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

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.

[1]  Sally J. Singh,et al.  Exercise-Based Rehabilitation for Heart Failure: Cochrane Systematic Review, Meta-Analysis, and Trial Sequential Analysis. , 2019, JACC. Heart failure.

[2]  Sally J. Singh,et al.  Exercise-based cardiac rehabilitation for adults with heart failure. , 2019, The Cochrane database of systematic reviews.

[3]  Sally J. Singh,et al.  The effects and costs of home-based rehabilitation for heart failure with reduced ejection fraction: The REACH-HF multicentre randomized controlled trial , 2018, European journal of preventive cardiology.

[4]  W. Kraus,et al.  Relationship between changing patient‐reported outcomes and subsequent clinical events in patients with chronic heart failure: insights from HF‐ACTION , 2018, European journal of heart failure.

[5]  Sally J. Singh,et al.  A randomised controlled trial of a facilitated home-based rehabilitation intervention in patients with heart failure with preserved ejection fraction and their caregivers: REACH-HFpEF pilot study , 2018, British Journal of General Practice.

[6]  A. Sabbag,et al.  The prognostic significance of improvement in exercise capacity in heart failure patients who participate in cardiac rehabilitation programme , 2018, European journal of preventive cardiology.

[7]  A. Verbeek,et al.  Absence of Fitness Improvement Is Associated with Outcomes in Heart Failure Patients , 2017, Medicine and science in sports and exercise.

[8]  M. Uhlemann,et al.  Molecular effects of exercise training in patients with cardiovascular disease: focus on skeletal muscle, endothelium, and myocardium. , 2017, American journal of physiology. Heart and circulatory physiology.

[9]  B. Pavy,et al.  Effects of combined exercise training and electromyostimulation treatments in chronic heart failure: A prospective multicentre study , 2017, European journal of preventive cardiology.

[10]  R. Wachter,et al.  Exercise training in Diastolic Heart Failure (Ex‐DHF): rationale and design of a multicentre, prospective, randomized, controlled, parallel group trial , 2017, European journal of heart failure.

[11]  A. Cohen-Solal,et al.  Effects of a cardiac rehabilitation programme on plasma cardiac biomarkers in patients with chronic heart failure , 2017, European journal of preventive cardiology.

[12]  P. Doherty,et al.  Frailty and cardiac rehabilitation: A call to action from the EAPC Cardiac Rehabilitation Section , 2017, European journal of preventive cardiology.

[13]  Erik Southard,et al.  Improving quality of life and decreasing readmissions in heart failure patients in a multidisciplinary transition‐to‐care clinic , 2017, Heart & lung : the journal of critical care.

[14]  S. Nanas,et al.  Exercise training improves characteristics of exercise oscillatory ventilation in chronic heart failure , 2017, European journal of preventive cardiology.

[15]  A. Støylen,et al.  High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction , 2017, Circulation.

[16]  Aaron Saguil,et al.  Impact of Exercise-Based Cardiac Rehabilitation. , 2016, American family physician.

[17]  C. Lewinter,et al.  Predictors of exercise capacity following exercise-based rehabilitation in patients with coronary heart disease and heart failure: A meta-regression analysis , 2016, European journal of preventive cardiology.

[18]  H. Kemps,et al.  The influence of training characteristics on the effect of aerobic exercise training in patients with chronic heart failure: A meta-regression analysis. , 2016, International journal of cardiology.

[19]  G. Schuler,et al.  Long-Term Exercise Training in Patients With Advanced Chronic Heart Failure: SUSTAINED BENEFITS ON LEFT VENTRICULAR PERFORMANCE AND EXERCISE CAPACITY , 2016, Journal of cardiopulmonary rehabilitation and prevention.

[20]  W. Kraus,et al.  Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure. , 2016, Journal of the American College of Cardiology.

[21]  S. Ebrahim,et al.  Exercise-based cardiac rehabilitation for coronary heart disease. , 2016, The Cochrane database of systematic reviews.

[22]  O Kuss,et al.  Statistical methods for meta‐analyses including information from studies without any events—add nothing to nothing and succeed nevertheless , 2015, Statistics in medicine.

[23]  A. Dehkordi,et al.  Effect of Exercise Training on the Quality of Life and Echocardiography Parameter of Systolic Function in Patients With Chronic Heart Failure: a Randomized Trial , 2015 .

[24]  Sally J. Singh,et al.  Exercise-based rehabilitation for heart failure: systematic review and meta-analysis , 2015, Open Heart.

[25]  T. Brunini,et al.  Chronic exercise leads to antiaggregant, antioxidant and anti-inflammatory effects in heart failure patients , 2014, European journal of preventive cardiology.

[26]  Jiming Liu,et al.  Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range , 2014, BMC Medical Research Methodology.

[27]  Mark D. Huffman,et al.  Heart disease and stroke statistics--2014 update: a report from the American Heart Association. , 2014, Circulation.

[28]  M. Drazner,et al.  2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2013, Journal of the American College of Cardiology.

[29]  M. Hertzog,et al.  Effects of Exercise Training versus Attention on Plasma B‐type Natriuretic Peptide, 6‐Minute Walk Test and Quality of Life in Individuals with Heart Failure , 2012, Cardiopulmonary physical therapy journal.

[30]  W. Kraus,et al.  Relation between volume of exercise and clinical outcomes in patients with heart failure. , 2012, Journal of the American College of Cardiology.

[31]  R. Belardinelli,et al.  10-year exercise training in chronic heart failure: a randomized controlled trial. , 2012, Journal of the American College of Cardiology.

[32]  Gerasimos S Filippatos,et al.  Exercise training in heart failure: from theory to practice. A consensus document of the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation , 2011, European journal of heart failure.

[33]  J. McMurray,et al.  The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature‐based meta‐analysis , 2009, European journal of heart failure.

[34]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement , 2009, BMJ : British Medical Journal.

[35]  W. Kraus,et al.  Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. , 2009, JAMA.

[36]  W. Kraus,et al.  Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. , 2009, JAMA.

[37]  Sally J. Singh,et al.  A randomized trial of the addition of home‐based exercise to specialist heart failure nurse care: the Birmingham Rehabilitation Uptake Maximisation study for patients with Congestive Heart Failure (BRUM‐CHF) study , 2009, European journal of heart failure.

[38]  M. Risberg,et al.  Long-term effects of a group-based high-intensity aerobic interval-training program in patients with chronic heart failure. , 2008, The American journal of cardiology.

[39]  Jacky Austin,et al.  Five-year follow-up findings from a randomized controlled trial of cardiac rehabilitation for heart failure , 2008, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[40]  G. Fonarow,et al.  Effects of a home-based exercise program on clinical outcomes in heart failure. , 2007, American heart journal.

[41]  J. Myers,et al.  Exercise capacity, physical activity patterns and outcomes six years after cardiac rehabilitation in patients with heart failure , 2007, Clinical rehabilitation.

[42]  M. Sydes,et al.  Practical methods for incorporating summary time-to-event data into meta-analysis , 2007, Trials.

[43]  K. Kawecka-Jaszcz,et al.  Physical training in patients with chronic heart failure of ischemic origin: effect on exercise capacity and left ventricular remodeling , 2007, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[44]  H. Middlekauff,et al.  Effects of home‐based exercise training on neurovascular control in patients with heart failure , 2006, European journal of heart failure.

[45]  M. Emdin,et al.  Aerobic training decreases B-type natriuretic peptide expression and adrenergic activation in patients with heart failure. , 2006, Journal of the American College of Cardiology.

[46]  K. Kawecka-Jaszcz,et al.  Effect of physical training on quality of life and oxygen consumption in patients with congestive heart failure. , 2005, International journal of cardiology.

[47]  Jacky Austin,et al.  Randomised controlled trial of cardiac rehabilitation in elderly patients with heart failure , 2005, European journal of heart failure.

[48]  W. Mosterd,et al.  Endothelial markers in chronic heart failure: training normalizes exercise‐induced vWF release , 2004, European journal of clinical investigation.

[49]  Sally Freels,et al.  Extracting summary statistics to perform meta‐analysis of the published literature for survival endpoints , 2004 .

[50]  L. Tavazzi,et al.  Antiremodeling Effect of Long-Term Exercise Training in Patients With Stable Chronic Heart Failure: Results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) Trial , 2003, Circulation.

[51]  Salim Yusuf,et al.  Effects of exercise training in patients with heart failure: the Exercise Rehabilitation Trial (EXERT). , 2002, American heart journal.

[52]  G. Schuler,et al.  Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: A randomized trial. , 2000, JAMA.

[53]  V. Froelicher,et al.  Exercise training and myocardial remodeling in patients with reduced ventricular function: one-year follow-up with magnetic resonance imaging. , 2000, American heart journal.

[54]  S. Keteyian,et al.  Effects of exercise training on chronotropic incompetence in patients with heart failure. , 1999, American heart journal.

[55]  R. Belardinelli,et al.  Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life, and clinical outcome. , 1999, Circulation.

[56]  M. Parmar,et al.  Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. , 1998, Statistics in medicine.

[57]  S. Adamopoulos,et al.  Effects of physical training in chronic heart failure , 1990, The Lancet.

[58]  H. Saner,et al.  Interval training early after heart failure decompensation is safe and improves exercise tolerance and quality of life in selected patients , 2018, European journal of preventive cardiology.

[59]  P. Ponikowski,et al.  2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure , 2016 .

[60]  Martin R Cowie National Institute for Health and Care Excellence. , 2015, European heart journal.

[61]  J. Higgins Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration , 2011 .

[62]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[63]  E. Kouidi,et al.  Quality of life, psychological and physiological changes following exercise training in patients with chronic heart failure. , 2004, Journal of rehabilitation medicine.