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International Journal of Gerontology 4 (2010) 165e170
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International Journal of Gerontology
journal homepage: www.ijge-online.com
Review Article
The Effects and Safety of Exercise Training in Subjects With Chronic Heart
FailuredDo Elder Subjects Gain Similar Benefits?q
Shiau-Fu Hsieh 1, Gwo-Chi Hu 1 *, Yao-Chia Chuang 1, Chun-Yen Chen 2, Yu-Ning Hu 3
1
Department of Rehabilitation Medicine, Mackay Memorial Hospital, Taipei, Taiwan, 2 Department of Cardiology and Occupational Medicine, Mackey Memory Hospital, Taipei,
Taiwan, 3 Institute of Economics and Social studies, National United University, Miaoli, Taiwan.
a r t i c l e i n f o
s u m m a r y
Article history:
Received 28 March 2010
Accepted 3 August 2010
Traditionally, chronic heart failure (CHF) subjects are often recommended to rest and restrict physical
activity; however, this advice may exacerbate the disease. Exercise training is associated with many central
and peripheral adaptations that improve clinical outcomes. Exercise training can restore the abnormal
autonomic function, attenuate the production of proinflammatory cytokines and the N-terminal precursor
of brain natriuretic peptide (NT-pro-BNP), and improve the endothelial dysfunction and the oxidative
capacity of peripheral muscle. The current evidence supports the concept that exercise training can effectively improve the exercise capacity and quality of life of subjects with CHF, to some extent, as well as reduce
hospitalization and risk of mortality. Structured exercise training is proved to be safe for CHF subjects.
Exercise training had no detrimental effects on the left ventricular remodeling. Ultimately, trained subjects
showed a significant improvement in left ventricle function. An important limitation of current published
studies is that only a few have included significant proportions of elderly subjects with CHF. The limited data
available suggests that elderly subjects derive similar benefits from exercise training as younger subjects. In
summary, exercise training is an inexpensive and effective intervention for subjects with CHF. This article
reviews the current knowledge of the effects of exercise training on the exercise capacity, quality of life, and
mortality and morbidity of subjects with CHF and elderly subjects. A major challenge for the future is the
inclusion of representative proportions of elderly and frail subjects in heart failure training trials.
Copyright Ó 2010, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier
Taiwan LLC. All rights reserved.
Keywords:
heart failure,
exercise capacity,
quality of life,
mortality,
exercise training
1. Introduction
Over the past decades, the incidence and prevalence of chronic
heart failure (CHF) have been steadily increasing.1 These trends are
mainly because of aging of the population and improved survival
after myocardial infarction and other heart diseases. CHF is the
common final stage of various heart diseases, and it is associated
with poor prognosis. It, therefore, results in high levels of health
care utilization and cost.2,3 CHF has, subsequently, become an
increasingly important challenge we face in the elder society.
Although major advances in pharmacological and device therapies have improved the survival rate of CHF subjects, many remain
burdened by fatigue, dyspnea, exercise intolerance, and reduced
quality of life.4 Although bed rest and restriction of physical activity
were traditionally recommended for subjects with CHF, it has been
reported that rest and physical inactivity may actually worsen
symptoms of heart failure and further reduce exercise capacity
and worsen quality of life.4,5
Exercise training results in significant peripheral muscle adaptations and central hemodynamic changes, which may help alleviate symptoms and reduce exercise intolerance, and it may also
have a beneficial effect on clinical outcomes. As a consequence,
exercise training is now being intensively evaluated for any additional benefits in the treatment of CHF. This article reviews the
current evidence of the effects of exercise training on clinical
outcomes in subjects with CHF. We also address the safety issues of
exercise training in CHF subjects.
2. Physiological Benefits of Exercise Training on CHF Subjects
q All contributing authors declare no conflict of interest.
* Correspondence to: Dr Gwo-Chi Hu, Department of Rehabilitation Medicine,
Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei 10449,
Taiwan.
E-mail address: [email protected] (G.-C. Hu).
2.1. Endothelial effects
Dysfunctional vascular endothelial cells are prone to vasoconstriction, vasculitis, atherosclerosis, and thrombosis. Recent studies
1873-9598/$ e see front matter Copyright Ó 2010, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. All rights reserved.
doi:10.1016/j.ijge.2010.11.001
166
S.-F. Hsieh et al.
Fig. 1. Potential mechanisms by which exercise training improves clinical outcomes.
have demonstrated that endothelium-dependent vasodilatation is
impaired in CHF subjects.6 Exercise training increases shear stress
on the vascular endothelial cell, which promotes endothelial
nitric oxide synthase expression and reduces nitric oxide
scavenging, thereby enhancing production of nitric oxide, causing
vasodilation.7,8 Exercise training has a profound impact on
vascular endothelial function by enhancing the production and
release of nitric oxide from vascular endothelium and causing
vasodilatation.8 Also, exercise training can increase capillary
density, enhance angiogenesis, and reduce peripheral vascular
resistance, all of which contribute to improvement in local
circulation.
2.2. Metabolic effects
CHF is associated with intrinsic muscle abnormalities, including
decreased capillary density, a shift from fatigue-resistant Type I
fibers to fatigue-prone Type II fibers, a reduced number and altered
structure of mitochondria, and decreased levels of oxidative
enzymes, which contribute to exercise intolerance and dyspnea.9
Exercise training induces muscle hypertrophy and hyperplasia,
which appear to reverse skeletal muscle wasting in CHF subjects.
It has also been demonstrated to cause an increase in aerobic
enzymes and an improvement in mitochondrial function.10,11
Exercise training produces a prominent reduction in phosphocreatine depletion during exercise and increase in phosphocreatine
resynthesis rate during recovery period, indicating an increased
capacity for oxidative metabolism.10,12 Moreover, exercise training
can increase the relative amount of Type I fibers, which derive
energy mainly from aerobic metabolism.10 As a result, lactic acid
production decreases, the efficiency of oxygen utilization
improves, and exercise tolerance increases.12
2.3. Neuroendocrine effects
Exaggerated sympathetic activation leads to chronic vasoconstriction and muscle inflammation in CHF subjects. Increased
plasma catecholamine level and reduced cardiac vagal tone are
associated with a poor prognosis in subjects with CHF. Persistent
neuroendrocrine abnormality, however, results in deterioration of
myocardial function, end-organ damage, and skeletal muscle
derangement in CHF subjects. Exercise training significantly
decreases plasma catecholamine levels at rest and during exercise.11 It has been demonstrated that exercise training can
significantly reduce NT-pro-brain natriuretic peptide, vasopressin,
aldosterone, and arterial natriuretic peptide.13e15 Abnormalities in
heart rate variability and heart rate responses during exercise are
partially corrected.16 These data indicate that exercise training
causes parasympathetic activation, modifies cardiovascular reflex,
and reduces the risks of arrhythmia and sudden death.17
2.4. Anti-inflammatory effects
Enhanced inflammatory response has been proposed as an
important factor in the pathophysiology of CHF.18 The abnormal
level of inflammatory cytokines would result in some aspects of
the syndrome of CHF, such as the endothelial dysfunction,
impaired myocardial contractility, and peripheral myopathy,
either by increasing the production of oxygen free radicals or by
triggering apoptosis in myocardial, skeletal muscle, and
endothelial cells.19e21 Proinflammatory cytokines, such as tumor
necrosis factor and interleukin-6, have been recognized to play
a significant role in the mechanistic underpinnings of CHF
subjects.22 Studies have shown that exercise training can reduce
plasma levels of interleukin-6, tumor necrosis factor, and other
inflammatory cytokines.23e25 Exercise training can be considered
a valuable and anti-inflammatory therapeutic strategy for subjects
with CHF. Fig. 1 summarizes the potential mechanisms by which
exercise training may improve clinical outcomes in CHT subjects.
3. Exercise Prescription in CHF Subjects
Standardized guidelines for exercise training in CHF subjects
have not been established, although some recommendations have
been based on previous studies or on experiences from experts.
Table 1 summarizes the recommendations of exercise prescription
for CHF subjects. Exercise prescription for CHF subjects should be
individualized, tailored to the results of a symptom-limited
cardiopulmonary stress test with gas exchange measurement and
to the subjects’ clinical status.26,27 Exercise prescription should
define the appropriate mode, intensity, and duration of each
session; the frequency of exercise sessions; and the rate of progress.
Exercise Training and Heart Failure
Table 1
Recommendations for exercise prescription for CHF subjects
Aerobic exercise
Mode
Cycle ergometer training
Most favorable type for CHF subjects with severe exercise intolerance
Walking
Workload applicable for subjects at a broad range of exercise capacity
Jogging
Not advisable for chronic heart failure subjects
Swimming
CHF subjects should refrain from swimming
Intensity (steady-state exercise)
40e80% of peak VO2; low intensity compensated for by longer
duration or higher frequency
60e80% heart rate reserve and 60e80% of the predetermined peak heart
Training heart rate should be as low as possible to
allow myocardial recovery
Rating of perceived exertion <13 (<somewhat hard)
Used only as an adjunct
Duration and frequency
If functional capacity of <3 METs: multiple short daily exercise sessions
of 5e10 min each
If functional capacity of 3e5 METs: 1e2 sessions/d of 15 min each
If functional capacity of >5 METs: 3e5 sessions/wk for 20e30 min each
Rate of exercise progression
Increase in this order: duration, frequency, intensity
Initial stage
40e50% peak VO2 until an exercise duration of 10e15 min is achieved
Exercise duration and frequency are adjusted
Improvement stage
Intensity: 50% / 60% / 70% peak VO2 if tolerated
Duration: 15e20 min / 30 min/session if tolerated
Maintenance stage
After the first 6 mo of training
Long-term maintenance is suggested
CHF ¼ chronic heart failure; peak VO2 ¼ peak oxygen consumption; MET ¼ metabolic
equivalent.
From Working Group on Cardiac Rehabilitation & Exercise Physiology and Working
Group on Heart Failure of the European Society of Cardiology.28
As a guide,28 it is suggested that the exercise intensity of CHF
subjects should be based on a symptom-limited treadmill or cycle
ergometer evaluation, using a target heart rate corresponding to
40e70% of peak VO2, three to five times per week, and 20e40
minutes per session. Fast walking, bicycling, or other aerobic
exercises using large muscle groups are preferred exercise modes.
Running and jogging are not advisable for heart failure subjects,
because they are associated with exaggerated cardiovascular
response. Swimming and water exercises with head-out
immersion may result in left ventricular overload and increased
pulmonary capillary wedge pressure. Subjects with CHF should
refrain from swimming. Resistance training may be added in
stable subjects, and it is believed to improve the symptoms of
fatigue and breathlessness.29 The rate of progression of exercise
training should be specific to the individual subject. It is
dependent on the baseline functional capacity, clinical status, and
individual adaptability to the training program.29
There are special considerations we should keep in mind when
prescribing exercise programs to heart failure subjects:30 the training
plan should allow for long warm-up and cool-down periods, and the
total duration of the sessions should be brief initially. Based on the
current evidence, supervised, hospital-based training programs are
strongly recommended, especially during the initial phase, to
monitor individual responses and tolerability and to promptly
detect the symptoms of cardiovascular decompensation.26,28
To assure the safety and compliance in training elderly subjects,
several distinctive features of their response to exercise training
must be appreciated. More time allowed to warm up and cool down
167
is appropriate for elderly subjects. Because their exercise heart rate
returns more slowly to the resting values, longer rest periods are
required between the components of exercise training. Risks of
musculoskeletal injuries can be minimized by avoiding highimpact activities. Exercise training should not cause syndromes
other than mild fatigue. The ability of sweating and temperature
regulation during exercise reduced with aging; it warrants reduction of the intensity of training for elderly subjects in hot and
humid environments.
4. Effects of Exercise Training on Exercise Capacity
The most profound effects of exercise training were found in
measures of outcome that reflect increased exercise capacity by
determining the maximal oxygen consumption (VO2max). Exercise
training has been demonstrated to improve cardiac output and
peripheral oxygen extraction, which are jointly responsible for the
clinically significant increase in VO2max. However, it remains
unclear to what extent each mechanism contributes.
Generally, many studies have demonstrated improvement in
VO2max after exercise training. However, these studies included only
a small number of subjects. In a statement issued by the American
College of Cardiology/American Heart Association,27 pooled
analysis of data from 15 exercise training trials in systolic heart
failure subjects found a modest but significant improvement in
VO2max (range: 12e30%). Most of the improvement occurred
by Week 3 but could continue for up to 6 months if the
training program continued. A Cochrane review31 of 29 studies
reported that exercise training significantly increased VO2max by
2.16 mL/kg/min (95% confidence interval [CI],2.82e1.49).
Improvements in VO2max were greater for a training program of
greater intensity and duration. Later, several meta-analyses
confirmed these results.32,33
Another widely used test for exercise capacity is the 6-minute
walk-distance test. It is usually well accepted by subjects, is easily
administered, and has an acceptable reproducibility. Furthermore,
the test has close similarities to daily-living activities.
According to the Cochrane review,31 pooling data showed
a 40.9-m (95% CI, 17.1e64.7) increase in the walking distance in
the exercise training group. Another recently published metaanalysis showed that the 6-minute walk distance improved by
46.2 m in the exercise training group compared with that in
control group.32 This distance should, therefore, be regarded not
only as significant, but also as clinically relevant.34
5. Effects of Exercise Training on Quality of Life
An improvement in health-related quality of life is a major
objective in the treatment of subjects with chronic disease. Subjects
with CHF experience progressive disability and decline in healthrelated quality of life, both of which are associated with dyspnea
and fatigue during activities of daily living. In addition, feelings of
depression and isolation are common. Numerous instruments are
available to measure health-related quality of life of subjects. The
Minnesota Living With Heart Failure Questionnaire, a reliable and
valid disease-specific questionnaire, was found to be more sensitive
in detecting change than generic questionnaires.35 Although some
studies claimed that exercise training provides no significant
benefits,36,37 most of the trials on this issue showed positive
effects of exercise training on the quality of life in heart failure
subjects.38e40 This improvement was observed in young and
elderly subjects.41 One meta-analysis examined the effects of
exercise training on quality of life in heart failure subjects.32 In
this analysis of nine studies that included measurement of the
Minnesota Living With Heart Failure Questionnaire score in 463
168
subjects, the authors found a significant 9.7-point improvement in
the score (28% improvement), which is considered to be a clinically
meaningful difference.27 Of the nine trials included in the metaanalysis, only one study showed a significant positive correlation
between gain in exercise capacity and change in quality of life.
This implies that there may be other unknown factors affecting
the subject’s perception of quality of life besides the change in
exercise capacity.
6. Effects of Exercise Training on Mortality and Morbidity
Heart failure subjects with a higher peak VO2 have a greater
survival rate; hence, improving peak VO2 may improve survival.
Exercise training can improve autonomic control of the cardiovascular system by reducing sympathetic spillover and enhancing
vagal activity, which can, in turn, improve survival and, possibly,
decrease the hospitalization rate. In addition, exercise training
improves endothelial function of coronary and peripheral vasculature, which result in increased coronary blood flow and reduced
ischemic events. Therefore, exercise training is expected to affect
mortality and morbidity in CHF subjects.
Many mechanisms have been proposed to explain the potential
benefits of exercise training on mortality in heart failure subjects.
However, conflicting results were found in two meta-analyses.
Smart and Marwick33 performed a systematic review of studies on
exercise training and analyzed 871 CHF subjects from 17
randomized controlled trials. They found no significant difference
in total mortality between the treatment and comparison groups
(odds ratio ¼ 0.71; 95% CI, 0.37e1.02). However, a meta-analysis
by the ExTraMATCH42 collaborative group examined nine
randomized studies, comprising a total of 801 subjects with
a mean follow-up of 705 days, and found that exercise training
reduced mortality (hazard ratio, 0.65; 95% CI, 0.46e0.92). In
addition, the composite outcome of death or hospital admission
for heart failure was reduced (hazard ratio, 0.72; 95% CI, 0.56e0.93).
The most likely explanation of this difference is that ExTraMATCH included the recent 3-year follow-up of the Belardinelli
et al. trial,38 a large and positive trial not included at the time of the
systematic review by Smart and Marwick.33 There are intrinsic
weaknesses of meta-analyses. For example, pooled results
incorporate the biases of individual studies and embody new
sources of bias, mostly because of the selection of studies and the
heterogeneity among them. When the results of systematic
reviews and meta-analyses are inconclusive, the results of large
randomized controlled trials are considered the gold standard.43,44
A large, multicenter, randomized controlled clinical trial heart
failure: a controlled trial investigating outcomes of exercise
training (HF-ACTION) has just been completed.45 This landmark
trial randomized 2,331 subjects with CHF to exercise training
group and usual-care group. The subjects in the training group
underwent monitored exercise training supervised by trained
professionals in the hospital setting three times per week for 3
months, and then progressively shifted to home-based selfmonitored exercise programs. In the mean follow-up time of 30
months, the primary endpoint of all-cause mortality or
hospitalizations was reduced by 7% (p ¼ 0.13) in the exercise
training group compared with that in the control group. After
preplanning adjustment for confounding factors (baseline
exercise capacity, ejection fraction, Beck Depression Inventory
score, and history of atrial fibrillation), there was an 11%
(p ¼ 0.03) reduction in all-cause mortality or hospitalizations.
Therefore, these results support the argument that exercise
training has at least modest efficacy in preventing major
cardiovascular events.
S.-F. Hsieh et al.
7. Effects of Exercise Therapy for Elderly Heart Failure
Subjects
Elderly subjects with heart failure tend to have more comorbidities, such as arthritis, orthopedic and neurological disorders, and
pulmonary disease, which limit the type and intensity of training
that they can participate in. Normally, exercise capacity and muscle
strength undergo steady decline with age; these make elderly
subjects especially vulnerable to the cardiovascular and peripheral
changes associated with CHF.46 Impairments in vision, hearing, and
balance function introduce new elements of risk in training elderly
subjects. Although multiple trials have demonstrated favorable
effects of exercise training in CHF subjects, many of such trials did
not include significant proportions of elderly subjects with CHF.
In the few trials that have examined the VO2max response to
training in elderly subjects, results have been, in general, favorable
for younger subjects. After appropriate exercise training, significant
improvements in VO2max and 6-minute walk distance have been
documented in some studies.36,47 Data on mortality and hospitalization are lacking. Some trials found significant improvements in
quality of life,47,48 but others did not.36,49 As elderly subjects
constitute most of the population with CHF, more studies will need
to investigate whether exercise training would have beneficial
effect on clinical outcomes in this population. If such a benefit is
established, the optimal duration and intensity would also need to
be determined.
8. Safety of Exercise Training in CHF Subjects
Although there are potentially many advantages associated with
exercise training, there remains a safety concern regarding exercise
training in subjects with CHF. Age, presence of heart disease, and
intensity of exercise are the most important factors related to the
risk of exercise training.50 Subjects with CHF are usually elderly and
always have other forms of cardiac disease. They are, therefore, at
greater risk of a clinical event during exercise training than
healthy subjects. Hence, in subjects with heart failure, safety of
exercise training requires special attention.51
The systematic review by Smart and Marwick33 found no
reports of deaths directly related to exercise during more than
60,000 patient hours of exercise training. In the HF-ACTION trial,
which recruited stable heart failure subjects with functional
capacity The New York Heart Association (NYHA) Functional
Classification Class IIeIV, 37 exercise training group subjects
(3.2%) and 22 control-group subjects (1.9%) were hospitalized
because of adverse events during exercise training or within 3
hours after training. Five exercise-related deaths in each group
were reported. The author concluded that exercise training was
relatively safe for stable heart failure subjects.45
Another concern about exercise training in heart failure subjects
is that exercise training might place additional load on the left
ventricle and lead to deterioration of heart function. This concern
was based on a report that subjects, after acute myocardial infarction, had a further increase in asynergy and decrease in left
ventricular ejection fraction after 12 weeks of exercise training.52
However, most studies did not find the negative effects of exercise
training on left ventricular function.53,54 One meta-analysis by
Haykowsky et al.,55 which analyzed 812 subjects from 14 trials,
found that exercise training improved left ventricular ejection
fraction by 2.59% (95% CI, 1.44e3.74); decreased left ventricular
end-diastolic volume by 11.49 mL (95% CI, 3.02e19.95); and
decreased left ventricular end-systolic volume by 12.87 mL (95%
CI, 7.93e17.8). Exercise training had no negative impact on left
ventricular morphology and showed a trend toward improvement
of left ventricular function in stable CHF subjects.
Exercise Training and Heart Failure
9. Conclusion
Exercise training is one of the nonpharmacological treatments
for CHF. Current evidence supports the notion that exercise training
can improve exercise capacity and quality of life in heart failure
subjects. Results of the HF-ACTION trial demonstrated that exercise
training was associated with modest reductions in both all-cause
mortality and hospitalization. Growing evidence also supports
the safety of training in properly evaluated CHF subjects. However,
the subjects enrolled in the trials were relatively young compared
with the general population with heart failure. Few trials had
investigated the effect of exercise training on subjects with diastolic
heart failure. The application and role of exercise training in elderly
or diastolic heart failure subjects remain to be addressed. The
growing literature on exercise training in CHF subjects supplies
several fundamental answers but, at the same time, raises
a number of important problems. Questions about optimal training
modality and intensity remain unanswered. Whether the training
effect could be maintained over a long period of time is still
unknown. In addition, the possible interaction among pharmacological therapies has not been thoroughly evaluated. Further
studies are warranted to answer these questions. The evidence to
date reveals that the benefits outweigh the risks of exercise training
in properly evaluated CHF subjects.
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