important lifestyle intervention for the primary prevention of HF for the initial four risk factors listed. Due to the physiologic adaptations that occur secondary to heart failure, aerobic exercise training could be an important adjunctive treatment for stable heart failure patients.
Quantification of Functional Limitations in Heart Failure
There are a number of ways to quantify the functional limitations caused by HF. The NYHA functional scalerated from I (asymptomatic) to IV (dyspneic with any exertion)is in widespread use, though is subject to significant differences in inter-observer interpretation.6 The 6-minute walk distance7 is useful prognostically, but serial changes in walking distance do not necessarily parallel clinical status changes. Maximal exercise testing with peak oxygen uptake has been used to identify patients for cardiac transplantation, to establish disability determination, and to assist in designing a prescription for exercise training.8
Risks of Exercise Testing
Exercise training was contraindicated in patients with moderate-to-severe left ventricular failure because, in the short term, initiation of exercise in formerly sedentary patients increased the risks for myocardial infarction and sudden death. This continues to be a concern; therefore, all patients considered for exercise training should undergo cardiopulmonary exercise (CPE) testing with a modified Naughton protocol (a type of graded exercise test better suited for diseased populations with a more gradual increase in intensity of 1 metabolic equivalent per stage) to rule out abnormal blood pressure responses, significant arrthymias, or ischemic changes that would preclude participation in exercise training and prompt further evaluation and therapeutic interventions. The purpose of the CPE is to establish the target heart rate for exercise. Safety guidelines target heart rate to 60% of the heart rate reserve (HRR, the difference between the peak heart rate, derived from a patient's recent exercise test, and the resting heart rate).9 The American College of Cardiology/American Heart Association (ACC/AHA) Practice Guidelines recommend that stable patients with chronic HF participate initially in exercise training as part of a supervised protocol in conjunction with evidence-based pharmacologic and device therapy. Subsequently, they can be transitioned to a home program with periodic follow-up.10
Obstacles to Exercise Training
Older patients with lower ejection fractions (less than 20%) tend to have higher attrition rates for exercise training. Other factors that impact compliance include lack of family support, transportation issues, multiple co-existent medical problems such as arthritis and movement disorders, and living alone. Patients with low exercise capacity need increased motivation, individual attention, and positive, ongoing feedback regarding progress.11
Pathophysiology of Heart Failure
HF results in neurohumoral excitation with elevations in levels of catecholamines, renin, vasopressin, and atrial naturietics as the body compensates for reduced cardiac output and tissue perfusion.12 Persistence of this excitation, however, results in deterioration of cardiac function with inflammation, end organ damage, and remodeling, which further compromises cardiac output. Additionally, patients with heart failure have reduced parasympathetic activity with decreased heart rate variability and baroreflex sensitivity with increased risk of malignant arrythmias.13
In addition to the cardiac adaptations, diminished flow states and proinflammatory cytokines such as tumor necrosis factor and interleukin (IL)-6 cause skeletal muscle and respiratory muscle myopathy with decreased capillary density, as well as shift from high aerobic capacity to low aerobic capacity muscle fibers with decreased mitochondrial density and structure with decreased oxidative enzymes. As a result, there is increased muscle fatigue and accumulation of metabolic byproducts, which contributes to dyspnea and reduced exercise tolerance.14
Although not listed in Table 1 because their effects on morbidity and mortality are unknown,10 loop diuretics are important in the treatment of HF because they can relieve symptoms of pulmonary and peripheral edema within hours, which is much quicker than the onset of effects for any other HF drug. Diuretics have also been shown to improve exercise tolerance in patients with HF.15 Close attention to changes in body weight and daily sodium intake restriction to 1,500 mg are important lifestyle and dietary measures essential to the success of exercise training in HF.16
Cardiovascular Adaptations to Exercise Training
In theory, the limited ability of heart failure patients to increase stroke volume and, therefore, cardiac output with exercise training would preclude improvements in exercise capacity. However, patients with heart failure do respond positively to exercise training with increases in maximal peak oxygen uptake (V02) ranging from 8% to 30%.8,17 This is because although the degree of cardiac adaptation is limited, HF patients are able to rely on improvements in pulmonary-mediated oxygen uptake and enhanced oxygen extraction and utilization via the peripheral musculature. Exercise training can enhance pulmonary functioning by increasing strength and endurance of pulmonary musculature. Exercise training also decreases neurohumoral tone by decreasing sympathetic activation and increasing parasympathetic activation, which increases cellular oxidative enzyme activity and reduces plasma levels of inflammatory cytokines such as TNF-alpha, IL-6, and IL-1 beta, improving endothelial vasodilatation.18
Clinical Studies of Exercise Training for Heart Failure
Keteyian et al trained HF patients for 24 weeks and found that approximately 85% of the total increase in peak oxygen uptake occurred after 12 weeks.8 Unsustained exercise training (less than 12 weeks) does not result in the same salutary effects as exercise of longer duration.19
Nilsson et al conducted a randomized controlled trial (RCT) of 80 patients (22% female; average age, 70.1 years) with stable CHF (LVEF of 30%) on optimal medical therapy. Forty patients were assigned to 16-week, group-based, aerobic high-intensity interval training twice weekly for 60-80 minutes/d and were compared to a standard-care control group. After 16 weeks, functional capacity (as assessed with a 6-minute walk test and cycle ergometer test) significantly improved in the exercise group, which gained an average of 58 meters improvement in the 6-minute walk, vs the control group, which lost an average of 15 meters (P < 0.001). Quality-of-life scores, measured with the Minnesota Living with Heart Failure Questionnaire, significantly improved in the exercise group compared with the control group and there was a significant inverse correlation between quality-of-life score and functional capacity.20
The HF-ACTION multicenter RCT followed more than 2,000 patients (median age 59 years; 27% female) with NYHA class II-IV HF and LVEF of 35% or less randomized to evidence-based medical therapy (EBMT) plus 36 sessions of supervised aerobic (walking, treadmill, or stationary cycling) exercise training (ET) at 60-70% of HRR three times weekly followed by home-based training at the same intensity five times weekly vs EBMT alone. Quality-of-life scores as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score improved by 54% in the patients treated with EBMT plus ET compared with 29% of patients in the EBMT-only group from baseline to three months. This improvement persisted throughout the median 2.5-year follow-up but reached a plateau after the three-month follow-up, probably secondary to the impact of the social support during the supervised exercise training sessions.
Exercise training effects included significant improvements in the 6-minute walk test and peak oxygen consumption of 20 vs 5 meters and 0.6 vs 0.2 mL/min/kg in the EBMT plus ET vs the EBMT-only group, respectively. The time to all-cause mortality or hospitalization was modestly decreased in the EBMT plus ET group vs the EBMT-only group and exercise training was well tolerated and safe, with 3.2% of patients in the exercise group experiencing an exercise-related hospitalization and 0.4% experiencing death after exercise compared to 1.9% and 0.4%, respectively, in the EBMT-only group.9,21 Notably, in contrast to earlier studies, exercise-related benefits were consistent across sex, race, and age.22
Contribution of Depression to HF Symptoms
At baseline, 99% of patients entered into the HF-ACTION trial completed the Beck Depression Inventory (BDI), and it was notable that in this ambulatory, outpatient, relatively young population, depression (defined as a BDI score greater than 10) was common at 43%. This BDI-identified depression was highly correlated with KCCQ score and NYHA class, measurements highly influenced by perception, though the depression score was not associated with objective parameters of function such as the left ventricular ejection fraction. Gottlieb et al found that patients with increased BDI scores had more subjective heart failure symptoms of dyspnea and functional limitations, despite the fact that there were no differences in the more objective measures of disease severity such as left ventricular ejection fraction (25.1% vs 25.3% in depressed and nondepressed patients, respectively). These findings suggest that depression influences the perception of disease severity to a greater extent than severe HF causes depression. Thus, diagnosis and treatment of depression in HF patients has the potential to markedly improve symptoms.23 Since exercise training has salutary effects on clinical depression,24 this would be another reason to recommend this lifestyle intervention to stable HF patients.
According to the ACC/AHA guidelines, patients with HF are advised to perform 30 minutes of moderate-intensity activity, and if unable to continue for 30 minutes to move for as long as possible (an effort level which does not cause the individual to sweat or become short of breath), five days per week. Safety guidelines target exercise heart rate to 60% of the HRR.10 An effective training session would consist of a warm-up period with stretching and range of motion exercises, followed by light aerobics with a gradual increase in activity to target HR or a Borg perceived exertion of 11-14 on the Borg rating of perceived exertion scale (runs from 6 [easy] to 20 [very intense])25 for 15-30 minutes, followed by a 10-minute cool-down.8
Exercise training has cardiovascular benefits and is associated with pulmonary and skeletal muscle metabolic adaptations that benefit patients with heart failure. CPE should be performed to rule out contraindications to exercise and to establish the target heart rate training zone. Supervised exercise training programs modeled upon cardiac rehabilitation should be considered for patients with stable heart failure who are receiving optimal heart failure therapy (unless a contraindication or intolerance exists) according to the guidelines established by the American College of Cardiology/American Heart Association.10 These patients should be subsequently transitioned to a home program and encouraged to perform 30 minutes or as long as tolerated of moderate-intensity aerobic activity (walking, treadmill, or bicycle) daily as recommended by ACC/AHA guidelines. Regular exercise may also improve depression syndromes, which can negatively impact HF symptoms.
Stable HF patients may benefit from supervised exercise training programs tailored to a target heart rate of 60% of the HRR for 30 minutes daily or as long as tolerated in conjunction with optimal heart failure pharmacologic and device therapy. Patients should be referred to a cardiac rehabilitation program for initiation of exercise training. HF patients should be screened for depression and treated as this may negatively impact the clinical course of their HF. Physicians should encourage patients to carefully follow daily weights and monitor dietary sodium intake.
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