Physical activity interventions for people with congenital heart disease

Abstract

Background
Congenital heart disease (ConHD) affects approximately 1% of all live births. People with ConHD are living longer due to improved medical intervention and are at risk of developing non‐communicable diseases. Cardiorespiratory fitness (CRF) is reduced in people with ConHD, who deteriorate faster compared to healthy people. CRF is known to be prognostic of future mortality and morbidity: it is therefore important to assess the evidence base on physical activity interventions in this population to inform decision making.

Objectives
To assess the effectiveness and safety of all types of physical activity interventions versus standard care in individuals with congenital heart disease.

Search methods
We undertook a systematic search on 23 September 2019 of the following databases: CENTRAL, MEDLINE, Embase, CINAHL, AMED, BIOSIS Citation Index, Web of Science Core Collection, LILACS and DARE. We also searched ClinicalTrials.gov and we reviewed the reference lists of relevant systematic reviews.

Selection criteria
We included randomised controlled trials (RCT) that compared any type of physical activity intervention against a 'no physical activity' (usual care) control. We included all individuals with a diagnosis of congenital heart disease, regardless of age or previous medical interventions.

Data collection and analysis
Two review authors (CAW and CW) independently screened all the identified references for inclusion. We retrieved and read all full papers; and we contacted study authors if we needed any further information. The same two independent reviewers who extracted the data then processed the included papers, assessed their risk of bias using RoB 2 and assessed the certainty of the evidence using the GRADE approach. The primary outcomes were: maximal cardiorespiratory fitness (CRF) assessed by peak oxygen consumption; health‐related quality of life (HRQoL) determined by a validated questionnaire; and device‐worn ‘objective’ measures of physical activity.

Main results
We included 15 RCTs with 924 participants in the review. The median intervention length/follow‐up length was 12 weeks (12 to 26 interquartile range (IQR)). There were five RCTs of children and adolescents (n = 500) and 10 adult RCTs (n = 424). We identified three types of intervention: physical activity promotion; exercise training; and inspiratory muscle training. We assessed the risk of bias of results for CRF as either being of some concern (n = 12) or at a high risk of bias (n = 2), due to a failure to blind intervention staff. One study did not report this outcome. Using the GRADE method, we assessed the certainty of evidence as moderate to very low across measured outcomes.

When we pooled all types of interventions (physical activity promotion, exercise training and inspiratory muscle training), compared to a 'no exercise' control CRF may slightly increase, with a mean difference (MD) of 1.89 mL/kg−1/min−1 (95% CI −0.22 to 3.99; n = 732; moderate‐certainty evidence). The evidence is very uncertain about the effect of physical activity and exercise interventions on HRQoL. There was a standardised mean difference (SMD) of 0.76 (95% CI −0.13 to 1.65; n = 163; very low certainty evidence) in HRQoL. However, we could pool only three studies in a meta‐analysis, due to different ways of reporting. Only one study out of eight showed a positive effect on HRQoL. There may be a small improvement in mean daily physical activity (PA) (SMD 0.38, 95% CI −0.15 to 0.92; n = 328; low‐certainty evidence), which equates to approximately an additional 10 minutes of physical activity daily (95% CI −2.50 to 22.20).

Physical activity and exercise interventions likely result in an increase in submaximal cardiorespiratory fitness (MD 2.05, 95% CI 0.05 to 4.05; n = 179; moderate‐certainty evidence). Physical activity and exercise interventions likely increase muscular strength (MD 17.13, 95% CI 3.45 to 30.81; n = 18; moderate‐certainty evidence). Eleven studies (n = 501) reported on the outcome of adverse events (73% of total studies). Of the 11 studies, six studies reported zero adverse events. Five studies reported a total of 11 adverse events; 36% of adverse events were cardiac related (n = 4); there were, however, no serious adverse events related to the interventions or reported fatalities (moderate‐certainty evidence). No studies reported hospital admissions.

Authors' conclusions
This review summarises the latest evidence on CRF, HRQoL and PA. Although there were only small improvements in CRF and PA, and small to no improvements in HRQoL, there were no reported serious adverse events related to the interventions. Although these data are promising, there is currently insufficient evidence to definitively determine the impact of physical activity interventions in ConHD. Further high‐quality randomised controlled trials are therefore needed, utilising a longer duration of follow‐up.

Full text

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Cochrane Database of Systematic Reviews
Physical activity interventions for people with congenital heart
disease (Review)

Williams CA, Wadey C, Pieles G, Stuart G, Taylor RS, Long L 
WilliamsCA, WadeyC, PielesG, StuartG, TaylorRS, LongL.
Physical activity interventions for people with congenital heart disease.
Cochrane Database of Systematic Reviews 2020, Issue 10. Art. No.: CD013400.
DOI: 10.1002/14651858.CD013400.pub2.
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Physical activity interventions for people with congenital heart disease (Review)
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T A B L E  O F  C O N T E N T S
HEADER......................................................................................................................................................................................................... 1
ABSTRACT..................................................................................................................................................................................................... 1
PLAIN LANGUAGE SUMMARY....................................................................................................................................................................... 2
SUMMARY OF FINDINGS.............................................................................................................................................................................. 3
BACKGROUND.............................................................................................................................................................................................. 5
OBJECTIVES.................................................................................................................................................................................................. 5
METHODS..................................................................................................................................................................................................... 6
Figure 1.................................................................................................................................................................................................. 8
RESULTS........................................................................................................................................................................................................ 11
Figure 2.................................................................................................................................................................................................. 12
Figure 3.................................................................................................................................................................................................. 13
Figure 4.................................................................................................................................................................................................. 13
Figure 5.................................................................................................................................................................................................. 14
Figure 6.................................................................................................................................................................................................. 14
Figure 7.................................................................................................................................................................................................. 15
Figure 8.................................................................................................................................................................................................. 16
DISCUSSION.................................................................................................................................................................................................. 17
AUTHORS' CONCLUSIONS........................................................................................................................................................................... 19
ACKNOWLEDGEMENTS................................................................................................................................................................................ 19
REFERENCES................................................................................................................................................................................................ 20
CHARACTERISTICS OF STUDIES.................................................................................................................................................................. 29
RISK OF BIAS................................................................................................................................................................................................ 63
DATA AND ANALYSES.................................................................................................................................................................................... 67
Analysis 1.1. Comparison 1: Physical activity promotion, exercise training and inspiratory muscle training interventions versus
no activity (usual care) in people with congenital heart disease, Outcome 1: Maximal cardiorespiratory fitness..........................
68
Analysis 1.2. Comparison 1: Physical activity promotion, exercise training and inspiratory muscle training interventions versus
no activity (usual care) in people with congenital heart disease, Outcome 2: Health-related quality of life...................................
69
Analysis 1.3. Comparison 1: Physical activity promotion, exercise training and inspiratory muscle training interventions versus
no activity (usual care) in people with congenital heart disease, Outcome 3: Physical activity (device-worn)...............................
69
Analysis 1.4. Comparison 1: Physical activity promotion, exercise training and inspiratory muscle training interventions versus
no activity (usual care) in people with congenital heart disease, Outcome 4: Submaximal cardiorespiratory fitness (gas
exchange threshold).............................................................................................................................................................................
69
Analysis 1.5. Comparison 1: Physical activity promotion, exercise training and inspiratory muscle training interventions versus
no activity (usual care) in people with congenital heart disease, Outcome 5: Muscular strength...................................................
70
Analysis 1.6. Comparison 1: Physical activity promotion, exercise training and inspiratory muscle training interventions versus
no activity (usual care) in people with congenital heart disease, Outcome 6: Maximal cardiorespiratory fitness (type of ConHD
subgroup analysis)................................................................................................................................................................................
70
ADDITIONAL TABLES.................................................................................................................................................................................... 70
APPENDICES................................................................................................................................................................................................. 78
HISTORY........................................................................................................................................................................................................ 86
CONTRIBUTIONS OF AUTHORS................................................................................................................................................................... 86
DECLARATIONS OF INTEREST..................................................................................................................................................................... 86
SOURCES OF SUPPORT............................................................................................................................................................................... 87
DIFFERENCES BETWEEN PROTOCOL AND REVIEW.................................................................................................................................... 87
NOTES........................................................................................................................................................................................................... 87
Physical activity interventions for people with congenital heart disease (Review)
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[Intervention Review]
Physical activity interventions for people with congenital heart disease
Craig A Williams1, Curtis Wadey1, Guido Pieles2, Graham Stuart2, Rod S Taylor3, Linda Long4
1Children's Health and Exercise Research Centre, University of Exeter, Exeter, UK. 2National Institute for Health Research (NIHR)
Cardiovascular Biomedical Research Centre, Bristol Heart Institute, Bristol, UK. 3MRC/CSO Social and Public Health Sciences Unit &
Robertson Centre for Biostatistics, Institute of Health and Well Being, University of Glasgow, Glasgow, UK. 4Institute of Health Research,
University of Exeter Medical School, Exeter, UK
Contact address: Craig A Williams, c.a.williams@exeter.ac.uk.
Editorial group: Cochrane Heart Group.
Publication status and date: New, published in Issue 10, 2020.
Citation: WilliamsCA, WadeyC, PielesG, StuartG, TaylorRS, LongL. Physical activity interventions for people with congenital heart
disease. Cochrane Database of Systematic Reviews 2020, Issue 10. Art. No.: CD013400. DOI: 10.1002/14651858.CD013400.pub2.
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Congenital heart disease (ConHD) aectsapproximately 1% of all live births. People with ConHD are living longer due to improved
medical intervention and are at risk of developing non-communicable diseases. Cardiorespiratory fitness (CRF) is reduced in people
with ConHD, who deterioratefaster compared to healthy people. CRF is known to be prognostic of future mortality and morbidity:
itisthereforeimportant to assess the evidence base on physical activity interventions in this population to inform decision making.
Objectives
To assess the eectiveness and safety of all types of physical activity interventions versusstandard carein individuals with congenital
heart disease.
Search methods
We undertook asystematicsearch on23September 2019 of the following databases: CENTRAL,MEDLINE, Embase,CINAHL, AMED, BIOSIS
Citation Index,Web of Science Core Collection, LILACS andDARE. We also searched ClinicalTrials.gov and wereviewed the reference lists
of relevant systematic reviews.
Selection criteria
We included randomised controlled trials (RCT) that compared any type of physical activity intervention against a 'no physical
activity' (usual care) control. We included all individualswith a diagnosis ofcongenital heart disease, regardless of age or previous medical
interventions.
Data collection and analysis
Two review authors (CAW and CW)independently screened all the identified references for inclusion. We retrieved and read all full papers;
and we contacted study authors if we needed any further information. The same two independent reviewers who extracted the data
thenprocessed the included papers, assessed their risk of bias using RoB 2and assessed the certainty of the evidence using the GRADE
approach.The primary outcomes were: maximal cardiorespiratory fitness (CRF) assessed by peak oxygen consumption; health-related
quality of life (HRQoL) determined by a validated questionnaire; and device-worn ‘objective’ measures of physical activity.
Main results
We included 15RCTs with 924participants in the review. The median intervention length/follow-up length was 12 weeks (12 to 26
interquartile range (IQR)).There were five RCTs of children and adolescents (n = 500) and 10 adult RCTs (n = 424). We identified three types
of intervention: physical activity promotion; exercise training; and inspiratory muscle training. We assessed the risk of bias of results for
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CRF as either being of some concern (n = 12) or ata high risk of bias (n=2), due to afailure to blindintervention sta. One study did not
report this outcome. Using the GRADE method, we assessed the certainty of evidence as moderate to very low across measured outcomes.
When we pooled all types of interventions (physical activity promotion, exercise training and inspiratory muscle training), compared to a
'noexercise' controlCRF may slightly increase, with amean dierence (MD) of 1.89 mL/kg−1/min−1 (95% CI −0.22 to3.99; n = 732; moderate-
certainty evidence).The evidence is very uncertain about the eect of physical activity and exercise interventions on HRQoL. There was a
standardised mean dierence (SMD) of 0.76(95% CI −0.13 to 1.65;n = 163; very low certainty evidence) in HRQoL. However, we could pool
only threestudies in a meta-analysis, due to dierent ways of reporting. Only one study out of eight showed a positive eect on HRQoL.
There may be a small improvement in mean daily physical activity (PA) (SMD 0.38,95% CI −0.15 to0.92; n = 328; low-certainty evidence),
which equates toapproximately an additional 10 minutes of physical activity daily (95% CI −2.50 to22.20).
Physical activity and exercise interventions likely result in an increase in submaximal cardiorespiratory fitness (MD 2.05, 95% CI 0.05 to
4.05; n = 179; moderate-certainty evidence). Physical activity and exercise interventions likely increase muscular strength (MD 17.13, 95%
CI 3.45 to 30.81; n = 18; moderate-certainty evidence).Eleven studies (n = 501) reported on the outcome of adverse events (73% of total
studies). Of the 11 studies, sixstudies reported zeroadverse events. Fivestudies reported a total of 11 adverse events; 36% of adverse events
were cardiac related(n= 4); there were, however, no serious adverse eventsrelated to the interventions or reportedfatalities (moderate-
certainty evidence).No studies reported hospital admissions.
Authors' conclusions
This review summarises the latest evidence on CRF, HRQoL and PA. Although there were only small improvements in CRF and PA, and
small to noimprovements in HRQoL, there were no reported seriousadverse events related to the interventions. Although these data are
promising, there is currentlyinsuicient evidence to definitively determine the impact of physical activityinterventions in ConHD. Further
high-quality randomised controlled trials are therefore needed, utilisinga longer duration of follow-up.
P L A I N  L A N G U A G E  S U M M A R Y
Physical activity interventions for people with congenital heart disease
Review question
This review aimed to gather evidence for the use of any physical activity intervention for people with congenital heart disease. We aimed
to compare interventions including exercise training, physical activity promotion or lung training with no intervention (usual care).
Background
Congenital heart disease is the term used for a range of birthdefects that aect howthe heart works. People with congenital heart disease
have reduced life expectancy, physicalfitness and quality of life. However, due to better prenatal diagnoses, surgical procedures (oen
performed in the early years of life) and earlier interventions, the survival rate for those born with this disease has improved dramatically,
such that most people will now live into adulthood. Exercise training and physical activity interventions are known to improve fitness,
physical activity, survival and quality of life in healthy people, but it is not clear how eective these programmes are for people with long-
term medical conditions.
Study characteristics
We searched for studies in September 2019 and identified 15 studies involving 924 participants. The studies used three main types of
interventions, including programmes designed to increase physical activity, aerobic fitness and health-related quality of life and compared
physical activity intervention and control interventions in people with congenital heart disease.
Key results
We included 15 trials with 924participants. Half of the participants were female. Of the 15 trials,5 used a total of 500 young people (less
than 18 years of age)and10 trials used a total of 424 adult participants.We found that physical fitness and physical activity may slightly
increasebut we are very uncertain about quality of life. There is currently no data to say if this small increase in fitness will result in fewer
visits to the hospital. But there were no recorded deaths or serious events that were related to participation in physical activity.
Quality of evidence
Using a validated scientific approach (GRADE), the certainty in the evidence base was moderate for fitness, low for physical activity and
very low forquality of life.Most outcomes were limited due to small study participant numbers and poor reporting of study details.
Physical activity interventions for people with congenital heart disease (Review)
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S U M M A R Y  O F  F I N D I N G S

Summary of findings 1.  Summary of findings for the main comparison. Physical activity and exercise interventions compared to usual care for
people with congenital heart disease.
Patient or population: people with congenital heart disease.
Setting: hospital-based and home-based settings.
Intervention: physical activity promotion, inspiratory muscle training and exercise training interventions.
Comparison: usual care.
Anticipated absolute effects* (95% CI)Outcomes
Length of intervention in weeks
(Median, (IQR)) Risk with usual
care

Risk with allinterventions

No. of par-
ticipants
(studies)
Certain-
ty of the
evidence
(GRADE)
Comments
Maximal cardiorespiratory fitness
(CRF)
Assessed with: treadmill or cycle
ergometry
(12 (12, 26))
Mean 22to 46 MD 1.89 higher (0.22 lower
to 3.99 higher)
732
(14RCTs
(15 training
arms))
⊕⊕⊕⊝ab
MODERATE
Physical activity and exercise interventions may in-
crease cardiorespiratory fitness slightly. Sensitivity
analyses did not change the inference to a clinical-
ly important MD.
Health-related quality of life
(HRQoL)Assessed with: Question-
naires
(12 (12, 12))
-SMD 0.76 higher (0.13 low-
er to 1.65 higher)
163 (3 RCTs) ⊕⊝⊝⊝cde
VERY LOW
The evidence is very uncertain about the effect
of physical activity and exercise interventions on
health-related quality of life.
Physical activity (PA)
Assessed with: Accelerometer
(19 (12, 46))
Mean 11to 41 SMD 0.38
(0.15 lower to 0.92 higher)
328(4RCTs) ⊕⊕⊝⊝ce
LOW
Physical activity and exercise interventions may in-
crease physical activity slightly.
Submaximal cardiorespiratory fit-
ness
Assessed with: VO2mL.kg.min at
the gas exchange threshold.
(12 (12, 15))
Mean 18to 22 MD 2.05 (0.05 higher to 4.05
higher)
179(5RCTs
(6 training
arms))
⊕⊕⊕⊝e
MODERATE
Physical activity and exercise interventions likely
results in an increase in submaximal cardiorespira-
tory fitness.
Muscular strength Mean 103 MD 17.13 (3.45 higher to
30.81 higher)
18 (1RCT) ⊕⊕⊕⊝e
MODERATE
Physical activity and exercise interventions likely
increases muscular strength.
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(12) 
Adverse events
(12 (12, 26))
A total of 11 adverse events were reported in a
population of 501 (2.2%), 7 of which were mild
(1.4%). Mild adverse events included dizziness,
discomfort, musculoskeletal (strains/ sprains)
and a minor head injury. The 4 (0.8%) moder-
ate adverse events were cardiac. There were no
major adverse events reported.
501(11RCTs) ⊕⊕⊕⊝f
MODERATE
Physical activity promotion and exercise training
interventions did not lead to any serious adverse
events.
Hospital admissions No data available
CI: confidence interval; IQR: 25th and 75th quartiles; MD: mean difference; SMD: standardised mean difference; RCT: randomised controlled trial;CRF: Cardiorespiratory fit-
ness; HRQoL: Health-related quality of life. The mean SMD effect size was interpreted using Cohen effect sizes, i.e. 0.2 represents a small effect, 0.5 a moderate effect, and
0.8 a large effect.
GRADE Working Group grades of evidence.
High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is
substantially different.
Low certainty: our confidence in the effect estimate is limited;the true effect may be substantially different from the estimate of the effect.
Very low certainty: we have very little confidence in the effect estimate;the true effect is likely to be substantially different from the estimate of effect.
a Statistical heterogeneity was present in CRF(I2 = 75%). But it was explained using asensitivity analysisby excluding high risk of bias studies (I2 = 18%). Therefore, we chose
not to downgrade by 1 level evidence due to inconsistency.
bThe confidence interval includesboth appreciable harm and appreciable benefit (i.e. 95% CI spans 0).Therefore, the certainty of evidence was downgraded by 1 leveldue to
imprecision.
cInconsistent directions of eect and considerable heterogeneity (HRQoL, I2 = 82%; PA, I2 = 77%). Therefore, the certainty of evidence was downgraded by 1 level due to
inconsistency.
dTotal high risk of bias in all studies included within the analysis, hence bias highly likely. Therefore, the certainty of evidence was downgraded by 2 levels due to the
methodological limitations (risk of bias).
eImprecise due to small numbers of events (< 400) (Ryan 2016). Therefore, the certainty of evidence was downgraded by 1leveldue to imprecision.
fOver 25% of studies did not report data on adverse events.Therefore, the certainty of evidence was downgraded by 1 leveldue to publication bias.

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B A C K G R O U N D
Description of the condition
Congenital heart disease (ConHD) is a term for a range of
developmental abnormalities of the heart or intrathoracic vessels,
or both (Mitchell 1971).There are over 18 distinct types of ConHD,
ranging in complexity (Rhodes 2008; Sommer 2008a; Sommer
2008b), that can be broadly classified as mild, moderate or
severe (Homan 2002). During the period 2010 to 2017 the birth
prevalence of ConHD is approximately 1% of all live births (9.41 per
1000 births; 95% confidence interval (CI)8.60 to 10.25), with the
mild conditions representing65% (95% CI58.7% to 71.7%) of the
total ConHD births (Liu2019).
Long-term survival is reduced in ConHD, but due to improved
medical care this has improved dramatically over previous
decades. The most recent meta-analysis reported that survival
up to the age of 10 years was 81.4% (95% CI 73.80 to
87.90); however, 87.0% of the between-article variance can be
accounted for by the year of the study (Best 2016). Consequently,
survival up to the age of 10 years of age has increased from 75%
to 90% over the past two decadesdue to improvements in surgical
correction, prenatal diagnosis and earlier interventions (Best 2016).
ConHD is therefore a changing chronic medical condition with the
highest proportion of deaths now occurring in geriatrics (Khairy
2010).
In both healthy and clinical (coronary heart disease)
populations, impaired physical activity (PA) and cardiorespiratory
fitness (CRF) are associated with the development of non-
communicabledisease,morbidityand mortality(Franklin 2013;Lee
2012; Letnes 2019). People with ConHD have reduced levels
of fitness (Amedro 2017); reduced health-related quality of life
(HRQoL) (Amedro 2015); and are less physically active (Brudy
2020; Dua 2007; McCrindle 2007; Sandberg 2016). Fitness has
also been heavily associated with future health outcomes in
this population (Dimopoulos 2006; Giardini 2009; Müller
2015;Udholm2018). It is crucial, therefore, that people with ConHD
lead an active lifestyle, butthere is currently no consensus on how
best to improve PA,CRFand HRQoL in people with ConHD.
Description of the intervention
Physical activity consists of any bodily movement involving
skeletal muscles that results in increased energy expenditure,
whereas exercise training is a planned and structured period
of PA with the intention of maintaining or improving physical
fitness components (Caspersen 1985). The current guidelines for
PAare an average of 60 minutes of moderate to vigorous physical
activity (MVPA) a day for young people (< 18 years old) and
150 minutes of MVPA a week in adults (Department of Health
2011). Currently within specialist paediatric cardiac clinics physical
activityrecommendations arenot adequately discussed due to a
lack of training, time and knowledge of the current exercise
recommendations for people with ConHD (Williams 2017).
Interventions that aim to improve CRF, PA and HRQoL typically
consist of a PA promotion (goal setting, motivational interviews
etc.), or exercise training (aerobic/resistance training, sports
participation etc.), or a combination of both. PA promotion
interventions aim to increase habitual PA behaviours by
using psychologicalconceptual frameworks in orderto promote
self-eicacy, goal-settingandintrinsic motivation. Exercise training
interventions, on the other hand, usually prescribe a set 'dose' of
exercise either within a hospital, centre or at home. Inspiratory
muscle training (IMT) is a newmethod of intervention, recently
gaining popularity in people with chronic cardiorespiratory
conditionsand aiming to improveventilatory power and eiciency.
IMT is distinctly dierent from PA promotion and exercise training
as it involves training the inspiratory chest muscles against a
breathing resistance by using a handheld device.
How the intervention might work
The 'gold standard' measure of cardiorespiratory fitness is maximal
oxygen consumption, which is explained by the Fick equation
where oxygen uptake is the product of the cardiac output and the
arteriovenous oxygen dierence( VO2= Q * a- VO2 di ). Improving
cardiorespiratory fitness must target improving oxygen delivery
(Q) and/or oxygen extraction at the peripheral sites (a- VO2 di)
of the body, namely the muscles. PA and exercise training are
known to improve both cardiac output and oxygen extraction
through complex molecular interactions improving myocardial
contractility, mitochondrial activity, stem cell proliferation, nitric
oxide bioavailability and muscle fibre adaptations (Adams
2017; Gielen 2010). There is evidence that supports inspiratory
muscle training to improve ventilatory eiciency and fitness
in people with chronic cardiorespiratory pathologies and
in healthy people, but the adaptation mechanisms are not well
understood(Shei2018;Wong 2011). It is proposed that the increase
in ventilatory eiciency is due to a combination of factors, inclusive
of, but not limited to, changing motor recruitment 'diaphragm
sparing' and the release of inflammatory cytokines (Shei2018).
Why it is important to do this review
Cardiorespiratory fitness is lower in people with ConHD and
deterioratesfaster compared to healthy people (Amedro 2017). This
has significant implications as CRFhas been associated withfuture
mortality and morbidity in several ConHD conditions (Dimopoulos
2006; Giardini 2009; Müller 2015;Udholm 2018). Currently, there
is a dearth of evidence to adequately inform the eectiveness
of interventions to improve CRF and consequently long-term
outcomes.
Recent reviews have included both non-randomised and
randomised controlled trials (RCTs), focused on specific types of
interventions (e.g. home-based) or have restricted to particular
age groups (Gomes-Neto 2016; Li 2019; Meyer 2020). Therefore,
we present thefirst Cochrane Review to assess the eectiveness
of all types of physical activity interventions and inclusive of all
age groups, usingonly RCT data in people with ConHD.We hope
by conducting this review that we can provide clarity on the
eectiveness of physical activity interventions, highlight future
avenues for research andinform future healthcare policy.
O B J E C T I V E S
To assess the eectiveness and safety of all types of physical activity
interventions versusstandard carein individuals with congenital
heart disease.
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M E T H O D S
Criteria for considering studies for this review
Types of studies
We planned to include all types of randomised controlled trial
(RCT), inclusive of but not limited to parallel, cross-over andcluster
designs. We included only parallel and randomised cross-over
designs: these trials compared all types of physical activity
interventionsto a 'no physical activity/no exercise' comparator. We
included trials irrespective of their duration of follow-up.
Types of participants
We included all individualswith a diagnosis ofConHD,who were
deemed suitable for participation in a physical activity orexercise
training intervention. We included all types of congenital heart
disease, regardless of previous medical care and categorisedthem
as mild, moderate or severe (Homan 2002). We also included
paediatric (5 to 18 years old) and adult populations (> 18 years old).
Types of interventions
We identified and included three types of intervention: physical
activity (PA) promotion; exercise training; and inspiratory muscle
training (IMT). PA promotion studies incorporated psychological
components to promote and educate participants on the
benefits of exercise, whereasexercise training studies 'prescribed'
exercise at a set dose either in a hospital or in a home-
based setting. IMT was not an anticipated intervention type
at the protocol phase; we included it due to its increasing
use in clinical care (Pufulete 2019). Furthermore, we included
interventions whether they were structured versus unstructured,
supervised versusunsupervised, home versushospital and single
versus multicomponent. All interventions were compared to 'no
physical activity/physical activity as usual' control; and both the
intervention and control group received usual medical care.
Types of outcome measures
Studies should have intended to assess any of the outcomes in
both the intervention and the control groups. At the protocol phase
we intended toextractoutcomes at two time points:at the end of
intervention and atlong-term follow-up (> 12 months). Due to the
lack of long-term follow-up data, we only extracted the data at the
end of the intervention. We sought to report the following primary
and secondary outcomes, but they did not form the basis of our
inclusion/exclusion criteria.
Primary outcomes
•Maximal cardiorespiratory fitness (CRF)
•Health-related quality of life determined by a validated
questionnaire
•Device-worn ‘objective’ measures of physical activity
Secondary outcomes
•Submaximal CRF
•Validated questionnaire-based ‘subjective’ measures of physical
activity
•Return to work or full-time education
•Hospital admissions
•Muscular strength determined by:
*grip strength
*isokinetic testing
*muscular endurance capacity
•Adverse events
We anticipated there would be substantial variability in the
reported outcome measures and we approached the primary
outcomesas follows.
Cardiorespiratory fitness (CRF)
We pooled peak oxygen consumption (peak VO) measured
in millilitres per kilogram per minute (mL.kg−1.min−1) as
our measure of maximal CRF. Peak VO2 was assessed by
validated cardiopulmonary exercise test protocols, measuring
oxygen consumption directly or indirectly (by estimated oxygen
consumption), using either a treadmill or cycle ergometer. The
submaximalCRF outcome was oxygen consumption per kilogram
of body mass ( VO2 mL.kg−1.min−1) at the gas exchange threshold
(GET).
Health-related quality of life (HRQoL)
As anticipated there was large variability in the HRQoL scales
used;we pooled HRQoL data in a meta-analysis where appropriate
and reported all HRQoLin Table 1and summarised in text.
Device-worn measures of physical activity
Physical activity was measured by accelerometryonly. We pooled
data regardless of device (Actigraph GT3X, Actigraph GT1M), device
settings (epoch ranged 5 to 60 seconds) and activity parameter
measured (time spent in MVPAper day as a percentage (n = 1) and
minutes spent in MVPA per day) as per the protocol. There were no
heart rate data to analyse.and activity parameter measured (time
spent in MVPAper day as a percentage (n = 1) and minutes spent in
MVPA per day) as per the protocol. There were no heart rate data to
analyse.
Search methods for identification of studies
Electronic searches
We undertook asystematicsearch of the following databases on 23
September 2019.
•CENTRAL in the Cochrane Library (Issue 9 of 12, 2019)
•Epub Ahead of Print, In-Process & Other Non-Indexed Citations,
MEDLINE Daily and MEDLINE (Ovid, 1946 to 19 September 2019)
•Embase (Ovid, 1980 to 2019 week 38)
•Cumulative Index to Nursing and Allied Health Literature
(CINAHL) (EBSCOHost, 1937 to 23 September2019)
•Allied and Complementary Medicine Database (AMED) (Ovid,
1985 to September 2019)
•BIOSIS Citation Index (Clarivate Analytics, 1926 to 23 September
2019)
•Web of Science Core Collection (Clarivate Analytics, 1900 to 23
September 2019)
•Latin American and Caribbean Health Sciences Literature
(LILACS) (Bireme, 1982 to 23 September 2019)
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•DARE (NIHR Centre for Reviews and Dissemination
www.crd.york.ac.uk, from inception to 31 March 2015 (when this
databasestopped adding records)).
We applied the Cochrane sensitivity-maximising RCT filter for
MEDLINE and for Embaseterms as recommended in the Cochrane
Handbook for Systematic Reviews of Interventions (Lefebvre
2011; Higgins 2011).For CINAHL, we used the Cochrane CINAHL
RCT filter (Glanville2019). For all other databases, except CENTRAL,
LILACS and DARE, we applied an adaptation of the Cochrane RCT
filter. SeeAppendix 1for the search strategies.
Searching other resources
We searched ClinicalTrials.gov on 11 September 2020 for ongoing
or unpublished trials.
We also searched by hand the reference list of relevant reviews,
randomised and non-randomised studies, and editorials for
additional studies. We contactedauthors of studies and experts in
the field to ask for any missed, unreported or ongoing trials. We
also searched for any retraction statements and errata for included
studies.
Data collection and analysis
Selection of studies
Two review authors (CAW and CW)independently screened titles
and abstracts for inclusion from all the potential trials we
identifiedfrom the searches. Wethen sourced full texts and both
review authors (CAW and CW)independently read them to confirm
eligibility; in the event of exclusion, we documented the reasons.
This was facilitated byCovidencesystematic review soware. Two
authors (LL and RST) arbitrated if any disagreements arose that
could not be rectified through discussion,. We have recorded
the selection process with a PRISMA flow diagram (Figure 1)
andCharacteristics of excluded studies(Liberati 2009).

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Figure 1.  Study flow diagram


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Figure 1.  (Continued)

Data extraction and management
Two authors (CAW and CW)independently piloted a data collection
form and independently extracted outcome data from included
studies. One review author (CW) transferred data intoRevMan Web
2019; and CAW checked that the data was entered correctly.
We extracted the following study characteristics.
•Participants: N randomised, N lost to follow-up, N analysed,
mean age (± standard deviation), gender, severity of
condition*,inclusion criteria, and exclusion criteria.
•Methods: study design, total duration of study, study setting,
date of study, withdrawals, number of study centres and
location.
•Interventions: intervention description (including the
frequency, intensity, duration and modalityof the intervention),
comparison, and co-interventions.
•Outcomes: primary and secondary outcomes specified and
collected, and time points reported.
•Notes: funding for trial, and notable conflicts of interest of trial
authors.
*As ConHD is an incredibly varied and complex disease we have
classified the severity of the condition using the Homan 2002
criteria as ‘mild’, ‘moderate’ or ‘severe’ (see Appendix 2 for further
information). We have chosen the Homan classification as it is
very inclusive and does not bias against individual intra-diagnosis
dierences; it has since been adopted in the most recent guidelines
from the US Task Force for adult congenital heart disease (Warnes
2008). We have used these criteria to describe the study data (to aid
the reader); we have not used it forsubgroup analyses.
Assessment of risk of bias in included studies
Two review authors (CAW and CW) independently assessed risk
of bias for each study using the recently revised 'Risk of bias in
randomised trials (RoB 2)' tool (accessed: 28 January 2020) (Higgins
2019).
We assessed risk of bias for each study outcome using the following
Cochrane RoB 2criteria (Higgins 2019).
•Bias arising from the randomisation process
•Bias due to deviations from intended interventions
•Bias due to missing outcome data
•Bias in measurement of the outcome
•Bias in selection of the reported result
For each domain a series of signalling questions with the answers
(yes, probably yes, no information, probably no, no) determine the
risk of bias (low risk, some concerns and high risk). We includedtext
alongside the judgements to provide supporting information for
our decisions (see Risk of bias in included studies). We decided
the risk of bias for an outcome (e.g. health-related quality of life
(HRQoL)) by its performance in each domain: if we judged one
domain 'some concerns' or 'high risk' this judgement was taken
for the whole outcome. We assessed the risk of bias of maximal
and submaximal cardiorespiratory fitness (CRF), HRQoL, physical
activity (PA) and muscular strength at follow-up. The eect of
assignmentor 'intention to treat' was oureect of interest and we
have summarised the risk of bias intraic lights on the forest plots,
inTable 1for HRQoL and in text.
Measures of treatment eect
We analysed continuous data as mean dierence with 95%
confidence intervals (CIs). Where an outcome was measured and
reported in more than one way, we report a standardised mean
dierence (SMD) with 95% CIs. We interpreted the SMD using the
two approaches recommended in the Handbook (Schünemann
2017). First, we interpreted the mean SMD eect size using the
following rule of thumb based on Cohen eect sizes (i.e. 0.2
represents a small eect, 0.5 a moderate eect, and 0.8 a large
eect) (Faraone 2008). In addition, for physical activity data we
have converted the SMD back to the original scale units (minutes
of moderate to vigorous activity) by multiplying the pooled mean
SMD by an among-person standard deviation for a particular trial
(Opotowsky 2018).We have corrected for any dierences in the
direction of the scales forHRQoL (i.e. when some scales have a
lower score for a better QoL, a reduction in score would indicate an
improvement, whereas a scale that awards higher scores for better
QoL would see an increase in score indicating a positive outcome).
We included HRQoL data in the meta-analysis only if it was the
overall or total HRQoL score. For the outcome 'adverse events'
where there was a dichotomous variable(event or no event), we
analysed this using count data and summarised in text. Where
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data were skewed and reported as medians and interquartile
ranges, we converted them to means and standard deviations using
validatedequations (Wan 2014).
Unit of analysis issues
We only identified studies with individual randomisation. Only
one study presented long-term follow-up data (Winter 2012); in
this instance we extracted data at the end of the intervention
to keep consistency with all the other trials. One trialcontained
threearm:continuous exercise training;interval exercise training;
and a control group (Novakovic 2018). In this case we divided
the number randomised to the control group in half to obtain
the denominator for data analysis; the means and standard
deviation for the control group remained unchanged for both
comparisons.One study had a randomised cross-over design, but
only contributed data prior to the cross-over (Fritz 2020); it was
therefore not necessary to consider awashout period.
Dealing with missing data
We contacted multiple authors to verify key study characteristics
(such as randomisation), clarify data queries and obtain
missing numerical outcome data. Where data were presented
graphicallyand we were unable to obtain numerical data from the
authors, we used WebPlotDigitizerto extract this information.
Assessment of heterogeneity
We explored heterogeneity amongst included studies qualitatively
(through visual inspection of forest plots and by comparing the
characteristics of included studies), and quantitatively (using the
Chi test of heterogeneity and the I statistic). Weused a threshold
of I greater than 50% to represent substantial heterogeneity for
continuous outcomes(Deeks 2017).
Assessment of reporting biases
We were able to pool more than 10 studies in our primary outcome
'maximal cardiorespiratory fitness'.We subsequently created and
examined a funnel plot and used the Egger test to explore possible
small-study biases for thisprimary outcome(Egger 1997).
Data synthesis
We performed meta-analyses with 95% CIs including all
available studies where appropriate (i.e. when treatments,
participants, and the underlying clinical question were similar
enough for pooling to be appropriate). We used random-eects
meta-analyses for all analyses due to the qualitative (types
of interventions and severities of ConHD) and quantitative
(statistical) heterogeneity present. Evidence of substantial
heterogeneity was confirmed using the I2 statistic of more
than50%, giving further justification for a random-eects analysis.
Random eects provides a more conservative statistical approach,
as the confidence interval around a random-eects estimate is
wider than a confidence interval around a fixed-eect estimate
(Heran 2008a; Heran 2008b). Where an outcome was measured and
reported in more than one way, we report a standardised mean
dierence (SMD) with 95% CI.
Weprocessed data in accordance with guidance in the Handbook
(Higgins 2011). We completed data synthesis and analyses using
RevMan Web soware (RevMan Web 2019); and we conducted
meta-regression analysis using the “metareg” command in Stata
version 14.2 (Stata 2015 [Computer program]). We created
additional figures using GraphPad(GraphPadPrism).
We could not pool some HRQoL. In this instance we adopted
a modified version of a vote counting table, allowing us to
summarise descriptive data, risk of bias and the direction of
eect.Whilstthis synthesis without meta-analysis (SWiM) method
has significantlimitations, we believe it to be the only SWiM method
that allows us to communicate the results in a transparent and
concise format (Campbell 2020).
Subgroup analysis and investigation of heterogeneity
We split the outcome 'maximal cardiorespiratory fitness' into two
subgroup analyses:Analysis 1.1 reports the eect of the type of
physical activity intervention (i.e. PA promotion, exercise training
and inspiratory muscle training (IMT); andAnalysis 1.6 reportsthe
eect of the intervention in each group of ConHD (i.e. single
ventricle, tetralogy of Fallot and other/mixed ConHD).
 We used meta-regression to assess the potential treatment
eect modifiers from all interventions (PA promotion, exercise
training and IMT) on maximal cardiorespiratory fitness. Due to the
limited number of studies to co-variate ratio we limited the meta-
regression to univariate analysis only (Higgins 2011). The meta-
regression included the followingco-variates.
•Type of intervention (PA promotion or exercise training or IMT
(categorical variable)).
•‘Dose’ of exercise intervention (dose = number of weeks of
exercise training × average number of sessions/week × average
duration of session in minutes)(continuous variable).
•Length of intervention/follow-up period (continuous variable).
•Sample size (continuous variable).
•Setting (home- or centre-based) (categorical variable).
•Study location (North America or Europe or Asia) (categorical
variable).
•Age of participants (paediatrics or adults) (categorical variable).
•Percentage of male participants (continuous variable).
•Baseline cardiorespiratory fitness (continuous variable).
•Risk of bias (categorical variable).
Due to the lack of data, we pooled all individual ConHD
lesions (Table 2). This has limitations due to the within-condition
and between-condition heterogeneity in clinical status (Amedro
2017;Kempny 2012).We therefore used pre-intervention (baseline)
cardiorespiratory fitness as a meta-regression covariate to account
for the heterogeneity.
Sensitivity analysis
We performed the following sensitivity analyses for the outcome
of maximal cardiorespiratory fitness: removal of high risk of bias
studies; direct versus indirect methods of measuring/estimating
peak VO2; the use of a fixed-eect model;insertion of all available
change scores; and the removal of computed outcome scores
(converting medians and interquartile ranges to means± standard
deviations).We did not perform sensitivity analyses for the other
outcomes within the review, due to the lack of studies included in
the respective outcomes and the similarity of the studies pooled.
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Summary of findings and assessment of the certainty of the
evidence
Wecreated the ‘Summary of findings 1' usingRevMan Web 2019and
reported the following outcomes: maximal cardiorespiratory
fitness (CRF), health-related quality of life (HRQoL), device-worn
‘objective’ measures of physical activity (PA), submaximal CRF,
muscular strength, and adverse events.
Two reviewers (CAW & CW) independently conducted GRADE
analysis using GRADEpro GDT. Where disagreements arose, we
asked co-authors (LL & RST) to arbitrate. We used GRADE to
assess the certainty of the available evidence, helping to inform
decisions based on this evidence (Schünemann 2017). We used
the five GRADE considerations (study limitations, consistency of
eect, imprecision, indirectness, and publication bias) to assess
the quality of the body of evidence, as it relates to the studies
that contribute data to the meta-analyses for the prespecified
outcomes.We justified all decisions to downgrade the quality of
studies using footnotes.
Weused methods and recommendations described in Section 8.5
and Chapter 12 of the Cochrane Handbook for Systematic Reviews of
Interventions using GRADEpro soware (Higgins 2011). Long-term
follow-up (> 12 months) post intervention was our follow-up period
of most interest. However, as only one study reported long-term
follow-up, we only report short-term follow-up (immediately post
intervention) in the 'Summary of findings' table.
R E S U L T S
Description of studies
See:Characteristics of included studies; Characteristics of excluded
studies; Characteristics of ongoing studies; Characteristics of
studies awaiting classification.
Results of the search
We identified 3806 references through our electronic and manual
searches. Aer de-duplication and title and abstract screening, we
retrieved 124 references. Aer screening the full text, we identified
15 RCTs from 39references (see Figure 1).Searching of the reference
lists of eligible publications did not reveal additional publications
for inclusion.
We contacted 18 corresponding authors for further information
regarding study inclusion.When we could not reach the authors, we
includedthese studies (n = 5) in theStudies awaiting classification
table.
Included studies
Population
We included 15RCTswith 924participants(50% ± 12% male) in the
review. There were five paediatric RCTs and 10adult RCTs with 500
participants and424 participants respectively. All paediatric RCTs
were based in Europe, whereas adult trials were based in Europe
(n = 6), North America (n = 3) and Asia (n = 1). There were 11 RCTs
that included severe classification participants(n = 559);three RCTs
that pooled mild, moderate and severe classifications (n = 254);
and one RCT that included mild classification participants only (n =
111).Table 2reports the individualConHDlesionsthat we pooled
into the meta-analyses.
Intervention
We identified three distinct types of interventions:exercise training
(n = 11); physical activity promotion (n = 3); and inspiratory
muscle training (IMT)(n = 1). SeeTable 3for the characteristicsof
exercise training trials. Physical activity promotion aims were
varied: Morrison 2013 and Klausen 2016 used motivational
techniques (interviewing and goal setting vs. text 'e-based'
encouragement) to improve physical activity and fitness in children
and adolescents; whereas another intervention used a family-
based psychological intervention with a subcomponent of physical
activity promotion with the aim of improving HRQoL, time/
behaviourin school and sports enjoyment in young children (van
der Mheen 2019).The only IMT study included within the review
aimed to assess the eicacy of IMT in adults with severe ConHD
(Fontan circulations). The intervention was a randomised cross-
over design using a commercially available inspiratory muscle
trainer. The participants completing three sets of 10 to 30
repetitions every day for six months, the intensity could beadjusted
from 10 cm H2O to 90 cm H2O and was individualised for every
training session to maintain an optimal training eect (Fritz 2020).
Comparison
All studies compared to usual care for their region. Only one study
had three arms: two intervention arms (interval and continuous
training) and a control arm (Novakovic 2018).
Primary Outcomes
Maximal cardiorespiratory fitness (CRF) was measured in 14 out
of 15 (93.3%) studies.Health-related quality of life(HRQoL) was
reported in8 out of 15 (53.3%) studies, using a variety of validated
questionnaires summarised inTable 1. Device-worn measures of
physical activity wasreported by four (26.6%) studies, using a range
of accelerometers, cutpoints and parameters such as time spent
as a percentage in moderate to very vigorous activity, average
minutes of moderate to vigorous activity (MVPA) andtotal minutes
per day spent in MVPA assessed using accelerometer cut-points
greater than 2000 counts (Duppen 2015; Klausen 2016; Morrison
2013; Opotowsky 2018). No study used disease-specific cut points.
Secondary Outcomes
Only one study numerically reported questionnaire-basedphysical
activity (Duppen 2015). Klausen 2016 used questionnaires in
combination with device-worn measures but did not report
the questionnaire data as it reported similar results. No study
measured return to work or full-time education. One study reported
episodes o school for one or more days, however(van der Mheen
2019). No study reported on hospital admissions.Submaximal CRF
was reported in a variety of ways: the most commonly reported
was the oxygen consumption at the gas exchange threshold
(GET) scaled to body mass (mL.kg−1.min− 1) (n = 5 studies) and
the ventilatory equivalents ( VE) over volume of carbon dioxide
production ( VE/ VCO2 slope) (n = 4 studies) (Avila 2016; Duppen
2015; Fritz 2020; Moalla 2006; Novakovic 2018; Opotowsky 2018; van
Dissel 2019; Westho-Bleck 2013). Absolute oxygen consumption
at the GET (mL.min−1), power output in watts at the GET, VE at
the GET, heart rate at the GET and the oxygen uptake eiciency
slope were all reported once. Muscular strength was only reported
by one study using isokinetic testing (Moalla 2006); and adverse
events were reported by 11 studies, independent of whether an
adverse event actually took place (Avila 2016; Duppen 2015; Fritz
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2020; Klausen 2016; Novakovic 2018; Opotowsky 2018; Sandberg
2018; Therrien 2003; van Dissel 2019; Westho-Bleck 2013; Winter
2012).
Excluded studies
We excluded 85 references during the full-text review, amongst
which were 32 due to wrong study design, 15 because they
are ongoing trials and 8 because they included the wrong
patient population. For more regarding exclusions see Figure
1andCharacteristics of excluded studies.
Risk of bias in included studies
Risk of bias assessmentsfor each outcome, including all domain
judgements and support for judgement, is located in the Risk
of bias section (located aer the Characteristics of included
studies),atthe side of all forest plots andinTable 1for HRQoL.To
access further detailed risk of bias assessmentdata, please use the
following link(doi.org/10.24378/exe.2363).
Risk of bias of outcomes across all studies was similar
and predominately of 'some concerns'. Study authors reported
poorly
the details of blinding outcome assessors (patient-facing
members of sta conducting the outcome assessments, i.e. the
person conducting the exercise test or questionnaire) and pre-
agreedstatistical analysis plans with suicient detail.
Across most outcomes risk of bias was similar: we judged it as
'some concerns'. The only exception was HRQoL which we judged
to be at high risk of bias due to the nature of self-reported
questionnaires, the lack of blinding of the participants and other
outcome assessors.
Eects of interventions
See: Summary of findings 1 Summary of findings for the main
comparison. Physical activity and exercise interventions compared
to usual care for people with congenital heart disease.
See Summary of findings 1 and forest plots(Figure 2, Figure 3,
Figure 4, Figure 5, Figure 6).

Figure 2.  Physical activity promotion, exercise training and inspiratory muscle training interventions versus no
activity (usual care) in people with congenital heart disease. Outcome: Maximal cardiorespiratory fitness( ̇VO2
mL.kg-1.min-1at maximal exercise).
Study or Subgroup
1.1.1 Exercise training
Therrien 2003
Moalla 2006
Madhavi 2011
Winter 2012
Westhoff-Bleck 2013
Duppen 2015
Avila 2016
Novakovic 2018 (1)
Opotowsky 2018
Sandberg 2018
Novakovic 2018 (2)
van Dissel 2019
Subtotal (95% CI)
Heterogeneity: Tau² = 10.92; Chi² = 40.79, df = 11 (P < 0.0001); I² = 73%
Test for overall effect: Z = 2.26 (P = 0.02)
1.1.2 Physical activity promotion
Morrison 2013
Klausen 2016
Subtotal (95% CI)
Heterogeneity: Tau² = 1.68; Chi² = 1.60, df = 1 (P = 0.21); I² = 37%
Test for overall effect: Z = 1.14 (P = 0.25)
1.1.3 Inspiratory muscle training
Fritz 2020
Subtotal (95% CI)
Heterogeneity: Not applicable
Test for overall effect: Z = 0.25 (P = 0.80)
Total (95% CI)
Heterogeneity: Tau² = 11.06; Chi² = 55.03, df = 14 (P < 0.00001); I² = 75%
Test for overall effect: Z = 1.76 (P = 0.08)
Test for subgroup differences: Chi² = 5.34, df = 2 (P = 0.07), I² = 62.5%
Physical activity
Mean [mL/kg/min]
24.3
33
43.84
29
25.9
35.9
28.6
26.5
1
25.1
24
25.4
37.4
43.2
24
SD [mL/kg/min]
8.2
6.2
10.33
7
6.1
7.4
7.1
12.5
1.5
6.16
6.2
6.6
8.8
9.7
8.3
Total
9
10
51
24
19
43
13
9
13
13
9
17
230
62
81
143
18
18
391
No activity (usual care)
Mean [mL/kg/min]
22.1
29.6
30.99
26
23.5
34.2
28.5
23.3
-1.2
24.03
23.3
27.7
37.5
46.3
23.3
SD [mL/kg/min]
6.5
7.2
7.96
8
5.3
8.6
6.01
8.5
2.3
3.33
8.5
5.6
8.6
10.1
9.1
Total
8
8
61
22
21
30
4
5
15
10
4
17
205
39
77
116
20
20
341
Weight
4.8%
5.4%
8.1%
7.2%
8.0%
7.8%
4.8%
2.7%
9.9%
7.6%
3.5%
7.4%
77.3%
8.1%
8.5%
16.6%
6.1%
6.1%
100.0%
Mean Difference
IV, Random, 95% CI [mL/kg/min]
2.20 [-4.80 , 9.20]
3.40 [-2.90 , 9.70]
12.85 [9.38 , 16.32]
3.00 [-1.36 , 7.36]
2.40 [-1.16 , 5.96]
1.70 [-2.09 , 5.49]
0.10 [-6.94 , 7.14]
3.20 [-7.85 , 14.25]
2.20 [0.78 , 3.62]
1.07 [-2.86 , 5.00]
0.70 [-8.56 , 9.96]
-2.30 [-6.41 , 1.81]
2.74 [0.36 , 5.12]
-0.10 [-3.58 , 3.38]
-3.10 [-6.19 , -0.01]
-1.71 [-4.64 , 1.22]
0.70 [-4.83 , 6.23]
0.70 [-4.83 , 6.23]
1.89 [-0.22 , 3.99]
Mean Difference
IV, Random, 95% CI [mL/kg/min]
-10 -5 0 5 10
Favours no activity (usual care) Favours physical activity
Risk of Bias
A
-
?
-
?
?
+
+
+
+
+
+
?
?
+
?
B
+
+
?
+
+
+
+
+
+
+
+
+
+
+
+
C
+
+
-
?
?
+
+
+
+
+
+
?
?
?
+
D
?
?
-
?
?
?
?
?
?
+
?
?
?
+
?
E
?
?
?
?
?
?
?
?
?
?
?
?
?
+
?
F
-
?
-
?
?
?
?
?
?
?
?
?
?
?
?
Footnotes
(1) interval training arm
(2) continuous training arm
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions: Cardiorespiratory fitness
(C) Bias due to missing outcome data: Cardiorespiratory fitness
(D) Bias in measurement of the outcome: Cardiorespiratory fitness
(E) Bias in selection of the reported result: Cardiorespiratory fitness
(F) Overall bias: Cardiorespiratory fitness


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Figure 3.  Exercise training versus no activity (usual care) in people with congenital heart disease. Outcome: Health
related quality of life.
Study or Subgroup
Madhavi 2011 (1)
Opotowsky 2018 (2)
Sandberg 2018 (3)
Total (95% CI)
Heterogeneity: Tau² = 0.50; Chi² = 10.87, df = 2 (P = 0.004); I² = 82%
Test for overall effect: Z = 1.67 (P = 0.09)
Test for subgroup differences: Not applicable
Physical activity
Mean
72.28
-20.1
76.2
SD
8.071
11.4
15.2
Total
51
13
13
77
No activity (usual care)
Mean
57.93
-27.7
76.3
SD
11.019
10.9
20.7
Total
61
15
10
86
Weight
37.9%
31.6%
30.5%
100.0%
Std. Mean Difference
IV, Random, 95% CI
1.46 [1.04 , 1.88]
0.66 [-0.10 , 1.43]
-0.01 [-0.83 , 0.82]
0.76 [-0.13 , 1.65]
Std. Mean Difference
IV, Random, 95% CI
-4 -2 0 2 4
Favours no activity (usual care) Favours physical activity
Risk of Bias
A
-
+
+
B
?
+
+
C
-
+
+
D
-
-
-
E
?
?
?
F
-
-
-
Footnotes
(1) SF-36 (total score)
(2) MLHFQ
(3) EQ5D VAS
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions: Health-related quality of life
(C) Bias due to missing outcome data: Health-related quality of life
(D) Bias in measurement of the outcome: Health-related quality of life
(E) Bias in selection of the reported result: Health-related quality of life
(F) Overall bias: Health-related quality of life


Figure 4.  Physical activity promotion andexercise training interventions versus no activity (usual care) in people
with congenital heart disease. Outcome: Physical activity (device-worn).
Study or Subgroup
Duppen 2015 (1)
Klausen 2016
Morrison 2013
Opotowsky 2018
Total (95% CI)
Heterogeneity: Tau² = 0.22; Chi² = 13.81, df = 3 (P = 0.003); I² = 78%
Test for overall effect: Z = 1.42 (P = 0.16)
Test for subgroup differences: Not applicable
Physical activity
Mean
12.7
40.3
57.2
103
SD
8.1
21.8
32.2
56
Total
28
81
62
11
182
No activity (usual care)
Mean
11.8
41.3
29.2
75
SD
6.2
22.9
27.3
25
Total
18
77
39
12
146
Weight
23.7%
30.2%
27.8%
18.3%
100.0%
Std. Mean Difference
IV, Random, 95% CI
0.12 [-0.47 , 0.71]
-0.04 [-0.36 , 0.27]
0.91 [0.49 , 1.33]
0.63 [-0.21 , 1.47]
0.38 [-0.15 , 0.92]
Std. Mean Difference
IV, Random, 95% CI
-2 -1 0 1 2
Favours no activity (usual care) Favours physical activity
Risk of Bias
A
+
+
?
+
B
+
+
+
+
C
+
?
?
+
D
?
+
?
?
E
?
+
?
?
F
?
?
?
?
Footnotes
(1) Measure of activity: time spent in moderate-to-very-vigorous activity as a percentage. All other studies report minutes of MVPA per day.
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions: Physical activity (device-worn)
(C) Bias due to missing outcome data: Physical activity (device-worn)
(D) Bias in measurement of the outcome: Physical activity (device-worn)
(E) Bias in selection of the reported result: Physical activity (device-worn)
(F) Overall bias: Physical activity (device-worn)


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Figure 5.  Exercise traininginterventions versus no activity (usual care) in people with congenital heart disease..
Outcome: Sub-maximal cardiorespiratory fitness ( ̇VO2 mL.kg-1.min-1at the gas exchange threshold).
Study or Subgroup
Moalla 2006
Westhoff-Bleck 2013
Duppen 2015
Avila 2016
Novakovic 2018 (1)
Novakovic 2018 (2)
Total (95% CI)
Heterogeneity: Tau² = 2.01; Chi² = 7.52, df = 5 (P = 0.18); I² = 33%
Test for overall effect: Z = 2.01 (P = 0.04)
Test for subgroup differences: Not applicable
Physical activity
Mean [mL/kg/min]
23.6
16.2
20.9
21
20.1
22.6
SD [mL/kg/min]
3.3
5.3
5.9
6.7
5.4
5.4
Total
10
19
46
13
9
9
106
No activity (usual care)
Mean [mL/kg/min]
18.1
15.5
20.6
21.8
18.1
18.1
SD [mL/kg/min]
4.1
3.7
6.2
6.7
4.2
4.2
Total
8
21
31
4
4
5
73
Weight
20.0%
25.1%
26.0%
6.2%
10.8%
11.9%
100.0%
Mean Difference
IV, Random, 95% CI [mL/kg/min]
5.50 [2.00 , 9.00]
0.70 [-2.16 , 3.56]
0.30 [-2.47 , 3.07]
-0.80 [-8.31 , 6.71]
2.00 [-3.42 , 7.42]
4.50 [-0.60 , 9.60]
2.05 [0.05 , 4.05]
Mean Difference
IV, Random, 95% CI [mL/kg/min]
-10 -5 0 5 10
Favours no activity (usual care) Favours physical activity
Risk of Bias
A
?
?
+
+
+
+
B
+
+
+
+
+
+
C
+
?
+
+
+
+
D
?
?
?
?
?
?
E
?
?
?
?
?
?
F
?
?
?
?
?
?
Footnotes
(1) continuous training arm.
(2) interval training arm
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions: Submaximal cardiorespiratory fitness (gas exchange threshold)
(C) Bias due to missing outcome data: Submaximal cardiorespiratory fitness (gas exchange threshold)
(D) Bias in measurement of the outcome: Submaximal cardiorespiratory fitness (gas exchange threshold)
(E) Bias in selection of the reported result: Submaximal cardiorespiratory fitness (gas exchange threshold)
(F) Overall bias: Submaximal cardiorespiratory fitness (gas exchange threshold)


Figure 6.  Exercise traininginterventions versus no activity (usual care) in people with congenital heart disease.
Outcome: Muscular strength.
Study or Subgroup
Moalla 2006
Physical activity
Mean [MVC (N·m)]
120.2
SD [MVC (N·m)]
19.4
Total
10
No activity (usual care)
Mean [MVC (N·m)]
103.07
SD [MVC (N·m)]
9.4
Total
8
Mean Difference
IV, Random, 95% CI [MVC (N·m)]
17.13 [3.45 , 30.81]
Mean Difference
IV, Random, 95% CI [MVC (N·m)]
-20 -10 0 10 20
Favours no activity (usual care) Favours physical activity
Risk of Bias
A
?
B
+
C
+
D
+
E
?
F
?
Risk of bias legend
(A) Bias arising from the randomization process
(B) Bias due to deviations from intended interventions: Muscular strength
(C) Bias due to missing outcome data: Muscular strength
(D) Bias in measurement of the outcome: Muscular strength
(E) Bias in selection of the reported result: Muscular strength
(F) Overall bias: Muscular strength

Maximal cardiorespiratory fitness
A total of 14 studies (15 training arms, 732 participants) reported
maximal CRF using peak oxygen consumption (peak VO2) scaled
to body mass (mL.kg−1.min− 1). One study had a long-term follow-
up at 36 months post intervention (Winter 2012);all other studies'
follow-up was at the cessation of the intervention (median 12, IQR
12 to 26 weeks). Most studies reported the post-score mean and
standard deviation. However,van Dissel 2019reported both a post
score and a change score from baseline andOpotowsky 2018only
reported change score from baseline. To ensure consistency,
change scores were included only when no post score was
reported.
We pooled all available studies into a random-eects meta-
analysis,with a subgroup analysis comparing the dierent types
of intervention; we did not consider the result of the subgroup
analysis to be significant (Chi = 5.34, df = 2, P = 0.07, I = 62.5%).In
the pooled analysis there was a mean dierence (MD) of 1.89
mL.kg−1.min− 1 (95% CI −0.22 to 3.99; 14 studies (15 training
arms), 732 participants;I2 = 75%). The subgroup exercise training
consisted of 11 studies (435 participants) and there was a mean
dierence of 2.74 mL.kg−1.min− 1 (95% CI 0.36 to 5.12; I2 = 73%)
versus a mean dierence of −1.71 mL.kg−1.min− 1 (95% CI −4.64
to 1.22, I2 = 37%) and 0.70 mL.kg−1.min− 1 (95% CI −4.83 to6.23)
in physical activity promotion and inspiratory muscle training
respectively (Figure 2).
Weperformed a further subgroup analysis for the type of congenital
heart disease, which reported a pooled mean dierence of
1.90mL.kg−1.min− 1 (95% CI −0.14to3.95; 14 studies (15 training
arms), 732 participants;I2 =73%). The test for subgroup dierences
revealed no dierences between subgroups (P = 1.00); single
ventricle (MD 2.06, 95% CI −0.25 to 4.38; n = 153), tetralogy of
Fallot (MD 1.97, 95% CI −1.11 to 5.05; n = 104)and other or mixed
populations (MD 1.98,95% CI −1.67to 5.62; n = 474) all had a similar
response toa physical activity intervention (Analysis 1.6).
We performed several separate sensitivity analyses removinghigh
risk of bias studies (MD 0.92, 95% CI −0.27 to 2.11; 12 studies
(13 training arms), 603 participants; I2 = 18%) (Madhavi 2011;
Therrien 2003); and studies that estimated peak VO2 using
validated protocols (MD 1.07, 95% CI −0.14 to 2.28; 12 studies
(13training arms), 519participants) (Madhavi 2011; Morrison 2013).
We also report the use of fixed-eect meta-analyses (MD 2.00,
95% CI 1.09 to 2.91; 14 studies, 732 participants (15 training
arms)); the insertion of all available change scores(MD 1.98, 95%
CI 0.09 to 3.86; 14 studies (15 training arms), 732 participants)
(Sandberg 2018);and the removal of computed outcome scores
(converting medians and interquartile ranges to means± standard
deviations from Avila 2016, Fritz 2020, Klausen 2016, Novakovic
2018, Sandberg 2018 and Winter 2012) (MD 2.84, 95% CI −0.21
to5.88; 8 studies, 423 participants).
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We used univariate meta-regression to assess individual
predictors of peak VO2. We regressed 10 predictors and
the risk of bias and the intervention length produced
significant associations (for regression coeicients and P values
see Table 4 and Figure 7). This indicates that the shorter the
intervention and the higher the risk of bias then the greater the
eect onpeak VO2.There was no evidence of publication bias (P =
0.268) (Figure 8). Using GRADE, we assessed the evidence to be of
moderatecertainty because of imprecision.

Figure 7.  Meta-regression analysesinvestigating the eect ofthe 'overall risk of bias'and the 'length of
intervention'. Outcome:Maximal cardiorespiratory fitness (see Table 4).


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Figure 8.  Funnel plot investigating publication bias. Outcome: Maximal cardiorespiratory fitness (Egger 1997test,
P=0.268).
-10mL/kg/min -5mL/kg/min 0mL/kg/min 5mL/kg/min 10mL/kg/min
MD
0
2
4
6
8
10
SE(MD)
Subgroups
Exercise training Physical activity promotion Inspiratory muscle training

Health-related quality of life (HRQoL)
HRQoL was reported by eight studies using a variety of validated
questionnaires and a median follow-up of 12 weeks (Table 1).
The '36-item short form health survey' (SF-36) was reported most
frequently(n = 5), followed by the 'Congenital heart disease - TNO/
AZL adult quality of life questionnaire' (ConHD TAAQoL) which
was reported twice. All other questionnaires were reported once.
Where possible we pooled HRQoL scores into a random-eects
meta-analysis;we could enter only three studies into the analyses
due to the variety of measurements reported. The result of the
analysis was a standardised mean dierence of 0.76(95% CI −0.13
to 1.65; I2 = 82%), which suggests a moderate eect size indicating
a possibly beneficial eect of interventions on HRQoL (Figure 3).
When we summarised all the evidence on HRQoL presented in the
vote counttable, however, this is not supported (Table 1). The vote
count tableaims tosummarise all studies and instruments used
to report HRQoL. Out of the 12 HRQoL questionnaires reported
by the eight studies, only one questionnaire found a significant
improvement in HRQoL (Madhavi 2011). Using GRADE, we judged
the certainty of the evidence to be 'very low' due to serious to
very serious concerns regarding risk of bias, inconsistency and
imprecision.
Device-worn 'objective' measures of physical activity
Four studies (328 participants) used device-worn measures of
physical activity and we entered their data into a random-eects
meta-analysis (Figure 4). The median follow-up was 19 weeks
(IQR 12 to 39 weeks). There is weak evidence of a small eect
on physical activity levels with a standardised mean dierence
of 0.38 (95% CI −0.15 to 0.92; I2 = 78%). The small eect
sizeindicatesa possiblybeneficial albeit small eectof moderate
to vigorous physical activity levels. Re-expressing these values
into the original scales we can report an approximate 10 minute
increase per day in moderate to vigorous physical activity (95%
CI −2.50 to22.20). UsingGRADE, we downgradedthe certainty of
evidence by two levels tolow, due to concerns over inconsistency
and imprecision.
Validated questionnaire-based ‘subjective’ measures of
physical activity
No study measured physical activity using only
questionnaire measures of physical activity; two studies used
them in combination with device-worn measures (Duppen 2015;
Klausen 2016). Active leisure time (sports, walking and cycling)
was not dierent aer an exercise intervention; passive leisure
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time (television and computer) reduced significantly in both the
intervention and control group, making its attribution to the
exercise intervention challenging (Duppen 2015). Klausen 2016 did
not report their questionnaire results as it did not dier from their
device-worn measures.
Return to work or full-time education
van der Mheen 2019 reported days o school for children
participating in a multicomponent (physical activity promotion
and psychological) intervention. The intervention group had 11
episodes of one or more days o school versus 13 episodes in
one month in the control group, reported by school teachers.
Interestingly when this was reported by mothers there was no eect
(15 vs. 15) and the direction of eect was the other direction when
reported by fathers (13 vs. 11).
Hospital admissions
No study reported this outcome.
Submaximalcardiorespiratory fitness
A total of nine studies (10 training arms) reported a measure
of submaximal CRF, with a median follow-up of 12 weeks. As
previously described in the Characteristics of included studies
there was a large variety of submaximal CRF parameters. Oxygen
consumption scaled to body mass (mL.kg−1.min− 1) at the
gas exchange threshold (GET) was reported most oen and
was subsequently entered into a random-eects meta-analysis,
showing a likely increase in favour of the intervention with
a mean dierence of 2.05 (95% CI 0.05 to 4.05; 5 studies (6
training arms), 179 participants;I2 = 33%) mL.kg−1.min− 1(Figure
5). All of the studies that contributed data to this meta-analysis
were exercise training interventions (i.e. not PA promotion or
IMT). Using GRADE, we judged the certainty of evidence as
moderate—we downgraded the certainty of theevidence one level
due toconcerns overimprecision (< 200participants).
Muscular strength
One study (18 participants) reported muscular strength measured
by maximal voluntary contraction (N·m) of knee extensions in
paediatrics with congenital heart disease. At the end of the exercise
(cycling) intervention (12 weeks) there wasa mean dierence of
17.13 (95% CI 3.45 to30.81)N·m in favour of exercise training (Figure
6). Using GRADE, we downgraded the certainty of evidence one
level tomoderate due to imprecision (only 18 participants).
Adverse events (AEs)
Eleven studies (501 participants) reported on the outcome of
adverse events, over a median follow-up period of 12 weeks (IQR
12 to 26 weeks) (Avila 2016; Duppen 2015; Fritz 2020; Klausen
2016; Novakovic 2018; Opotowsky 2018; Sandberg 2018; Therrien
2003; van Dissel 2019; Westho-Bleck 2013; Winter 2012). Of the
eleven studies, six studies reported zero adverse events and
five studies reported a total of elevenadverse events. Of the 11
AEs, seven were non-cardiac (63%), characterised by dizziness,
discomfort, minor musculoskeletal and minor head injuries. The
remaining four cardiac AEs were inclusive of one suspected
arrhythmia, one self-limiting supraventricular arrhythmia (beta-
blocker administered), one episode of ventricular premature
complexes (managed conservatively) and one episode of non-
sustained atrial tachycardia that could be related to exercise. There
were no reported serious adverse events or fatality.
Eight studies (377 participants) reported no adverse
myocardialchanges; seven studies reported no adverse changes
to cardiacbiomarker B-type natriuretic peptide(NT-proBNP), with
a further four studies reporting no structural or functional cardiac
eects using medical imaging (cardiac magnetic resonance and
echocardiography) post intervention.There were no major adverse
events reported. Our judgement of the certainty of evidence
using the GRADE approach wasmoderate due to concerns over
inconsistency.
D I S C U S S I O N
Summary of main results
We identified 15 studies (with924 participants) that were eligible
for inclusion in this review. This review shows that based on
moderate to very lowcertainty of evidence that all types of physical
activity interventions (physical activity promotion, exercise training
and inspiratory muscle training) when compared to usual care may
have a small eect on cardiorespiratory fitness and physical activity
level but little or no eect on HRQoL. It should be noted that
there was high statistical heterogeneity amongst studies assessing
cardiorespiratory fitness, physical activity and HRQoL. Seventy-
three per cent of studies reported adverse events (six studies
reported zero adverse events and five studies reported a total of
elevenadverse events), of whichseven of 11events were of a non-
cardiac nature, and there wereno reported serious adverse events
or fatalities related to the physical activityinterventions. We were
unable to find any data related to secondary outcomes on return to
work or hospital admissions. The risk of bias under the outcomesof
cardiorespiratory fitness andphysical activity was predominantly
of 'some concerns',for the outcome of health-related quality of life
it was judged to be a high risk of bias.
Overall completeness and applicability of evidence
The generalisability of previous systematic reviews was either
limited to only adults (Li 2019), to a specific type of
intervention (Meyer 2020), or to a specific population(Scheers
2020). This review is the first to include only randomised controlled
trial data, of all age groups, types of ConHD and types of physical
activity intervention. The findings of this review have potentially
better external and ecological validity. Many studies have small
sample sizes and all studies were published in the last 17 years. We
also report 15ongoing studies, which indicates there is continuing
interest in this area. The quality of the evidence was moderate to
very low for all outcomes, indicating further research is very likely
to have an important impact on our confidence in the estimate of
eect.
Quality of the evidence
Overall, there was a general lack of reporting details of the actual
intervention. Using GRADE we assessed the quality of evidence to
range from moderate to very lowacross all outcomes.
We downgraded the certainty of evidence for cardiorespiratory
fitness to moderate using GRADE, as the confidence interval
includesboth appreciable harm and appreciable benefit (i.e. 95%
CI spans 0).Therefore, we downgraded the certainty of evidence by
oneleveldue to imprecision.
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We downgraded the certainty of evidence for health-related quality
of life included in the meta-analysis to very low using GRADE. This
was due to an inconsistent directions of eect (i.e. 95% CI spans
0), considerable heterogeneity (HRQoL, I2 = 82%), a high risk of
bias across all studies and impression due to the low numbers
of participants (< 400). We therefore downgraded the certainty
of evidence by three levels due toinconsistency, methodological
limitations (risk of bias) and imprecision.
We downgraded the certainty of evidence for physical activity to
low using GRADE. This was due to an inconsistent direction of
eect and considerable heterogeneity (i.e. 95% CI spans 0; I2 =
77%); there was also a low number of participants (< 400). We
therefore downgradedthe certainty of evidence by two levelsdue
to inconsistency and imprecision.
We downgraded the certainty of evidence for submaximal
cardiorespiratory fitness and muscular strength to moderateusing
GRADE.This was due to the small numbers of events/participants(<
400). We therefore downgraded the certainty of evidence by
oneleveldue to imprecision.
The certainty of evidence for adverse events was downgraded to
moderate using GRADE. This is due to over 25% of studies not
reporting data on adverse events.We therefore downgradedthe
certainty of evidence by oneleveldue to publication bias.
Potential biases in the review process
We have documented and justified alterations to our methods from
the published protocol in the Dierences between protocol and
reviewsection (Williams 2019).
We believe this is the most comprehensive systematic review
to date of RCTs in people with ConHD. However, it has some
limitations as theoverall risk of bias for the included studies was
predominately of 'some concerns'. Specifically, blinding of outcome
assessors and statistical analysis plans were poorly reported. It is
impossible to blind a physical activity/exercise intervention;there
were, however, very few reported attempts to blindtrial sta to
the allocation of participants during randomisation, assessing the
outcomesand statistical analysis of the outcomes.
All included studies reported a 'no formal exercise training'
intervention comparator. However, there were three active types
of intervention and the amount of data is unequally distributed
between these types (PA promotion n = 3; exercise trainingn = 11;
and IMT n = 1). This reduces the certainty of evidence in the less
well represented types of interventions;they may have a significant
potential for improving primary and secondary outcomes, but it
could not be assessed with the limited data.
A limitation of the current data is that studies group patients
using their individual ConHD lesion (diagnosis) or group multiple
dierent types of ConHD together in a single cohort. Previous
studies have reported large variations in fitness and health
status between patients who have the same condition. Future
studies should adopt a function-based assessments/interventions
approach, which will enable scientiststo observe which types of
patients respond better to interventions, improvingthe evidence
base for individualising physical activityinterventions (Budts 2013;
Budts 2020;Cedars 2020; Moons 2020).
Agreements and disagreements with other studies or
reviews
Cardiorespiratory fitness
Both maximal and submaximalmeasures of CRF have been shown
to be prognostic of future mortality and morbidity in congenital
heart disease (Dimopoulos 2006; Giardini 2009; Müller 2015;
Udholm 2018). In the current review maximal cardiorespiratory
fitness increased by a mean dierence of 1.89 mL.kg−1.min−1
(95% CI −0.22 to 3.99). In a healthy population an increase of
3.5mL.kg−1.min−1(one MET) reduces the chance of cardiovascular
diagnosis or event by approximately 15% (Letnes 2019); and
in patients with cardiovascular disease a one MET increase
is associated with a 8% to 35% (median 16%) reduction in
mortality (Franklin 2013). Currently, in ConHDthere is noconsensus
regarding what the prognostic implication is ofan increaseof1.89
mL.kg−1.min−1.A recent systematic review in exercise training in
patients with Fontan circulations reported a similar estimate of
eectto the current studyof1.73 mL.kg−1.min−1although this was
not conducted using a meta-analysis (Scheers 2020).
Our ConHD subgroup analysis reported no dierence in the
response to the intervention between single ventricle, tetralogy of
Fallot and other/mixed ConHD populations (P = 1.0). All subgroups
responded similarly to the intervention; this may suggest that
a functional-based classification (over the traditional diagnosis/
lesion-based approach), may help to identify groups whorespond
better to interventions.
This was the first systematic review and meta-analysis that
assessed submaximalfitness parameters. The oxygen consumption
at the gas exchange threshold (GET) improved modestly (MD 2.05,
95% CI 0.05 to 4.05); this has also been accompanied with an
increase in power output (watts) at the GET (Moalla 2006; Westho-
Bleck 2013). Participantstherefore had a greater period of time
where they could operate in a predominantly aerobic state, which
is an indicator of improved fitness.
Health-related quality of life
Health-related quality of life was reported in a variety of ways
making pooling diicult:we pooled only three studies andthere
was astandardised mean dierence indicating a moderate eect
size (SMD 0.76, 95% CI −0.13 to 1.65), which we judged as very
low certainty of evidence.However, using a modified vote-counting
table (Table 1), only one study out of eight showed a significant
and positive eect on health-related quality of life (Madhavi
2011). Gratz 2009 and Amedro 2015 reported that people with
ConHD had a significantly poorer health-related quality of life
in the domains of physical functioning/physical well-being and
general health.Gratz 2009also statedthat the ConHD population
dangerously overestimate their exercise capacity and this could
explain the small to no increase in HRQoL within this review.
Physical activity
Re-calculating the eect estimateinto theoriginal scales (minutes
of moderate to vigorous physical activity (MVPA)), we can report
an approximate 10-minute increase per day in MVPA(95% CI −2.50
to 22.20). Whilst this is a small increase of MVPA, accumulatively
over the course of a week more participants will be achieving
the physical activity guidelines. To our knowledge this is the
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first review to quantitatively analyse the eects of physical
activity interventions on physical activityin people with ConHD.
However, were unable to perform a meta-regression on this
outcome, due to the lack of studies contributing to the analyses.
This review summarises the latest evidence on CRF, HRQoL and PA.
Although there were only small improvements in CRF and PA and
small to noimprovements in HRQoL, there were no seriousadverse
events related to the interventions or adverse cardiac remodelling.
These observations support the propositionthat physical activity
and exercise is safe and the benefits outweigh the potential
risks (Koyak 2012). Although these data are promising, there is
currentlyinsuicient evidence to definitively determine the impact
of physical activityinterventions in ConHD. Therefore,further high-
quality randomised control trials are needed utilising a longer
duration of follow-up.
A U T H O R S '  C O N C L U S I O N S
Implications for practice
Currently there are no guidelines outlined by the National Institute
for Health and Care Excellence (NICE) for physical activity and
exercise training in congenital heart disease. Moreover, in the UK
there isno provision for cardiac rehabilitation (inclusive of physical
activity interventions)for children and adolescents with congenital
heart disease and clinical teams are encouraged to develop
pathways to increase exercise and physical activity habits. By
targeting young people it is suggested that good health and
health behaviours will track into adulthood, subsequently reducing
hospital admissions, reducing future morbidity and contributing to
increasing survival rates.
Implications for research
This review reports small and modest improvements in maximal
and submaximal cardiorespiratory fitness, butthere is uncertainty
in the prognostic implications of this improvement over a long-
term follow-up. We require an international eort to produce
a large and long-term randomised multicentre trial of physical
activity and exercise interventions with long-term outcomes of
mortality, morbidity, cost eectiveness, cardiorespiratoryfitness
and health-related quality of life. Future interventions should
classify their patients (and modify the interventions) based on
their functional capacity over their lesion-specific diagnoses—
this should help define what types of populations respond to
interventions the best (Budts 2013; Budts 2020; Cedars 2020;
Moons 2020). A prognostic factors systematic review is also
required to assess the current evidence ofthe prognostic power
of cardiorespiratory fitness for patients with congenital heart
disease,as it will enable physical activity and exercise interventions
to be individualised and evaluated more eectively.
A C K N O W L E D G E M E N T S
The background and methods section of this review is based on
a standard template provided by Cochrane Heart. We would like
to thank the Cochrane Heart Group and in particular Nicole Martin
for their support in the draing of this paper. We would like to
acknowledge Kerry Dwanfrom the Cochrane Editorial and Methods
Department, Andrea Takeda,Charlene Bridges andAparna Kulkarni
from Cochrane Heart and peer reviewers ProfessorNeil A. Smart
 and Dr Ari Cedars M.D. Furthermore, we would also like to
acknowledge the University of Exeter,Bristol Heart Institute and the
University of Glasgow as host institutions.
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REFERENCES
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DuppenN, KapustaL, deRijkeYB, SnoerenM, KuipersIM,
KoopmanLP, et al. The eect of exercise training on cardiac
remodelling in children and young adults with corrected
tetralogy of Fallot or Fontan circulation: a randomized
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* DuppenN, EtnelJR, SpaansL, TakkenT, van den Berg-
EmonsRJ, BoersmaE, et al. 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. American Heart
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* FritzC, MüllerJ, OberhoerR, EwertP, HagerA. Inspiratory
muscle training did not improve exercise capacity and
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FritzC, MüllerJ, OberhoerR, EwertP, HagerA. Inspiratory
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Klausen 2016 {published data only}https://dx.doi.org/10.1016/
j.ijcard.2016.07.092
* KlausenSH, AndersenLL, SøndergaardL, JakobsenJC,
ZomannV, DideriksenK, et al. Eects of eHealth physical
activity encouragement in adolescents with complex
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KjaergaardH, et al. Eects on exercise capacity of eHealth
encouragements in adolescents with congenital heart disease;
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Physical activity interventions for people with congenital heart disease (Review)
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
20

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

Cochrane Database of Systematic Reviews
Madhavi 2011 {published data only}
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aerobic exercise in post-surgical adult acyanotic congenital
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Moalla 2006 {published data only}
MoallaW, GauthierR, MaingourdY, AhmaidiS. Six-minute
walking test to assess exercise tolerance and cardiorespiratory
responses during training program in children with congenital
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MoallaW, ElloumiM, ChamariK, DupontG, MaingourdY,
TabkaZ, et al. Training eects on peripheral muscle
oxygenation and performance in children with congenital
heart diseases. Applied Physiology, Nutrition and Metabolism
2012;37(4):621-30.
* MoallaW, MaingourdY, GauthierR, CahalinLP,
TabkaZAhmaidiS. Eect of exercise training on respiratory
muscle oxygenation in children with congenital heart
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Rehabilitation 2006;13(4):604-11.
Morrison 2013 {published data only}https://dx.doi.org/10.1136/
heartjnl-2013-303849
MorrisonML, SandsAJ, McCuskerCG, McKeownP, McMahonM,
 GordonJ, et al. Exercise training improves activity and
psychosocial wellbeing in adolescents with congenital heart
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* MorrisonML, SandsAJ, McCuskerCG, McKeownPP,
McMahonM, GordonJ, et al. Exercise training improves
activity in adolescents with congenital heart disease. BMJ
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Novakovic 2018 {published data only}https://
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* NovakovićM, ProkšeljK, RajkovičU, CudermanTV,
TronteljKJ, FrasZ, et al. Exercise training in adults with repaired
tetralogy of Fallot: a randomized controlled pilot study of
continuous versus interval training. International Journal of
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Opotowsky 2018 {published data only}https://
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* OpotowskyAR, RhodesJ, LandzbergMJ, BhattAB,
ShaferKM, YehDD, et al. A randomized trial comparing
cardiac rehabilitation to standard of care for adults with
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OpotowskyAR, RhodesJ, MokoL, BradleyR, SystromD,
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TikkanenAU, RhodesJ, LandzbergM, BhattA, SystromDM,
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Sandberg 2018 {published data only}https://dx.doi.org/10.1111/
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SandbergC, HedstromM, DellborgM, MagnussonA,
ZetterstomAK, WadellK, et al. Increased endurance capacity in
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interval exercise training on ergometer cycle. European Heart
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* SandbergC, HedstromM, WadellK, DellborgM, AhnfeltA,
ZetterstromAK, et al. Home-based interval training increases
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Therrien 2003 {published data only}
* TherrienJ, FredriksenP, WalkerM, GrantonJ, ReidG,
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van der Mheen 2019 {published data only}https://
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Van Der MheenM, McCuskerCG, Van BeynumIM, DulferK, Van
GalenE, BogersAJ, et al. CHIP-Family to improve psychosocial
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their families. Cardiology in the Young 2018:S28.
* van derMheenM, MeentkenMG, vanBeynumIM, Van Der
EndeJ, Van GalenE, ZirarA, et al. CHIP-Family intervention
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HooglugtJQ, Van DisselAC, De HaanFH, BlokIM, JorstadHR,
MulderBJ, et al. Eicacy and compliance of long-term,
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disease and heart failure symptoms: a randomized controlled
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* vanDisselAC, BlokIM, HooglugtJL, deHaanFH, JørstadHT,
MulderBJ, et al. Safety and eectiveness of home-based,
self-selected exercise training in symptomatic adults with
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https://dx.doi.org/10.1017/S1047951119001732]
Westho-Bleck 2013 {published data only}https://
dx.doi.org/10.1016/j.ijcard.2013.10.009
* Westho-BleckM, SchieerB, TegtburU, MeyerGP, HoyL,
SchaeferA, et al. Aerobic training in adults aer atrial switch
procedure for transposition of the great arteries improves
exercise capacity without impairing systemic right ventricular
Physical activity interventions for people with congenital heart disease (Review)
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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function. International Journal of Cardiology 2013;170(1):24-9.
[DOI: https://dx.doi.org/10.1016/j.ijcard.2013.10.009]
Winter 2012 {published data only}https://dx.doi.org/10.1016/
j.ijcard.2014.10.042
BalducciA, WinterMM, FabiM, DontiA, PrandstrallerD,
FormigariR, et al. Exercise training is beneficial and safe in
adult patients with a systemic right ventricle. Giornale Italiano
di Cardiologia 2011:16S.
Van Der BomT, WinterMM, De VriesLCS, BoumaBJ, Van
DijkAPJ, Van Der PlasMN, et al. Exercise training improves
exercise capacity in adult patients with a systemic right
ventricle. European Heart Journal 2010:Suppl 1:615.
Van Der BomT, WinterMM, KnaakeJL, CerviE, De VriesLS,
BalducciA, et al. Long-term benefits of exercise training
in patients with a systemic right ventricle. International
Journal ofCardiology 2015;179(105):105-11. [DOI: https://
dx.doi.org/10.1016/j.ijcard.2014.10.042]
* WinterMM, van derBomT, deVriesLC, BalducciA, BoumaBJ,
PieperPG, et al. Exercise training improves exercise capacity
in adult patients with a systemic right ventricle: a randomized
clinical trial. European Heart Journal 2012;33(11):1378-85. [DOI:
https://dx.doi.org/10.1093/eurheartj/ehr396]

References to studies excluded from this review
Ali Faisal 2016 {published data only}
Ali-FaisalSF, Benz ScottL, JohnstonL, GraceSL. Cardiac
rehabilitation referral and enrolment across an academic
health sciences centre with eReferral and peer navigation: a
randomised controlled pilot trial. BMJ Open 2016;6(3):e010214.
[DOI: https://dx.doi.org/10.1136/bmjopen-2015-010214]
Altamirano Diaz 2017 {published data only}
Altamirano-DiazL, RombeekM, De JesusS, WelischE,
PrapavessisH, DempseyAA, et al. Remote lifestyle
counselinginfluences cardiovascular health outcomes in youth
with overweight or obesity and congenital heart disease. Front
2017;5:269. [DOI: https://dx.doi.org/10.3389/fped.2017.00269]
Amedro 2019 {published data only}
AmedroP, GavottoA, LegendreA, LavastreK, BredyC, De La
VilleonG, et al. Impact of a centre and home-based cardiac
rehabilitation program on the quality of life of teenagers and
young adults with congenital heart disease: the QUALI-REHAB
study rationale, design and methods. International Journal
ofCardiology 2019;283:112-8. [DOI: https://dx.doi.org/10.1016/
j.ijcard.2018.12.050]
Babu 2013 {published data only}
BabuAS, PadmakumarR, MaiyaAG. A review of ongoing
trials in exercise based rehabilitation for pulmonary
arterial hypertension. Indian Journal of Medical Research
2013;137:900-6.
Babu 2017 {published data only}
BabuAS, RamachandranP, MaiyaAG. Eects of home-
based exercise training in Eisenmenger's syndrome:
secondary analysis from a RCT. Journal of Cardiopulmonary
Rehabilitation and Prevention 2017;37(5):367-8. [DOI: http://
dx.doi.org/10.1097/HCR.0000000000000293]
Becker Gruenig 2012 {published data only}
Becker-GruenigT, EhlkenN, GorenfloM, HagerA, HalankM,
KloseH, et al. Eicacy of exercise training in congenital
heart disease associated pulmonary hypertension. European
Respiratory Journal 2012;40(56):P927.
Bhasipol 2018 {published data only}
BhasipolA, SanjaroensuttikulN, PornsuriyasakP, YamwongS,
TangcharoenT. Eect of the home cardiac rehabilitation
program for adult with complex congenital heart disease: the
EMPOWER trial. European Heart Journal 2018;39(Suppl 1):22.
[DOI: http://dx.doi.org/10.1093/eurheartj/ehy564.226]
Bhasipol 2018a {published data only}
BhasipolA, SanjaroensuttikulN, PornsuriyasakP, YamwongS,
TangcharoenT. Eiciency of the home cardiac rehabilitation
program for adults with complex congenital heart disease.
Congenital Heart Disease 2018;13(6):952-8. [DOI: http://
dx.doi.org/10.1111/chd.12659]
BoaSorteSilva 2017 {published data only}
Boa Sorte SilvaNC, GregoryMA, GillDP, PetrellaRJ. Multiple-
modality exercise and mind-motor training to improve
cardiovascular health and fitness in older adults at risk for
cognitive impairment: a randomized controlled trial. Archives
of Gerontology and Geriatrics 2017;68:149-60. [DOI: 10.1016/
j.archger.2016.10.009]
Callaghan 2018 {published data only}
CallaghanS, MorrisonML, McCuskerC, McKeownP, CaseyF.
A structured intervention programme can improve the
biophysical wellbeing in children with congenital heart disease.
Ulster Medical Journal 2018;87(2):146.
Camargo 2007 {published data only}
CamargoDM, CamposMT, SarmientoJM, GarzónM,
NaviaJ, MerchánA. Hemodynamic response to training in
resistance and muscular strength of upper limbs in cardiac
rehabilitation [Respuesta hemodinámica con el entrenamiento
en resistencia y fuerza muscular de miembros superiores en
rehabilitación cardiaca]. Revista Colombiana de Cardiología
2007;14(4):198-206.
Chen 2017 {published data only}
ChenCW, FanjiangYY, ChiangYT, HoCL. Mobile health program
to promote self management in youths with congenital heart
disease design and development of the cool randomized
controlled trial. Cardiology in the Young 2017;27(4):S89. [DOI:
http://dx.doi.org/10.1017/S104795111700110X]
Coats 1992 {published data only}
CoatsAJ, AdamopoulosS, RadaelliA, McCanceA, MeyerTE,
BernardiL, et al. Controlled trial of physical training in chronic
heart failure. Exercise performance,hemodynamics, ventilation,
and autonomic function. Circulation 1992;85(6):2119-31. [DOI:
10.1161/01.Cir.85.6.2119]
Physical activity interventions for people with congenital heart disease (Review)
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
22

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Library
Trusted evidence.
Informed decisions.
Better health.


Cochrane Database of Systematic Reviews
Cordina 2013 {published data only}
CordinaRL, O'MeagherS, KarmaliA, RaeCL, LiessC,
KempGJ, et al. Resistance training improves cardiac
output, exercise capacity and tolerance to positive airway
pressure in Fontan physiology. International Journal of
Cardiology 2013;168(2):780-8. [DOI: https://doi.org/10.1016/
j.ijcard.2012.10.012]
Curnier 2012 {published data only}
CurnierD, LalondeF, MathieuME, FournierA, BigrasJL, MiroJ,
et al. Children with congenital heart disease and exercise
rehabilitation. Journal of Cardiopulmonary Rehabilitation and
Prevention 2012;32(4):232. [DOI: http://dx.doi.org/10.1097/
HCR.0b013e3182243798]
DRKS00011363 {published data only}
DRKS00011363. Breathing training in children, adolescents and
young adults with Tetralogy of Fallot aer total surgical repair.
www.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00011363
(accesed prior to 21 October 2020).
Du 2015 {published data only}
DuQ, ZhouX, WangX, ChenS, YangX, ChenN, et al. Passive
movement and active exercise for very young infants
with congenital heart disease: a study protocol for a
randomized controlled trial. Trials 2015;16:288. [DOI: https://
dx.doi.org/10.1186/s13063-015-0816-9]
Du 2017 {published data only}
DuQ, SalemY, LiuHH, ZhouX, ChenS, ChenN, et al. A home-
based exercise program for children with congenital heart
disease following interventional cardiac catheterization: study
protocol for a randomized controlled trial. Trials 2017;18(1):38.
[DOI: https://dx.doi.org/10.1186/s13063-016-1773-7]
Dua 2010 {published data only}
DuaJS, CooperAR, FoxKR, Graham StuartA. Exercise training
in adults with congenital heart disease: feasibility and benefits.
International Journal ofCardiology 2010;138(2):196-205. [DOI:
https://dx.doi.org/10.1016/j.ijcard.2009.01.038]
Fredriksen 2000 {published data only}
FredriksenPM, WalkerM, GrantonJ, WebbG, ReidG,
TherrienJ. A controlled trial of exercise training in adult
patients with repaired tetralogy of Fallot. Canadian Journal of
Cardiology 2000;16(Suppl F):137F.
Fredriksen 2000a {published data only}
FredriksenPM, KahrsN, BlaasvaerS, SigurdsenE,
GundersenO, RoeksundO, et al. Eect of physical training
in children and adolescents with congenital heart disease.
Cardiology in the Young 2000;10(2):107-14.
Gierat Haponiuk 2014 {published data only}
Gierat-HaponiukK, HaponiukI, JaworskiR, ChojnickiM,
SzalewskaD, LeszczynskaK, et al. Physical activity in
patients with grown-up congenital heart defects aer
comprehensive cardiac rehabilitation. Polish Journal of Thoracic
and Cardiovascular Surgery 2014;11(4):452-8. [DOI: https://
dx.doi.org/10.5114/kitp.2014.47352]
Goldbeck 2011 {published data only}
GoldbeckL, HollingI, SchlackR, WestC, BesierT. The impact
of an inpatient family-oriented rehabilitation program on
parent-reported psychological symptoms of chronically ill
children. Klinische Pädiatrie 2011;223(2):79-84. [DOI: https://
dx.doi.org/10.1055/s-0030-1262831]
Gomes Neto 2016 {published data only}
Gomes-NetoM, Saquetto, MB, da Silva e SilvaCM,
ConceicaoCS, CarvalhoVO. Impact of exercise training
in aerobic capacity and pulmonary function in children
and adolescents aer congenital heart disease surgery: a
systematic review with meta-analysis. Pediatric Cardiology
2016;37(2):217-24. [DOI: https://dx.doi.org/10.1007/
s00246-015-1270-x]
Gotink 2017 {published data only}
GotinkRA, YoungeJO, WeryMF, UtensE, MichelsM,
RizopoulosD, et al. Online mindfulness as a promising
method to improve exercise capacity in heart disease: 12-
month follow-up of a randomized controlled trial. PloS One
2017;12(5):e0175923. [DOI: 10.1371/journal.pone.0175923]
Hedlund 2018 {published data only}
HedlundER, LundellB, SoderstromL, SjobergG. Can
endurance training improve physical capacity and quality
of life in young Fontan patients? Cardiology in theYoung
2018;28(3):438-46. [DOI: 10.1017/s1047951117002360]
Hooglugt 2018a {published data only}
HooglugtJQ, van DisselAC, BlokIM, de HaanFH, JorstadHT,
BoumaBJ, et al. The eect of exercise training in symptomatic
patients with grown-up congenital heart disease: a review.
Expert Review of Cardiovascular Therapy 2018;16(6):379-86.
[DOI: https://dx.doi.org/10.1080/14779072.2018.1471356]
IlarrazaLomel 2008 {published data only}
Ilarraza LomelíH, QuirogaP, Rius SuárezMD. Cardiac
rehabilitation in children [Rehabilitación cardíaca en población
pediátrica. Más allá que ayudar a un niño a readaptar su
corazón]. Archivos de Cardiología de México 2008;78(2):129-33.
IoannisLaoutaris 2015 {published data only}
Ioannis LaoutarisID, DritsasA, KariofyllisP, ManginasA.
Benefits of inspiratory muscle training in patients with
pulmonary arterial hypertension. European Journal of
Preventive Cardiology 2015;22(Suppl 1):S78. [DOI: http://
dx.doi.org/10.1177/2047487315586736]
IRCT20180417039341N1 {published data only}
IRCT20180417039341N1. Evaluation of self-care education
on self-eicacy and quality of life in adolescents with
congenital heart disease. www.who.int/trialsearch/Trial2.aspx?
TrialID=IRCT20180417039341N1 (accessed prior to 21 October
2020).
ISRCTN74393113 {published data only}
ISRCTN74393113. Biophysical & psychosocial wellbeing
in children with congenital heart disease. www.who.int/
trialsearch/Trial2.aspx?TrialID=ISRCTN74393113 (accessed prior
to 21 October 2020).
Physical activity interventions for people with congenital heart disease (Review)
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
23

Cochrane
Library
Trusted evidence.
Informed decisions.
Better health.


Cochrane Database of Systematic Reviews
Joshi 2019 {published data only}
JoshiVL, TangLH, ZwislerAD, TaylorRS. Rehabilitation for
people with cardiac conditions: an overview of systematic
reviews. Physiotherapy (United Kingdom) 2019;105(Suppl
1):e11-2. [DOI: http://dx.doi.org/10.1016/j.physio.2018.11.250]
Kobashigawa 1999 {published data only}
KobashigawaJA, LeafDA, Lee, N, GleesonMP, LiuH,
HamiltonMA, et al. A controlled trial of exercise rehabilitation
aer heart transplantation. NewEngland Journal of Medicine
1999;340(4):272-7.
Lalonde 2014 {published data only}
LalondeD, WelischE, Altamirano-DiazL, De JesusS,
PrapavessisH, RombeekM, et al. The impact of a structured
lifestyle intervention on body composition and exercise
capacity in obese children with congenital heart defect
(Smart Heart Trial). Journal of Physical Activity and Health
2014;11:S163-4.
Lam 2014 {published data only}
LamK, DiasP, GreenG, MaioranaA. Echocardiographic
Findings of chronic heart failure patients following exercise
training. Journal of the American Society of Echocardiography
2014;27(6):B119.
Longmuir 1985 {published data only}
LongmuirPE, TurnerJA, RoweRD, OlleyPM. Postoperative
exercise rehabilitation benefits children with congenital heart
disease. Clinical and Investigative Medicine 1985;8(3):232-8.
Longmuir 2013 {published data only}
LongmuirPE, TyrrellPN, CoreyM, FaulknerG, RussellJL,
McCrindleBW. Home-based rehabilitation enhances daily
physical activity and motor skill in children who have
undergone the Fontan procedure. Pediatric Cardiology
2013;34(5):1130-51. [DOI: https://dx.doi.org/10.1007/
s00246-012-0618-8]
Lozada 2017 {published data only}
LozadaMA, BalderasJ, BunyiMI, SuarezC. Comparison of
the eectiveness of four(4) session play module versus the
conventional cardiovascular rehabilitation therapy among post
operative congenital heart disease pediatric patients ages 5 12
years old. Cardiology in the Young 2017;27(4):S144. [DOI: http://
dx.doi.org/10.1017/S104795111700110X]
Marra 2015 {published data only}
MarraAM, EgenlaufB, BossoneE, EichstaedtC, GrunigE,
EhlkenN. Principles of rehabilitation and reactivation:
pulmonary hypertension. Respiration 2015;89(4):265-73. [DOI:
10.1159/000371855]
McKillop 2018 {published data only}
McKillopA, GraceSL, GhisiGL, AllisonKR, BanksL, KovacsAH,
et al. Adapted motivational interviewing to promote exercise
in adolescents with congenital heart disease: a pilot trial.
Pediatric Physical Therapy 2018;30(4):326-34. [DOI: https://
dx.doi.org/10.1097/PEP.0000000000000534]
NCT00930800 {published data only}
NCT00930800. Exercise training in children with congenital
heart defect. clinicaltrials.gov/show/nct00930800 (first posted 2
July 2009).
NCT01463800 {published data only}
NCT01463800. Rehabilitation in patients with congenital heart
disease. clinicaltrials.gov/show/nct01463800 (first posted 2
November 2011).
NCT01671566 {published data only}
NCT01671566. Interval training in adults with congenital heart
disease a randomized trial. clinicaltrials.gov/show/nct01671566
(first posted 23 August 2012).
NCT01822769 {published data only}
NCT01822769. Cardiopulmonary rehabilitation for adolescents
and adults with congenital heart disease. clinicaltrials.gov/
show/nct01822769 (first posted 2 April 2013).
NCT02632253 {published data only}
NCT02632253. Eects of high-intensity interval training on
exercise capacity in patients with grown-up congenital heart
disease. clinicaltrials.gov/show/nct02632253 (first posted 16
December 2015).
NCT02643810 {published data only}
NCT02643810. Exercise training in adults with corrected
Tetralogy of Fallot. clinicaltrials.gov/show/nct02643810 (first
posted 31 December 2015).
NCT02980393 {published data only}
NCT02980393. Smart Heart Trial: structured lifestyle
intervention for overweight and obese youth with operated
heart defects. clinicaltrials.gov/show/nct02980393 (first posted
2 December 2016).
NCT03297918 {published data only}
NCT03297918. Impact of a structural phonation training on
respiratory muscle function in patients with structural heart
disease. clinicaltrials.gov/show/nct03297918 (first posted 29
September 2017).
Nehyba 2009 {published data only}
NehybaS, ChaloupkaV, SoucekR, ChaloupkovaS, VysokyR,
StetkaF, et al. The programme of managed ambulatory
rehabilitation for patients aer heart valve defect surgery.
Vnit ̆rn ́i L ́eka ̆rstv ́i 2009;55(12):1118-25.
NTR2527 {published data only}
NTR2527. High intensity interval training aer cardiac
resynchronization therapy. www.who.int/trialsearch/
Trial2.aspx?TrialID=NTR2527 (date of registration 25 September
2010).
NTR3041 {published data only}
NTR3041. Eects of high intensity interval training on cardiac
function at rest and during exercise. www.who.int/trialsearch/
Trial2.aspx?TrialID=NTR3041 (date of registration 19 August
2011).
Physical activity interventions for people with congenital heart disease (Review)
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
24

Cochrane
Library
Trusted evidence.
Informed decisions.
Better health.


Cochrane Database of Systematic Reviews
Rhodes 2006 {published data only}
RhodesJ, CurranTJ, CamilL, RabideauN, FultonDR,
GauthierNS, et al. Sustained eects of cardiac rehabilitation
in children with serious congenital heart disease. Pediatrics
2006;118(3):e586-93.
Rowland 2016 {published data only}
RowlandT. Cardiovascular physiology and disease in youth.
PediatricExercise Science 2016;28(1):44-7. [DOI: 10.1123/
pes.2016-0013]
Ruttenberg 1983 {published data only}
RuttenbergHD, AdamsTD, OrsmondGS, ConleeRK, FisherAG.
Eects of exercise training on aerobic fitness in children aer
open heart surgery. Pediatric Cardiology 1983;4(1):19-24.
Stefani 2014 {published data only}
StefaniL, GalantiG, InnocentiG, MercuriR, MaulliN. Exercise
training in athletes with bicuspid aortic valve does not result
in increased dimensions and impaired performance of the le
ventricle. Cardiology Research and Practice 2014;2014:238694.
[DOI: https://dx.doi.org/10.1155/2014/238694]
Sutherland 2018 {published data only}
SutherlandN, JonesB, Westcamp AgueroS, MelchioriT,
du PlessisK, KonstantinovIE, et al. Home- and hospital-
based exercise training programme aer Fontan surgery.
Cardiology in the Young 2018;28(11):1299-305. [DOI: https://
dx.doi.org/10.1017/S1047951118001166]
Tan 1996 {published data only}
TanLL, HuangJF, WangH. The eect of rehabilitation training
on postoperative recovery of children with congenital heart
disease. Chinese Journal of Nursing 1996;31(6):314-5.
Tikkanen 2016 {published data only}
TikkanenAU, RhodesJ, LandzbergM, BhattA, SystromDM,
WaxmanA, et al. Poster 26A: randomized trial of cardiac
rehabilitation for adolescents and adults with congenital
heart disease. PM&R 2016;8(9):S169. [DOI: 10.1016/
j.pmrj.2016.07.069]
Zhou 2017a {published data only}
ZhouX, Duqing, SunK. GW28-e0722 randomized controlled
trial of a home-based exercise program for children with
congenital heart disease following interventional cardiac
catheterization: a preliminary study. Journal of the American
College of Cardiology (JACC) 2017;70:C165. [DOI: 10.1016/
j.jacc.2017.07.601]
Zhou 2017b {published data only}
ZhouX, Duqing, SunK. Randomized controlled trial of a home-
based exercise program for children with congenital heart
disease following interventional cardiac catheterization:
a preliminary study. Journal of the American College of
Cardiology 2017;70(16 Supplement 1):C165. [DOI: http://
dx.doi.org/10.1016/j.jacc.2017.07.601]

References to studies awaiting assessment
Ali 2018 {published data only}
AliLA, PingitoreA, PiaggiP, BruciniF, PasseraM, MarottaM,
et al. Respiratory training late aer Fontanintervention:
impact on cardiorespiratory performance. PediatricCardiology
2018;39(4):695-704. [DOI: 10.1007/s00246-018-1808-9]
Callaghan 2017 {published data only}
CallaghanS, MorrisonML, McCuskerC, McKeownP, CaseyF.
A structured intervention programme can improve the
biophysical wellbeing in children with congenital heart disease.
Cardiology in the Young 2017;27(4):S228-9. [DOI: http://
dx.doi.org/10.1017/S104795111700110X]
Morrison 2015 {published data only}
MorrisonBN, DeSouzaAM, VossC, PottsJE, SandorGG,
HarrisKC. The use of individualized exercise prescription and
activity trackers to promote physical activity in children with
congenital heart disease. Canadian Journal of Cardiology
2015;31(10 Suppl 1):S123-4.
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* Indicates the major publication for the study
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C H A R A C T E R I S T I C S  O F  S T U D I E S
Characteristics of included studies [ordered by study ID]
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Study characteristics
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Physical activity interventions for people with congenital heart disease (Review)
Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
29

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Trusted evidence.
Informed decisions.
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Cochrane Database of Systematic Reviews
Methods Aim of study:to assess the impact of exercise on ventricular arrhythmias in adults with tetralogy of
Fallot
Study design: parallel-group randomised controlled trial (2:1 randomisation)
No. of centres: 1 (Montreal Heart Institute Adult Congenital Centre)
Country: Canada
Participants N randomised: 17(exercise 13; control4)
Diagnosis (% of pts):
ConHD total: 17 (100%); intervention: 13 (100%); comparator 4 (100%)
Severity of condition (corrected tetralogy of Fallot):
Exercise:severe = 13 (100%); Control:severe = 4 (100%)
Age (mean± SD), years: total: 35 ± 11.3; exercise: 35 ± 11.3: control: 34 ± 14.5 (converted from median
and IQR).
Percentage male: total 65%; exercise 69%; control 50%
Percentage white: not reported
Inclusion criteria: adults (≥ 18 years of age) with surgically repaired tetralogy of Fallot
Exclusion criteria: non-cardiac contraindications to exercising, prior sustained ventricular arrhyth-
mias, aborted sudden death, or New York Heart Association (NYHA) functional class III or IV symptoms.
Pregnant women and patients unable to provide informed consent.
Interventions Exercise:
•Total duration: 12 weeks
•Aerobic/resistance/mix: combined dynamic and resistance training
•Frequency: 1 to 2 training sessions per week (for 12 weeks)
•Duration: Ihour (including 10-min warm-up and 10-min cool-down period)
•Intensity: tailored to the individual in order to achieve 70% to 80% of the maximum heart rate. Exer-
cise intensity adjusted periodically (every month) and increased gradually according to progress and
tolerance.
•Modality: combined dynamic and resistance training (e.g. jogging, rowing, swimming and weight-
bearing exercises).
•Settings: hospital
•Other: supervised exercise (by physiologist and physician)
Control group/Comparison
Usual care (standard clinical care with encouragement to perform moderate-intensity aerobic activi-
ties for at least 30 minutes a minimum of 3 days per week, in conjunction with moderate intensity mus-
cle-strengthening activities at least 2 days per week).
Outcomes Maximaland submaximalCRF
Adverse events
Notes Adults randomised in a 2:1 ratio
All patients randomised to the exercise program were required to wear a portable 2-lead Holter moni-
tor (Quark 12, Cosmed, Rome, Italy) during each exercise session. But compliance to target heart rate
not reported.
Avila 2016(Continued)
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Country and settings: Canada; single centre
Follow-up: 3 months
Avila 2016(Continued)


Study characteristics
Methods Aim of study:assess effects of an exercise training program on cardiopulmonary fitness and daily
physical activity in patients with corrected tetralogy of Fallot (ToF) or Fontan circulation.
Study design: RCT
No. of centres: 5
Country: theNetherlands
Participants N randomised total: 93; intervention:56;comparator:37
Diagnosis of ConHD total:93; intervention: 56; comparator: 37
Severity of condition (corrected tetralogy of Fallot or Fontan):
•intervention: severe =56 (100%)
•comparator:severe =37 (100%)
Age (mean ± SD) total 15 ± 3; intervention 15 ± 3; control 16 ± 3
Percentage male total: 66 (73%); intervention 40 (76%); control 26 (70)
N lost to follow-up total:intervention: 1 refused; comparator:0
N analysed total: 90; intervention: 53; comparator:37
Inclusion criteria: correction of ToF, using the transatrial-transpulmonary approach, had to be per-
formed before the age of 3.5 years. The Fontan circulation had to be completed before the age of 6
years. All participants had to be able, both mentally as well as physically, to adhere to a training pro-
gramme.
Exclusion criteria: excluded were patients with contraindications for exercise, mental retardation,
standard contraindications for magnetic resonance imaging, or a ventricular outflow obstruction (peak
Doppler gradient > 60 mm Hg).
Interventions Description: standardised exercise training programme, aerobic dynamic cardiovascular training
Setting: hospital
Supervision: supervised
Detail of exercise
•Modality: aerobic dynamic
•Intensity: resting heart rate plus 60–70% of the heart rate reserve
•Resistance training included? No
•Dose
*1 - Length of session: 12 weeks
*2 - Frequency/no. of sessions a week: 2 to 3 (2.5)
*3 - Duration of session: 60 minutes
*Dose of exercise: 1*2*3 = 1800
Duppen 2015
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Outcomes •Maximal and submaximal CRF
•Physical activity
•HRQoL
Notes No. of centres: 5
Country: the Netherlands
Comparator:
Description: regular medical care
Co-interventions: none
Duppen 2015(Continued)


Study characteristics
Methods Aim of study: the aims of the current study were (1) to investigate the effect of a telephone supervised,
daily inspiratory muscle training for six months on exercise capacity and 2) on lung volumes in adult
patients with Fontan circulation.
Study design: RCT
No. of centres: 1
Country: Germany
Participants N randomised total: 42; intervention:20;comparator: 22
Age (mean ± SD) total: 28.6 (24.7; 36.5);intervention 28.8 (25.3; 38.3);control 27.7 (23.7; 36.0)
Percentage male total: 21 (50%); intervention: 11(55%); comparator: 10(45%)
Severity of condition:
•intervention: severe = 20(100%);
•comparator:severe = 22(100%);
Inclusion criteria: 18 years and older, Fontan physiology
Exclusion criteria: patients who underwent cardiac catheter examination in the last 6 months or heart
surgery in the last 12 months were excluded from the study. Further exclusion criteria were a change
in drug administration in the last 3 months, planned intervention in the near future, neuromuscular or
mental disorders, moderate to severe ventricular dysfunction as well as an unstable general state of
health.
Interventions Setting: home/hospital/internet delivery or combination: home
Supervision: supervised/unsupervised/not reported: telephone semi-supervised
Detail of exercise:
•3 sets with 10 to 30 reps daily.An adjustment from 10 cm H2O to 90 cm H2O was possible;inspiratory
load was adjusted individually until maximum for every training session to maintain an optimal train-
ing effect.
•Modality: inspiratory muscle training
•Resistance training included? No
Fritz 2020
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Outcomes •CRF
•Adverse events
Other outcomes measured:
•FVC FEV1
•Oxygen saturation
Notes 
Fritz 2020(Continued)


Study characteristics
Methods Aim of study: to assess benefit and harms of adding an eHealth intervention to health education and
individual counselling in adolescents with congenital heart disease
Study design: randomised clinical trial.
No. of centres: (nationwide?)
Country: Denmark
Participants N randomised total: 158; intervention: 81; comparator:77
N lost to follow-up total: 39; intervention:23; comparator:16
N analysed total:intervention: 81; comparator: 77
Severity of condition:
•intervention:severe = 81;
•comparator:severe = 77;
(Other reported – impossible to know so assumed severe; furthermore, included criteria state complex,
albeit not referencing Hoffman 2002 criteria).
Inclusion criteria: age between 13 and 16 years, previous repair for a complex CHD, and assignment to
lifelong medical follow-up
Exclusion criteria:residual defects significant for physical activity restrictions, assessed by the partici-
pants' regular cardiologist
Interventions Description: 52-week internet, mobile application,and SMS-based programme delivering individually
tailored text messages to encourage physical activity. Patients recorded exercise duration and type in
a mobile application that translated intensity into virtual points, a system designed to provide motiva-
tion.
Setting: home/internet delivery
Supervision: unsupervised but self-reported adherence using an app.
Detail of exercise:activity encouragement.
Modality :text/technology based PA encouragement
Intensity: text encouraged ‘high intensity’ but this it is probably more appropriate to state MVPA due to
a loose definition of high intensity.
Resistance training included? NR
Klausen 2016
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Impossible to assess dose
Outcomes •CRF
•Physical activity (accelerometer)
Notes Adherence to the eHealth program was assessed by patient registration of physical activities via the
eHealth application for at least two consecutive weeks during the trial.
Not statistically powered (needed 216 randomised)
Klausen 2016(Continued)


Study characteristics
Methods Aim of study: to find out the influence of graded aerobic exercise on post-surgical adult acyanotic con-
genital heart diseases.
Study design: RCT
Country: India
Participants N randomised total: 111; intervention: 60; comparator:51
N analysed total:NR; intervention: NR; comparator:NR
Severity of condition:
•intervention: mild = 60;moderate = 0; severe = 0
•comparator: mild = 51;moderate = 0; severe = 0
Inclusion criteria:atrial septal defect (ASD) with pulmonary stenosis, ventricular septal defect(VSD),
patent ductus arteriosus (PDA), le to right shunts.
Exclusion criteria:cyanotic heart disease; severepulmonary vascular disease; cardiomyopathy; sev-
ereatrioventricular valve regurgitation; exercise-induced ventriculararrhythmia; samples with moder-
ate to severe obstructive lesions
Interventions Description: individualized structured exercise protocol and were modified weekly as per the individ-
ual tolerance
Setting: home/hospital/internet delivery or combination: NR assumed hospital based
Supervision: supervised/unsupervised/not reported – assumed supervised
Detail of exercise:
•Modality :NR
•Intensity:NR
•Resistance training included? NR
•1 - Length of session: 12 weeks
•2 - Frequency/no. of sessions a week: NR
•3 - Duration of session: NR
Outcomes •HRQoL
•CRF
Notes 
Madhavi 2011
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

Study characteristics
Methods Aim of study: to assess exercise tolerance, and to investigate how the 6’WT could be a useful test in the
follow-up of rehabilitation programme in children with CHD
Study design: RCT
Country: France
Participants N randomised total: 18; intervention: 10; comparator:8
•intervention: mild = 3; severe = 7
•comparator:mild = 1; severe = 7
Age (mean ± SD); intervention: 13.0 ± 1.4; comparator: 12.8 ± 1.3
Inclusion criteria: the le ventricle ejection fraction (LVEF) of CHD group was < 40%. All patients had
undergone cardiac surgery reconstruction for complex heart disease. The CHD subjects had to be stabi-
lized with drug treatment for at least 3 months; their medication was the same during the training pe-
riod. Medical therapy included diuretics, cardiotonics, antivitamins K, and angiotensin-converting en-
zyme inhibitor.
Exclusion criteria: subjects with additional diagnoses of locomotor or mental disorders or other dis-
eases that could limit muscle performance were excluded from the study. Beta-blockers, pacemaker.
Interventions Description: cycling 12 week intervention
Setting: home
Supervision: unsupervised – pulse monitors checked weekly for compliance
Detail of exercise:
•Modality : cycling
•Intensity: Hr at the VT/GET
•Resistance training included? No
•1 - Length of session: 12 weeks
•2 - Frequency/no. of sessions a week: 3
•3 - Duration of session: 60 mins
•Dose of exercise: 1*2*3 = 2160
Outcomes •CRF maximal and submaximal
•Strength
•NIRS
Notes 
Moalla 2006


Study characteristics
Methods Aim of study: to ascertain if motivational techniques and a structured exercise programme can in-
crease activity in adolescents afflicted with congenital heart disease
Study design: RCT
Morrison 2013
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Country: Northern Ireland
Participants N randomised total:143; intervention: 72; comparator:71
N lost to follow-up total: 42; intervention: 10;comparator:32
N analysed total: 101; intervention: 62; comparator: 39
Severity of condition:mild = 39;moderate = 61; severe =43
Age (mean ± SD) intervention: 15.24; comparator: 15.89
Percentage male total: 60%; intervention:66.7%; comparator: 53.5%
Inclusion criteria: people with ConHD 12 to 20 years old
Exclusion criteria: patients were excluded if they had a syndromic diagnosis, major learning difficul-
ty, or if exercise was contraindicated (i.e.severe le ventricular outflow tract obstruction, severe aortic
stenosis).
Interventions Description:
6 activity interventions days. Motivational interviewing techniques promoting exercise/activity. Given
bespoke training plan to implement at home.
Setting: home/hospital combination: home-based
Supervision: unsupervised – patients were contacted 1 month into 6-month intervention to check
problems
Detail of exercise: programme suitable for their diagnosis no specifics reported
Not possible to calculate exercise dosage.
Outcomes •CRF
•Physical activity
Notes 
Morrison 2013(Continued)


Study characteristics
Methods Aim of study: the aim of the study was to compare high-interval exercise training with moderate con-
tinuous training in terms of improving exercise capacity, vascular function, disease-specific biomark-
ers, cardiac autonomic function (heart rate variability (HRV)) and post-exercise heart rate recovery
(HRR)) and HRQoL, in patients with repaired ToF.
Study design: RCT with 3 parallel groups
No. of centres: 1
Country: Slovenia
Participants N randomised total; HIE intervention: 10; CIE intervention: 10; comparator: 10
N lost to follow-up total: 3; HIE intervention:1;CIE intervention:1; comparator: 1
N analysed total:27; HIE intervention: 9; CIE intervention:9; comparator: 9
Severity of condition:
Novakovic 2018
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•HIE intervention: severe = 10
•CIE intervention:severe = 10
•comparator:severe = 10
Age (mean ± SD) total:38.5 (8.7); HIE intervention: 36.2 (6.8); 7 CIE intervention: 40.1 (10.4); compara-
tor: 38.4 (8.9)
Percentage male total: 37; HIE intervention:22;CIE intervention: 44; comparator: 44
Inclusion criteria: adults with surgically repaired ToF in childhood
Exclusion criteria: exclusion criteria included known or symptomatic atherosclerotic disease, unsta-
ble cardiovascular disease or recent (< 3 months prior to inclusion) cardiovascular events, acute illness
or recent (< 3 months prior to inclusion) non-cardiovascular diseases requiring hospitalisations, emer-
gency or unplanned specialist management, unstable or poorly controlled dysrhythmias, permanent
atrial fibrillation, pregnancy and intellectual development disorder.
Interventions High intensity interval training vs. continuousintensity exercise vs. Control group
Setting: h ome/hospital/Internet delivery or combination: not reported assumed hospital-based
Supervision: supervised/unsupervised/not reported: not reported assumed supervised
Detail of exercise:
•Modality : cycling or speed walking
•Intensity: 80 of HR peak (intensity increased 5% HR peak-points at 12th and 24th training session)
•Resistance training included? No
•1 - Length of session: 36 sessions (12 weeks)
•2 - Frequency/no. of sessions a week: 2/3 (2.5)
•3 - Duration of session: 42
•Dose of exercise: 1*2*3 = 1260
Outcomes •CRF
•HRQoL
Other:
•Echocardiography
•Disease specific biomarkers (NT-proBNP etc.)
•Heart rate variability
•Blood pressure
•Vascular function
Notes 
Novakovic 2018(Continued)


Study characteristics
Methods Aim of study: compare the effects of standard of careto SOC plus participant in a typical clinical CR
program in ACHD.
Study design: RCT
No. of centres: 4
Opotowsky 2018
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Country: USA
Participants N randomised total: 33; intervention: 18; comparator: 15
Diagnosis of ConHD total: 33; intervention: 18; comparator: 15
Severity of condition:
•intervention: mild =0; moderate to severe = 18
•comparator: mild =0;moderate to severe = 5
N analysed total: 28; intervention: 13; comparator: 15
(5 did not receive intervention due to geographical reasons)
Age (mean ± SD) total: 41.1 (12.1); intervention: 47.5 (9.0); comparator: 35.7 (11.9)
Percentage male total: 50; intervention: 53.9; comparator: 46.7
Inclusion criteria: age > 16 years, ability to provide informed consent, ability and willingness to partic-
ipate in a 12-week CR program and repeated cardiopulmonary exercise testing (CPET), impaired aer-
obic capacity defined as peak _VO2 < 80% predicted on baseline exercise test, baseline resting oxygen
saturation (sO2%) > 92%, and CHD of at least moderate complexity.
Exclusion criteria:cardiac intervention (catheterization or surgery) within the prior 6 months or
planned cardiac intervention within 12 months of enrolment, formal CR within 24 months prior to en-
rolment, current or recent pregnancy (delivery < 90 days prior to enrolment), pregnancy planned within
12 months, active heart failure or hospitalization or other major clinical change during the 30 days prior
to enrolment, and other recent or planned events expected to substantially impact exercise capacity.
Interventions Setting: hospital
Supervision: supervised
Detail of exercise
•Modality : walking, cycling, rowing, resistance
•Intensity: HR at gas exchange threshold
•Resistance training included? Yes
•1 - Length of session:12 weeks
•2 - Frequency/no. of sessions a week: 2
•3 - Duration of session: 1 hour
•Dose of exercise: 1*2*3 = 1440
Outcomes •CRF
•HRQoL
•Activity
Notes 
Opotowsky 2018(Continued)


Study characteristics
Methods Aim of study: effect of a home-based exercise training programme on fitness and HRQoL
Study design: RCT
No. of centres: 1
Sandberg 2018
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Country: Sweden
Participants N randomised total: 26; intervention: 16; comparator:10
N analysed total: 23; intervention:13; comparator:10
Severity of condition:
•intervention: severe = 13
•comparator:severe =10
Age (median (IQR)) total:30.1 (22.9 to 36.6); intervention: 31.3 (26.9 to 36.6); comparator: 26.3 (22.9 to
35.6)
Percentage male total: 52; intervention:62; comparator: 40
Inclusion criteria:complex ConHD e.g. Fontan, TGA ToF> 18yrs old
Exclusion criteria:the exclusion criteria were present exercise training > times/week aimed at increas-
ing or sustaining exercise capacity, arrhythmiaor other adverse events (e.g. important symptoms, drop
in blood pressure) at CPET, clinically relevant arrhythmia, intellectual disability or mental illness affect-
ing independent decision making, extracardiac disease affecting physical activity, peak VO2 > 30ml/kg/
min at run-in CPET, or no internet access.
Interventions Description: home-based cycling intervention
Setting: home
Supervision:semi-supervised
Detail of exercise:
•Modality : cycling
•Intensity: training heart rate (THR) was calculated according to the Karvonen method and to achieve
BORG 15 to 16.
•Resistance training included? No
•1 - Length of session: 12 weeks
•2 - Frequency/no. of sessions a week: 3
•3 - Duration of session: 31 mins (avg interval of 3.5 min and including workand rest unloaded inter-
vals)
•Dose of exercise: 1*2*3 = 1116 (individualised)
Outcomes •Cardiorespiratory fitness
•Health-related quality of life
Notes Compliance 79% (median 83%, 47% to 100%). Range of session completed 17 to 36.
Comparator:usual care
Sandberg 2018(Continued)


Study characteristics
Methods Aim of study: assess impact of exercise training on aerobic capacity in repaired tetralogy of Fallot (ToF)
patients.
Study design: RCT
No. of centres: 1
Therrien 2003
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Country: Canada
Participants Diagnosis of ConHD total:18; intervention:9; comparator: 9
Severity of condition: repaired ToF
•intervention: severe =9
•comparator:severe = 8
Age (mean ± SD)intervention:35 (9.5); comparator: 43.3 (7.3)
Percentage male %: total @ randomisation:55; intervention: 55; comparator: 55
N randomised total: 18; intervention:9; comparator: 9
N lost to follow-up total: 1; intervention:0; comparator: 1
N analysed total: 17; intervention: 9; comparator:8
Inclusion criteria:adult patients with repaired ToF
Exclusion criteria:recent surgery, syncope or malignant arrhythmia
Interventions Description: 12-week structured exercise programme, patients in the exercise group were evaluated
by an exercise physiologist (MW) and given an individualized aerobic training programme. Exercise ses-
sions were held once a week at the Toronto General Hospital Cardiac Rehabilitation Department under
the direct supervision of the exercise physiologist.
Setting: combination of home (2* weekly walking) and hospital based
Supervision: both supervised and unsupervised
Detail of exercise:
•Modality : cycling and walking
•Intensity: 60% to 85% of baseline peak VO2
•Resistance training included? No
•1 - Length of session: 12 weeks
•2 - Frequency/no. of sessions a week: 3 (1 hospital and 2 home)
•3 - Duration of session: 50 mins
•Dose of exercise: 1*2*3 =1800
Comparator:
Description: usual care; regular daily exercise
Co-interventions:
Outcomes CRF
Adverse events
Notes No deaths or morbid events occurred in either group, nor were any symptoms reported during the
study period. Occasional premature ventricular and atrial beats were recorded in 4 patients during ex-
ercise testing (at baseline study in 2 patients and follow-up study in 2 patients). None of these episodes
required any intervention or discontinuation of testing. Furthermore, no significant ST segment shi
was observed in any patient during the exercise or recovery period of either the baseline or follow-up
cardiopulmonary testing. Of note: patients were not on telemetry during hospitaltraining sessions.
Therrien 2003(Continued)

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Study characteristics
Methods Aim: does participating in the CHIP-Family intervention improve the psychosocial well-being of chil-
dren with CHD and their parents, family functioning, and parents’ disease-specific knowledge?
Study Design: single-blinded parallel randomised controlled trial
No. of centres: 1
Country:the Netherlands
Participants N randomised total: 93; intervention:49; comparator:44
Diagnosis of ConHD:total 90; intervention: 47;comparator: 43
Severity of condition: limited to 1: atrial septal defect, patent ductus arteriosus, pulmonary
valvestenosis, total anomalous pulmonary venous connection, ventricular septal defect.
Mild, moderate, severe: anomalous le coronary artery from the pulmonary artery, atrioventricular
septal defect, coarctation of the aorta, complex biventricular (e.g.truncus arteriosus, aortic arch de-
fects with ventricular septal defect), univentricular heart defects – Fontan circulation, Ebstein’s anom-
aly (sub)valvular aortic stenosis, tetralogy of Fallot (ToF) including main aorta to pulmonary connecting
artery, transposition of the great arteries
•intervention: limited to none: 14;mild to severe = 33
•comparator: limited to none: 12;mild tomoderate to severe = 31
Age (mean ± SD)intervention: 5.43 ± 1.30; comparator: 5.21 ± 1.26
Percentage male total: 50%; intervention: 53.2%; comparator: 46.5%
N lost to follow-up total: parents of three children did not complete any questionnaires after randomi-
sation.
N analysed total: 90; intervention:45 (Baseline assessment data: n = 47 families; Follow-up assess-
ment data: n = 45 families;Excluded from analyses: n = 2 (no complete questionnaires)); compara-
tor:40 (Baseline assessment data: n = 40 families; Follow-up assessment data: n = 40 families; Excluded
from analyses: n = 1 (no complete questionnaires)).
Inclusion criteria: underwent at least one invasive medical procedure for CHD (i.e.cardiac catheteri-
sation or open heart surgery or both); and (2) were attending kindergarten or first or second year of pri-
mary school at the time of first assessment and were eligible for participation. Can speak Dutch.
Exclusion criteria: children with known intellectual impairment (intelligence quotient ≤ 70) were ex-
cluded, as a sufficient level of intelligence was required to participate in the child intervention pro-
gramme. Moreover, prematurely born children (i.e.gestational age at birth < 37 weeks) with no CHD
other than a patent ductus arteriosus were excluded, as families of prematurely born children experi-
ence different psychosocial problems
Interventions Description: the CHIP-Family is an adaptation and extension of the CHIP-School intervention. 36 CHIP-
Family consisted of a 6-hour group workshop (3 to 5 families per workshop) for parents and children
and an individual 1-hour follow-up session per parent couple. The 1-day parent workshop consisted
of problem prevention therapy, psychoeducation, general parenting skills, skills specific to parenting
a child with CHD (provided by 2 senior clinical psychologists for 4 hours), and medical issues (provid-
ed by a paediatric cardiologist supported by a senior clinical psychologistfor 1 hour).Approximately
4 weeks after the workshop, each parent couple received an individual follow-up session provided by
a senior psychologist who was present at the parent workshop and a psychologist who was present at
the child workshop. The CHIP-Family module also comprised a specific child module. The child mod-
ule consisted of a workshop that was held concurrently with the parent workshop. The child workshop
consisted of cognitive behavioural exercises based on the evidence-based'Fun FRIENDS' protocol and
focused on strengthening self-esteem, regulating emotions, relaxation, problem-solving skills, and
positive thinking (provided by 2 junior psychologists who were supervised by 2 senior clinical psychol-
van der Mheen 2019
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ogists for 4 hours). The children also did sport exercises based on a standardisedexercise programme
specifically developed for children with CHD and their siblings (provided by a physiotherapist and as-
sistant for 1 hour). Each child was allowed to bring a 4- to 10-year-old sibling or friend to normalise par-
ticipation and to stimulate practice at home.
Setting: hospital
Supervision: supervised
Detail of exercise: as above
•Modality: range of dynamic sports exercises
•Intensity: moderate
•Resistance training included? No
•Dose: 1 day
•1 - Length of session: 1 to 4 hours
•2 - Frequency/no. of sessions a week: 3
•3 - Duration of session: 1 × 240 mins and 2 × 60 mins
•Dose of session: 1*2*3 = 720 (calculated as average 2 hours ×3 sessions ×120 min)
Outcomes •HRQoL
•Days o school
Notes Due to logistical reasons in the starting phase of the project, the first 4 families who consented to par-
ticipate were allocated to the CHIP-Family group without randomisation.
van der Mheen 2019(Continued)


Study characteristics
Methods Aim of the study: physical activity promotion and exercise training interventions for people with con-
genital heart disease
Study design: RCT
No. of centres: 1
Country: the Netherlands
Participants N randomised total: 40; intervention: 20; comparator: 20
Diagnosis of ConHD total: 40; intervention: 20; comparator: 20
Severity of condition: eligible patients were adults with CHD and New York Heart Association (NYHA)
classII or III symptoms: tetralogy of Fallot; transposition of the great arteries; Fontan circulation; pul-
monary atresia; other
•intervention: moderate = 2;severe =18
•comparator: moderate = 1;severe = 19
Age (mean ± SD) total; intervention: 39.9 ± 8.6; comparator: 40.0 ± 15.4
Percentage male total: 55%; intervention: 9 (45%); comparator: 13 (65%)
N lost to follow-up total: 6; intervention:3;comparator:3
N analysed total: 34; intervention: 17; comparator: 17
van Dissel 2019
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Inclusion criteria: eligible patients were adults with CHD and New York Heart Association (NYHA) class
II or III symptoms, included in the CONgenital CORvitia database, the Dutch nationwide registry and
DNA-bank for adults with CHD
Exclusion criteria: exclusion criteria were NYHA class I or IV, presence of exercise-induced arrhythmia,
major comorbidities or limitations that could interfere with exercise training, recent (≤ 6 months) ma-
jor cardiovascular events or procedures, cyanosis at rest, a resting blood pressure N200 mm Hg or dias-
tolic blood pressure N110 mm Hg, pregnancy (wish) or mental or physical incapability to participate in
a home-based exercise training programme.
Interventions Description: home-based exercise training programme, with a target training regimen of minimum 3
sessions of 45 minper week for the duration of 6 consecutive months.
Setting: home
Supervision: unsupervised - compliance and adherence monitored.
Detail of exercise:
•Modality: self-selected
•Intensity: 80% max HR achieved in CPET
•Resistance training included? No
•1 - Length of session: 26 weeks
•2 - Frequency/no. of sessions a week: 3
•3 - Duration of session: 45mins
•Dose of exercise: 1*2*3 = 3510
Control group/Comparator: patients randomised to the control group did not receive any formal ad-
vice on exercisetraining, and were neither encouraged, nor discouraged to participate in sports. All pa-
tients were asked to continue habitual daily activities, even if these included regular physical exercise.
Outcomes •Maximal and submaximal CRF
•HRQoL
Notes Patients in the exercise training group reportedly exercised for a median of 2.5 h per week. 13 of the
17 patients in the exercise training group exercised at or above the target training level of 2¼ h per
week. The remaining 4 patients exercised at least 1 h per week. The main reason patients could not ful-
ly adhere to the training regimen was lack of time related to work or family commitments. The types of
sports performed by patients in the exercise group are high-dynamic sports (76%) and a small subset of
those patients (23%) practised sports both at the highest static and dynamic level, such as rowing, cy-
cling and ice-skating.
van Dissel 2019(Continued)


Study characteristics
Methods Aim of study: investigated the effect of 6-month aerobic exercise training on cardiorespiratory and
subaortic RV function in a prospective randomised trial.
Study design: RCT
No. of centres: 1
Country: Germany
Participants N randomised total: 48; intervention: 24; comparator: 24
Diagnosis of ConHD: total 48; intervention: 24; comparator: 24
Westho-Bleck 2013
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Severity of condition: adult patients with previous atrial redirection surgery for D-TGA were eligible
for the study. At our institution all patients underwent the Mustard procedure.
•intervention: mild =0; moderate =0; severe = 24
•comparator: mild = 0;moderate = 0; severe = 24
Age (mean ± SD) total: 29.3 ± 3.4 ; intervention: 29.9 ± 3.1 ; comparator: 28.6 ± 3.1
Percentage male total: 31; intervention: 13; comparator: 18
N lost to follow-up total: 8; intervention: 5; comparator: 3
N analysed total: 40; intervention: 19; comparator: 21
Inclusion criteria: adult patients with previous atrial redirection surgery for D-TGA were eligible for the
study (mustard procedure). Additional inclusion criteria were: stable heart failure according to classifi-
cation of New York Heart association (NYHA) class I/II, unchanged medicationangiotensin-converting
enzyme inhibitors, beta-blockers) for the last 6 months, no physical training programme at inclusion,
and the physical and mental ability to follow a controlled training programme.
Exclusion criteria: exclusion criteria were: clinical diagnosis of NYHA functional class III–IV, known pul-
monary vascular disease, significant baffle-obstruction, recent onset or change of heart failure medica-
tion within the last 6 months, pregnancy, pacemaker or defibrillator implantation, history of ventricular
arrhythmias, renal/liver insufficiency, claustrophobia, and mental retardation.
Interventions Description: patients randomised to training participated in a structured exercise programme with a
goal of improved exercise capacity over a period of 24 weeks. As home equipment, patients received a
bicycle ergometer and heart rate monitors (Polar USA Inc. New York, New York). Patients in the training
group were advised to document heart rate and number and duration of training units.
Setting: home
Supervision: unsupervised weekly phone calls to monitor adherence.
Detail of exercise:
•Modality : cycling
•Intensity: heart rate corresponding to 50% of peak oxygen uptake
•Resistance training included? No
•1 - Length of session:
•2 - Frequency/no. of sessions a week:
•3 - Duration of session:
•Dose of exercise: 1*2*3 = 2550 (see calculation below)
*No Weeks * Frequency per * Duration of session
*3*3*10 = 90
*3*3*15 = 135
*3*5*15 = 225
*3*5*20 = 300
*12*5*30 = 1800
*1800+300+225+135+90 =2550
Comparator:
Description: usual care
Co-interventions:
Outcomes Other outcomes measured:
•MRI
Westho-Bleck 2013(Continued)
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•Bloods
Notes During the study, 2 patients in the training and 1 patient in the control group experienced an episode
of supra-ventricular tachycardia, which was terminated by cardioversion. None of these episodes were
timely related to physical training or to cardiac decompensation.
Westho-Bleck 2013(Continued)


Study characteristics
Methods Aim of study: the primary aim of our study was to determine whether exercise training improves maxi-
mal exercise capacity in adult patient with a systemic RV. Additionally, we aimed to determine whether
exercise training decreases serum N-terminal pro hormone brain natriuretic peptide (NT-proBNP) lev-
els and improves quality of life in these patients
Study design: RCT
No. of centres: 4
Country: theNetherlands (3 sites) Italy (1 site)
Participants N randomised total: 54; intervention: 28; comparator: 26
Diagnosis of ConHD total:54; intervention: 28; comparator: 26
Severity of condition: adults with a systemic RV due to a congenitally or surgically corrected TGA.
•intervention: mild =moderate = severe = 28
•comparator: mild =moderate = severe = 26
Age (mean ± SD) total:32 ± 11; intervention: 31 ± 10; comparator: 34 ± 11 
Percentage male total: 23;intervention: 9; comparator: 14
N lost to follow-up total: 8;intervention: 4; comparator: 4
N analysed total: 46; intervention: 24; comparator: 22
N randomised total: 54; intervention: 28; comparator: 26
N lost to follow-up total: 8; intervention: 6; comparator: 8
N analysed total: 40; intervention: 22; comparator: 18
Inclusion criteria: eligible participants were adults with a systemic RV due to a congenitally or surgi-
cally corrected TGA
Exclusion criteria: exclusion criteria were mental or physical incapability to participate in a home-
based exercise training programme, the presence of exercise-induced arrhythmia, symptomatic my-
ocardial ischaemia, a resting systolic blood pressure .200 mm Hg and/or diastolic blood pressure.110
mm Hg, New York Heart Association (NYHA) class III or IV, pregnancy during the training period, and
non-cardiac co-morbidity that could affect exercise performance or that could aggravate by exercise.
Interventions Description: the training protocol was home-based, and consisted of 3 sessions of steps aerobics per
week for the duration of 10 consecutive weeks.
Setting: home
Supervision: unsupervised but compliance followed up through email and calls
Detail of exercise:
Winter 2012
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•Modality : step aerobics
•Intensity: 75% to 90% of max heart rate (target HR increased with intervention length).
•Resistance training included? No
•1 - Length of session: 10 weeks
•2 - Frequency/no. of sessions a week: 3
•3 - Duration of session: 42 mins
•Dose of exercise: 1*2*3 = 1260
Comparator:
Description: usual care
Co-interventions: none
Outcomes Other outcomes measured:
•BP
•BNP
Notes Exercise tests could be performed without complications in all patients. One baseline exercise test was
aborted due to nausea of the patient, but was repeated successfully 6 h later. As stated above, 1 pa-
tient developed ventricular bigeminy in the recovery phase, and was excluded from participation in the
study. During the training protocol, 1 patient sustained calf injury during exercise, and had to discon-
tinue the protocol for 2 weeks. No other complaints or complications were reported.
Winter 2012(Continued)

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion
Ali Faisal 2016 Wrong intervention
Altamirano Diaz 2017 Wrong study design
Amedro 2019 Wrong study design
Babu 2013 Wrong study design
Babu 2017 Wrong study design
Becker Gruenig 2012 Wrong study design
Bhasipol 2018 Wrong study design
Bhasipol 2018a Wrong study design
BoaSorteSilva 2017 Wrong patient population
Callaghan 2018 Duplicate
Camargo 2007 Wrong comparator
Chen 2017 Wrong intervention
Coats 1992 Wrong patient population
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Study Reason for exclusion
Cordina 2013 Wrong study design
Curnier 2012 Wrong study design
DRKS00011363 Registry Report
Du 2015 Wrong study design
Du 2017 Wrong study design
Dua 2010 Wrong study design
Fredriksen 2000 Wrong study design
Fredriksen 2000a Wrong study design
Gierat Haponiuk 2014 Wrong study design
Goldbeck 2011 Wrong study design
Gomes Neto 2016 Wrong study design
Gotink 2017 Wrong intervention
Hedlund 2018 Wrong study design
Hooglugt 2018a Wrong study design
IlarrazaLomel 2008 Wrong study design
IoannisLaoutaris 2015 Wrong patient population
IRCT20180417039341N1 Registry report
ISRCTN74393113 Registry report
Joshi 2019 Wrong study design
Kobashigawa 1999 Data loss by researcher
Lalonde 2014 Wrong study design
Lam 2014 Wrong patient population
Longmuir 1985 Wrong study design
Longmuir 2013 Wrong study design
Lozada 2017 Wrong comparator
Marra 2015 Wrong study design
McKillop 2018 Wrong comparator
NCT00930800 Registry report
Physical activity interventions for people with congenital heart disease (Review)
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Study Reason for exclusion
NCT01463800 Study cancelled
NCT01671566 Registry report
NCT01822769 Registry report
NCT02632253 Study cancelled
NCT02643810 Registry report
NCT02980393 Wrong study design
NCT03297918 Registry report
Nehyba 2009 Wrong patient population
NTR2527 Wrong patient population
NTR3041 Wrong patient population
Rhodes 2006 Wrong study design
Rowland 2016 Wrong study design
Ruttenberg 1983 Wrong study design
Stefani 2014 Wrong study design
Sutherland 2018 Wrong comparator
Tan 1996 Wrong intervention
Tikkanen 2016 Duplicate
Zhou 2017a Duplicate
Zhou 2017b Paediatric population

Characteristics of studies awaiting classification [ordered by study ID]

Methods 
Participants Fontan patients
Interventions Controlled respiratory training
Outcomes CPET
Notes 
Ali 2018

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
Methods 
Participants ConHD
Interventions Physical activity
Outcomes Potentially HRQoL
Notes 
Callaghan 2017


Methods 
Participants ConHD
Interventions PA promotion
Outcomes Physical activity
Notes 
Morrison 2015


Methods 
Participants Fontan patients
Interventions Inspiratory muscle training
Outcomes Oxygen saturations
Notes 
Neidenbach 2017


Methods RCT
Participants Patients following aortic valve replacement
Interventions Exercise training
Outcomes Cardiopulmonary exercise testing
Notes 
Nilsson 2019

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Characteristics of ongoing studies [ordered by study ID]

Study name Impact of a structural phonation training on respiratory muscle function in patients with structural
heart disease - HeartChoir (Study NCT03297918)
Methods RCT
Participants Inclusion criteria:
•Informed consent as documented by signature (Appendix Informed Consent Form)
•Age ≥ 18 years
•Known cardiomyopathy from acquired heart disease (ischemic or dilated) or patients with com-
plex CHD (cyanotic congenital heart disease, Fontan palliation, subaortic right ventricle or re-
paired tetralogy of Fallot)
Interventions Active comparator: intervention group - patients will be asked to participate in a structured
singing and respiratory training for 12 weeks vs. no activity control.
Outcomes Primary outcome measures:
•Change of MIP (% predicted)
*Change of maximal inspiratory pressure after the intervention
Secondary outcome measures:
•Change of MEP
*Change of maximal expiratory pressure after the intervention
•Change of MVO2
*Change of maximal VO2 after the intervention
•Change of QoL
*Change of Quality of life
Starting date December 2017
Contact information PrincipalInvestigator: Daniel Tobler
Notes Unpublished. Author team contacted and they were unable to share data.
Ganzoni 2019


Study name Improving the effectiveness of psychological interventions for depression and anxiety in the car-
diac rehabilitation pathway: a single blind randomised controlled trial with four month and twelve
month follow up comparing GroupMCT plus usual CR (intervention) with usual CR (control).
Methods RCT. Metacognitive therapy vs. usual care control.
Participants Inclusion:
•Competent level of English language skills (able to read, understand and complete questionnaires
in English).
•Acute coronary syndrome used for any condition brought on by sudden, reduced blood flow to
the heart
•Following revascularisation is the restoration of perfusion to a body part or organ that has suffered
ischaemia
•Stable heart failure
ISRCTN74643496
Physical activity interventions for people with congenital heart disease (Review)
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•Stable angina is chest pain or discomfort that most often occurs with activity or stress
•Following implantation of cardioverter defibrillators/cardiac resynchronisation devices
•Heart valve repair/replacement
•Heart transplantation and ventricular assist devices
•Adult congenital heart disease identified in adulthood
•A score of = 8 on either the depression or anxiety subscale of the HADS.
Interventions Experimental: metacognitive therapy plus CR Group psychological treatment focused on reduc-
ing worry and rumination and modifying beliefs about thinking in addition to treatment as usual
(standard cardiac rehabilitation). Metacognitive therapy (MCT) helps clients to identify episodes of
worry and rumination in response to negative thoughts and bring these responses under control.
This process is facilitated by exercises that enhance the flexibility of attention control, challenge
unhelpful beliefs about thinking and enable new relationships with thoughts
2. Active Comparator: Usual group-based cardiac rehabilitation (treatment as usual) involving
stress management, exercise, education.
Outcomes Primary
•Change in Hospital Anxiety and Depression Scale (HADS) (time frame: baseline pre treatment,
four-month post baseline, 12 months' follow-up)
Secondary
•Metacognitions Questionnaire
•Cognitive Attentional Syndrome
•Impact of Event Scale-Revised
•Health-related quality of life
•Economic Patient Questionnaire (EPQ)
Starting date 1 June 2015
Contact information JaneGarnett,University of Manchester 5th Floor (Research) St. Mary's Hospital Oxford RoadM13
9WLManchesterUnited Kingdom
Notes Control group are exercise training. Mixed population of Non congenital heart as well as congenital
heart patients. Would not be eligible for inclusion into this review unless the intervention group un-
derwentno exercise/physical activity .
ISRCTN74643496(Continued)


Study name Influence of respiratory and exercise therapy on oxygen uptake, quality of life in patients with se-
vere associated pulmonary arterial hypertension (apah) as part of a congenital heart defect with/
without Eisenmenger's syndrome
Methods Randomizedparallel assignment
Participants Inclusion Criteria:
•signed consent form
•men and women> 18 years <80 years
•APAH with congenital heart defects with/without Eisenmenger syndrome (WHO functional class
II-IV), invasively diagnosed by right heart and le heart catheterization: mean pulmonary arterial
pressure (mPAP) ≥ 25 mmHg, with targeted PAH medication for at least two months stable before
study inclusion (exception: compensated WHO class II without vasodilating drug therapy)
Interventions Active comparator: respiratory and exercise therapy
NCT01397110
Physical activity interventions for people with congenital heart disease (Review)
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Randomized, prospective, controlled, blinded study of three-week inpatient rehabilitation and
subsequent continuing of the training at home for 12 weeks. The control group received conven-
tional rehabilitation without a specific training program. After 15 weeks training is also offered to
patients in the control group.
No Intervention: Control group without exercise training
Patients of the control group continue their sedentary lifestyle without given advice for exercise
training.
The time before start of rehabilitation (three months) serves as control group. Afterwards patients
take part in the training program as well.
Outcomes Primary outcomes
•Changes in the maximum 6-minute walk distance (6MGT) (time frame:up to 15 weeks)
•Changes in quality of life (time frame:up to 15 weeks)
Secondary outcomes
•Changes in maximum oxygen uptake
•Changes in exercise capacity: 6-minute walk distance, recumbent bike (watts), respiratory econ-
omy (EQO2, EQCO2)
•Improved condition(NYHA class, Borg scale)
•Changes in magnetic resonance tomography and echocardiographic parameters of right and le
ventricle: size and pump function
•Change of laboratory parameters, which are markers of right heart failure as NTproBNP, inter-
leukins
•Changes in haemodynamics (time frame:up to 15 weeks)
Starting date January 2012
Contact information Ekkehard Gruenig, MD+49 6221 396 8053ekkehard.gruenig@med.uni-heidelberg.de
Notes 
NCT01397110(Continued)


Study name Start-to-sport - feasibility and efficacy of individualized, telemonitored, home-based exercise for
adolescents and adults with congenital heart disease
Methods Randomized parallel assignment
Participants Inclusion Criteria:
•adolescents and adults with congenital heart disease
•16 to 65 years
Exclusion Criteria:
•congenital rhythm or conduction disorders
•isolated congenital coronary artery anomalies
•pregnancy
•being listed for heart transplantation
•inability to perform standard physical activities due to mental/physical disability.
NCT02240147
Physical activity interventions for people with congenital heart disease (Review)
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Interventions During a 30 minute face-to-face motivational interview with an exercise specialist, the patient will
be advised and coached about his exercise prescription, on how to implement it in his own daily
life and on how to prevent relapse. Furthermore, the patients will receive instructions on how to
monitor their exercise intensity and on recognising adverse signals. During the following 12 weeks,
patients will be asked to exercise 4.5 hours per week within the prescribed exercise intensity range
according to the guidelines
Outcomes peak oxygen uptake (time frame:baseline, post-intervention, after 1 year)
physical activity (time frame:baseline, post-intervention and after 1 year)
Starting date 1 January2015
Contact information Principal investigator: Roselien Buys, PhD KU Leuven
Principal investigator: Werner Budts, PhD KU Leuven
Notes Unpublished. Author team contacted and they were unable to share data.
NCT02240147(Continued)


Study name Cardiovascular, Pulmonary and Skeletal Muscle Evaluation in Late Postoperative Period of the
Fontan Surgery
Methods A long-term randomized clinical study that will include 60 patients between 12 and 30 years, sub-
mitted to total cavopulmonary connection for at least 5 years post operative at the Heart Institute,
University of São Paulo Medical School. The patients will be divided into four groups: 1) Exercise
training with aerobic exercise + lower and upper limb strength exercise (GTF-I); 2) Respiratory train-
ing with respiratory muscle exercise (GTF-II); 3) Exercise training with aerobic exercise + lower and
upper limb strength exercise + Respiratory training with respiratory muscle exercise (GTF-III); and
A non-exercise group as control group (GNTF-IV). The patients will be revaluated after the 4-month
period of intervention.
Participants Inclusion criteria:
•Both gender, aged between 12 and 30 years
•Patients undergoing the Fontan operation with time postoperatively ≥ 5 years
•Clinically stable patients, no arrhythmia in the last electrocardiogram or clinical assessment
•Consent by the cardiologist
•Patients who voluntarily signed the consent form.
Exclusion criteria:
•Patients with hypoplastic le heart syndrome
•Changes that reduce musculoskeletal walking skills
•Neurological sequelae, patients with associated genetic syndrome, disturbance cognitive or psy-
chiatric
•Patients with a history of ventricular arrhythmias, cardio respiratory arrest, users of anti-arrhyth-
mic drugs and/or underwent implantation of pacemaker
•Atrial arrhythmia requiring treatment in the last 6 months
•Patients with heart failure not controlled by medications and lung hypertension
•Patients with protein-losing enteropathy
•Severe hypoxemia (oxygen saturation <80% at rest)
•Symptomatic patients with a diagnosis of diaphragmatic paresis or paralysis postoperative pa-
tients, with or without plication
•Patients with moderate to severe asthma
NCT02283255
Physical activity interventions for people with congenital heart disease (Review)
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•Patients who live outside the area of Sao Paulo
Interventions Aerobic training: Aerobic training and muscle strength exercise for upper and lower limbs, 3 times a
week for 4 months.
Respiratory training: muscle training using POWERbreathe device, 7 times a week, 3 series of 30
repetitions per day, for 4 months.
Aerobic and respiratory training: aerobic training and muscle strength exercise for upper and lower
limbs, 3 times a week for 4 months and respiratory muscle training using POWERbreathe device, 7
times a week, 3 series of 30 repetitions per day, for 4 months.
No physical activity: control group (usual care)
Outcomes •Improvement exercise tolerance and physical capacity (timeframe:baseline and 4 months)
•Improvement in the functional capacity post exercise training programme (timeframe:baseline
and 4 months)
•Improvement in pulmonary function post physical exercise programme (timeframe:baseline and
4 months)
•Change in autonomic function post exercise training programme (timeframe: baseline and 4
months)
•Improvement in peripheral blood flow post exercise training programme (timeframe:baseline
and 4 months)
•Change in the plasma epinephrine level post exercise training programme (timeframe:baseline
and 4 months)
•Change in muscle metabolism post exercise training programme (time frame: baseline and 4
months)
Starting date 2014
Contact information Contact: Aida LR Turquetto, Researcher  +55 11 26615399 ext +5511981140723 aidaturquet-
to@me.com
Contact: Marcelo B Jatene, Researcher  +551126615399 ext +551126615399 marcelo.jatene@in-
cor.usp.br
Notes 
NCT02283255(Continued)


Study name Effect of resistance training in adults with complex congenital heart disease
Methods RCT
Behavioural: home-based resistance training
Participants Inclusion criteria:
•Complex congenital heart disease ( e.g. tetralogy of Fallot, transposition of the great arteries, pul-
monary atresia, patients palliated with Fontan procedure or total cavo-pulmonary connection).
•Clinically stable without significant change the last 3 months.
•Adult (> 18 years of age).
•Informed consent.
Exclusion criteria:
•Cognitive impairment affecting the ability of independent decision making.
NCT02658266
Physical activity interventions for people with congenital heart disease (Review)
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•Present strategy of regularly executing resistance training > 2times per week in purpose to in-
crease muscle strength.
•Other comorbidity affecting physical activity.
•Other circumstance making participation unsuitable.
Interventions Home-based resistance training 12 weeks home based resistance training 3 times per week, 10 to
12 reps, 2 sets
Outcomes •Change in muscle endurance (number of repetitions) (timeframe:change from baseline muscle
endurance at 12 weeks' follow-up)
•Change in total body skeletal muscle mass (kg) (time frame: change from baseline total body
skeletal muscle mass at 12 weeks' follow-up)
•Change in appendicular skeletal muscle mass (kg) (time frame: change from baseline appendicu-
lar skeletal muscle mass at 12 weeks' follow-up)
•Change in body fat percentage (time frame: change from baseline body fat percentage at 12
weeks' follow-up)
•Change in bone mineral density (g/cm2) (time frame: change from baseline bone mineral density
at 12 weeks' follow-up)
•Muscle metabolism (time frame: change from baseline muscle metabolism at 12 weeks' follow-up)
•Compliance to study protocol (time frame: at completion of study protocol 12 weeks)
•Adverse events (time frame: once a week from the date of onset of the home based exercise regi-
men until the follow-up at 12 weeks)
Starting date 2017
Contact information Contact: Bengt Johansson, MD, PhD  +46907852782 bengt.johansson@medicin.umu.se
Contact: Camilla Sandberg, RPT, PhD  +46907858441 camilla.sandberg@medicin.umu.se
Notes 
NCT02658266(Continued)


Study name Congenital Heart Disease Physical Activity Lifestyle Study (CHD-PALS)
Methods Randomized. Study includes 2 possible conditions to which participants are randomized: (1) Fitbit
only and (2) Fitbit + coaching sessions.
Participants Inclusion Criteria:
•Between the ages of 15 and 18 (if 18, must be in high school and/or still living at home)
•Are diagnosed with moderate or complex structural congenital heart disease
•Live within 120 miles of Nationwide Children's Hospital
•Able to complete an exercise stress test on a treadmill
Interventions Intervention: In the Fitbit + Coaching Sessions arm, participant will receive their exercise prescrip-
tion, as devised from their baseline exercise stress test results, a Fitbit, and will have 8 sessions
with a coach (interventionist) over the course of 20 weeks. They will undergo a 9 week (interim) and
a 22 week assessment (follow-up).
Control: In the Fitbit Only arm, participants will receive their exercise prescription, as devised from
their baseline exercise stress test results, and a Fitbit. They will undergo a 9 week (interim) and a 22
week assessment (follow-up).
Outcomes Primary outcome measures:
NCT03335475
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•Number of minutes spent in moderate to vigorous physical activity as measured by an accelerom-
eter
*Moderate to vigorous physical activity (time frame: from baseline to follow-up (approximately
22 weeks))
Secondary outcome measures:
•Number of minutes spent being sedentary as measured by an accelerometer.
•Maximal oxygen utilization during physical activity as measured by V02max during an exercise
stress test.
•Sedentary behaviour (time frame: from baseline to follow-up (approximately 22 weeks))
•Exercise tolerance (time frame: from baseline to follow-up (approximately 22 weeks))
Starting date 7 November 2017
Contact information Principal investigator: Jamie L Jackson, PhD Nationwide Children's Hospital
Notes 
NCT03335475(Continued)


Study name Impacting child physical and mental health outcomes in congenital heart disease: a randomized,
controlled trial of enhanced physical activity support in clinical care
Methods Cluster-randomized trial, with randomization by within each site by week (i.e.site-week)
Participants Inclusion criteria:
•All patients 5 to 17 years with CHD diagnoses classified as moderate or severe in complexity by
the American College of Cardiology/American Heart Association joint guidelines.
Exclusion criteria:
•Cardiac intervention (catheterization or surgery) in preceding 6 months. Syndrome/diagnosis af-
fecting physical activity (e.g., developmental disability) or the ability to complete the assessment
questionnaires.
Interventions Clinician counselling about physical activity using standardised tools to promote daily physical ac-
tivity.
Outcomes Primary outcome:
•Pedometer step counts per day
*Change in daily physical activity (time frame: baseline then first week of each month for 6
months)
Secondary outcomes:
•Children's Self-Perceived Adequacy and Predilection for Physical Activity Scale
•Paediatric Quality of Life Inventory (PedsQL),
•PLAY Tools Run2 and screening question
*Change in physical activity adequacy and predilection (time frame: baseline, 6 months)(time
frame: baseline, 6 months)
*Change in quality of life (time frame: baseline, 6 months)
*Change in physical literacy (time frame: baseline, 6 months)
Starting date March 5, 2018
NCT03435354
Physical activity interventions for people with congenital heart disease (Review)
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Contact information Principal Investigator: Patricia Longmuir, PhD Scientist
Notes 
NCT03435354(Continued)


Study name Remotely monitored and coached exercise based cardiac rehabilitation in northern Sweden
Methods RCT
Participants Inclusion criteria:
•Scheduled appointment with physiotherapist for follow-up after cardiac event: myocardial infarc-
tion (MI)
•Per cutaneous coronary intervention (PCI) due to MI or angina pectoris
•Open heart surgery due to coronary artery disease or valvar disease
•Living in the catchment area of Heart centre, University Hospital of Umeå.
Interventions Remotely monitored and coached exercise training in real time using the REMOTE-CR system. The
patients randomized to remotely monitored exercise can either work out with self-selected ac-
tivities e.g. Nordic-walking, cycling, skiing or participate in supervised exercise session via video
link.The patients randomized to be controls will receive individualized information and instruc-
tions regarding current exercise recommendations but will not be monitored or coached during
their exercise sessions (usual care).
Outcomes Primary outcome:
The aerobic exercise capacity (W) will be evaluated using a standardised submaximal exercise test
on cycle ergometer
•Change in submaximal aerobic exercise capacity (time frame: baseline and 12 weeks)
Secondary outcome:
•Number of repetitions achieved during test of Unilateral isotonic shoulder flexion and Unilateral
isotonic heel-li
•Isometric grip strength
•International Physical Activity Questionnaire
•The Swedish version of the Tampa scale for Kinesiophobia Heart (TSK-SV Heart) The scale com-
prises 17 items assessing subjective rating of kinesiophobia. The total score varies between 17-68
and a score > 37 defines a high level of kinesofobia.
Starting date 3 September 2019
Contact information Camilla Sandberg, PhD+46907858441camilla.sandberg@umu.se
Notes Most likely will not meet participant inclusion criteria
NCT03479957


Study name Impact of cardiovascular rehabilitation on the quality of life of adolescents and young adults with
congenital heart disease: a randomized controlled multicentre trial
NCT03690518
Physical activity interventions for people with congenital heart disease (Review)
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Methods 
Participants Inclusion Criteria:
•Patient aged 13 to 25 years included
•With a congenital heart diseases (CHD) as defined in the international CHD classification.
•Recent (< 3 months) cardio-pulmonary exercise test (CPET)with maximum oxygen uptake
(VO2max) <80% of theoretical values and/or first ventilatory anaerovic threshold (VAT) <55% of
VO2max.
•Consent of the adult patient or the parents or legal guardians of the minor patient.
•Beneficiary of the social security scheme.
Interventions Cardiac rehabilitation: rehabilitation will have a regular follow-up with intervention (rehabilitation
program)
Outcomes Primary outcomes:
•Evolution of the PedsQL 4.0 self-reported scores from month 0 to month 12
•Quality of life score (PedsQL, 24 items), range score from 0 to 100, higher score indicating better
quality of life. (time frame:follow-up of patients over 12 months)
Secondary outcomes:
•Disease knowledge questionnaire (Leuven questionnaire, 34 items, total range score from 0 to
100, a higher score indicating better knowledge)
•Number of consultation in cardiology, number of hospitalization in cardiology, number of cardio-
vascular events
•Score of physical activity (Ricci and Gagnon questionnaire, 9 items, total range score from 6 to 45,
higher score indicating a higher level of physical activity)
•NYHA functional class= New York Association functional class from the World Health Organization
•Variation of cardiac output during exercise tests measured by impedance measurement (Phys-
ioflow)
*Peak oxygen uptake (VO2max, ml/kg/min) (time frame:Month 0 and Month 12)
*Ventilatory anaerobic threshold (VAT, ml/kg/min) (time frame:Month 0 and Month 12)
*Knowledge of the disease (time frame:Month 0 and Month 12)
*Cardiac events (time frame:Month 0 and Month 12)
*Physical activity scoring (time frame:Month 0 and Month 12)
*Functional NYHA class (time frame:Month 0 and Month 12)
*Cardiac output during exercise (time frame:Month 0 and Month 12)
Starting date 27 July 2018
Contact information Contact: Sophie GUILLAUMONT0467336632s-guillaumont@chu-montpellier.fr
Contact: Pascal AMEDRO0467336632p-amedro@chu-montpellier.fr
Notes Amedro P, Gavotto A, Legendre A, Lavastre K, Bredy C, De La Villeon G, Matecki S, Vandenberghe D,
Ladeveze M, Bajolle F, Bosser G, Bouvaist H, Brosset P, Cohen L, Cohen S, Corone S, Dauphin C, Du-
lac Y, Hascoet S, Iriart X, Ladouceur M, Mace L, Neagu OA, Ovaert C, Picot MC, Poirette L, Sidney F,
Soullier C, Thambo JB, Combes N, Bonnet D, Guillaumont S. Impact of a centre and home-based
cardiac rehabilitation program on the quality of life of teenagers and young adults with congeni-
tal heart disease: The QUALI-REHAB study rationale, design and methods. Int J Cardiol. 2019 May
15;283:112-118. doi: 10.1016/j.ijcard.2018.12.050. Epub 2018 Dec 20.
NCT03690518(Continued)


Physical activity interventions for people with congenital heart disease (Review)
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Study name Sophrology and congenital heart disease (SOPHRO CARE)
Methods RCT
Participants Inclusion criteria:
•Patient aged 13 to 25 years old
•With a congenital heart disease (CHD) as defined in the international anatomic and clinical clas-
sification (ACC) - CHD classification
•Informed consent from adult patients or parents/legal guardians for minor patients
Interventions Sophrology sessions
Outcomes Primary outcome:
VO2max Variation
1. Maximum oxygen uptake (VO2 max) (time frame: variation between baseline (M0) and at 12
months (M12))
Secondary outcomes:
•Quality of life score variation (PedsQL, 24 items), range score from 0 to 100, higher score indicating
better quality of life.
•Score of physical activity (Ricci and Gagnon questionnaire, 9 items, total range score from 6 to 45,
higher score indicating a higher level of physical activity)
*Quality of life score (time frame: evolution of the PedsQL 4.0 self-reported scores from month
0 to month 12)
*Physical activity score (time frame: variation between Baseline (M0) and at 12 months (M12))
Starting date 19 July 2019
Contact information Pascal AMEDRO, MD0467336632p-amedro@chu-montpellier.fr
Notes 
NCT03999320


Study name Young Adult Congenital Heart Disease Physical Activity Lifestyle Study (YACHD-PALS)
Methods This study will adapt a physical activity lifestyle intervention to emerging adult congenital heart
disease (CHD) survivors with the primary goal of increasing physical activity levels.
The study will be split into 2 phases. In Phase 1, participants will be asked to complete question-
naires, wear an accelerometer around the waist for 7 days, and undergo an exercise stress test. The
accelerometer and exercise stress test will be used to determine whether participants are eligible
to be randomized for the intervention study. In Phase 2, participants will be randomized to one of
two conditions: 1) receiving a physical activity tracker (a Fitbit) or 2) receiving a Fitbit AND engag-
ing in videoconferencing sessions with a physical activity coach. During Phase 2, participants will
also be asked to complete 3 assessments (weeks 9 and 22, and a 6-month follow-up). The week 9
assessment will consist of completing questionnaires and wearing an accelerometer for 7 days.
Week 22 will be similar to week 9 with the addition of a final exercise stress test. The 6-month fol-
low-up will mirror the week 9 assessment.
Participants Inclusion Criteria:
•Between the ages of 18 and 25 (if 18, must no longer be in high school and no longer living at home)
NCT04135859 (YACHD-PALS)
Physical activity interventions for people with congenital heart disease (Review)
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•Diagnosed with moderate or complex structural congenital heart disease
•Live within 120 miles of Nationwide Children's Hospital
•Able to complete an exercise stress test on a treadmill
Exclusion Criteria:
•Do no speak or write proficiently in English
•Have cognitive impairments that would interfere with the completion of study procedures
•Are diagnosed with a genetic syndrome (e.g.Downs, Marfans)
•Have been engaged in a formal exercise program within the past 6 months
•Underwent open-heart surgery or have had a transcatheter valve replacement in the last 3 months
•Are otherwise prohibited by their cardiologist to engage in at least moderate levels of physical
activity
•Are unable to complete a treadmill-based exercise stress test
•Are currently pregnant
•Have contraindications for exercise based on an exercise stress test (e.g., exercise-induced ar-
rhythmias or evidence of cardiac ischaemia)
•> 150 min/weekday of moderate-to-vigorous physical activity per the accelerometer
•Do not have access or a device for videoconferencing with the coach
Interventions In the Fitbit Only arm, participants will receive their exercise prescription, as devised from their
baseline exercise stress test results, and a Fitbit. They will undergo a 9 week (interim) and a 22
week assessment (follow-up).
Intervention: Behavioral: Physical Activity Monitoring
In the Fitbit + Coaching Sessions arm, participants will receive their exercise prescription, as de-
vised from their baseline exercise stress test results, a Fitbit, and will have 8 sessions with a coach
(interventionist) over the course of 20 weeks. They will undergo a 9 week (interim) and a 22 week
assessment (follow-up).
Interventions:
•Behavioral: physical activity lifestyle intervention
•Behavioral: physical activity monitoring
•Active Comparator: Fitbit only
•Experimental: Fibit + coaching sessions
Outcomes Number of minutes spent in moderate to vigorous physical activity as measured by an accelerome-
ter.
Starting date 2019
Contact information Jamie Jackson, Nationwide Children's Hospital
Notes 
NCT04135859 (YACHD-PALS)(Continued)


Study name Exercise training strategies for children with repaired tetralogy of Fallot
Methods RCT
Participants Paediatrics with repaired tetralogy of Fallot
NCT04208893
Physical activity interventions for people with congenital heart disease (Review)
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Interventions The aerobic training intervention will include 60 minutes/session, 3 times/week for 12 weeks at an
intensity of 65% to 85% of participants' heart rate reserve (HRR), as determined by the CPET. Pa-
tients will be asked to wear a fitness-tracking device to monitor their heart rate response and in or-
der to comply with the prescribed training intensity. All training sessions will start with a 10-minute
warm up, 40-minute aerobic interventions, and ends with a 10-minutescool down. One study doc-
tor will be on call during in-hospital training. Onsite supervised aerobic interventions will include
play-based activities, whereas home-based aerobic activities will include stationary bikes and exer-
cise activities that would target desired heart rate ranges. Home exercise equipment will be provid-
ed.
Outcomes Primary
•Consent rate (time frame:1 year)
•Enrolment rate (time frame:1 year)
•Adherence rate (time frame:1 year)
•Completion rate (time frame:1 year)
•Attrition rate (time frame:1 year)
•Acceptability questionnaire
Secondary
•The effect of aerobic training only versus combined aerobic and strength training on exercise ca-
pacity using cardiopulmonary exercise test in children with repaired tetralogy of Fallot (ToF) (peak
exercise ml/kg/min) (time frame: from baseline to 3 months post intervention)
•The effect of aerobic training only versus combined aerobic and strength training on pulmonary
measures using pulmonary function test in children with repaired tetralogy of Fallot (ToF) (Change
in time in force vital capacity (FVC) (litres)) (time frame: from baseline to 3 months post interven-
tion).
•Many others planned outcomes see registry
Starting date 2019
Contact information Brian McCrindle, MDThe Hospital for Sick Children, Toronto, Canada
Notes 
NCT04208893(Continued)


Study name Long-term effectiveness of an mHealth intervention for improving the disease knowledge and
physical activity of youth With congenital heart disease: arandomized controlled trial
Methods •No Intervention: control group
•Experimental: one active intervention group
•Experimental: the other active intervention group
Participants Inclusion criteria:
•being diagnosed with CHD by a paediatric cardiologist and qualifying as having simple or moder-
ate CHD complexity according to the 2008 American College of Cardiology/American Heart Asso-
ciation guidelines;
•having a regular pulse;
•being 15 to 24 years of age;
•being conversant in Mandarin and Taiwanese;
•possessing a smartphone with Internet connection;
•agreeing to wear an exercise-monitoring wristband to record physiological data;
NCT04264650
Physical activity interventions for people with congenital heart disease (Review)
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•agreeing to engage in exercises designed to test cardiopulmonary endurance;
•agreeing to participate in the study and sign an informed consent form for a relevant interview.
For participants under 20 years of age, guardian approval by signing a written consent form was
required.
Exclusion criteria:
•having cognitive impairment to the extent of being noncommunicative;
•having CHD complicated with other congenital abnormalities;
•having undergone a cardiac catheter-related intervention or surgery within the past 6 months;
•being pregnant
Interventions The COOL program is a 12-month randomized controlled trial that compared two active interven-
tion groups to a standard-care control group (n = 47). Participants with simple and moderate CHD
aged 15-24 years were recruited from paediatric or adult CHD outpatient departments. Participants
in one active intervention group (n = 49) were provided with COOL Passport, a mobile healthcare
application. Those in the other group (n = 47) were provided with access to the Health Promotion
Cloud system and use of game-based interactive platforms along with COOL Passport. Outcomes
were the Leuven Knowledge Questionnaire for CHD and the International Physical Activity Ques-
tionnaire-Taiwan Show-Card Version.
Outcomes Cardiac disease knowledge and physical activity
Starting date 2020
Contact information Chi-Wen Chen, PhD National Yang Ming University
Notes 
NCT04264650(Continued)


Study name Evaluation test about safety and efficacy of the respiratory muscle training therapy by abdominal
respiratory weight exercises in chronic cardiovascular disease patients
Methods Parallel randomized
Participants Inclusion criteria:
•Patients with chronic cardiovascular disease in outpatient or in hospital of Kurume University
hospital
•Patients with informed consent
•Patients with chronic cardiovascular disease shown in the following
•Ischaemic heart disease
•Valvular heart disease
•Hypertensive heart disease
•Cardiomyopathy
•Arrhythmia
•Adult congenital heart disease
•Pulmonary hypertension
•Exclusion criteria: Patients with obstructive respiratory disease
•Patients with the device planted
•Patients with difficult musculoskeletal disease
•Patients with symptoms at rest
•Patients with pulmonary hypertension of the WHO classification 3 more
UMIN000021661
Physical activity interventions for people with congenital heart disease (Review)
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•Patients with hypoxaemia in spite of the use of breathing ancillary equipment
•Patients with uncontrolled high blood pressure
•Patients with poor control of arrhythmia, such as adverse effects on haemodynamics
•Patients that may be in or pregnancy
•Others, patients who are judged that this study is unsuitable by physician
Interventions The respiratory muscle training therapy is performed in addition to performing conventional car-
diac rehabilitation. The respiratory muscle training therapy is abdominal muscle training method.
Intervention period is 6 months
Outcomes •Cardiac function
•Respiratory function
•Exercise capacity
•Relief of symptoms
•Autonomic function
•Body composition
•Physical function
•Carbohydrate metabolism
•Lipid metabolism
Starting date 4 April 2016
Contact information Miki Biwa
biwa_miki@med.kurume-u.ac.jp
Notes 
UMIN000021661(Continued)

R I S K  O F  B I A S
Legend: Low risk of bias  High risk of bias  Some concerns  

Risk of bias for analysis 1.1 Maximal cardiorespiratory fitness
Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Subgroup 1.1.1 Exercise training
Therrien 2003
Moalla 2006
Madhavi 2011
Winter 2012
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Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Westhoff-Bleck
2013
Duppen 2015
Avila 2016
Novakovic 2018
Opotowsky 2018
Sandberg 2018
Novakovic 2018
van Dissel 2019
Subgroup 1.1.2 Physical activity promotion
Morrison 2013
Klausen 2016
Subgroup 1.1.3 Inspiratory muscle training
Fritz 2020


Risk of bias for analysis 1.2 Health-related quality of life
Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Madhavi 2011
Opotowsky 2018
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Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Sandberg 2018


Risk of bias for analysis 1.3 Physical activity (device-worn)
Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Duppen 2015
Klausen 2016
Morrison 2013
Opotowsky 2018


Risk of bias for analysis 1.4 Submaximal cardiorespiratory fitness (gas exchange threshold)
Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Moalla 2006
Westhoff-Bleck
2013
Duppen 2015
Avila 2016
Novakovic 2018
Novakovic 2018
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

Risk of bias for analysis 1.5 Muscular strength
Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Moalla 2006


Risk of bias for analysis 1.6 Maximal cardiorespiratory fitness (type of ConHD subgroup analysis)
Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Subgroup 1.6.1 Population with a single ventricle
Winter 2012
Westhoff-Bleck
2013
Duppen 2015
Fritz 2020
Subgroup 1.6.2 Population with repaired Tetralogy of Fallot
Therrien 2003
Duppen 2015
Avila 2016
Novakovic 2018
Novakovic 2018
Subgroup 1.6.3 Other or mixed ConHD populations
Moalla 2006
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Bias
Study Randomisation
process
Deviations
from intended
interventions
Missing
outcome data
Measurement
of the outcome
Selection of
the reported
results
Overall
Madhavi 2011
Morrison 2013
Klausen 2016
Opotowsky 2018
Sandberg 2018
van Dissel 2019


D A T A  A N D  A N A L Y S E S

Comparison 1.  Physical activity promotion, exercise training and inspiratory muscle training interventions versus
no activity (usual care) in people with congenital heart disease
Outcome or subgroup title No. of
studies
No. of
partici-
pants
Statistical method Effect size
1.1 Maximal cardiorespiratory fit-
ness
14 732 Mean Difference (IV, Random, 95% CI) 1.89 [-0.22, 3.99]
1.1.1 Exercise training 11 435 Mean Difference (IV, Random, 95% CI) 2.74 [0.36, 5.12]
1.1.2 Physical activity promotion 2 259 Mean Difference (IV, Random, 95% CI) -1.71 [-4.64, 1.22]
1.1.3 Inspiratory muscle training 1 38 Mean Difference (IV, Random, 95% CI) 0.70 [-4.83, 6.23]
1.2 Health-related quality of life 3 163 Std. Mean Difference (IV, Random, 95% CI) 0.76 [-0.13, 1.65]
1.3 Physical activity (device-worn) 4 328 Std. Mean Difference (IV, Random, 95% CI) 0.38 [-0.15, 0.92]
1.4 Submaximal cardiorespiratory
fitness (gas exchange threshold)
5 179 Mean Difference (IV, Random, 95% CI) 2.05 [0.05, 4.05]
1.5 Muscular strength 1  Mean Difference (IV, Random, 95% CI) Totals not selected
1.6 Maximal cardiorespiratory fit-
ness (type of ConHD subgroup
analysis)
14 732 Mean Difference (IV, Random, 95% CI) 1.90 [-0.14, 3.95]
Physical activity interventions for people with congenital heart disease (Review)
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Outcome or subgroup title No. of
studies
No. of
partici-
pants
Statistical method Effect size
1.6.1 Population with a single ven-
tricle
4 154 Mean Difference (IV, Random, 95% CI) 2.05 [-0.25, 4.35]
1.6.2 Population with repaired
Tetralogy of Fallot
4 104 Mean Difference (IV, Random, 95% CI) 1.97 [-1.11, 5.05]
1.6.3 Other or mixed ConHD popula-
tions
7 474 Mean Difference (IV, Random, 95% CI) 1.98 [-1.67, 5.62]


Analysis 1.1.  Comparison 1: Physical activity promotion, exercise training and
inspiratory muscle training interventions versus no activity (usual care) in people
with congenital heart disease, Outcome 1: Maximal cardiorespiratory fitness
Study or Subgroup
1.1.1 Exercise training
Therrien 2003
Moalla 2006
Madhavi 2011
Winter 2012
Westhoff-Bleck 2013
Duppen 2015
Avila 2016
Novakovic 2018 (1)
Opotowsky 2018
Sandberg 2018
Novakovic 2018 (2)
van Dissel 2019
Subtotal (95% CI)
Heterogeneity: Tau² = 10.92; Chi² = 40.79, df = 11 (P < 0.0001); I² = 73%
Test for overall effect: Z = 2.26 (P = 0.02)
1.1.2 Physical activity promotion
Morrison 2013
Klausen 2016
Subtotal (95% CI)
Heterogeneity: Tau² = 1.68; Chi² = 1.60, df = 1 (P = 0.21); I² = 37%
Test for overall effect: Z = 1.14 (P = 0.25)
1.1.3 Inspiratory muscle training
Fritz 2020
Subtotal (95% CI)
Heterogeneity: Not applicable
Test for overall effect: Z = 0.25 (P = 0.80)
Total (95% CI)
Heterogeneity: Tau² = 11.06; Chi² = 55.03, df = 14 (P < 0.00001); I² = 75%
Test for overall effect: Z = 1.76 (P = 0.08)
Test for subgroup differences: Chi² = 5.34, df = 2 (P = 0.07), I² = 62.5%
Physical activity
Mean [mL/kg/min]
24.3
33
43.84
29
25.9
35.9
28.6
26.5
1
25.1
24
25.4
37.4
43.2
24
SD [mL/kg/min]
8.2
6.2
10.33
7
6.1
7.4
7.1
12.5
1.5
6.16
6.2
6.6
8.8
9.7
8.3
Total
9
10
51
24
19
43
13
9
13
13
9
17
230
62
81
143
18
18
391
No activity (usual care)
Mean [mL/kg/min]
22.1
29.6
30.99
26
23.5
34.2
28.5
23.3
-1.2
24.03
23.3
27.7
37.5
46.3
23.3
SD [mL/kg/min]
6.5
7.2
7.96
8
5.3
8.6
6.01
8.5
2.3
3.33
8.5
5.6
8.6
10.1
9.1
Total
8
8
61
22
21
30
4
5
15
10
4
17
205
39
77
116
20
20
341
Weight
4.8%
5.4%
8.1%
7.2%
8.0%
7.8%
4.8%
2.7%
9.9%
7.6%
3.5%
7.4%
77.3%
8.1%
8.5%
16.6%
6.1%
6.1%
100.0%
Mean Difference
IV, Random, 95% CI [mL/kg/min]
2.20 [-4.80 , 9.20]
3.40 [-2.90 , 9.70]
12.85 [9.38 , 16.32]
3.00 [-1.36 , 7.36]
2.40 [-1.16 , 5.96]
1.70 [-2.09 , 5.49]
0.10 [-6.94 , 7.14]
3.20 [-7.85 , 14.25]
2.20 [0.78 , 3.62]
1.07 [-2.86 , 5.00]
0.70 [-8.56 , 9.96]
-2.30 [-6.41 , 1.81]
2.74 [0.36 , 5.12]
-0.10 [-3.58 , 3.38]
-3.10 [-6.19 , -0.01]
-1.71 [-4.64 , 1.22]
0.70 [-4.83 , 6.23]
0.70 [-4.83 , 6.23]
1.89 [-0.22 , 3.99]
Mean Difference
IV, Random, 95% CI [mL/kg/min]
-10 -5 0 5 10
Favours no activity (usual care) Favours physical activity
Footnotes
(1) interval training arm
(2) continuous training arm
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Analysis 1.2.  Comparison 1: Physical activity promotion, exercise training
and inspiratory muscle training interventions versus no activity (usual care) in
people with congenital heart disease, Outcome 2: Health-related quality of life
Study or Subgroup
Madhavi 2011 (1)
Opotowsky 2018 (2)
Sandberg 2018 (3)
Total (95% CI)
Heterogeneity: Tau² = 0.50; Chi² = 10.87, df = 2 (P = 0.004); I² = 82%
Test for overall effect: Z = 1.67 (P = 0.09)
Test for subgroup differences: Not applicable
Physical activity
Mean
72.28
-20.1
76.2
SD
8.071
11.4
15.2
Total
51
13
13
77
No activity (usual care)
Mean
57.93
-27.7
76.3
SD
11.019
10.9
20.7
Total
61
15
10
86
Weight
37.9%
31.6%
30.5%
100.0%
Std. Mean Difference
IV, Random, 95% CI
1.46 [1.04 , 1.88]
0.66 [-0.10 , 1.43]
-0.01 [-0.83 , 0.82]
0.76 [-0.13 , 1.65]
Std. Mean Difference
IV, Random, 95% CI
-4 -2 0 2 4
Favours no activity (usual care) Favours physical activity
Footnotes
(1) SF-36 (total score)
(2) MLHFQ
(3) EQ5D VAS


Analysis 1.3.  Comparison 1: Physical activity promotion, exercise training
and inspiratory muscle training interventions versus no activity (usual care) in
people with congenital heart disease, Outcome 3: Physical activity (device-worn)
Study or Subgroup
Duppen 2015 (1)
Klausen 2016
Morrison 2013
Opotowsky 2018
Total (95% CI)
Heterogeneity: Tau² = 0.22; Chi² = 13.81, df = 3 (P = 0.003); I² = 78%
Test for overall effect: Z = 1.42 (P = 0.16)
Test for subgroup differences: Not applicable
Physical activity
Mean
12.7
40.3
57.2
103
SD
8.1
21.8
32.2
56
Total
28
81
62
11
182
No activity (usual care)
Mean
11.8
41.3
29.2
75
SD
6.2
22.9
27.3
25
Total
18
77
39
12
146
Weight
23.7%
30.2%
27.8%
18.3%
100.0%
Std. Mean Difference
IV, Random, 95% CI
0.12 [-0.47 , 0.71]
-0.04 [-0.36 , 0.27]
0.91 [0.49 , 1.33]
0.63 [-0.21 , 1.47]
0.38 [-0.15 , 0.92]
Std. Mean Difference
IV, Random, 95% CI
-2 -1 0 1 2
Favours no activity (usual care) Favours physical activity
Footnotes
(1) Measure of activity: time spent in moderate-to-very-vigorous activity as a percentage. All other studies report minutes of MVPA per day.


Analysis 1.4.  Comparison 1: Physical activity promotion, exercise training and inspiratory
muscle training interventions versus no activity (usual care) in people with congenital
heart disease, Outcome 4: Submaximal cardiorespiratory fitness (gas exchange threshold)
Study or Subgroup
Moalla 2006
Westhoff-Bleck 2013
Duppen 2015
Avila 2016
Novakovic 2018 (1)
Novakovic 2018 (2)
Total (95% CI)
Heterogeneity: Tau² = 2.01; Chi² = 7.52, df = 5 (P = 0.18); I² = 33%
Test for overall effect: Z = 2.01 (P = 0.04)
Test for subgroup differences: Not applicable
Physical activity
Mean [mL/kg/min]
23.6
16.2
20.9
21
20.1
22.6
SD [mL/kg/min]
3.3
5.3
5.9
6.7
5.4
5.4
Total
10
19
46
13
9
9
106
No activity (usual care)
Mean [mL/kg/min]
18.1
15.5
20.6
21.8
18.1
18.1
SD [mL/kg/min]
4.1
3.7
6.2
6.7
4.2
4.2
Total
8
21
31
4
4
5
73
Weight
20.0%
25.1%
26.0%
6.2%
10.8%
11.9%
100.0%
Mean Difference
IV, Random, 95% CI [mL/kg/min]
5.50 [2.00 , 9.00]
0.70 [-2.16 , 3.56]
0.30 [-2.47 , 3.07]
-0.80 [-8.31 , 6.71]
2.00 [-3.42 , 7.42]
4.50 [-0.60 , 9.60]
2.05 [0.05 , 4.05]
Mean Difference
IV, Random, 95% CI [mL/kg/min]
-10 -5 0 5 10
Favours no activity (usual care) Favours physical activity
Footnotes
(1) continuous training arm.
(2) interval training arm

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Analysis 1.5.  Comparison 1: Physical activity promotion, exercise training and inspiratory muscle training
interventions versus no activity (usual care) in people with congenital heart disease, Outcome 5: Muscular strength
Study or Subgroup
Moalla 2006
Physical activity
Mean [MVC (N·m)]
120.2
SD [MVC (N·m)]
19.4
Total
10
No activity (usual care)
Mean [MVC (N·m)]
103.07
SD [MVC (N·m)]
9.4
Total
8
Mean Difference
IV, Random, 95% CI [MVC (N·m)]
17.13 [3.45 , 30.81]
Mean Difference
IV, Random, 95% CI [MVC (N·m)]
-20 -10 0 10 20
Favours no activity (usual care) Favours physical activity


Analysis 1.6.  Comparison 1: Physical activity promotion, exercise training and inspiratory
muscle training interventions versus no activity (usual care) in people with congenital heart
disease, Outcome 6: Maximal cardiorespiratory fitness (type of ConHD subgroup analysis)
Study or Subgroup
1.6.1 Population with a single ventricle
Winter 2012
Westhoff-Bleck 2013
Duppen 2015
Fritz 2020
Subtotal (95% CI)
Heterogeneity: Tau² = 0.00; Chi² = 0.62, df = 3 (P = 0.89); I² = 0%
Test for overall effect: Z = 1.75 (P = 0.08)
1.6.2 Population with repaired Tetralogy of Fallot
Therrien 2003
Duppen 2015
Avila 2016
Novakovic 2018 (1)
Novakovic 2018 (2)
Subtotal (95% CI)
Heterogeneity: Tau² = 0.00; Chi² = 0.51, df = 4 (P = 0.97); I² = 0%
Test for overall effect: Z = 1.25 (P = 0.21)
1.6.3 Other or mixed ConHD populations
Moalla 2006
Madhavi 2011
Morrison 2013
Klausen 2016
Opotowsky 2018
Sandberg 2018
van Dissel 2019
Subtotal (95% CI)
Heterogeneity: Tau² = 20.53; Chi² = 54.14, df = 6 (P < 0.00001); I² = 89%
Test for overall effect: Z = 1.06 (P = 0.29)
Total (95% CI)
Heterogeneity: Tau² = 10.84; Chi² = 55.27, df = 15 (P < 0.00001); I² = 73%
Test for overall effect: Z = 1.82 (P = 0.07)
Test for subgroup differences: Chi² = 0.00, df = 2 (P = 1.00), I² = 0%
Physical activity
Mean [mL/kg/min]
29
25.9
33.2
24
24.3
38
28.6
26.5
24
33
43.84
37.4
43.2
1
25.1
25.4
SD [mL/kg/min]
7
6.1
6.5
8.3
8.2
7.6
7.1
12.5
6.2
6.2
10.33
8.8
9.7
1.5
6.16
6.6
Total
24
19
19
18
80
9
24
13
9
9
64
10
51
62
81
13
13
17
247
391
No activity (usual care)
Mean [mL/kg/min]
26
23.5
32.5
23.3
22.1
35.2
28.5
23.3
23.3
29.6
30.99
37.5
46.3
-1.2
24.03
27.7
SD [mL/kg/min]
8
5.3
9.6
9.1
6.5
8
6.01
8.5
8.5
7.2
7.96
8.6
10.1
2.3
3.33
5.6
Total
22
21
11
20
74
8
19
4
5
4
40
8
61
39
77
15
10
17
227
341
Weight
6.9%
7.7%
5.1%
5.8%
25.5%
4.6%
6.6%
4.6%
2.6%
3.3%
21.6%
5.1%
7.8%
7.8%
8.2%
9.6%
7.3%
7.1%
52.9%
100.0%
Mean Difference
IV, Random, 95% CI [mL/kg/min]
3.00 [-1.36 , 7.36]
2.40 [-1.16 , 5.96]
0.70 [-5.68 , 7.08]
0.70 [-4.83 , 6.23]
2.05 [-0.25 , 4.35]
2.20 [-4.80 , 9.20]
2.80 [-1.91 , 7.51]
0.10 [-6.94 , 7.14]
3.20 [-7.85 , 14.25]
0.70 [-8.56 , 9.96]
1.97 [-1.11 , 5.05]
3.40 [-2.90 , 9.70]
12.85 [9.38 , 16.32]
-0.10 [-3.58 , 3.38]
-3.10 [-6.19 , -0.01]
2.20 [0.78 , 3.62]
1.07 [-2.86 , 5.00]
-2.30 [-6.41 , 1.81]
1.98 [-1.67 , 5.62]
1.90 [-0.14 , 3.95]
Mean Difference
IV, Random, 95% CI [mL/kg/min]
-10 -5 0 5 10
Favours no activity (usual care) Favours physical activity
Footnotes
(1) interval training arm
(2) continuous training arm


A D D I T I O N A L  T A B L E S
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Author Sample size Type of inter-
vention
Question-
naire
Domain Intervention vs. control at follow
up
Mean (Standard deviation)& be-
tween group P value
Direction of effect Overall risk
of bias
SF-36 (8 do-
mains) +
Physical function-
ing
94.6 (10.9) 95.0 (8.5) P = 0.71 Exercise = control High
SF-36 (8 do-
mains) +
Bodily pain 96.6 (8.1) 93.2 (17.3)P = 0.96 Exercise = control High
SF-36 (8 do-
mains) +
General health 68.3 (27.9) 67.5 (19.1)P = 0.94 Exercise = control High
SF-36 (8 do-
mains) +
Vitality 71.7 (18.0) 70 (17.0)P = 0.56 Exercise = control High
SF-36 (8 do-
mains) +
Role limitations
due to physical lim-
itations
100 (0.0) 91.7 (21.2)P = 0.16 Exercise = control High
SF-36 (8 do-
mains) +
Social functioning 95.8 (10.0) 100.0 (0.0)P = 0.09 Exercise = control High
SF-36 (8 do-
mains) +
Rolelimitations
due to emotional
problems
100(0.0) 100 (0.0)P = 0.72 Exercise = control High
SF-36 (8 do-
mains) +
Mental health 85.0 (16.8) 81.3 (10.2)P = 0.65 Exercise = control High
TACQOL + Symptoms 95.6(7.90) 97.8 (3.7) P = 0.16 Exercise = control High
TACQOL + Impact of cardiac
surveillance
85 (6.30) 85.7 (4.80) P = 0.07 Exercise = control High
TACQOL + Worries 95.7(8.70) 88.6 (270) P = 0.67 Exercise = control High
Duppen 2015

73

Exercise train-
ing

TACQOL-CF
+
Pain and physical
symptoms
26.3 (6.2) 24 (7.15) P = 0.21 Exercise = control High
Table 1.  Health-related quality of life
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TACQOL-CF
+
Motor functioning 30.1 (1.9) 29.5 (4.37) P = 0.51 Exercise = control High
TACQOL-CF
+
Cognitive function-
ing
28.6 (6.2) 29.7 (6.9) P = 0.05 Exercise = control High
TACQOL-CF
+
Social functioning 31.5 (1.2) 32 (0) P = 0.45 Exercise = control High
TACQOL-CF
+
Positive emotional
functional
14.2 (3.5) 14.43 (2.9) P = 0.39 Exercise = control High
TACQOL-CF
+
Negative emotional
functioning
12.7 (2.12) 14.2 (2.2) P = 0.34 Exercise = control High
Madhavi 2011 112 Exercise train-
ing
SF-36 + SF36 total score 23.3 (13.2)11.3 (14.3) P < 0.001 Exercise > control High
Danish Pae-
diatric QoL
Inventory +
Generic NR Exercise = control HighKlausen 2016

158 Physical activ-
ity promotion

Danish Pae-
diatric QoL
Inventory +
Disease specific NR Exercise = control High
Opotowsky
2018
28 Exercise train-
ing
MLHFQ - MLHFQ 20.1 (11.4)27.7 (10.9) P = 0.13 Exercise = control High
Sandberg
2018
23 Exercise train-
ing
EQ5D VAS + EQ5D VAS 76.2 (15.2) 76.3 (20.7) P = 0.31 Exercise = control High
SF36 + Physical compo-
nent
86.7 (40.2) 101.0 (16.6)P > 0.05 Exercise = control HighNovakovic
2018

14 Exercise train-
ing(Interval)

SF36 + Mental component 80.0 (21.0) 87.3 (21.9) P > 0.05 Exercise = control High
SF36 + Physical compo-
nent
103 (5.2) 101.0 (16.6) P > 0.05 Exercise = control HighNovakovic
2018

13 Exercise train-
ing(Continu-
ous)
SF36 + Mental component 89.3 (18.4) 87.3 (21.9) P > 0.05 Exercise = control High
Table 1.  Health-related quality of life(Continued)
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West-
hoff-Bleck
2013
40 Exercise train-
ing
KCCQ + KCCQ NR Exercise = control High
SF-36 + Mental component P = 0.17 Exercise = control High
SF-36 + Physical compo-
nent
P = 0.20 Exercise = control High
Con-
HD-TAAQOL
+
Symptoms 85 (10.79) 83 (10.47) P = 0.31 Exercise = control High
Con-
HD-TAAQOL
+
Worries 77 (15.4) 84.5 (9.21) P = 0.30 Exercise = control High
Winter 2012


46


Exercise train-
ing


Con-
HD-TAAQOL
+
Impact 84 (7.19) 85.25 (6.20) P = 0.91 Exercise = control High
Table 1.  Health-related quality of life(Continued)
Each study's outcomeof health related quality of life was individuallyassessedusingrisk of bias 2; all studies were judgedas a high risk of bias under the domain 'Measurement
of the outcome'. '+' = ahigher scorerepresentsbetterhealth; '-'= alower scorerepresentsbetterhealth; HRQoL,Health related quality of life;SF-36, 36-Item Short Form Health
Survey;MLHFQ,Minnesota living with heart failure questionnaire;TACQOL, TNO/AZL child quality of life questionnaire;ConHD TAAQOL, The congenital heart disease - TNO/AZL
adult quality of life questionnaire;EQ5D VAS,EuroQol Vertical Visual Analogue Scale; KCCQ, Kansas City Cardiomyopathy Questionnaire.

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
Study Age Type of ConHD and (sample size, %) Classification
Avila 2016 35 ± 11 Repaired ToF (17, 100%) Severe
Fontan circulation (43, 48%)
[Intra-atrial lateral tunnel 47%; extracardiac conduit 44%; other 9%]
Duppen 2015 15 ± 3
Repaired ToF (47, 52%)

Severe
Fritz 2020 30 ± 9 Fontan circulations (42, 100%)
[Atrioventricular Anastomosis 19%; Atriopulmonary Anastomosis 21%; To-
tal Cavopulmonary Connection 60%]
Severe
Coarctation of the aorta (52, 33%)
TGA (35, 22%)
Steno–Fallot tetralogy (21, 13%)
Double outlet right ventricle (7, 4%)
Truncus arteriosus (4, 3%)
Atrioventricular septal defect (9, 6%)
TCPC (6, 4%)
Klausen 2016 15 ± 1
Other (24, 15%)
Severe
Madhavi 2011 29 ± 11 Acyanotic Congenital Heart Disease (112, 100%) Mild
Fontan (4, 22%)
TGA (Senning/Mustard procedure) (5, 28%)
Repaired ToF (5, 28%)
Moalla 2006 13 ± 1
Repaired ASD (4, 22%)
Mild to Severe
Minor CHD (nosurgical intervention)(39, 27%)
Acyanoticcorrected ConHD (61, 43%)
Cyanotic corrected (30, 21%)
Morrison 2013 15 ± 2
Cyanotic palliated (13, 9%)
Mild to Severe
Novakovic 2018 38 ± 8 Repaired ToF (30, 100%) Severe
ToF with pulmonary stenosis or atresia or, DORV (13, 46%)Opotowsky
2018
41 ±12
TGA with a systemic RV, (9, 32%)
Severe
Table 2.  Individual ConHD lesions pooled into the meta-analyses
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Fontan (2, 7%)
Pulmonary atresia with intact ventricular septum with biventricular repair
(2, 7%)
Truncus arteriosus (1, 4%)
Ebstein anomaly (1, 4%)
ToF (5, 22%)
ccTGA & d-TGA (8, 35%)
TCPC (5, 22%)
PA (2, 9%)
Complete AV-septal defect (1, 4%)
Ebsteinanomaly (1, 4%)
Sandberg 2018 30 ± 11
Miscellaneous (1, 4%)
Severe
Therrien 2003 35 ± 9 Repaired ToF (18, 100%) Severe
Westhoff-Bleck
2013
29 ± 3 Systemic right ventricle - TGA [Mustard] (48, 100%) Severe
Winter 2012 32 + 11 Systemic right ventricle - TGA and ccTGA (46, 100%) Severe
ToF (12, 30%)
TGA (13, 33%)
Fontan circulation (9, 22%)
Pulmonary atresia (3, 7.5%)
van Dissel 2019

40 ± 9

Other (3, 7.5%)
Severe

Table 2.  Individual ConHD lesions pooled into the meta-analyses(Continued)
ToF, tetralogy of Fallot; TGA, transposition of the great arteries; ccTGA, congenitally corrected transposition of the great arteries; d-TGA,
dextro-transposition of the great arteries; ASD, atrial septal defect; TCPC, Total cavopulmonary connection; DORV, double-outlet right
ventricle; RV, right ventricle.
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Study Age group &
severity
Location &
supervision
Frequencya
(sessions
per week)
Intensity Timeb (min-
utes)
Type Durationc
(Weeks)
Dose
(a*b*c)
Avila 2016 Adult & severe
(ToF)
Hospital & su-
pervised
1 to 2 70% to 80% of the maximum HR (in-
creased throughout intervention)
60 Combina-
tion of resis-
tance and
aerobic dy-
namic (run-
ning, row-
ing etc.) ex-
ercise
12 1080
Duppen
2015
Paediatric & se-
vere (ToF and
Fontan)
Hospital & su-
pervised

2 to 3 Resting heart rate plus 60% to 70% of
the HR reserve
60

Aerobic dy-
namic
12

1800

Madhavi
2011
Adult & mild NR NR Individualised (NR)

NR

NR 12 N/A
Moalla2006 Paediatric&
mild/severe
Home & se-
mi-supervised
3

HR at the gas exchange threshold 60

Cycling 12 2160

80% of HRpeak in high intensity exer-
cise
Novakovic
2018

Adult & severe
(ToF)

NR

2 to 3
70% of HRpeak in continuous intensity
exercise
42

Cycling or
speed walk-
ing
12

1260


Opotowsky
2018
Adult & severe Hospital & su-
pervised
2

HR at Gas Exchange Threshold 60

Combina-
tion of resis-
tance and
aerobic dy-
namic
12

1440

Sandberg
2018
Adult & severe Home & se-
mi-supervised
3 HR was calculated according to the Kar-
vonen method and to achieve BORG 15
to 16
31 Cycling 12 1116
Therrien
2003
Adult& severe
(ToF)
Hospital and
home (1:2 ra-
tio) & super-
vised
3 60% to 85% of pre training peak VO2 50 Cycling and
walking

12 1800
Table 3.  Characteristics of exercise training interventions
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West-
hoff-Bleck2013

Adult& severe
(Mustard proce-
dure)
Home & se-
mi-super-
vised
3-5 HR corresponding to 50% of peak VO2 10 to 30 Cycling 24 2550d
Winter 2012 Adult& severe Home & se-
mi-super-
vised
3 75% to 90% of max heart rate(in-
creased throughout intervention)
42 Step aero-
bics
10 1260
van Dissel
2019
Adult & Moder-
ate and Severe
Home & se-
mi-super-
vised
3

80% of the maximum HR 45

Self-select-
ed
26 3510
Table 3.  Characteristics of exercise training interventions(Continued)
ToF, Tetralogy of Fallot; HR, Heart Rate; NR, Not Reported; d See dose calculations inCharacteristics of included studies
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
Potential effectmodifiers Regression coefficientand
(Standard error)
P value
Age (adult vs. paediatric) 2.5 (2.2) 0.262
Baseline CRF (peak VO2mL.kg.min-1)−0.2 (0.1) 0.186
Dose (intervention length*no. sessions per week*session length) −0.2 (0.3) 0.614
Follow-up period/intervention length(weeks) −0.18 (0.1) 0.031
Percentage of male −0.5 (0.3) 0.083
Risk of bias 9.1 (2.2) < 0.01
Sample size −0.001 (0.02) 0.963
Setting (home or hospital based) −2.3 (1.6) 0.171
Study location (Continent) −3.5 (1.8) 0.070
Type of intervention (exercise training, PA promotion, IMT) −2.3 (1.7) 0.208
Table 4.  Univariate meta-regression analysis
Bold = statistically significant; CRF, Cardiorespiratory fitness;


A P P E N D I C E S
Appendix 1. Search strategy
CENTRAL
#1 MeSH descriptor: [Exercise] explode all trees
#2 MeSH descriptor: [Physical Fitness] this term only
#3 MeSH descriptor: [Sports] explode all trees
#4 MeSH descriptor: [Rehabilitation] this term only
#5 MeSH descriptor: [Dance Therapy] this term only
#6 MeSH descriptor: [Exercise Therapy] explode all trees
#7 MeSH descriptor: [Recreation Therapy] this term only
#8 MeSH descriptor: [Physical Exertion] this term only
#9 MeSH descriptor: [Physical Education and Training] explode all trees
#10 MeSH descriptor: [Dancing] this term only
#11 exercis*
#12 aerobic*
#13 sport*
#14 walk*
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#15 bicycle*
#16 ((lifestyle or life-style) NEAR/5 activ*)
#17 ((lifestyle or life-style) NEAR/5 physical*).tw.
#18 (physical* NEAR/5 (fit* or train* or activ* or endur* or exert* or perform* or inact*))
#19 anaerobic
#20 rehabilitat*
#21 heart rate recovery
#22 danc*
#23 (run* or jog*)
#24  #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or
#21 or #22 or #23
#25 MeSH descriptor: [Heart Defects, Congenital] explode all trees
#26 MeSH descriptor: [Heart Diseases] explode all trees and with qualifier(s): [congenital - CN]
#27 (heart NEAR/2 (defect* or abnormal* or malform*))
#28 (congenital NEAR/2 (heart or cardiac or cardio*))
#29 #25 or #26 or #27 or #28
#30 #24 and #29
MEDLINE Ovid
1 exp Exercise/
2 Physical Fitness/
3 exp Sports/
4 Rehabilitation/
5 Dance Therapy/
6 exp Exercise Therapy/
7 Recreation Therapy/
8 Physical Exertion/
9 exp "Physical Education and Training"/
10 Dancing/
11 exercis*.tw.
12 aerobic$.tw.
13 sport$.tw.
14 walk$.tw.
15 bicycle$.tw.
16 ((lifestyle or life-style) adj5 activ$).tw.
17 ((lifestyle or life-style) adj5 physical$).tw.
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18 (physical$ adj5 (fit$ or train$ or activ$ or endur$ or exert$ or perform* or inact*)).tw.
19 anaerobic.tw.
20 rehabilitat$.tw.
21 heart rate recovery.tw.
22 danc*.tw.
23 (run* or jog*).tw.
24 or/1-23
25 exp Heart Defects, Congenital/
26 exp Heart Diseases/cn [Congenital]
27 (heart adj2 (defect* or abnormal* or malform*)).tw.
28 (congenital adj2 (heart or cardiac or cardio*)).tw.
29 or/25-28
30 24 and 29
31 randomized controlled trial.pt.
32 controlled clinical trial.pt.
33 randomized.ab.
34 placebo.ab.
35 drug therapy.fs.
36 randomly.ab.
37 trial.ab.
38 groups.ab.
39 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38
40 exp animals/ not humans.sh.
41 39 not 40
42 30 and 41
Embase Ovid
1 exp exercise/
2 fitness/
3 exp sport/
4 rehabilitation/
5 dance therapy/
6 exp kinesiotherapy/
7 recreational therapy/
8 exp physical education/
9 dancing/
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10 exercis*.tw.
11 aerobic$.tw.
12 sport$.tw.
13 walk$.tw.
14 bicycle$.tw.
15 ((lifestyle or life-style) adj5 activ$).tw.
16 ((lifestyle or life-style) adj5 physical$).tw.
17 (physical$ adj5 (fit$ or train$ or activ$ or endur$ or exert$ or perform* or inact*)).tw.
18 anaerobic.tw.
19 rehabilitat$.tw.
20 heart rate recovery.tw.
21 danc*.tw.
22 (run* or jog*).tw.
23 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22
24 exp congenital heart malformation/
25 heart disease/cn [Congenital Disorder]
26 (heart adj2 (defect* or abnormal* or malform*)).tw.
27 (congenital adj2 (heart or cardiac or cardio*)).tw.
28 24 or 25 or 26 or 27
29 23 and 28
30 random$.tw.
31 factorial$.tw.
32 crossover$.tw.
33 cross over$.tw.
34 cross-over$.tw.
35 placebo$.tw.
36 (doubl$ adj blind$).tw.
37 (singl$ adj blind$).tw.
38 assign$.tw.
39 allocat$.tw.
40 volunteer$.tw.
41 crossover procedure/
42 double blind procedure/
43 randomized controlled trial/
44 single blind procedure/
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45 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44
46 (animal/ or nonhuman/) not human/
47 45 not 46
48 29 and 47
CINAHL
S52 S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 
S51 S49 not S50 
S50 MH (human) 
S49 S46 OR S47 OR S48 
S48 TI (animal model*) 
S47 MH (animal studies)  S46 MH animals+ 
S45 AB (cluster W3 RCT) 
S44 MH (crossover design) OR MH (comparative studies) 
S43 AB (control W5 group)
S42 PT (randomized controlled trial) 
S41 MH (placebos)
S40 MH (sample size) AND AB (assigned OR allocated OR control) 
S39 TI (trial) 
S38 AB (random*) 
S37 TI (randomised OR randomized) 
S36 MH cluster sample 
S35 MH pretest-posttest design 
S34 MH random assignment 
S33 MH single-blind studies
S32 MH double-blind studies 
S31 MH randomized controlled trials 
S30 S24 AND S29 
S29 S25 OR S26 OR S27 OR S28 
S28 TX (congenital n2 (heart or cardiac or cardio*))
S27 TX (heart n2 (defect* or abnormal* or malform*)) 
S26 (MH "Heart Diseases+/FG") 
S25 (MH "Heart Defects, Congenital+") 
S24 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR
S19 OR S20 OR S21 OR S22 OR S23
S23 TX (run* or jog*) 
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S22 TX danc* 
S21 TX heart rate recovery
S20 TX rehabilitat*
S19 TX anaerobic 
S18 TX (physical* n5 (fit* or train* or activ* or endur* or exert* or perform* or inact*)) 
S17 TX ((lifestyle or life-style) n5 physical*)
S16 TX ((lifestyle or life-style) n5 activ*) 
S15 TX bicycle* 
S14 TX walk* 
S13 TX sport* 
S12 TX aerobic* 
S11 TX exercis* 
S10 (MH "Dancing") 
S9 (MH "Physical Education and Training+") 
S8 (MH "Exertion") 
S7 (MH "Recreational Therapy") 
S6 (MH "Therapeutic Exercise+") 
S5 (MH "Dance Therapy")
S4 (MH "Rehabilitation") 
S3 (MH "Sports+")
S2 (MH "Physical Fitness")
S1 (MH "Exercise+")
AMED
1 exp Exercise/
2 Physical fitness/
3 exp Sports/
4 Rehabilitation/
5 Dance therapy/
6 exp Exercise therapy/
7 Recreation/
8 Exertion/
9 exp Physical education/
10 Dancing/
11 exercis*.tw.
12 aerobic$.tw.
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13 sport$.tw.
14 walk$.tw.
15 bicycle$.tw.
16 ((lifestyle or life-style) adj5 activ$).tw.
17 ((lifestyle or life-style) adj5 physical$).tw.
18 (physical$ adj5 (fit$ or train$ or activ$ or endur$ or exert$ or perform* or inact*)).tw.
19 anaerobic.tw.
20 rehabilitat$.tw.
21 heart rate recovery.tw.
22 danc*.tw.
23 (run* or jog*).tw.
24 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or
25 exp Heart defects congenital/
26 (heart adj2 (defect* or abnormal* or malform*)).tw.
27 (congenital adj2 (heart or cardiac or cardio*)).tw.
28 25 or 26 or 27
29 24 and 28
30 randomized controlled trial.pt.
31 controlled clinical trial.pt.
32 randomized.ab.
33 placebo.ab.
34 randomly.ab.
35 trial.ab.
36 groups.ab.
37 30 or 31 or 32 or 33 or 34 or 35 or 36
38 exp animals/ not humans.sh.
39 37 not 38
40 29 and 39
Web of Science and BIOSIS
# 20 #19 AND #18
# 19 TS=(random* or blind* or allocat* or assign* or trial* or placebo* or crossover* or cross-over*)
# 18 #17 AND #14
# 17 #16 OR #15
# 16 TS=(congenital NEAR/2 (heart or cardiac or cardio*))
# 15 TS=(heart NEAR/2 (defect* or abnormal* or malform*))
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# 14 #13 OR #12 OR #11 OR #10 OR #9 OR #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 OR #1
# 13 TS=(run* or jog*)
# 12 TS=danc*
# 11 TS=heart rate recovery
# 10 TS=rehabilitat*
# 9 TS=anaerobic
# 8 TS=(physical* NEAR/5 (fit* or train* or activ* or endur* or exert* or perform* or inact*))
# 7 TS=((lifestyle or life-style) NEAR/5 physical*)
# 6 TS=((lifestyle or life-style) NEAR/5 activ*)
# 5 TS=bicycle*
# 4 TS=walk*
# 3 TS=sport*
# 2 TS=aerobic*
# 1 TS=exercis*
LILACS
(heart or cardiac$ or cardio$) AND (defect or congenital or malform$ or abnormal$) [Words] and Exercise$ or aerobic$ or sport$ or walk$
or bicycle$ or anaerobic$ or rehabilitat$ or heart rate recovery$ or danc$ or run$ or jog$ or active$ or train$ or fit$ [Words]
DARE
heart or cardiac* or cardio* AND defect or congenital or malform* or abnormal* AND exercise* or aerobic* or sport* or walk* or bicycle* or
anaerobic* or rehabilitat* or heart rate recovery* or danc* or run* or jog* or active* or train* or fit*
ClinicalTrials.gov
Condition or disease: Congenital Heart Disease
Other terms: exercise
Study type: Interventional studies (Clinical Trials)
Appendix 2. Severity classification in congenital heart disease
Severity of congenital heart disease is most oen classified by lesion-specific data. While this approach is appropriate in most cases, it
must be stressed that severity is highly individual and should be judged by a physician using validated criteria (Budts 2013;Budts 2020).
Mild ConHD
Mild ConHD is the least severe classification in our planned review. Patients with mild ConHD may be asymptomatic and have no significant
murmur. Some example lesions of mild ConHD are as follows.
•Bicuspid aortic valve (BAV)
•Small atrial septal defects (ASD)
•Small ventricular septal defects (VSD)
•Small patent ductus arteriosus (PDA)
Moderate ConHD
Patients with moderate ConHD are likely to be symptomatic and the lesions will likely be identified in a clinical study. For example:
•mild or moderate aortic stenosis (AS) or aortic incompetence;
•moderate pulmonary stenosis (PS) or incompetence;
•non-critical coarctation of the aorta;
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•large atrial septal defect;
•complex forms of ventricular septal defect.
Severe ConHD
This category includes complex conditions that usually require immediate medical intervention. Some example lesions are:
•dextro-transposition of the great arteries;
•tetralogy of fallot, including pulmonary atresia and absent pulmonary valve;
•hypoplastic right heart;
•tricuspid atresia;
•pulmonary atresia with an intact ventricular septum;
•Ebstein anomaly;
•hypoplastic le heart;
*aortic atresia
*mitral atresia
•hypoplastic le heart;
*aortic atresia
*mitral atresia
•double outlet right ventricle;
•truncus arteriosus;
•total anomalous pulmonary venous connection;
•large atrioventicular septal defect; large VSD; large PDA;
•severe AS and/or severe PS;
•critical coarctation of the aorta.
This framework has been adopted from the work of Homan 2002 and Warnes 2008.
H I S T O R Y
Protocol first published: Issue 8, 2019
Review first published: Issue 10, 2020
C O N T R I B U T I O N S  O F  A U T H O R S
CAW andCW independently completedtitle and abstract screening, full text review, risk of bias assessments, data extraction andGRADE.
CAW had overall control of the design of the study and co-wrote the manuscript.
CW assisteddata analysis, produced the SoF tableand co-wrote themanuscript.
GEPgave specialistclinical insight into the literature and population with congenital heart disease.
GSgave specialistclinical insight into the literature and population with congenital heart disease
RST designed and carried out the statistical analysis and arbitrated any discrepancies.
LL was the lead author overseeing the project andarbitrated any discrepancies.
All authors contributed to the peer review and agreed on the final versionof this manuscript.
D E C L A R A T I O N S  O F  I N T E R E S T
CAW has received funding from Heart Research UK and Canon Medical Systems Ltd to complete research into the heart health of young
people. The author had full control of the design of the study, methods used, outcome parameters, analysis of the data and production of
any manuscripts. Neither of these organisations have a financial interest in this review.
CW has a funded PhD scholarship from the University of Exeter and Canon Medical.Canon Medical Systems Ltd does not have a financial
interest in this review.
GEP is lead researcher in a contractual research partnership between the University of Bristol and Canon Medical Systems UK Ltd.Canon
Medical Systems Ltd does not have a financial interest in this review.
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GS is Medical Director of Sports Cardiology UK. Research grant from Heart research UK to evaluate an exercise prescription programme
in congenital heart patients. Fee for lecturing at scientific meetings and financial support for educational arrhythmia meeting in February
2019 from Medtronic Actelion.None of the organisations named have a financial interest in this review.
LL has no known conflicts of interest.
RST has no known conflicts of interest.
S O U R C E S  O F  S U P P O R T
Internal sources
•Canon Medical UK Ltd., UK
C Wadey was funded by an industrial PhD studentship from the University of Exeter and Canon Medical Systems UK Ltd.
GE Pieles is lead researcher in a contractual research partnership between the University of Bristol and Canon Medical Systems UK Ltd.
investigating cardiac function during exercise in children.
Authors had full control of the design of the study, methods used, outcome parameters, analysis of the data and production of any
manuscripts.
External sources
•NIHR, UK
This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Heart Group. The
views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme,
NIHR, NHS or the Department of Health and Social Care.
D I F F E R E N C E S  B E T W E E N  P R O T O C O L  A N D  R E V I E W
•WHO ICTRPwas unavailable due to increased traic to the site because of COVID 19,therefore it was not searched. Clinical trials.gov
was searched.
•Two studies estimated cardiorespiratory fitness (CRF) using validated CPET protocols, these were pooled with direct measures (gas
analysis) of CRF
•Baseline CRFand risk of bias were added to the univariate meta regression.
•A vote counting table was used to synthesise all the information regarding health related quality of life.
•Sensitivity analysis was changed from 'all studies versus only including those studies we judge to have overall low risk of bias (low risk in
all domains)' to all studies versusexclusion of high risk studies. This was changed as only one study had a low risk of bias in all domains.
N O T E S
None
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