Exercise-based cardiac rehabilitation for adults with atrial fibrillation

Abstract

Background: Exercise-based cardiac rehabilitation may benefit adults with atrial fibrillation or those who had been treated for atrial fibrillation. Atrial fibrillation is caused by multiple micro re-entry circuits within the atrial tissue, which result in chaotic rapid activity in the atria.

Objectives: To assess the benefits and harms of exercise-based rehabilitation programmes, alone or with another intervention, compared with no-exercise training controls in adults who currently have AF, or have been treated for AF.

Search methods: We searched the following electronic databases; CENTRAL and the Database of Abstracts of Reviews of Effectiveness (DARE) in the Cochrane Library, MEDLINE Ovid, Embase Ovid, PsycINFO Ovid, Web of Science Core Collection Thomson Reuters, CINAHL EBSCO, LILACS Bireme, and three clinical trial registers on 14 July 2016. We also checked the bibliographies of relevant systematic reviews identified by the searches. We imposed no language restrictions.

Selection criteria: We included randomised controlled trials (RCT) that investigated exercise-based interventions compared with any type of no-exercise control. We included trials that included adults aged 18 years or older with atrial fibrillation, or post-treatment for atrial fibrillation.

Data collection and analysis: Two authors independently extracted data. We assessed the risk of bias using the domains outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed clinical and statistical heterogeneity by visual inspection of the forest plots, and by using standard Chi² and I² statistics. We performed meta-analyses using fixed-effect and random-effects models; we used standardised mean differences where different scales were used for the same outcome. We assessed the risk of random errors with trial sequential analysis (TSA) and used the GRADE methodology to rate the quality of evidence, reporting it in the 'Summary of findings' table.

Main results: We included six RCTs with a total of 421 patients with various types of atrial fibrillation. All trials were conducted between 2006 and 2016, and had short follow-up (eight weeks to six months). Risks of bias ranged from high risk to low risk.The exercise-based programmes in four trials consisted of both aerobic exercise and resistance training, in one trial consisted of Qi-gong (slow and graceful movements), and in another trial, consisted of inspiratory muscle training.For mortality, very low-quality evidence from six trials suggested no clear difference in deaths between the exercise and no-exercise groups (relative risk (RR) 1.00, 95% confidence interval (CI) 0.06 to 15.78; participants = 421; I² = 0%; deaths = 2). Very low-quality evidence from five trials suggested no clear difference between groups for serious adverse events (RR 1.01, 95% CI 0.98 to 1.05; participants = 381; I² = 0%; events = 8). Low-quality evidence from two trials suggested no clear difference in health-related quality of life for the Short Form-36 (SF-36) physical component summary measure (mean difference (MD) 1.96, 95% CI -2.50 to 6.42; participants = 224; I² = 69%), or the SF-36 mental component summary measure (MD 1.99, 95% CI -0.48 to 4.46; participants = 224; I² = 0%). Exercise capacity was assessed by cumulated work, or maximal power (Watt), obtained by cycle ergometer, or by six minute walking test, or ergospirometry testing measuring VO2 peak. We found moderate-quality evidence from two studies that exercise-based rehabilitation increased exercise capacity, measured by VO2 peak, more than no exercise (MD 3.76, 95% CI 1.37 to 6.15; participants = 208; I² = 0%); and very low-quality evidence from four studies that exercise-based rehabilitation increased exercise capacity more than no exercise, measured by the six-minute walking test (MD 75.76, 95% CI 14.00 to 137.53; participants = 272; I² = 85%). When we combined the different assessment tools for exercise capacity, we found very low-quality evidence from six trials that exercise-based rehabilitation increased exercise capacity more than no exercise (standardised mean difference (SMD) 0.86, 95% CI 0.46 to 1.26; participants = 359; I² = 65%). Overall, the quality of the evidence for the outcomes ranged from moderate to very-low.

Authors' conclusions: Due to few randomised patients and outcomes, we could not evaluate the real impact of exercise-based cardiac rehabilitation on mortality or serious adverse events. The evidence showed no clinically relevant effect on health-related quality of life. Pooled data showed a positive effect on the surrogate outcome of physical exercise capacity, but due to the low number of patients and the moderate to very low-quality of the underpinning evidence, we could not be certain of the magnitude of the effect. Future high-quality randomised trials are needed to assess the benefits and harms of exercise-based cardiac rehabilitation for adults with atrial fibrillation on patient-relevant outcomes.

Conflict of interest statement

Signe S Risom, Selina K Berg, Kirstine L Sibilitz, Pernille Palm Johansen, Christian Gluud, Jane Lindschou, Jesper Hastrup Svendsen, and Ann‐Dorthe Zwisler are involved in conducting three randomised trials, investigating the effect of cardiac rehabilitation for 1) people with atrial fibrillation treated with radiofrequency ablation, 2) people treated for infective endocarditis, and 3) people after heart valve surgery; and one trial about sexual rehabilitation.

Rod S Taylor is an author on a number of other Cochrane cardiac rehabilitation reviews and is currently the co‐chief investigator on the programme of research with the overarching aims of developing and evaluating a home‐based cardiac rehabilitation intervention for people with heart failure and their carers (PGfAR RP‐PG‐0611‐12004).

Figures

1

Study flow diagram

2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

3

Mortality. Trial Sequential Analysis on mortality in the six trials was performed based on the proportion with mortality in the control group set at 0.5%, a relative risk reduction of 20%, a type I error of 5%, a type II error of 20% (80% power), and diversity of 1%. The diversity‐adjusted required information size was 140,645 participants. The blue line represents the cumulative Z‐score of the meta‐analysis. The green lines represent the conventional statistical boundaries of P = 0.05. The cumulative Z‐curve (blue line) does not cross the conventional statistical boundaries. The trial sequential monitoring boundaries and the diversity‐adjusted required information size are not shown as the accrued number of participants only amounted to 421/140,645 (0.3%).

4

Serious adverse events. Trial Sequential Analysis on serious adverse events in four trials was performed based on the proportion with serious adverse events in the control group set at 2.9%, a relative risk reduction of 20%, a type I error of 5%, a type II error of 20% (80% power), and diversity of 0%. The diversity‐adjusted required information size was 23,723 participants. The blue line represents the cumulative Z‐score of the meta‐analysis. The light blue lines represent the conventional statistical boundaries of P = 0.05. The trial sequential monitoring boundaries and the diversity‐adjusted required information size are not shown as the accrued number of participants only amounted to 351/23723 (1.48%).

5

Quality of life, SF‐36 physical component score. Trial sequential analysis on quality of life assessed with SF‐36 physical component score assessing a minimal relevant clinical difference of 7 points, and variance of 70 points (empirical data), was performed based on a type I error of 5%, a type II error of 20% (80% power), and diversity of 75.78%. The diversity‐adjusted required information size was 175 participants. The blue line represents the cumulative Z‐score of the meta‐analysis. The green lines represent the conventional statistical boundaries of P = 0.05. The red inward sloping lines represent the trial sequential monitoring boundaries. The cumulative Z‐curve crossed the diversity‐adjusted required information size (red vertical line), indicating that sufficient information was provided.

6

Quality of life, SF‐36 mental component score. Trial sequential analysis on quality of life assessed with SF‐36 mental component score assessing a minimal relevant clinical difference of 7 points, and variance of 89 points (empirical data), was performed based on a type I error of 5%, a type II error of 20% (80% power), and diversity of 0%. The diversity‐adjusted required information size was 57 participants. The blue line represents the cumulative Z‐score of the meta‐analysis. The green lines represent the conventional statistical boundaries of P = 0.05. The red inward sloping lines represent the trial sequential monitoring boundaries. The cumulative Z‐curve (blue line) did not cross the trial sequential monitoring boundaries for benefit or harm (red inward sloping lines). The cumulative Z‐curve crossed the diversity‐adjusted required information size (red vertical line) indicating that sufficient information was provided.

7

Exercise capacity, VO2 peak. Trial sequential analysis on exercise capacity assessed with VO2 peak assessing a minimal relevant clinical difference of 3 mL/kg/min, and variance of 78 mL/kg/min (empirical data), was performed based on a type I error of 5%, a type II error of 20% (80% power), and diversity of 0%. The diversity‐adjusted required information size was 271 participants. The blue line represents the cumulative Z‐score of the meta‐analysis. The green lines represent the conventional statistical boundaries of P = 0.05. The red inward sloping lines represent the trial sequential monitoring boundaries. The cumulative Z‐curve (blue line) crosses the trial sequential monitoring boundaries for benefit, indicating that sufficient information was obtained.

8

Physical capacity, 6‐minute walking test. Trial sequential analysis on exercise capacity assessed with 6‐minute walking test assessing a minimal relevant clinical difference of 25 meters, and variance of 8280 m (empirical data), was performed based on a type I error of 5%, a type II error of 20% (80% power), and diversity of 87.74%. The diversity‐adjusted required information size was 3392 participants. The blue line represents the cumulative Z‐score of the meta‐analysis. The green lines represent the conventional statistical boundaries of P = 0.05. The cumulative Z‐curve (blue line) crosses the conventional statistical boundaries. However, the trial sequential monitoring boundaries and the diversity‐adjusted required information size are not crossed, indicating that insufficient information is obtained.

1.1. Analysis

Comparison 1 Exercise versus no exercise, Outcome 1 Mortality.

1.2. Analysis

Comparison 1 Exercise versus no exercise, Outcome 2 Mortality (worst‐best case scenario).

1.3. Analysis

Comparison 1 Exercise versus no exercise, Outcome 3 Mortality (best‐worst case scenario).

1.4. Analysis

Comparison 1 Exercise versus no exercise, Outcome 4 Serious adverse events.

1.5. Analysis

Comparison 1 Exercise versus no exercise, Outcome 5 Serious adverse events (worst‐best case scenario).

1.6. Analysis

Comparison 1 Exercise versus no exercise, Outcome 6 Serious adverse events (best‐worst case scenario).

1.7. Analysis

Comparison 1 Exercise versus no exercise, Outcome 7 Quality of life, SF‐36, Physical Component Score.

1.8. Analysis

Comparison 1 Exercise versus no exercise, Outcome 8 Quality of life, SF‐36, Mental Component Score.

1.9. Analysis

Comparison 1 Exercise versus no exercise, Outcome 9 Quality of Life, SF‐36, Physical Function.

1.10. Analysis

Comparison 1 Exercise versus no exercise, Outcome 10 Quality of Life, SF‐36, Role‐Physical.

1.11. Analysis

Comparison 1 Exercise versus no exercise, Outcome 11 Quality of Life, SF‐36, Bodily Pain.

1.12. Analysis

Comparison 1 Exercise versus no exercise, Outcome 12 Quality of Life, SF‐36, General Health.

1.13. Analysis

Comparison 1 Exercise versus no exercise, Outcome 13 Quality of Life, SF‐36, Vitality.

1.14. Analysis

Comparison 1 Exercise versus no exercise, Outcome 14 Quality of Life, SF‐36, Social Functioning.

1.15. Analysis

Comparison 1 Exercise versus no exercise, Outcome 15 Quality of Life, SF‐36, Role Emotional.

1.16. Analysis

Comparison 1 Exercise versus no exercise, Outcome 16 Quality of Life, SF‐36, Mental Health.

1.17. Analysis

Comparison 1 Exercise versus no exercise, Outcome 17 Exercise capacity (VO2 peak).

1.18. Analysis

Comparison 1 Exercise versus no exercise, Outcome 18 Exercise capacity (6MWT).

1.19. Analysis

Comparison 1 Exercise versus no exercise, Outcome 19 Exercise capacity (SMD).

References

References to studies included in this review Hegbom 2006 {published data only}

Malmo 2016 {published data only} Osbak 2011 {published data only} Pippa 2007 {published data only} Risom 2016 {published data only} Zeren 2016 {published data only} References to studies excluded from this review Angergard K 2015 {published data only} Borland 2015 {published data only} Frederix 2015 {published data only} Kim 2014 {published data only} Mertens 1996 {published data only} Vanhees 2000 {published data only} References to ongoing studies NCT01673139 {unpublished data only} NCT01721863 {unpublished data only} NCT01817998 {unpublished data only} Additional references Aliot 2014 Anderson 2014 Anderson 2016 Andrews 2013a Andrews 2013b ATS statement 2002 Atwood 2007 BACPR 2012 Ball 2013 Balshem 2011 Berg 2015 Blair 1996 Brenyo 2011 Brunetti 2013 Calkins 2009 Camm 2010 Camm 2012 Chan 2013 Chen 2012 Clausen 1976 Dabrowski 2010 Deeks 2011 DeMets 1987 DerSimonian 1986 Dorian 2000 Dorian 2002 Furukawa 2006 Giacomantonio 2013 Go 2001 GRADEpro GDT 2014 [Computer program] Gremeaux 2011 Guyatt 2008 Guyatt 2011a Guyatt 2011b Guyatt 2011c Guyatt 2011d Guyatt 2011e Guyatt 2011f Guyatt 2011g Guyatt 2011h Guyatt 2013a Guyatt 2013b Guyatt 2013c Hambrecht 2000 Hawley 2014 Hendriks 2012 Hendriks 2014 Higgins 2011 Higgins 2011a Higgins 2011b ICH‐GCP 2015 Jakobsen 2013 Kang 2004 Kirchhof 2007 Kirchhof 2016 Lafuente‐Lafuente 2012 Lane 2015 Lefebvre 2011 Levy 1998 Loke 2011 Lowres 2011 McCabe 2011 Mustafa 2013 Myers 2002 National Board of Health 2013 Nguyen 2013 Piepoli 2014 Plisiene 2008 Reed 2013 RevMan 5 2014 [Computer program] Ruigomez 2005 Savovic 2012 Sterne 2011 Stewart 2001 Stewart 2002 Taylor 2014 Thorlund 2009a Thorlund 2009b Thrall 2006 TSA 2011 [Computer program] Wetterslev 2008 Wetterslev 2009 Wise 2005 Wood 2008