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

doi:10.1016/j.ijcard.2014.10.031

International Journal of Cardiology

Volume 179, 20 January 2015, Pages 97-104

https://doi.org/10.1016/j.ijcard.2014.10.031 Get rights and content

Highlights

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Multi-centre randomized controlled trial
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Children and young adults with corrected tetralogy of Fallot or Fontan circulation
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A 12 week standardized aerobic dynamic exercise training program
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Ventricular parameters, cardiac dimensions and neurohormonal markers did not change.
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No adverse cardiac remodelling occurred.

Abstract

Background

Exercise can improve physical fitness in children and adults with congenital heart disease. We hypothesized that exercise training would not lead to adverse cardiac remodelling in this population.

Methods and results

This multi-centre randomized controlled trial included children and young adults (10 to 25 years) with either corrected tetralogy of Fallot or Fontan circulation. The exercise-group was enrolled in a 12 week standardized aerobic dynamic exercise training program. The control-group continued their life-style and received care as usual. Both groups underwent cardiopulmonary exercise testing, cardiac magnetic resonance imaging (MRI), echocardiography and neurohormonal assessment, within 2 weeks before and 2 weeks after the intervention period. Fifty-six patients were randomized to the exercise-group and 37 to the control-group. We assessed changes between the pre- and the post-intervention period for the exercise group compared to the changes in the control-group. Peak load increased significantly in the exercise-group compared to the control-group (exercise-group 6.9 ± 11.8 W; control-group 0.8 ± 13.9 W; p = 0.047). There were no adverse events linked to the study. Ventricular systolic parameters, cardiac dimensions and neurohormonal markers during follow-up did not change in patients allocated to the exercise-group and control-group. Although there were some isolated minor changes in inflow parameters, there was no consistent pattern of changes, indicating a lack of true change in the diastolic function.

Conclusion

We demonstrated that no clinically relevant adverse cardiac remodelling occurred after 12 weeks of exercise training in patients with either corrected tetralogy of Fallot or Fontan circulation.

Clinical trial registration: www.trialregister.nl, identification NTR2731.

Introduction

The long-term prognosis for patients with congenital heart disease (ConHD) has increased considerably in recent years. However, reduced exercise performance and increased risk of cardiovascular diseases are common problems facing this population [1]. Current public-health guidelines state that exercise has to be performed and encouraged even in patients with ConHD [2], [3]. However, many patients with ConHD do not exercise, partly out of fear and from overprotection of peers and parents [4]. In addition, practitioners taking care of these patients may be reluctant to advise physical exercise. Limited knowledge on adverse cardiac events during exercise as well as the effect of exercise on cardiac remodelling in these patients may hamper executing these public-health guidelines [5].

Cardiac size and function may change by exercise. In healthy individuals, including children, exercise results in enhancement of function and adaptive hypertrophy (physiological cardiac remodelling) [6], [7], [8]. It is currently unknown if exercise in patients with ConHD will also result in physiological cardiac remodelling or in adverse cardiac remodelling, the latter resulting in an enlarged heart with decreased cardiac function [6], [7].

Various studies have evaluated the effects of exercise training in adolescents and young adults with ConHD. While most of these studies demonstrated that exercise performance can be improved in patients with ConHD, effects on cardiac remodelling have hardly been studied [9].

Patients with tetralogy of Fallot and with a Fontan circulation are amongst those with the highest chance of developing heart failure [1]. Thus these patients may be considered candidates to benefit most from exercise training, but at the same time may be at the highest risk for adverse remodelling in response to exercise training.

Therefore, we aimed to assess the effects of a 12 week standardized aerobic dynamic exercise training program on cardiac remodelling in children and young adults with corrected tetralogy of Fallot (ToF patients) and with Fontan circulation (Fontan patients). We hypothesized that exercise training would not lead to clinically relevant adverse cardiac remodelling.

Section snippets

Design

A multi-centre prospective, randomized controlled trial was conducted in 5 tertiary referral centres for ConHD in The Netherlands (Academic Medical Centre in Amsterdam, Leiden University Medical Centre in Leiden, Erasmus MC-Sophia in Rotterdam, Radboud University Nijmegen Medical Centre in Nijmegen and University MC Utrecht-Wilhelmina Children's Hospital in Utrecht). The study was designed according to Consolidated Standards of Reporting Trials (CONSORT) guidelines [10].

Participants

Eligible were

Patient characteristics

Three hundred and sixty-two patients were contacted to participate in this study. Age and age at ToF repair or completion of Fontan circulation did not significantly differ between participants and those that declined to participate. Ninety-three patients were randomized to either the exercise or the control-group. Three patients in the exercise-group dropped out, due to the demanding study design (Fig. 1, flow chart). Patient characteristics of the 90 participants did not differ between the

Discussion

Our study shows that no clinically relevant adverse remodelling occurs after aerobic dynamic exercise training in patients after surgical correction of tetralogy of Fallot or with a Fontan circulation. No adverse event directly linked to the exercise training program occurred in our study. To the best of our knowledge this is the first study demonstrating these favourable outcomes in congenital heart patients with important loading abnormalities of the heart.

The findings of our study put the

Conclusions

We demonstrated that no clinically relevant adverse cardiac remodelling occurred after 12 week exercise training in children and young adult patients with either a corrected tetralogy of Fallot or a Fontan circulation.

Conflict of interest

No conflict of interest.

Acknowledgments

The authors thank Drs S den Boer, Drs G Weijers, Dr E.Friesema and Mrs M de Waart.

References (34)

K. Norozi et al.
Incidence and risk distribution of heart failure in adolescents and adults with congenital heart disease after cardiac surgery
Am. J. Cardiol.
(2006)
P.E. Longmuir et al.
Physical activity restrictions for children after the Fontan operation: disagreement between parent, cardiologist, and medical record reports
Am. Heart J.
(2009)
J.N. Cohn et al.
Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling
J. Am. Coll. Cardiol.
(2000)
A. La Gerche et al.
Athlete's heart: the potential for multimodality imaging to address the critical remaining questions
JACC Cardiovasc. Imaging
(2009)
S. Sharma et al.
Physiologic limits of left ventricular hypertrophy in elite junior athletes: relevance to differential diagnosis of athlete's heart and hypertrophic cardiomyopathy
J. Am. Coll. Cardiol.
(2002)
N. Duppen et al.
Systematic review of the effects of physical exercise training programmes in children and young adults with congenital heart disease
Int. J. Cardiol.
(2013)
D. Robbers-Visser et al.
Safety and observer variability of cardiac magnetic resonance imaging combined with low-dose dobutamine stress-testing in patients with complex congenital heart disease
Int. J. Cardiol.
(2011)
W.W. Lai et al.
Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography
J. Am. Soc. Echocardiogr.
(2006)
M.J. Haykowsky 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)
R.S. Taylor et al.
Effects of exercise training for heart failure with preserved ejection fraction: a systematic review and meta-analysis of comparative studies
Int. J. Cardiol.
(2012)

R.L. Cordina et al.

Resistance training improves cardiac output, exercise capacity and tolerance to positive airway pressure in Fontan physiology

Int. J. Cardiol.

(2013)

C. Passino et al.

Aerobic training decreases B-type natriuretic peptide expression and adrenergic activation in patients with heart failure

J. Am. Coll. Cardiol.

(2006)

M. Cantinotti et al.

Nomograms for blood flow and tissue Doppler velocities to evaluate diastolic function in children: a critical review

J. Am. Soc. Echocardiogr.

(2013)

A. Hirth et al.

Recommendations for participation in competitive and leisure sports in patients with congenital heart disease: a consensus document

Eur. J. Cardiovasc. Prev. Rehabil.

(2006)

T. Takken et al.

Recommendations for physical activity, recreation sport, and exercise training in paediatric patients with congenital heart disease: a report from the Exercise, Basic & Translational Research Section of the European Association of Cardiovascular Prevention and Rehabilitation, the European Congenital Heart and Lung Exercise Group, and the Association for European Paediatric Cardiology

Eur. J. Cardiovasc. Prev. Rehabil.

(2012)

T. Reybrouck et al.

Physical performance and physical activity in grown-up congenital heart disease

Eur. J. Cardiovasc. Prev. Rehabil.

(2005)

K.F. Schulz et al.

CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials

BMJ

(2010)

Cited by (36)

Stress imaging in patients with a Fontan circulation: A systematic review
2023, International Journal of Cardiology
The aims of this study were to provide an overview of the cardiac stress response in Fontan patients and of the use, safety and clinical value of stress imaging in Fontan patients.
Studies evaluating cardiac function using stress imaging in Fontan patients published up until 12 December 2021 were included in this review.
From 1603 potential studies, 32 studies met the inclusion criteria. In total, stress imaging tests of 728 Fontan patients were included. Cardiac function was most often measured using physical stress (61%), all other studies used dobutamine-induced stress.
Stroke volume (SV) increased in most studies (71%), mean SV at rest ranged from 27 mL/m² to 60 mL/m² versus 27 mL/m² to 101 mL/m² during stress, and increased with an average of 4%. Ejection fraction increased in almost all studies, whereas both end-systolic volume and end-diastolic volume decreased during stress. Higher heart rates were obtained with physical stress (82–180) compared to dobutamine induced stress (73–128). Compared to controls, increases in heartrate and SV were lower and end-diastolic volume decreased abnormally in 75% of reporting studies. No major adverse events were reported. Poorer cardiac stress response was related to decreased exercise capacity and higher risk for long-term (adverse) outcomes in Fontan patients.
Cardiac stress response in Fontan patients differs from healthy subjects, reflected by lower increases in heart rate, diminished preload and decreased cardiac output, especially during higher levels of exercise. Stress imaging is safe, however the added clinical value needs to be investigated in more detail.
Exploring the Promise of Telemedicine Exercise Interventions in Children and Adolescents With Congenital Heart Disease
2023, Canadian Journal of Cardiology
Youth with congenital heart disease (CHD) have reduced exercise capacity via various physical and psychosocial mechanisms. In addition to limited physiologic exercise capacity, these patients experience lower levels of physical activity, physical activity self-efficacy, health-related quality of life, and endothelial function. The study of exercise interventions and cardiac rehabilitation programs in pediatric CHD populations remains limited, particularly home-based interventions that incorporate real-time physiologic monitoring. Home-based interventions provide improved access and convenience to patients. This is principally important for patients from geographically disperse regions who receive their care at centralized subspecialty centres, as is the case for Canadian pediatric cardiac care. These programs, however, have traditionally not permitted the supervision of safety, technique, and adherence that are afforded by hospital/facility-based programs. As such, telemedicine is an important evolving area that combines the benefits of traditional home and facility-based cardiac rehabilitation. An additional key area lacking study surrounds the types of exercise interventions in youth with CHD. To date, interventions have often centred around moderate-intensity continuous exercise. High-intensity interval training might offer superior cardiorespiratory advantages but remains understudied in the CHD population. In this review, we highlight the existing evidence basis for exercise interventions in youth with CHD, explore the promise of incorporating telemedicine home-based solutions, and highlight key knowledge gaps. To address identified knowledge gaps, we are undertaking a 12-week randomized crossover trial of a home-based telemedicine high-intensity interval training intervention in youth with repaired moderate-severe CHD using a video game-linked cycle ergometer (known as the MedBIKE; https://spaces.facsci.ualberta.ca/ahci/projects/medical-projects/remote-rehab-bike-projects).
La capacité d’effort des jeunes atteints de cardiopathie congénitale est réduite par divers mécanismes physiques et psychosociaux. En plus de leur capacité d’effort physiologique limitée, ces patients ont des niveaux réduits d’activité physique, de connaissance de leurs propres capacités en matière d’activité physique, de qualité de vie liée à la santé et de fonction endothéliale. L’étude des interventions axées sur l’activité physique et des programmes de réadaptation cardiaque chez les populations pédiatriques atteintes de cardiopathie congénitale demeure limitée, particulièrement en ce qui a trait aux interventions à domicile qui intègrent une surveillance physiologique en temps réel. Les interventions à domicile offrent aux patients un accès et une commodité améliorés. C’est d’autant plus important pour les patients vivant dans des régions éloignées qui reçoivent leurs soins dans des établissements centralisés sous-spécialisés, comme c’est le cas pour les soins cardiaques des enfants au Canada. Ces programmes n’offrent toutefois pas la possibilité de surveiller l’innocuité, la technique et l’observance thérapeutiques, ce que permettent les programmes offerts dans un hôpital ou en établissement. À ce titre, la télémédecine est un important domaine en évolution qui associe les bienfaits de la réadaptation cardiaque classique à domicile à ceux offerts en établissement. Les types d’interventions axées sur l’activité physique chez les jeunes atteints d’une cardiopathie congénitale représentent un autre domaine pour lequel les études sont insuffisantes. Jusqu’à ce jour, les interventions sont souvent axées sur l’activité physique continue d’intensité modérée. L’entraînement par intervalles à haute intensité peut offrir des bienfaits cardiorespiratoires supérieurs, mais demeure sous-étudié dans la population des patients atteints de cardiopathie congénitale. Dans cet examen, nous indiquons les données probantes existantes sur lesquelles se fondent les interventions axées sur l’activité physique pour les jeunes atteints de cardiopathie congénitale, nous explorons les promesses de l’intégration de solutions à domicile offertes par la télémédecine et nous soulignons les lacunes en matière de connaissances. Afin de recenser ces lacunes, nous entreprenons un essai avec permutation d’une durée de 12 semaines d’une intervention à domicile d’entraînement par intervalles à haute intensité offerte par l’intermédiaire de la télémédecine aux jeunes atteints d’une cardiopathie congénitale modérée ou grave réparée, au moyen d’un ergocycle lié à un jeu vidéo (MedBike : https://spaces.facsci.ualberta.ca/ahci/projects/medical-projects/remote-rehab-bike-projects).
Safety and efficacy of exercise training in children and adolescents with congenital heart disease: A systematic review and descriptive analysis
2022, American Heart Journal
Citation Excerpt :
Of the 6 trials, 4 reported on the incidence of adverse events.38,41,43,44 Of the trials that did document adverse events, the only incident was a Fontan participant who experienced a collapse whilst walking on the street 1 month after starting the training program.38 The authors reported: ‘Further investigation did not clarify the reason for collapsing’.
While exercise training is beneficial in the prevention and management of many chronic diseases, the role of exercise training in children and adolescents with congenital heart disease is less understood. We sought to determine the safety and efficacy of exercise training in children and adolescents with congenital heart disease.
We conducted a systematic search of the following databases: PubMed, CINAHL, EMBASE, Web of Science and SportDiscus. We included randomised controlled trials that incorporated an exercise intervention compared with a non-exercising comparator group and examined safety and efficacy in children and adolescents with congenital heart disease. A descriptive analysis of the included trials was then conducted.
A total of 9 articles from 6 trials (642 participants with varying conditions and disease severity) were included. Significant variability of study participants and outcomes were observed across the trials. No adverse events linked to the exercise interventions were stated. The articles reported numerous positive changes to clinically relevant fitness measures. Exercise capacity improved with exercise training in 3 of 4 trials in which it was measured. Cardiorespiratory fitness showed improvements in 3 of 4 trials. Neuromuscular fitness increased in 1 of 2 trials. Physiological and metabolic parameters were improved, and negative changes were not observed to several clinically important measures (e.g. muscular oxygenation, cardiac measures) in 2 of 2 trials. Physical activity increased in 1 of 3 trials. No articles reported on changes in measures of body composition. Outcomes are varied with little consensus on measurements or assessment methods.
Exercise training appears to be safe and efficacious for improving physical fitness in children and adolescents with congenital heart disease who have been appropriately screened by their medical team. However, the certainty of the evidence for these findings is low to moderate.
Comparative Costs of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot
2022, Journal of the American College of Cardiology
Citation Excerpt :
It is important to acknowledge that mortality, major adverse events, reintervention, and cost are not the only relevant clinical outcomes, nor are they a comprehensive assessment of functional status. For instance, neurodevelopment,28,29 cardiopulmonary exercise performance,30-32 and health-related quality of life33 are all diminished in cohorts of repaired TOF patients. The impact of PR or SR on these important outcomes in this vulnerable cohort is not incorporated into this analysis.
Recent data have demonstrated that overall mortality and adverse events are not significantly different for primary repair (PR) and staged repair (SR) approaches to management of neonates with symptomatic tetralogy of Fallot (sTOF). Cost data can be used to compare the relative value (cost for similar outcomes) of these approaches and are a potentially more sensitive measure of morbidity.
This study sought to compare the economic costs associated with PR and SR in neonates with sTOF.
Data from a multicenter retrospective cohort study of neonates with sTOF were merged with administrative data to compare total costs and cost per day alive over the first 18 months of life in a propensity score–adjusted analysis. A secondary analysis evaluated differences in department-level costs.
In total, 324 subjects from 6 centers from January 2011 to November 2017 were studied (40% PR). The 18-month cumulative mortality (P = 0.18), procedural complications (P = 0.10), hospital complications (P = 0.94), and reinterventions (P = 0.22) did not differ between PR and SR. Total 18-month costs for PR (median $179,494 [IQR: $121,760-$310,721]) were less than for SR (median: $222,799 [IQR: $167,581-$327,113]) (P < 0.001). Cost per day alive (P = 0.005) and department-level costs were also all lower for PR. In propensity score–adjusted analyses, PR was associated with lower total cost (cost ratio: 0.73; P < 0.001) and lower department-level costs.
In this multicenter study of neonates with sTOF, PR was associated with lower costs. Given similar overall mortality between treatment strategies, this finding suggests that PR provides superior value.
Barriers to completion of a novel pediatric cardiac rehabilitation program
2021, Progress in Pediatric Cardiology
Pediatric cardiac rehabilitation addresses physical and emotional challenges related to underlying heart disease. While the benefits of cardiac rehabilitation have largely been established, the challenges that patients and their families experience when participating in these programs have yet to be examined in detail. In this study, we evaluated the barriers that families face when asked to complete a structured cardiac rehabilitation program.
The objectives of this study were to measure the success of a novel pediatric cardiac rehabilitation program and to evaluate the barriers that families face when asked to complete a structured cardiac rehabilitation program.
Parents of patients referred for cardiac rehabilitation and who attended at least one session were recruited to participate in a phone survey regarding their experience using a published psychometric validation of the cardiac rehabilitation barriers scale.
9 families participated in the study. 67% of patients were male and 3 patients completed the program in its entirety. Challenges associated with time, travel, and insufficient insurance coverage, were the highest rated barriers to completion of the rehabilitation program. Families universally enjoyed the program. 5 of 9 felt that the biggest positive of the experience was gaining an understanding of what exercise is safe. 3 of 9 stated that cardiac rehabilitation should be a standard component of therapy for all pediatric cardiology patients.
Pediatric cardiac rehabilitation is effective and liked by families. The barriers to completing a structured in-person program are difficulty getting to appointments due to time and travel and level of insurance coverage for the program. As such, ensuring insurance coverage and perhaps virtual rehab programs would be beneficial.
Negative Impact of Obesity on Ventricular Size and Function and Exercise Performance in Children and Adolescents With Repaired Tetralogy of Fallot
2020, Canadian Journal of Cardiology
Up to 25% of children with congenital heart disease are obese, which may have negative physiologic consequences for patients with repaired tetralogy of Fallot (rTOF).
Patients with rTOF who underwent cardiac magnetic resonance (CMR) imaging and cardiopulmonary exercise testing from 2007 to 2018 were reviewed. Complex rTOF patients were excluded. Obese patients (body mass index [BMI] ≥ 95th percentile) were compared with normal-weight patients (BMI < 85th percentile). CMR data were indexed to actual body surface area (aBSA), height, and BSA assuming ideal body weight (iBSA).
We compared 32 obese patients matched with 64 normal-weight patients. Obese vs normal-weight patients had significantly lower right (RV; median 45% [interquartile range 42%-48%] vs 52% [47%-55%]; P < 0.0001) and left (LV; 52% [47%-56%] vs 56% [54%-60%]; P < 0.0001) ventricular ejection fractions (EFs). There were no statistically significant differences regarding aBSA-indexed volumes of the RV or LV at either end-diastole (EDV) or end-systole (ESV). However, when indexed to either height or iBSA, obese patients had significantly greater RVEDV and LVEDV, greater LV mass, and higher RV and LV stroke volumes. Obese patients had lower peak oxygen consumption and oxygen consumption at anaerobic threshold. These results did not change after adjusting for degree of pulmonary regurgitation.
Obesity is associated with increased biventricular size, decreased biventricular EFs, and impaired exercise performance after rTOF. These data suggest a potential role for cardiac rehabilitation for weight management and to optimize fitness.
Jusqu'à 25 % des enfants atteints de cardiopathie congénitale sont obèses, ce qui peut avoir des conséquences physiologiques néfastes pour les patients atteints de tétralogie de Fallot réparée (rTOF pour repaired tetralogy of Fallot).
Les patients atteints de rTOF qui ont subi une résonance magnétique cardiaque (RMC) et des tests d'effort cardiopulmonaire de 2007 à 2018 ont été examinés. Les patients ayant subi une rTOF complexe ont été exclus. Les patients obèses (indice de masse corporelle [IMC] ≥ 95^e percentile) ont été comparés aux patients de poids normal (IMC < 85^e percentile). Les données de RMC ont été indexées en fonction de la surface corporelle avérée (aBSA pour actual body surface area), de la taille et de la surface corporelle en supposant un poids corporel idéal (iBSA pour ideal body surface area).
Nous avons comparé 32 patients obèses à 64 patients de poids normal. Par rapport aux patients de poids normal, les patients obèses avaient des fractions d'éjection (FE) ventriculaire droite (VD) et gauche (VG) significativement plus faibles [FE ventriculaire droite (FEVD) 45 % (écart interquartile 42-48) contre 52 % (47-55), P < 0.0001; et FEVG 52 % (47-56) contre 56 % (54-60), P < 0.0001, respectivement]. Aucune différence statistiquement significative n'a été constatée concernant les volumes du VD ou du VG indexés sur l'aBSA, que ce soit en fin de diastole (VFD) ou en fin de systole. Cependant, lorsqu'ils étaient indexés sur la taille ou sur l'iBSA, les patients obèses présentaient des VFD-VD et VFD-VG significativement plus élevés, une masse du VG plus importante et des volumes systoliques du VD et du VG plus élevés. Les patients obèses présentaient une consommation maximale d'oxygène plus faible et une consommation d'oxygène au seuil anaérobie réduite. Ces résultats n'ont pas varié après ajustement en fonction du degré d’insuffisance pulmonaire.
L'obésité est associée à une augmentation de la taille des deux ventricules, à une diminution de la FE des deux ventricules et à une diminution des performances à l'effort après un rTOF. Ces données suggèrent un rôle potentiel de la réadaptation cardiaque pour la gestion du poids et pour une optimisation de la condition physique.

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^☆: Funding: this study was sponsored by a research grant from the Netherlands Heart Foundation (grant 2008B026) and by the Stichting Rotterdams Kinderrevalidatie Fonds Adriaanstichting (2006/0106).

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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☆

Highlights

Abstract

Background

Methods and results

Conclusion

Introduction

Section snippets

Design

Participants

Patient characteristics

Discussion

Conclusions

Conflict of interest

Acknowledgments

Am. J. Cardiol.

Am. Heart J.

J. Am. Coll. Cardiol.

JACC Cardiovasc. Imaging

J. Am. Coll. Cardiol.

Int. J. Cardiol.

Int. J. Cardiol.

J. Am. Soc. Echocardiogr.

J. Am. Coll. Cardiol.

Int. J. Cardiol.

Int. J. Cardiol.

J. Am. Coll. Cardiol.

J. Am. Soc. Echocardiogr.

Recommendations for participation in competitive and leisure sports in patients with congenital heart disease: a consensus document

Eur. J. Cardiovasc. Prev. Rehabil.

Eur. J. Cardiovasc. Prev. Rehabil.

Physical performance and physical activity in grown-up congenital heart disease

Eur. J. Cardiovasc. Prev. Rehabil.

CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials

BMJ