{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:41:24Z","timestamp":1775583684971,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Despite advances in the surgical management of patients with Fontan circulation, their exercise capacity and quality of life remain significantly impaired. Exercise-based cardiac rehabilitation (CR) offers promising improvements in these areas, but the implementation and adherence to these programmes are often inconsistent. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Materials and Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted on 24 August 2023. Studies were screened and assessed for quality using the Cochrane RoB Tool 2 and STROBE checklist. Meta-analysis was performed using a continuous random-effects model to determine the effectiveness of various CR interventions, including aerobic exercise training (AET), resistance training, and inspiratory muscle training (IMT). Results: A total of 26 studies (7 RCTs, 19 cohorts) comprising 22 distinct cohorts were included, with a total sample size of 428 Fontan patients. The interventions ranged from 4 weeks to 24 months and included AET (18 studies), resistance training (11 studies), and IMT (6 studies). The meta-analysis revealed significant improvements in exercise capacity, with a pooled mean difference in peak VO2 of 1.947 (95% CI: 1.491 to 2.402, p &lt; 0.001). Subgroup analyses showed that combined AET and resistance training had the most robust effect, with a mean difference of 2.11 (95% CI: 1.57 to 2.65, p &lt; 0.001). Home-based interventions showed significant benefits, while supervised and hybrid interventions did not show statistically significant differences. Publication bias was identified, particularly in home-based interventions, where smaller studies demonstrated larger effect sizes, as confirmed by Egger\u2019s test (Intercept = 2.417, 95% CI: 1.498 to 3.337, p = 0.001). However, no significant bias was detected in supervised or hybrid interventions, which displayed symmetrical distributions in funnel plots and non-significant Egger\u2019s test results. Conclusions: CR appears to be an effective intervention for improving exercise capacity in Fontan patients, particularly when combining AET with resistance training. Home-based programmes offer promising results, though the potential for publication bias, especially in smaller studies, warrants cautious interpretation of these findings. Further research is needed to refine protocols, explore long-term outcomes, and determine the underlying mechanisms, particularly for patients with more severe clinical presentations. The low incidence of adverse events across the studies reinforces the safety of these interventions.<\/jats:p>","DOI":"10.3390\/medicina60111817","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T05:30:53Z","timestamp":1730784653000},"page":"1817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cardiac Rehabilitation for Fontan Circulation Patients: A Systematic Review, and Meta-Analysis"],"prefix":"10.3390","volume":"60","author":[{"given":"Luna van de","family":"Ven","sequence":"first","affiliation":[{"name":"Department of Paediatric Cardiology, Children\u2019s Hospital, University Medical Center Utrecht, P.O. Box 85090, AB 3508 Utrecht, The Netherlands"}]},{"given":"Ana Clara","family":"F\u00e9lix","sequence":"additional","affiliation":[{"name":"Unidade Local de Sa\u00fade S\u00e3o Jos\u00e9 EPE, Pediatric Cardiology Department, Hospital de Santa Marta, Reference Center for Congenital Heart Diseases, Member of the European Reference Network for Rare, Low Prevalence Complex Diseases of the Heart (ERN GUARD-Heart), 1150-199 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9597-4689","authenticated-orcid":false,"given":"Joana","family":"Suarez","sequence":"additional","affiliation":[{"name":"Unidade Local de Sa\u00fade S\u00e3o Jos\u00e9 EPE, Pediatric Cardiology Department, Hospital de Santa Marta, Reference Center for Congenital Heart Diseases, Member of the European Reference Network for Rare, Low Prevalence Complex Diseases of the Heart (ERN GUARD-Heart), 1150-199 Lisbon, Portugal"}]},{"given":"Jorge","family":"Dias","sequence":"additional","affiliation":[{"name":"Unidade Local de Sa\u00fade S\u00e3o Jos\u00e9 EPE, Physical and Medical Rehabilitation Department, Hospital de Santa Marta, 1169-024 Lisbon, Portugal"}]},{"given":"F\u00e1tima F.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Unidade Local de Sa\u00fade S\u00e3o Jos\u00e9 EPE, Pediatric Cardiology Department, Hospital de Santa Marta, Reference Center for Congenital Heart Diseases, Member of the European Reference Network for Rare, Low Prevalence Complex Diseases of the Heart (ERN GUARD-Heart), 1150-199 Lisbon, Portugal"},{"name":"Cl\u00ednica Universit\u00e1ria de Cardiologia Pedi\u00e1trica, Centro Cl\u00ednico Acad\u00e9mico de Lisboa, 1169-024 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2169-4024","authenticated-orcid":false,"given":"S\u00e9rgio","family":"Laranjo","sequence":"additional","affiliation":[{"name":"Unidade Local de Sa\u00fade S\u00e3o Jos\u00e9 EPE, Pediatric Cardiology Department, Hospital de Santa Marta, Reference Center for Congenital Heart Diseases, Member of the European Reference Network for Rare, Low Prevalence Complex Diseases of the Heart (ERN GUARD-Heart), 1150-199 Lisbon, Portugal"},{"name":"Cl\u00ednica Universit\u00e1ria de Cardiologia Pedi\u00e1trica, Centro Cl\u00ednico Acad\u00e9mico de Lisboa, 1169-024 Lisbon, Portugal"},{"name":"Comprehensive Health Research Center, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM, Universidade NOVA de Lisboa, 1099-085 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/chd.12570","article-title":"Five decades of the Fontan operation: A systematic review of international reports on outcomes after univentricular palliation","volume":"13","author":"Kverneland","year":"2018","journal-title":"Congenit. Heart Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ijcard.2016.05.035","article-title":"The Fontan epidemic: Population projections from the Australia and New Zealand Fontan registry","volume":"219","author":"Schilling","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e234","DOI":"10.1161\/CIR.0000000000000696","article-title":"Evaluation and management of the child and adult with Fontan circulation: A scientific statement from the American Heart Association","volume":"140","author":"Rychik","year":"2019","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jtcvs.2017.01.056","article-title":"Long-term survival after the Fontan operation: Twenty years of experience at a single center","volume":"154","author":"Downing","year":"2017","journal-title":"J. Thorac. Cardiovasc. Surgery."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1177\/2047487320942869","article-title":"Physical exercise training in patients with a Fontan circulation: A systematic review","volume":"28","author":"Scheffers","year":"2021","journal-title":"Eur. J. Prev. Cardiology."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1136\/adc.2006.105239","article-title":"Physical activity levels in children and adolescents are reduced after the Fontan procedure, independent of exercise capacity, and are associated with lower perceived general health","volume":"92","author":"McCrindle","year":"2007","journal-title":"Arch. Dis. Childhood."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1017\/S1047951113001649","article-title":"Exercise capacity in the Fontan circulation","volume":"23","author":"Goldberg","year":"2013","journal-title":"Cardiol. Young."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1136\/hrt.2004.051789","article-title":"The fontan circulation","volume":"91","author":"Gewillig","year":"2005","journal-title":"Heart"},{"key":"ref_9","first-page":"F1000 Faculty Rev-935","article-title":"State of the art of the Fontan strategy for treatment of univentricular heart disease","volume":"7","author":"Bogers","year":"2018","journal-title":"F1000Research"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.hlc.2015.03.005","article-title":"Should we recommend exercise after the Fontan procedure?","volume":"24","author":"Sutherland","year":"2015","journal-title":"Heart Lung Circ."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1161\/CIR.0b013e318293688f","article-title":"Promotion of physical activity for children and adults with congenital heart disease: A scientific statement from the American Heart Association","volume":"127","author":"Longmuir","year":"2013","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cjcpc.2022.05.001","article-title":"Importance of Physical Activity and Exercise in Paediatric Fontan Patients","volume":"1","author":"Longmuir","year":"2022","journal-title":"CJC Pediatr. Congenit. Heart Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: A revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/bmj.39335.541782.AD","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"335","author":"Altman","year":"2007","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s11192-019-03317-3","article-title":"Using STROBE checklist to assess the reporting quality of observational studies affiliated with Shiraz University of Medical Sciences, and its correlates: A scientometric study from Iran","volume":"122","author":"Rahmani","year":"2020","journal-title":"Scientometrics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.21037\/cdt-22-308","article-title":"Clinical aspects and targeted inspiratory muscle training in children and adolescents with Fontan circulation: A randomized controlled trial","volume":"13","author":"Neidenbach","year":"2023","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0002-9149(01)01822-7","article-title":"Effect of aerobic training on exercise performance in patients after the Fontan operation","volume":"88","author":"Minamisawa","year":"2001","journal-title":"Am. J. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.amjcard.2004.08.085","article-title":"Effects of aerobic exercise training in children after the Fontan operation","volume":"95","author":"Opocher","year":"2005","journal-title":"Am. J. Cardiology."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ijcard.2020.01.015","article-title":"Inspiratory muscle training did not improve exercise capacity and lung function in adult patients with Fontan circulation: A randomized controlled trial","volume":"305","author":"Fritz","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ijcard.2021.01.058","article-title":"Aerobic exercise and inspiratory muscle training increase functional capacity in patients with univentricular physiology after Fontan operation: A randomized controlled trial","volume":"330","author":"Turquetto","year":"2021","journal-title":"Int J Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jadohealth.2013.12.010","article-title":"Aerobic exercise influences quality of life of children and youngsters with congenital heart disease: A randomized controlled trial","volume":"55","author":"Dulfer","year":"2014","journal-title":"J. Adolesc. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ijcard.2014.10.031","article-title":"The effect of exercise training on cardiac remodelling in children and young adults with corrected tetralogy of Fallot or Fontan circulation: A randomized controlled trial","volume":"179","author":"Duppen","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.ahj.2015.06.018","article-title":"Does exercise training improve cardiopulmonary fitness and daily physical activity in children and young adults with corrected tetralogy of Fallot or Fontan circulation? A randomized controlled trial","volume":"170","author":"Duppen","year":"2015","journal-title":"Am. Heart J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1017\/S1047951118001166","article-title":"Home- and hospital-based exercise training programme after Fontan surgery","volume":"28","author":"Sutherland","year":"2018","journal-title":"Cardiol. Young"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/chd.12330","article-title":"Can a Home-based Cardiac Physical Activity Program Improve the Physical Function Quality of Life in Children with Fontan Circulation?","volume":"11","author":"Jacobsen","year":"2016","journal-title":"Congenit. Heart Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ppedcard.2018.06.003","article-title":"Can a home-based cardiac physical activity program improve and sustain quality of life and exercise capacity in children with Fontan circulation?","volume":"50","author":"Jacobsen","year":"2018","journal-title":"Prog. Pediatr. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dirks, S., Kramer, P., Schleiger, A., Speck, H.M., Wolfarth, B., Thouet, T., Berger, F., Sallmon, H., and Ovroutski, S. (2021). Home-Based Long-Term Physical Endurance and Inspiratory Muscle Training for Children and Adults with Fontan Circulation-Initial Results from a Prospective Study. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.784648"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e027464","DOI":"10.1161\/JAHA.122.027464","article-title":"Peak Work Rate Increases with Lower Extremity-Focused Exercise Training in Adolescents with Fontan Circulation","volume":"11","author":"Avitabile","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Perrone, M.A., Pomiato, E., Palmieri, R., Di Gia, G., Piemonte, F., Porzio, O., and Gagliardi, M.G. (2022). The Effects of Exercise Training on Cardiopulmonary Exercise Testing and Cardiac Biomarkers in Adult Patients with Hypoplastic Left Heart Syndrome and Fontan Circulation. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9060171"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s00246-021-02806-8","article-title":"Exercise Prescription Enhances Maximal Oxygen Uptake and Anaerobic Threshold in Young Single Ventricle Patients with Fontan Circulation","volume":"43","author":"Rahkonen","year":"2022","journal-title":"Pediatr. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1053\/j.semtcvs.2018.07.014","article-title":"A Pilot Study of Inspiratory Muscle Training to Improve Exercise Capacity in Patients with Fontan Physiology","volume":"30","author":"Wu","year":"2018","journal-title":"Semin. Thorac. Cardiovasc. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1017\/S1047951117002360","article-title":"Can endurance training improve physical capacity and quality of life in young Fontan patients?","volume":"28","author":"Hedlund","year":"2018","journal-title":"Cardiol. Young"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1017\/S1047951118000902","article-title":"Impaired lung function in children and adolescents with Fontan circulation may improve after endurance training","volume":"28","author":"Hedlund","year":"2018","journal-title":"Cardiol. Young"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s00246-018-1854-3","article-title":"A Novel Mechanism for Improved Exercise Performance in Pediatric Fontan Patients after Cardiac Rehabilitation","volume":"39","author":"Wittekind","year":"2018","journal-title":"Pediatr. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s00246-018-1808-9","article-title":"Respiratory Training Late After Fontan Intervention: Impact on Cardiorespiratory Performance","volume":"39","author":"Pingitore","year":"2018","journal-title":"Pediatr. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.ijcard.2012.10.012","article-title":"Resistance training improves cardiac output, exercise capacity and tolerance to positive airway pressure in Fontan physiology","volume":"168","author":"Cordina","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1007\/s00246-012-0618-8","article-title":"Home-based rehabilitation enhances daily physical activity and motor skill in children who have undergone the Fontan procedure","volume":"34","author":"Longmuir","year":"2013","journal-title":"Pediatr. Cardiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.ijcard.2005.02.038","article-title":"Impact of exercise training on muscle function and ergoreflex in Fontan patients: A pilot study","volume":"107","author":"Brassard","year":"2006","journal-title":"Int. J. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/eurjpc\/zwad286","article-title":"Leg-focused high-weight resistance training improves ventricular stroke volume, exercise capacity and strength in young patients with a Fontan circulation","volume":"31","author":"Scheffers","year":"2023","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1017\/S1047951123003153","article-title":"Cardiovascular remodelling in response to exercise training in patients after the Fontan procedure: A pilot study","volume":"34","author":"Bano","year":"2023","journal-title":"Cardiol. Young"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e005750","DOI":"10.1161\/JAHA.117.005750","article-title":"Inspiratory Muscle Training Is Associated with Improved Inspiratory Muscle Strength, Resting Cardiac Output, and the Ventilatory Efficiency of Exercise in Patients with a Fontan Circulation","volume":"6","author":"Laohachai","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ahj.2023.02.006","article-title":"Design and rationale of re-energize fontan: Randomized exercise intervention designed to maximize fitness in fontan patients","volume":"259","author":"Tierney","year":"2023","journal-title":"Am Heart J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1017\/S104795111800015X","article-title":"Lower limb exercise generates pulsatile flow into the pulmonary vascular bed in the setting of the Fontan circulation","volume":"28","author":"Cordina","year":"2018","journal-title":"Cardiol. Young"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:26:37Z","timestamp":1760113597000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,5]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["medicina60111817"],"URL":"https:\/\/doi.org\/10.3390\/medicina60111817","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,5]]}}}