Exercise-based cardiac rehabilitation in patients with reduced left ventricular ejection fraction: The Cardiac Rehabilitation Outcome Study in Heart Failure (CROS-HF): A systematic review and meta-analysis

Abstract

Background: In heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established.

Design: The design of this study involved a structured review and meta-analysis.

Methods: Evaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later.

Results: Out of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39-1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66-2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26-3.16, seven studies). In addition there was no significant difference between the groups with respect to 'hospitalization-for-any-reason' (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41-1.53, four studies), or 'hospitalization-due-to-heart-failure' (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12-2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07-9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35-3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference -4.19, 95% confidence interval -10.51-2.12, seven studies; six-months follow-up: mean difference -5.97, 95% confidence interval -16.17-4.23, four studies).

Conclusion: No association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

Keywords: Meta-analysis; cardiac rehabilitation; exercise training; heart failure; systematic review.

Figure 1.

A summary of study inclusion/exclusion process.

Figure 2.

Risk of bias for individual studies. HR: hazard ratio; RR: relative risk.

Figure 3.

Risk of bias: the visual examination of the funnel plot.

Figure 4.

Primary endpoint: all-cause-mortality, results of the primary analysis. CI: confidence interval; ebCR: exercise-based cardiac rehabilitation; HR: hazard ratio; RR: relative risk.

Figure 5.

Secondary endpoint: hospital admission for any reason. CI: confidence interval; ebCR: exercise-based cardiac rehabilitation; HR: hazard ratio; RR: relative risk.

Figure 6.

Secondary endpoint: hospital admission due to worsening heat failure. CI: confidence interval; ebCR: exercise-based cardiac rehabilitation; HR: hazard ratio; RR: relative risk.

Figure 7.

Secondary endpoint: cardiopulmonary exercise capacity (peak oxygen uptake (VO_2peak)). No pooled effect sizes estimated due to high heterogeneity (mean difference (MD) after 12–14 months: 94.92%, MD after six months: (86.66%). CI: confidence interval; ebCR: exercise-based cardiac rehabilitation; FV: final value (raw value obtained after end of intervention); SD: standard deviation.

Figure 8.

Secondary endpoint: health-related quality of life: Kansas City Cardiomyopathy Questionnaire (KCCQ). CI: confidence interval; ebCR: exercise-based cardiac rehabilitation; FV: final value (raw value obtained after end of intervention); MD: mean difference (publication reported mean difference); SD: standard deviation.

Figure 9.

Secondary endpoint: health-related quality of life: Minnesota Living With Heart Failure Questionnaire (MLWHF). CI: confidence interval; CS: change score (difference between final value and baseline value; ebCR: exercise-based cardiac rehabilitation; FV: final value (raw value obtained after end of intervention); SD: standard deviation.