SEARCH

SEARCH BY CITATION

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

©2012 Wiley Periodicals, inc.

Exercise training appears to improve peak oxygen consumption (VO2) and quality of life (QOL) in heart failure patients, although disease etiology, patient demographics and medication may alter the rate of adaptation. The authors sought to identify rate of change from baseline in fitness, QOL, and depression following exercise training in a cohort of patients with congestive heart failure. Thirty male systolic heart failure patients (aged 63.8±8.3 years, baseline peak VO2 12.2±4.8 mL/kg/min, left ventricular ejection fraction 28.2±9.4%, New York Heart Association class II/II 22/8) undertook 52 weeks of exercise training, 16 weeks as an outpatient and a further 36 weeks of home exercise. Peak VO2 and QOL was measured using the Minnesota Living With Heart Failure (MLWHF) questionnaire and depression using the Hare-Davis scale. The authors analyzed the rate of change in peak VO2 and MLWHF after grouping patients according to clinical, demographic, and pharmacologic characteristics. Peak VO2 measurements varied over time, with no effect of disease pathology or β-blocker on peak VO2. The rate of change in physical MLWHF score was significantly greater (improved) during 0 to 16 weeks in patients with dilated pathology, but was not significantly affected by β-blocker use or age. The exercise training venue and supervision, or lack thereof, is the major determinant of adaptation to the intervention in heart failure patients, although age, β-adrenergic medication, and heart failure etiology also explain some of the variation in adaptive responses observed.

Exercise training has been shown to elicit improvements in various prognostic measures of congestive heart failure including cardiorespiratory fitness,1 quality of life (QOL),2 cardiac function,3 and neurohormonal markers of disease severity.4,5 Typically, cardiac rehabilitation programs consist of 36 sessions delivered over a 12-week period, but this may yield suboptimal changes in fitness and QOL.6–8 Previous reviews of change in QOL in heart failure patients due to exercise training have suggested change is likely, but the magnitude may be dependent on the duration of the program2,9 and the rate of change varies with each individual patient.4 Previous investigations have suggested that the more disadvantaged or deconditioned the patient is at baseline (eg, elderly, New York Heart Association [NYHA] class III, lowest baseline peak oxygen consumption [VO2], ischemic etiology) the larger the likely improvement.10 This hypothesis resonates with some who may argue that exercise training adaptations may be grossly overestimated11 or at least partially explained by regression to the mean. Other works have suggested reasons for the sizeable variations in exercise training responses, most notably seen in the recent Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study.12 The explanations given for variations in training responses are suboptimal or β-blocker medication,13 disease pathology (particularly if it is unstable), participant age or disease severity,10 suboptimal compliance or crossover from sedentary control to exercise intervention, baseline depression score,12 exercise program delivery,14,15 and transition from an outpatient to unsupervised home exercise program.6

We sought to identify rate of change from baseline in QOL following exercise training in a cohort of patients with systolic congestive heart failure.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

Patient Selection

Patients with symptomatic heart failure and a left ventricular ejection fraction (LVEF) <35% were identified at the time of presentation for echocardiography and from advertisements in the local media. Other than the exclusion of patients with severe valvular heart disease or inability to exercise, inability to attend the initial hospital-based rehabilitation, lack of stabilization on appropriate medications at a constant dose for at least 1 month before study entry, and inability to provide informed consent, there was no other selection criterion for these patients. Patients with exertional ischemia were admitted into the study provided that they were not limited by angina. The study was approved by the ethics committee of the Princess Alexandra Hospital and all patients gave written informed consent. All patients were categorized as having either NYHA class II or III. Patients with class II had mild limitation of activity (comfortable with rest or with mild exertion). Class III patients exhibited marked limitation of activity (comfortable only at rest).

Exercise Testing

All patients underwent metabolic exercise testing on a cycle ergometer using a 10 W/min stepped protocol. Electrocardiography was continuously monitored for ST-segment changes and arrhythmias; blood pressure and 12-lead electrocardiography were recorded before exercise, every 2 minutes during the test, and during the recovery period after exercise. Tests were symptom limited, with the usual endpoints being dyspnea and leg fatigue, and some participants were limited by arrhythmia and decreased or exaggerated blood pressure response. Measured peak VO2 was obtained by breath-by-breath analyses of expired gas (V29C Sensormedics, Yorba Linda, CA), averaged over 20-second intervals. Every 3 sequential measurements were averaged and peak VO2 was defined as the greatest mean value during exercise. Anerobic threshold (AT) was calculated using the V-slope method.16

QOL Measures

Two previously validated questionnaires assessing QOL were completed by all patients at baseline and 8 and 16 weeks. The Minnesota Living With Heart Failure (MLWHF) questionnaire is specific to heart failure; its 21 questions provide a total score and physical and emotional dimensional scores.17 The Hare-Davis Cardiac Depression Scale is a general tool administered to the cardiac patient population.18 As with the MLWHF questionnaire, lower scores indicate that patients perceive their health to be improving.

Exercise Training

All patients initially undertook 16 weeks of cycle ergometer exercise training (ExT) at 60 RPM, at a workload (in Watts) corresponding to an initial intensity of 60% to 70% peak VO2, 3 sessions per week. In addition, during weeks 8 to 16, patients also performed a series of 5 strength exercises including wall pushups, alternating leg lunges, tricep dips, bicep curls, and sits to stands from a chair. Exercise intensity was titrated upward by 2 to 5 W/wk, provided that patients were tolerating the cycle training. In patients who were paced or experienced frequent ectopy, rate of perceived exertion (RPE) was also used to guide exercise intensity, using a target RPE of 3 to 5 (moderate to hard) on the modified Borg scale.19 In patients who were most limited by shortness of breath, a respiratory rate <30 breaths per minute was used to limit intensity.

Data Analysis

The data consisted of 5 measurements made on each of 30 patients at 0, 8, 16, and 52 weeks after treatment commenced. The measurements were peak VO2, total physical and emotional MLWHF score and Hare-Davis cardiac depression score, disease pathology (ischemic or dilated cardiomyoapthy), and treatment with a β-adrenergic receptor blocker. At each sample time, the measurements were plotted as a biplot to discern relationships among the variables. The exploratory plots revealed all vectors to be colinear except for the peak VO2 vector that was orthogonal to the others.

Further exploratory data plots indicated that all measurements varied over time. The effects of pathology, β-blocker use, and age did not appear to explain the responses of MLWHF or Hare-Davis scores. There were likely effects of pathology, age, and their interactions with sample time on peak VO2. The data were sampled at 0, 8, 16, and 52 weeks and the data were interpreted by considering the rates of change for the first 16 weeks (outpatient exercise program) and then by comparing the change in measurement from 16 to 52 weeks (home exercise program). Because the data were repeated measures from each patient, the statistical model needs to account for the variation between patients and the correlation among the repeated measures. Exploratory data plots of individual patient traces over time showed that initial differences among patients were maintained over time and that there was little divergence of the traces. That diagnostic suggests that the data be modeled using a mixed model with a single random effect for patient differences.

The general form of the model is:

  • image
  • image
  • image

where Yijt is the response from patient i, treatment j at time t, inline image is the expected value of Yijt, conditional on the patient effect ui, ui is a random effect due to patient and is normally distributed with zero mean and patient variance inline image is the linear change in the response over weeks t=0, 8 16, δj is the change in the measurement from 16 to 52 weeks for treatment j.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

Thirty patients with systolic heart failure (LVEF <35%) were recruited and baseline demographic and clinical characteristics and medication use can be seen in Table I. More than 70% of patients were medicated with triple therapy (β-blocker, diuretic, and ACE inhibitor) and exhibited peak VO2 and LVEF (%) reflective of moderate to severe heart failure. The baseline, 16- and 52-week peak VO2, QOL, and depression scores are seen in Table II. Compliance to the exercise program was 83%±8% for weeks 0 to 16 and 65%±15% for weeks 0 to 52.

Table I.   Baseline Demographics, Clinical and Characteristics, and Medication Use of Patients
VariableMean (±Standard Deviation)
Demographics
 Age, y63.77 (8.25)
 Weight, kg82.80 (13.93)
 Male/female sex30/0
 Peak oxygen consumption, mL/kg/min12.18 (4.80)
 Left ventricular ejection fraction, %28.20 (9.40)
 New York Heart Association class II/III22/8
Symptoms/risk factorsFrequency (%)
 Previous myocardial infarction19 (63.3)
 Symptoms of dyspnea26 (86.7)
 Edema symptoms20 (66.7)
 Diabetes mellitus9 (30.0)
 Hypertension24 (80.0)
 Smoking11 (36.7)
Medication
 Aspirin22 (73.3)
 β-Blocker28 (93.3)
 HMG-CoA reductase inhibitor24 (80.0)
 Diuretic26 (70.0)
 Angiotensin-converting enzyme inhibitor29 (95.0)
Table II.   Peak VO2, Minnesota Quality of Life, and Hare-Davis Depression Scores at Baseline and 16 and 52 Weeks
 Baseline16 Weeks52 Weeks P Value, Baseline vs 16 Weeks P Value, Baseline vs 52 Weeks
  1. Abbreviations: NS, not significant; VO2, oxygen consumption. Values are expressed as mean±standard deviation.

Peak VO2 mL/kg/min12.2±4.815.1±5.213.2±3.8<.001NS
Peak work, W56±971±1260±10<.01NS
Minnesota total43.516.631.6±18.033.9±18.8<.001.01
Minnesota physical14.5±6.910±7.311.4±7.9NSNS
Minnesota emotional9.3±5.85.9±4.36.2±5.0NSNS
Hare-Davis94.7±17.977.6±21.686.5±20.7<.001.04

Peak VO2

Peak VO2 measurements varied over time, as shown in Figure 1, with no effect of disease pathology or β-blocker on peak VO2. Participants’ age influenced peak VO2 responses as two participants aged 48 and 49 years exhibited greater rate of reduction in peak VO2 at week 0 vs week 16 and also at week 16 vs week 52, than the other 28 patients who were 54 years or older. The younger participants had highest peak VO2 values and this difference was accounted for by forming a categorical variable for age with categories of younger than 50 and older than 50 years. However, the small sample size for the younger than 50 years category limits inference for that group. There was negligible change in peak VO2 for the patients who were younger than 50 during the supervised program and a reduction in peak VO2 at the measurement 1 year later. The older group of patients showed a slight improvement in the peak VO2 during the supervised exercise program (albeit off a low initial peak VO2) and the 1-year follow-up mean peak VO2 for this group was similar to that at the end of the supervised period. The age-related changes in peak VO2 during initial and follow-up stages are summarized in Table III.

image

Figure 1.  Profiles over time and 95% confidence regions for peak oxygen consumption (VO2) in patients younger than 50 (>50) and those older than 50 years (<50).

Download figure to PowerPoint

Table III.   Rate of Change in Peak Oxygen Consumption During 0 vs 16 Weeks and 16 vs 52 Weeks for Patients Age Groups
 0 to 16 Weeks16 to 52 Weeks
Age group, yMean Rate, mL/kg/min95% Confidence IntervalMean Rate, mL/kg/min95% Confidence Interval
<50 (n=2)−0.028(−0.3 to 0.2)−5.2 (−8.8 to −1.7)
≥50 (n=28)0.2(0.1 to 0.3)−1.6 (−2.6 to −0.7)

MLWHF QOL and Hare-Davis Depression Scores

The rate of change in physical MLWHF score was significantly greater (improved) during 0 to 16 weeks in patients with dilated pathology, but was not significantly affected by β-blocker use or age. Changes in the physical dimension of the MLWHF questionnaire scores fell (improved) during weeks 0 to 16, but worsened during weeks 0 to 52. The rate of change (improvement) was more rapid in the dilated cardiomyopathy participants (Figure 2). The rates of change are listed in Table IV. There were no changes or treatment effects for the emotional dimension of the MLWHF. The Hare-Davis depression measurement varied over time, but these data were not affected by disease pathology, β-blocker, or age.

image

Figure 2.  Profiles over time and 95% confidence regions for change in physical Physical Minnesota Living With Heart Failure (MLWHF) dimension in pathology and β-blocker (BB) categories. Dil indicates dilated cardiomyopathy; Isch, ischemic cardiomyopathy.

Download figure to PowerPoint

Table IV.   Changes in the Physical Minnesota Living With Heart Failure Dimension in the Two Study Intervals
 Rate of Change 0 to 16 WeeksChange 16 to 52 Weeks
PathologyMean rate95% Confidence IntervalMean change95% Confidence Interval
Dilated−0.42(−0.67 to −0.17)0.5(−3.4 to 4.4)
Ischemic−0.22(− 0.4 to − 0.04)2(−0.8 to 4.7)

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

Our longitudinal study shows that age and disease pathology, but not β-blocker use, may affect the rate of adaptation to exercise training in participants with systolic heart failure. Our findings concur with previous work that has suggested that patients with dilated rather than ischemic cardiomyopathy may experience larger and faster health benefits from exercise training. Furthermore, our work shows that outpatient exercise training programs (0–16 weeks in this study) are effective in effecting change in peak VO2 and QOL; however, transition to home exercise training (16–52 weeks) demonstrated evidence of de-training, although some residual health benefits were observed at 52 weeks.

Our work has suggested the rate of change of peak VO2 is faster in patients younger than 50 years, which appears intuitive. Our work also suggested that there was no difference in rate of change of peak VO2 in dilated vs ischemic cardiomyopathy. Previous work has shown that patients with idiopathic dilated cardiomyopathy have significantly increased peak VO2 and decreased left ventricular dimensions compared with those with coronary artery disease, although no information is available on the rate of change.20 Other work has shown that once patients transitioned from outpatient (0–16 weeks) to home exercise programs (16–52 weeks), changes in peak VO2 plateau or even fall,6,7 and this was the case with our participants, although the 52-week trend in peak VO2 was higher than baseline values.

Our data suggest that the physical, but not emotional, dimension of MLWHF QOL score improved (lower) more rapidly in patients with dilated vs ischemic cardiomyopathy during outpatient training (weeks 0–16). Moreover, these benefits were lost more slowly during home exercise training (0–52 weeks) in patients with dilated cardiomyopathy. There were no noticeable differences in QOL scores between patients who did and did not take β-adrenergenic blockade medication. Previous work has suggested that patients with ischemic cardiomyopathy are likely to exhibit smaller improvements in cardiorespiratory fitness (peak VO2) and QOL than patients with dilated cardiomyopathy.10,20,21 Our work did not elicit any variable that created variation in change in Hare-Davis depression score across both outpatient and home exercise periods. It appears that elevated depression scores are elevated in heart failure patients and that they do follow expected improvements (become lower) with outpatient exercise training that are partially lost during home exercise training. The difference between depression and physical fitness and QOL is that no clinical, medicinal, or demographic characteristic appears to create a variation in the rate or size of the response. The primary limitations of this work are the variation in exercise adherence in the home (16–52 week) part of the study and the small sample size n=30.

The venue and presence or absence of exercise supervision clearly had the greatest bearing on the rate of adaptation to exercise training in heart failure patients. That said, age, β-adrenergic blockade, and disease etiology also produced variations to the rate and magnitude of adaption. These findings have implications for outpatient-based rehabilitation programs that may have a finite capacity to train patients. Perhaps preference should be given to older (>50 years) patients who are not taking β-blockers, but exhibit ischemic, rather than dilated, cardiomyopathy.

Conclusions

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

The exercise training venue and supervision, or lack thereof, is the major determinant of adaptation to the intervention in heart failure patients, although age, β-adrenergic medication, and heart failure etiology may also partially explain the variation in adaptive responses observed.

Acknowledgment:  We thank Professor Tom Marwick for advice and access to his laboratories and patients.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References
  • 1
    Smart N, Marwick TH. Exercise training for patients with heart failure: a systematic review of factors that improve mortality and morbidity. Am J Med. 2004;116:693706.
  • 2
    Van Tol BA, Huijsmans RJ, Kroon DW, et al. Effects of exercise training on cardiac performance, exercise capacity and quality of life in patients with heart failure: a meta-analysis. Eur J Heart Fail. 2006;8(8):841850.
  • 3
    Haykowsky MJ, Liang Y, Pechter D, et al. 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. 2007;49:23292336.
  • 4
    Smart N, Meyer T, Butterfield J, et al. Individual patient meta-analysis of exercise training effects on systemic brain natriuretic peptide expression in heart failure. Eur J Prev Cardiol. 2012;19:428435.
  • 5
    Smart NA, Larsen AI, Le Maitre JP, et al. Effect of exercise training on interleukin-6, tumour necrosis factor alpha and functional capacity in heart failure. Cardiol Res Pract. 2011;2011:532620.
  • 6
    McKelvie RS, Teo KK, Roberts R, et al. Effects of exercise training in patients with heart failure: the Exercise Rehabilitation Trial (EXERT). Am Heart J. 2002;144:2330.
  • 7
    Smart N, Haluska B, Jeffriess L, et al. Predictors of a sustained response to exercise training in patients with chronic heart failure: a telemonitoring study. Am Heart J. 2005;150:12401247.
  • 8
    Hwang R, Marwick T. Efficacy of home-based exercise programmes for people with chronic heart failure: a meta-analysis. Eur J Cardiovasc Prev Rehabil. 2009;16:527535.
  • 9
    Lloyd-Williams F, Mair FS, Leitner M. Exercise training and heart failure: a systematic review of current evidence. Br J Gen Pract. 2002;52:4755.
  • 10
    Piepoli MF, Davos C, Francis DP, et al. Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH). Br Med J. 2004;328:189.
  • 11
    Meyer T, Scharhag J, Kindermann W. Peak oxygen uptake. Myth and truth about an internationally accepted reference value. Z Kardiol. 2005;94:255265.
  • 12
    O’Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009;301:14391450.
  • 13
    Pozehl B, Duncan K, Krueger S, et al. Adjunctive effects of exercise training in heart failure patients receiving maximum pharmacologic therapy. Prog Cardiovasc Nurs. 2003;18:177183.
  • 14
    Smart N. A comparison of 16 weeks of continuous versus intermittent exercise training in chronic heart failure patients. Congest Heart Fail. 2012;18(4):205211.
  • 15
    Smart NA, Dieberg G, Giallauria F. Intermittent versus continuous exercise training in chronic heart failure: a meta-analysis. Int J Cardiol. 2011 Nov 16. [Epub ahead of print]
  • 16
    Wasserman K, Whipp BJ, Koyl SN, et al. Anaerobic threshold and respiratory gas exchange during exercise. J Appl Physiol. 1973;35:236243.
  • 17
    Rector TS, Cohn JN. Assessment of patient outcome with the Minnesota Living with Heart Failure questionnaire: reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group. Am Heart J. 1992;124:10171025.
  • 18
    Hare DL, Davis CR. Cardiac Depression Scale: validation of a new depression scale for cardiac patients. J Psychosom Res. 1996;40:379386.
  • 19
    Borg G. ed. Borg’s Perceived Exertion and Pain Scales. Champaign, IL: Human Kinetics; 1998.
  • 20
    Webb-Peploe KM, Chua TP, Harrington D, et al. Different response of patients with idiopathic and ischaemic dilated cardiomyopathy to exercise training. Int J Cardiol. 2000;74:215224.
  • 21
    Smart N. Exercise training for heart failure patients with and without systolic dysfunction: an evidence-based analysis of how patients benefit. Cardiol Res Pract. 2010 Sep 30;2011.