(Circulation. 1999;99:1173-1182.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Randomized, Controlled Trial of Long-Term Moderate Exercise Training in Chronic Heart Failure
Effects on Functional Capacity, Quality of Life, and Clinical Outcome
Presented at the 46th Meeting of the American College of Cardiology, Anaheim, Calif, March 16–19, 1997.
From Servizio di Cardiologia Riabilitativa, Istituto Cardiologico "G.M. Lancisi" (R.B., G.C., A.P.), Ancona, Italy, and Department of Medicine, Columbia University (D.G.), New York, NY.
Correspondence to Romualdo Belardinelli, MD, Via Rismondo, 5, 60100 Ancona, Italy. E-mail R.Bellardinelli{at}fastnet.it
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—It is still a matter of debate whether exercise training (ET) is a beneficial treatment in chronic heart failure (CHF).
Methods and Results—To determine whether long-term moderate ET
improves functional capacity and quality of life in patients with CHF
and whether these effects translate into a favorable outcome,
110 patients with stable CHF were initially recruited, and 99 (59±14
years of age; 88 men and 11 women) were randomized into 2 groups. One
group (group T, n=50) underwent ET at 60% of peak
O2, initially 3 times a week for 8
weeks, then twice a week for 1 year. Another group (group NT, n=49) did
not exercise. At baseline and at months 2 and 14, all patients
underwent a cardiopulmonary exercise test, while 74 patients
(37 in group T and 37 in group NT) with ischemic heart disease
underwent myocardial scintigraphy. Quality of life was
assessed by questionnaire. Ninety-four patients completed the protocol
(48 in group T and 46 in group NT). Changes were observed only in
patients in group T. Both peak O2 and
thallium activity score improved at 2 months (18% and 24%,
respectively; P<0.001 for both) and did not change
further after 1 year. Quality of life also improved and paralleled
peak O2. Exercise training was
associated both with lower mortality (n=9 versus n=20 for those with
training versus those without; relative risk (RR)=0.37; 95% CI, 0.17
to 0.84; P=0.01) and hospital readmission for heart
failure (5 versus 14; RR=0.29; 95% CI, 0.11 to 0.88;
P=0.02). Independent predictors of events were
ventilatory threshold at baseline (ß-coefficient=0.378) and
posttraining thallium activity score (ß-coefficient -0.165).
Conclusions—Long-term moderate ET determines a sustained improvement in functional capacity and quality of life in patients with CHF. This benefit seems to translate into a favorable outcome.
Key Words: exercise training • heart failure • quality of life • prognosis
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Acommon finding in patients with chronic heart failure is exercise intolerance, which causes a progressive functional deterioration.1 2 This vicious circle can be interrupted by discouraging a sedentary lifestyle and promoting physical activity. Controlled clinical studies have recently demonstrated that both in-hospital and home-based exercise training programs of various intensities induce favorable clinical effects by significantly increasing aerobic capacity, delaying the onset of anaerobic metabolism, reducing the sympathetic drive, and increasing the vagal tone.3 4 5 6 7 Because peak
O2 is a good predictor of
prognosis in patients with chronic heart failure, the improvement in
exercise tolerance after exercise training may be associated with a
more favorable outcome. Moreover, it is unclear whether improvements in
myocardial perfusion and left ventricular function,
recently demonstrated in animals8 and humans9
with ischemic heart disease after a short-term moderate
exercise training program, can affect the clinical outcome. The primary objective of the present study was to determine whether long-term moderate exercise training can improve functional capacity in patients with stable chronic heart failure and whether this improvement can translate into a favorable outcome. Other objectives of the study were as follows: (1) to assess the effect of exercise training on quality of life, (2) to identify patients who can benefit the most from exercise training, and (3) to select the independent predictors of outcome.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Initially, 110 consecutive patients with chronic heart failure in stable condition were recruited. However, after the screening visit at baseline, 11 patients decided not to participate. Thus, 99 patients (mean age, 59±14 years) were studied. All patients were clinically stable in the 3 months before the study. Criteria for eligibility were heart failure, left ventricular ejection fraction
40%, and sinus rhythm. The diagnosis of chronic heart
failure was based on clinical symptoms and signs and/or radiological
evidence of pulmonary congestion. Clinical characteristics of
the patients are summarized in Table 1
. The cause of heart failure was
ischemic cardiomyopathy (85%) or
idiopathic dilated cardiomyopathy (15%). Mitral
insufficiency was present in 42 patients and was mild in all.
Exclusion criteria were unstable angina, recent acute myocardial
infarction, decompensated congestive heart failure,
hemodynamically significant valvular heart
disease, significant chronic pulmonary illness, uncontrolled
hypertension, renal insufficiency (serum creatinine 
2.5
mg/dL), and orthopedic or neurological limitations. Medications were
not altered throughout the duration of the study and were administered
at standard doses.
|
Protocol
The protocol, approved by the Ethical Committee of the Lancisi
Institute, was a prospective, randomized, controlled study. All
patients gave written informed consent.
Patients were randomized into 2 homogeneous groups. The exercise group (group T, n=50) underwent exercise training for 14 months. The control group (group NT, n=49) did not exercise. On study entry and at the 2nd and 14th months, all patients performed an exercise test with gas exchange analysis and an echocardiographic study. At the same times, the subgroup of patients with ischemic heart disease (37 in group T and 37 in group NT) underwent thallium myocardial scintigraphy to evaluate the effects of exercise training on myocardial perfusion at different times. All studies were performed by skilled operators and evaluated by 2 experienced observers blinded to each other's interpretation. A third observer was asked to resolve differences when agreement was not achieved. A consensus decision was obtained in all cases.
Exercise Training
Exercise training was performed in 2 phases. Initially, patients
exercised 3 times a week for 8 weeks at 60% of peak
O2. This protocol was followed
by a 12-month maintenance program of the same intensity but
with only 2 sessions a week. Each session lasted 
1 hour, beginning
with a warm-up phase of stretching exercises (15 to 20 minutes)
followed by 40 minutes of cycling on an electronically braked cycle
ergometer (Sensorimedics 800S). Blood pressure and heart rate were
measured at rest before exercising, at the middle of work on the cycle
ergometer, and after 5 minutes of loadless recovery. All sessions were
held at the hospital gymnasium under the supervision of a
cardiologist.
Echocardiography
M-mode and 2-dimensional echocardiographic
studies were performed at baseline and at months 2 and 14 in all
patients according to the recommendations of the American Society of
Echocardiography.10 We used an
ultrasound system with a 2-dimensional mechanical sector scanner (2.5
MHz, ESAOTE). Left ventricular end-diastolic
volume (EDV) and end-systolic volume (ESV) were obtained from
the apical 4- and 2-chamber views by a modified Simpson's rule, from
which ejection fraction was automatically calculated as the difference
between EDV and ESV normalized to EDV. We used a biplane algorithm to
calculate left ventricular volumes. Normal values from our
laboratory and reproducibility data have been published
recently.11
Cardiopulmonary Exercise Test
In the fasting state, an incremental exercise test was performed
until volitional fatigue or symptoms or signs of myocardial
ischemia appeared.12 Patients pedaled in the
upright position on an electronically braked cycle ergometer
(Ergometrics 800 S) at a constant rate of 60 rpm. The work rate was
increased 1 W every 5 seconds (ramp). Expired gases were
analyzed by use of a metabolic chart (Sensormedics
2900 Z). Calibration of volumes and gases (O2 and
CO2) was carefully performed before each test.
The ventilatory threshold was measured by the V-slope
method.13 Peak oxygen uptake was the mean oxygen uptake
over the last 30 seconds of exercise.
Thallium Scintigraphy
At the end of the exercise test, 3 mCi of thallium was injected
into an antecubital vein. Planar 201Tl imaging
was begun within 5 minutes in the anterior, 45° left anterior
oblique, and 70° left anterior oblique views (Apex Elscint).
Redistribution studies were performed 3 hours after stress imaging.
Twenty-four hours later, 1 mCi of thallium was reinjected in patients
with scintigraphic evidence of a fixed defect noted in the
redistribution images. After reinjection, a third set of images was
reacquired within 15 minutes.
Data Analysis
At baseline and during follow-up, thallium images were
analyzed both qualitatively and quantitatively, as recently
described.9 Briefly, the serial images were interpreted by
visual analysis with the aid of computer
quantification.14 The left ventricle on each view was
divided into 5 segments (15 segments in total). Each segment was
visually graded on a 5-point scale, where 0 indicated normal uptake, 1
was mild reduction, 2 was evident reduction, 3 was severe reduction,
and 4 indicated absent uptake. We defined the thallium activity score
index as the sum of the thallium score of each myocardial segment
divided by the number of segments analyzed. "White on
black" display with a linear gray scale was used. Segments with a
score 2 on stress images were considered abnormal. Segments with an
initial perfusion abnormality were considered completely reversible
when the score was <2 on delayed scans and partially reversible when
the score improved by 1 grade on delayed images. Defects with no change
in thallium score between initial and delayed images were considered
irreversible. Myocardial segments with irreversible defects were
considered to have enhanced thallium activity after reinjection
compared with the redistribution study if the regional score decreased
by 1. Circumferential count profile analysis was also
performed. Thallium images obtained in the follow-up studies were read
by the same methods as the baseline study and compared side by side
with the corresponding pretraining images. Improvement in thallium
uptake, compared with the initial study, was defined as an increase in
thallium activity by 1 grade in any of the 3 acquisition imaging
series.
Quality of Life
Quality of life was assessed at baseline and after 2, 14, and 26
months in both groups with the Minnesota Living With Heart Failure
Questionnaire.15 This instrument is a patient
self-assessment measure and consists of 21 items focused on patient
perceptions concerning the effects of congestive heart failure on their
physical, psychological, and socioeconomic lives. Recent studies have
shown this questionnaire to be responsive to changes in quality of life
in patients with chronic heart failure.16
Follow-Up and Outcome Measures
Follow-up started the day after the end of the
maintenance exercise training protocol, that is, after 14
months of exercise training. Patients were monitored for an average of
1214±56 days (range, 1161 to 1268 days). Follow-up ended at the time
of study closure or with an adverse event. Measures of outcome were
prospectively defined as mortality from all causes and
cardiovascular morbidity (development of congestive
heart failure requiring hospitalization and adjustment of medical
therapy, unstable angina, and myocardial infarction). Detailed
information on medical history and clinical profile were collected at
the time of enrollment and at every visit during the follow-up
period. Patients regularly visited our institution every 3 months
during the follow-up period. A record was maintained on each
patient's clinical and functional status. Both the exercise and
control groups were subjected to the same scrutiny and management
regimen apart from the exercise component.
Statistical Analysis
All analyses were performed on an intention-to-treat
basis, and probability values were 2-sided. 
2
statistics and unpaired t tests were used to evaluate
differences in baseline characteristics between the 2 groups. Multiple
comparisons were assessed by repeated-measures ANOVA. Changes in the
exercise group were compared with changes in the control group by use
of a nonparametric test (Wilcoxon rank sum test).
The effects of training on thallium uptake were analyzed on the
basis of patients. We created a scoring system as follows: 0=no change;
+1=improvement; -1=deterioration. Univariate
analysis of peak oxygen uptake with metabolic,
clinical, and scintigraphic variables at baseline and after
training by use of change was performed. Variables with
significant correlations were then entered into a stepwise linear
regression model to determine the best predictor(s) of posttraining
change in peak oxygen uptake. Stepwise logistic regression of
occurrence of events was also performed. The Kaplan-Meier method was
used for survival analysis, and cardiac mortality between
trained and untrained patients was compared by log-rank test. The
relative risk (RR) and 95% CIs were calculated, when appropriate, to
compare outcomes between groups by Cox proportional hazard models. Data
were expressed as mean±SD. Statistical significance was assumed at
P0.05.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
One patient in the exercise group did not complete the protocol because of orthopedic limitations after a car accident. Another patient refused to continue after the first week. Three patients in the control group decided to withdraw from the program after a few weeks. A total of 94 patients completed the protocol (48 in group T, 46 in group NT).
Baseline Characteristics
The baseline characteristics of the study population are shown in
Table 1
. The 2 groups were well balanced with respect to most
characteristics, including peak
O2, New York Heart Association
functional class, and left ventricular ejection fraction.
There were no differences in type and doses of medications, blood
chemistry, and previous cardiac events.
Adverse Events During Exercise Training
No significant cardiovascular events occurred
during the training sessions. Ten patients had sporadic
supraventricular and ventricular premature
contractions during exercise and recovery. No patient had angina during
the training sessions. Compliance with exercise training, defined as
percentage of sessions attended, averaged 89% (range, 72% to
100%).
Hemodynamic and Metabolic Parameters
At baseline, no significant differences in
hemodynamic and metabolic
parameters were observed in the 2 groups (Table 2). Eleven patients (5 in group T, 6 in
group NT) with ischemic heart disease had a positive exercise
test. After 2 months, all 5 patients with a positive exercise test at
baseline had an increase in the ischemic threshold (18±5%),
and 2 had a normal exercise test at the end of the protocol. No changes
in the ischemic threshold were observed in control patients. In
particular, 3 patients developed low-threshold angina during the final
exercise test, and 3 patients with a normal exercise test at baseline
had a positive exercise test during follow-up. Oxygen uptake, oxygen
pulse, and ventilation were all significantly increased at peak
exercise in trained patients compared with controls
(P<0.001 versus nontrained for all). However, there were no
additional changes at the end of the maintenance program. The
ventilatory threshold was also increased from baseline in the trained
group (30%; P<0.001 versus nontrained), whereas the
respiratory exchange ratio was similar in both groups in all tests.
Resting heart rate was lower in trained patients after 2 months and
remained significantly lower at the end of the training protocol
(P<0.01 versus nontrained).
|
Echocardiography
No significant changes in left ventricular
diameter were observed after 2 or 14 months in either group. Fractional
shortening and ejection fraction were also unchanged (Table 3).
|
Thallium Uptake
At baseline, there was no difference in thallium activity on
stress images or after redistribution-reinjection between the 2 groups
(Table 4). After 2 months, the percentage
of both myocardial defects with improved thallium activity and
reversible defects with higher thallium uptake was significantly higher
in trained than in control patients (23% and 21%, respectively;
P<0.001 trained versus control for both). Furthermore, 75%
of trained and only 2% of untrained patients with ischemic
heart disease had a greater thallium uptake (95% CI for difference,
0.44 to 0.89; P<0.001).
|
After 14 months, no additional changes in thallium uptake were observed in either group.
Quality of Life
As shown in Figure 1, the
questionnaire score improved significantly only in trained patients
after 2 months and remained stable after the subsequent 12-month
exercise training program and during follow-up. The changes in the
score paralleled the changes in peak
O2 in trained patients
(r=0.80; P<0.001).
|
Outcome
Of the 99 patients included in the analysis, 54 (55%) had
cardiac events, 13 during the training period and 41 during the
follow-up period. As shown in Table 5,
cardiac events were more frequent in the control group (37 versus 17
events; P=0.006 versus trained). They comprised 25 nonfatal
events (8 in the training group and 17 in the control group) and 29
deaths (9 and 20, respectively). During the initial 2 months of
training, 1 event occurred in the exercise group and 3 occurred in the
control group. In the subsequent 12 months, 3 events occurred in
trained patients and 6 in controls.
|
The clinical and echocardiographic characteristics of
patients with and without cardiac events are summarized in Table 6. Patients who had cardiac events during
follow-up had significantly higher values on the
201Tl uptake score index as well as
end-systolic diameter after training and a lower fractional
shortening at baseline than patients who had no events.
|
Nonfatal Cardiac Events
Of the 25 patients who suffered nonfatal events, 3 had
unstable angina, 3 had acute myocardial infarction, and 19 were
hospitalized for worsening heart failure. In the control group, 6
patients were hospitalized twice. Patients with ischemic events
did not differ from the subgroup of patients without ischemic
events with respect to age, clinical condition, and ejection fraction.
Three patients in the training group and 1 in the control group
underwent cardiopulmonary bypass surgery. Two patients
underwent heart transplantation.
Hospital Readmissions
All 25 patients who suffered nonfatal cardiac events were
hospitalized. The rate of hospital readmission for heart failure was
significantly higher in control than in trained patients (RR=0.29; 95%
CI, 0.11 to 0.84; P=0.02) (Figure 2). Multiple readmissions were more
frequent in the control group (6 versus 1; P=0.001). As
shown by the Cox proportional hazards model, the strongest predictors
of readmission were peak
O2 (P=0.001),
end-diastolic diameter (P=0.01), and
systolic wall thickening score index (P=0.02).
|
Cardiac Deaths
Mortality was significantly lower in trained than in untrained
patients (RR=0.37; 95% CI, 0.17 to 0.84; P=0.01). All
deaths (6 during the training phase and 23 during follow-up) were
cardiac in nature (congestive heart failure, myocardial infarction, or
arrhythmia), and death occurred more frequently in patients
with than in those without ischemic heart disease (24 versus 5
deaths, respectively). Six deaths were sudden. Patients who died had
higher resting heart rate, end-diastolic diameter, and wall
thickening score index and lower systolic blood pressure and
oxygen uptake at peak exercise than patients who survived.
Univariate and Multivariate Analyses
On univariate analysis, the best predictors of
improvement in functional capacity were the change in ventilatory
threshold and ventilation after training (r=0.67 and 0.62,
respectively; P<0.001 for both). Stepwise forward logistic
regression was performed to assess the independent predictors of
posttraining changes in peak
O2 using the
univariate variables with higher correlation
coefficients. The most significant predictors of posttraining change in
peak O2 were
201Tl uptake score index (ß-coefficient -0.15;
P=0.006) and peak
O2 at baseline
(ß-coefficient 1.05; P=0.001). Patients with a
201Tl uptake score index >2.1 and a peak
O2 <11.3 mL ·
kg-1 · min-1 at
baseline had the lowest probability of improving their functional
capacity (log rank 6.47; P=0.01).
The survival model showed an overall effect of exercise training on
predicting all cardiac events (log rank 14.29; P=0.002)
(Figure 3). A lower event-free
survival rate was observed in untrained patients with higher
end-systolic diameter (P=0.008) and ventilation at
baseline (P=0.01) and lower change in fractional shortening
after exercise training (P=0.02). Moreover, there was a
significant difference between survival curves when separated by
exercise training (log rank 6.24; P=0.01) (Figure 4). Patients with thallium uptake score
<2 at baseline had a significantly lower mortality rate (log rank
15.08; P<0.001) and a lower incidence of overall cardiac
events (log rank 9.56; P=0.002). However, the trend of
survival curves was similar when patients were separated by age, cause
of heart failure, number of diseased vessels, and number of prior
myocardial infarctions. Analysis by Cox proportional hazards
model with cardiac death as the dependent variable showed that
ventilatory threshold at baseline and thallium uptake score index after
training were the only independent predictors (ß-coefficients 0.378
and -0.165, P=0.0004 and 0.008, respectively).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The results of this longitudinal study demonstrate that long-term moderate exercise training improves functional capacity in patients with stable chronic heart failure. This beneficial effect translated into a favorable outcome. As a matter of fact, although no significant difference in the frequency of nonfatal cardiac events was observed between the 2 groups over either the training period or the follow-up, a significantly lower rate of hospital readmission for heart failure and a lower cardiac mortality rate were observed in patients who improved their functional capacity after exercise training. Quality of life paralleled the improvement in peak oxygen uptake but was not an independent predictor of cardiac events.
Functional Capacity and Quality of Life
The improvement in peak oxygen uptake and ventilatory threshold
(18% and 30%, respectively; P<0.001 trained versus
untrained for both comparisons) began to be evident after the initial 2
months of the exercise training regimen and did not further increase at
the end of the maintenance program. These changes appear to be
unrelated to loading conditions, because both EDV and systolic
blood pressure were unchanged after exercise training.
Previous reports were generally concordant in demonstrating an increase in peak oxygen uptake after short-term exercise training. Coats et al4 observed a mean increase of 18% after 8 weeks of home-based exercise training at 60% to 80% of peak heart rate. Sullivan et al3 demonstrated a similar improvement after 4 to 6 months of aerobic training. However, it is unclear whether this beneficial effect can be maintained with a long-term exercise regimen. Recently, the Exert trial demonstrated that peak oxygen uptake significantly increased after the first 3 months of exercise training and then remained stable at 1 year.17 In the present study, the response of peak oxygen uptake to exercise training was similar. This result is not surprising, because although the intensity of training was the same throughout the study and all sessions were supervised, the 1-year maintenance program had a lower number of sessions per week. Nonetheless, at the end, peak oxygen uptake remained higher in trained patients than in controls. In our opinion, this is a remarkable result that confirms that a low number of sessions per week can be sufficient to maintain a higher functional capacity at levels close to those achieved with short-term physical training of the same intensity. It is conceivable that patients may have better compliance with an exercise regimen with a lower weekly session rate.
The improvement in functional capacity after physical training seems related for the most part to peripheral adaptations.3 18 19 20 However, the posttraining improvement in thallium activity score index observed in the present study in patients with coronary artery disease suggests that enhanced myocardial perfusion may also play a role. In fact, posttraining changes in peak oxygen uptake and thallium uptake score index were correlated (r=-0.52; P<0.01), and the best independent predictors of improvement in functional capacity after exercise training were thallium activity score index and peak oxygen uptake at baseline. Patients with higher myocardial perfusion at baseline seemed to benefit most from exercise training. In fact, both quality of life and functional capacity were similarly higher after training in those patients with greater thallium uptake on initial evaluation. By contrast, patients with a thallium score index >2.1 and a peak oxygen uptake<11.3 mL · kg-1 · min-1 had no improvement in functional capacity after training.
It is unclear, however, why an improvement in myocardial perfusion after exercise training was not accompanied by changes in ejection fraction at rest. Previous reports also failed to demonstrate any change in left ventricular systolic performance at rest.3 9 However, an increase in stroke volume after exercise training has been observed during submaximal exercise21 as well as during low-dose dobutamine infusion.9 This implies that stroke volume is higher during moderate activities of intensities similar to those of daily life. Thus, by prolonging the duration of training, a greater stroke volume at comparable exercise intensities can be maintained for a longer time.
There are conflicting results on the effects of exercise training on
quality of life in patients with chronic heart failure. No changes were
observed in the Exert trial.17 In another
study,22 however, the improvement in quality of life
followed the course of peak oxygen uptake, which increased by 15% from
baseline and plateaued at 16 to 26 weeks of a 12-month exercise
training regimen. This is in agreement with the results of the
present study. A long-term, supervised program can improve the
quality of clinical care and offer more valid psychological support to
patients and their family. The parallel course of quality of life and
peak O2 responses to
conditioning suggests similar underlying mechanisms.
Outcome
The improvement in exercise capacity after exercise training was
associated with a better outcome. Patients who completed the exercise
training program had a lower cardiovascular mortality
rate than sedentary controls (Figure 4). Among trained patients
with posttraining ejection fraction <29% and thallium score index
>2.2, the RR was 8.75 times lower than for untrained patients (95%
CI, 4.7 to 15; P<0.001), whereas the estimated risk was not
significantly different between trained and control subjects when
all-cause morbidity was considered (RR=1.41; 95% CI for difference,
-0.23 to 0.09; P=0.56). Moreover, trained patients had a
significantly lower rate of hospital readmission for heart failure than
did controls.
The reasons why moderate exercise training improves the outcome of
patients with chronic heart failure are still a matter of speculation.
The relatively higher functional capacity after exercise training may
be a stimulus for a more active lifestyle that contributes to the
maintenance of a higher peak
O2. Another possible
explanation may be that moderate exercise training improves myocardial
perfusion. The improvement in myocardial perfusion may be due to a
mechanism of vessel neoformation due to intermittent ischemia
or vasodilation of preexisting coronary vessels due to
reduction of endothelial dysfunction.8 23
By prolonging exercise conditioning, all these favorable effects,
already seen after short-term physical training, may persist and
contribute to maintenance of higher myocardial perfusion. An
interaction between ejection fraction and a favorable prognosis has
been demonstrated recently after exercise training in patients who
suffered a myocardial infarction.24 A favorable outcome in
trained patients can in part be the result of a direct inhibition of
the deleterious effects of neurohumoral activation. A recent
study4 demonstrated the efficacy of exercise training in
reducing adrenergic tone and increasing vagal tone, as suggested by an
increase in heart rate variability indexes and its high-frequency
component. This effect has been associated with higher
ventricular fibrillation threshold in trained
dogs.25
Study Limitations
The population studied was composed predominantly of men
with ischemic cardiomyopathy. The
percentage of women was 11%. We used planar imaging, which poorly
differentiates between underlying or overlying normal or dysfunctional
myocardium. However, the planar technique has been
validated previously by several groups with homogeneous
results.26 Moreover, we performed myocardial thallium
imaging at baseline and during follow-up in trained and untrained
patients with ischemic heart disease, and the results were
interpreted by experienced cardiologists blinded to each other's
interpretation and unaware of the clinical picture. We did not measure
changes in skeletal muscle oxidative capacity or changes in autonomic
balance after exercise training. As a consequence, the related
variables could not be considered in the
multivariate analysis. This factor, combined
with a small sample size, could have overestimated the importance and
the role of the improvement in myocardial perfusion in predicting a
lower rate of cardiac events in trained patients with ischemic
cardiomyopathy.
In conclusion, the results of this longitudinal study demonstrate that long-term moderate exercise training improves functional capacity and quality of life in patients with stable chronic heart failure. Both benefits were observed immediately after 2 months of physical training and were maintained at 1 year with a supervised program of the same intensity but with a lower number of sessions per week. The sustained improvement in functional capacity seems to translate into a lower rate of hospital readmission for cardiac insufficiency and a lower mortality rate. Quality of life paralleled the improvement in peak oxygen uptake but was not an independent predictor of cardiac events. The beneficial effect of long-term physical conditioning on outcome appears to be related, at least in patients with ischemic heart disease, to a sustained improvement in myocardial perfusion that becomes evident after 24 exercise sessions. The clinical implication is that moderate physical activity should be recommended in conjunction with traditional pharmacological therapy in patients with chronic heart failure.
|
Acknowledgments |
|---|
We thank the statisticians Prof Bruno Mannello and Prof Franco Mastrosanti for their valuable contribution to the statistical analysis.
Received July 15, 1998; revision received November 3, 1998; accepted November 23, 1998.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Sullivan MJ, Hawthorne MH. Exercise intolerance in
patients with chronic heart failure. Prog Cardiovasc
Dis. 1995;38:1–12.[Medline]
[Order article via Infotrieve]
-
Mancini DM, Walter G, Reichek N, Lenkinski R, McCully
KK, Mullen JL, Wilson JR. Contribution of skeletal muscle atrophy to
exercise intolerance and altered muscle metabolism in heart
failure. Circulation. 1992;85:1364–1373.
[Abstract/Free Full Text]
-
Sullivan MJ, Higginbotham MB, Cobb FR. Exercise
training in patients with severe left ventricular
dysfunction: hemodynamic and metabolic
effects. Circulation. 1988;78:506–515.
[Abstract/Free Full Text]
-
Coats AJS, Adamopoulos S, Radaelli A, McCance A, Meyer
TE, Bernardi L, Solda PL, Davey P, Ormerod O, Forfar C, Conway J,
Sleight P. Controlled trial of physical training in chronic heart
failure: exercise performance, hemodynamics,
ventilation, and autonomic function. Circulation. 1992;85:2119–2131.
[Abstract/Free Full Text]
-
Oberman A, Fletcher GF, Lee J, Nanda N, Fletcher B,
Jensen B, Caldwell ES. Efficacy of high-intensity exercise training on
left ventricular ejection fraction in men with
coronary artery disease (the Training Level Comparison Study).
Am J Cardiol. 1995;76:643–647.[Medline]
[Order article via Infotrieve]
-
Bilman GE, Schwartz PJ, Stone HL. The effects of daily
exercise on susceptibility to sudden cardiac death.
Circulation. 1984;69:1182–1189.
[Abstract/Free Full Text]
-
Hull SS Jr, Vanoli E, Adamson PB, Verrier RL, Foreman
RD, Schwartz PJ. Exercise training confers anticipatory protection from
sudden death during acute myocardial ischemia.
Circulation. 1994;89:548–552.
[Abstract/Free Full Text]
-
Laughlin MH, McAllister RM. Exercise training-induced
coronary vascular adaptation. J Appl Physiol. 1992;73:2209–2225.
[Abstract/Free Full Text]
-
Belardinelli R, Georgiou D, Ginzton L, Cianci G,
Purcaro A. Effects of moderate exercise training on thallium uptake and
contractile response to low-dose dobutamine of
dysfunctional myocardium in patients with ischemic
cardiomyopathy. Circulation. 1998;97:553–561.
[Abstract/Free Full Text]
-
Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux
R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I,
Silverman NH, Tajik AJ. Recommendations for quantitation of the left
ventricle by two-dimensional echocardiography:
American Society of Echocardiography Committee on
Standards, Subcommittee on Quantitation of Two-Dimensional
Echocardiograms. J Am Soc Echocardiogr. 1989;2:358–367.[Medline]
[Order article via Infotrieve]
-
Belardinelli R, Georgiou D, Purcaro A. Low dose
dobutamine echocardiography predicts
improvement in functional capacity after exercise training in patients
with ischemic cardiomyopathy: prognostic
implication. J Am Coll Cardiol. 1998;31:1027–1034.
[Abstract/Free Full Text]
-
Subcommittee on Exercise Testing. Guidelines for
exercise testing: a report of the joint American College of
Cardiology-American Heart Association Task Force on
assessment of cardiovascular procedures. J
Am Coll Cardiol. 1986;8:725–738.[Medline]
[Order article via Infotrieve]
-
Beaver WL, Wasserman K, Whipp BJ. A new method for
detecting anaerobic threshold by gas exchange. J
Appl Physiol. 1986;60:2020–2027.
[Abstract/Free Full Text]
-
Wackers FJ, Fetterman RC, Mattera JA, Clements JP.
Quantitative planar thallium-201 stress scintigraphy: a
critical evaluation of the method. Semin Nucl Med. 1985;15:46–58.[Medline]
[Order article via Infotrieve]
-
Rector TS, Cohn JN, with the Pimobendan Multicenter
Research Group. Assessment of patient outcome with the Minnesota Living
with Heart Failure questionnaire: reliability and validity during a
randomized, double-bind, placebo-controlled trial of pimobendan.
Am Heart J. 1992;1024:1017–1025.
-
Kubo SH, Gollub S, Bourge R, Rahko P, Cobb F, Jessup M,
Brozena S, Brodsky M, Kirlin P, Shanes J, Konstam M, Gradman A,
Morledge J, Cinquegrani M, Singh S, LeJemtel T, Nicklas J, Troha J,
Cohn J. Beneficial effects of pimobendan on exercise tolerance and
quality of life in patients with heart failure: results of a
multicenter trial. Circulation. 1992;85:942–949.
[Abstract/Free Full Text]
-
McKelvie RS, Teo KK, McCartney RS, Roberts RS,
Costantini LA, Montague TJ, Humen DP, Guyatt GH, Yusuf S. Randomized
controlled trial of exercise training in patients with congestive heart
failure (EXERT). J Am Coll Cardiol. 1998;31(suppl
A):1226–1231.
-
Belardinelli R, Georgiou D, Scocco V, Barstow TJ,
Purcaro A. Low intensity exercise training in patients with chronic
heart failure. J Am Coll Cardiol. 1995;26:975–982.[Abstract]
-
Hambrecht R, Niebauer J, Fiehn E, Kalberer B, Offner B,
Hauer K, Riede U, Schlierf G, Kubler W, Schuler G. Physical training in
patients with stable chronic heart failure: effects on
cardiorespiratory fitness and ultrastructural abnormalities of leg
muscles. J Am Coll Cardiol. 1995;25:1239–1249.[Abstract]
-
Hornig B, Maier V, Drexler H. Physical training
improves endothelial function in patients with chronic
heart failure. Circulation. 1996;93:210–214.
[Abstract/Free Full Text]
-
Hagberg JM, Ehsani AA, Holloszy JO. Effects of 12
months of intense exercise training on stroke volume in patients with
coronary artery disease. Circulation. 1983;67:1194–1199.
[Abstract/Free Full Text]
-
Kavanagh T, Myers MG, Baigrie RS, Mertens DJ, Sawyer P,
Shephard RJ. Quality of life and cardiorespiratory function in chronic
heart failure: effects of 12 months' aerobic training.
Heart. 1996;76:42–46.
[Abstract/Free Full Text]
-
White FC, Roth DM, McKirnan D, Carroll SM, Bloor CM.
Exercise induced coronary collateral development: a comparison
to other models of myocardial angiogenesis. In: Schaper W, Schaper J,
eds. Collateral Circulation. Norwell, Mass: Kluwer Academic
Publishers; 1993:261–289.
-
Specchia G, DeServi S, Scirè A, Alessandri J,
Berzuini C, Angoli L, La Rovere MT, Cobelli F. Interaction between
exercise training and ejection fraction in predicting prognosis after a
first myocardial infarction. Circulation. 1996;94:978–982.
[Abstract/Free Full Text]
-
Vanoli E, DeFerrari GM, Stramba-Badiale M, Hull SS Jr,
Foreman RD, Schwartz PJ. Vagal stimulation and prevention of sudden
death in conscious dogs with a healed myocardial infarction. Circ
Res. 1991;68:1471–1481.
[Abstract/Free Full Text]
-
Inglese E, Brambilla M, Dondi M, Coccolini S,
Cannizzaro G, Pirelli S, Cappagli M, Bertoli D, Pieri PL, Moscatelli G,
Giordano A, Trani C, Bertelli P. Thallium-201: what do we gain from new
clinical protocols and acquisition procedures? J Nucl Biol
Med.. 1992;36:253–258.
This article has been cited by other articles:
 |
|
 |
|
  R. Belardinelli, F. Lacalaprice, C. Ventrella, L. Volpe, and E. Faccenda Waltz Dancing in Patients With Chronic Heart Failure: New Form of Exercise Training Circ Heart Fail, July 1, 2008; 1(2): 107 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Nunes, M. Tonetto, N. Machado, M. Chazan, T. G. Heck, A. B. G. Veiga, and P. Dall'Ago Physical exercise improves plasmatic levels of IL-10, left ventricular end-diastolic pressure, and muscle lipid peroxidation in chronic heart failure rats J Appl Physiol, June 1, 2008; 104(6): 1641 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Beer, D. Wagner, J. Myers, J. Sandstede, H. Kostler, D. Hahn, S. Neubauer, and P. Dubach Effects of Exercise Training on Myocardial Energy Metabolism and Ventricular Function Assessed by Quantitative Phosphorus-31 Magnetic Resonance Spectroscopy and Magnetic Resonance Imaging in Dilated Cardiomyopathy J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1883 - 1891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Eisen Exercise Training and Myocardial Energetics in Patients With Heart Failure: When More Is Less J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1892 - 1895. [Full Text] [PDF]
|
|
|
|
|
|
T. M. Mousa, D. Liu, K. G. Cornish, and I. H. Zucker Exercise training enhances baroreflex sensitivity by an angiotensin II-dependent mechanism in chronic heart failure J Appl Physiol, March 1, 2008; 104(3): 616 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. J. Kemi, M. A. Hoydal, P. M. Haram, A. Garnier, D. Fortin, R. Ventura-Clapier, and O. Ellingsen Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan Cardiovasc Res, October 1, 2007; 76(1): 91 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Akima, B. Takase, S. Kosuda, F. Ohsuzu, T. Kawai, M. Ishihara, and K. Akira Systemic Peripheral Vascular Resistance as a Determinant of Functional Cardiac Reserve in Response to Exercise in Patients With Heart Disease Angiology, September 1, 2007; 58(4): 463 - 471. [Abstract] [PDF]
|
|
|
|
|
|
M. J. Haykowsky, Y. Liang, D. Pechter, L. W. Jones, F. A. McAlister, and A. M. Clark A Meta-Analysis of the Effect of Exercise Training on Left Ventricular Remodeling in Heart Failure Patients: The Benefit Depends on the Type of Training Performed J. Am. Coll. Cardiol., June 19, 2007; 49(24): 2329 - 2336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Belardinelli Exercise Training in Chronic Heart Failure: How to Harmonize Oxidative Stress, Sympathetic Outflow, and Angiotensin II Circulation, June 19, 2007; 115(24): 3042 - 3044. [Full Text] [PDF]
|
|
|
|
|
|
L. Gao, W. Wang, D. Liu, and I. H. Zucker Exercise Training Normalizes Sympathetic Outflow by Central Antioxidant Mechanisms in Rabbits With Pacing-Induced Chronic Heart Failure Circulation, June 19, 2007; 115(24): 3095 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Maloyan, J. Gulick, C. G. Glabe, R. Kayed, and J. Robbins Exercise reverses preamyloid oligomer and prolongs survival in {alpha}B-crystallin-based desmin-related cardiomyopathy PNAS, April 3, 2007; 104(14): 5995 - 6000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ventura-Clapier, B. Mettauer, and X. Bigard Beneficial effects of endurance training on cardiac and skeletal muscle energy metabolism in heart failure Cardiovasc Res, January 1, 2007; 73(1): 10 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rondon, M. S. Brasileiro-Santos, E. D. Moreira, M. U. P. B. Rondon, K. C. Mattos, M. A. Coelho, G. J. J. Silva, P. C. Brum, P. Fiorino, M. C. Irigoyen, et al. Exercise training improves aortic depressor nerve sensitivity in rats with ischemia-induced heart failure Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2801 - H2806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zheng, Y.-F. Li, I. H. Zucker, and K. P. Patel Exercise training improves renal excretory responses to acute volume expansion in rats with heart failure Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1148 - F1156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Belardinelli, A. Mucaj, F. Lacalaprice, M. Solenghi, G. Seddaiu, F. Principi, L. Tiano, and G. P. Littarru Coenzyme Q10 and exercise training in chronic heart failure Eur. Heart J., November 2, 2006; 27(22): 2675 - 2681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jelic and T. H. Le Jemtel Diagnostic Usefulness of B-Type Natriuretic Peptide and Functional Consequences of Muscle Alterations in COPD and Chronic Heart Failure. Chest, October 1, 2006; 130(4): 1220 - 1230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Passino, S. Severino, R. Poletti, M. F. Piepoli, C. Mammini, A. Clerico, A. Gabutti, G. Nassi, and M. Emdin Aerobic Training Decreases B-Type Natriuretic Peptide Expression and Adrenergic Activation in Patients With Heart Failure J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1835 - 1839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Kutner, R. Zhang, Y. Huang, and C. A. Herzog Cardiac Rehabilitation and Survival of Dialysis Patients after Coronary Bypass J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1175 - 1180. [Abstract] [Full Text] [PDF] |