Download Am J Cardiol. 105

Exercise Performance and Activity Level in Children With
Transposition of the Great Arteries Treated by the Arterial
Switch Operation
Elsje van Beek, MSca, Mathijs Binkhorst, MDa, Marieke de Hoog, MSca, Patricia de Groot, PhDa,*,
Arie van Dijk, MD, PhDb, Michiel Schokking, MD, PhDb, and Maria Hopman, MD, PhDa
The exercise capacity of children after arterial switch for transposition of the great arteries
(TGA) is known to be at the lower limit of normal. We aimed to ascertain whether this
results from compromised hemodynamics or deconditioning. A total of 17 children with
TGA (12 male and 5 female children; age 12.1 ⴞ 2.0 years) treated with the arterial switch
operation were compared with 20 age-matched controls (13 male and 7 female children; age
12.8 ⴞ 2.4 years) regarding their peak exercise capacity, peak workload, and peak heart
rate, as assessed by cycle ergometry. The children’s physical activity level was monitored
for a 7-day period using a pedometer and diary, and a questionnaire was used to assess
physical activity participation and overprotection. The results demonstrated that TGA
children showed a significantly reduced peak exercise capacity (47.4 ⴞ 6.4 vs 41.1 ⴞ 6.6
ml/kg/min; p <0.05), maximal workload (3.7 ⴞ 0.5 vs 3.1 ⴞ 0.6 W/kg; p <0.01), and
maximal heart rate (189 ⴞ 9 vs 180 ⴞ 14 beats/min; p <0.05) compared to the controls. No
significant differences were found in the physical activity pattern or overprotection. In
conclusion, given the comparable physical activity level, but reduced exercise capacity in
the TGA children, these children most likely fall short in their exercise performance
because of restrictive hemodynamics rather than deconditioning from reduced daily life
activity. © 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:398 – 403)
Previous studies have shown that the exercise capacity of
children after arterial switch for transposition of the great
arteries (TGA) is, in general, slightly lower than that of their
healthy peers.1–3 Although previous research focused on
either exercise capacity or activity pattern (24-hour heart
rate monitoring4 survey5), the present study has uniquely
addressed both physical fitness and the physical activity
pattern of children with TGA treated by the arterial switch
operation (ASO).
Moreover, the physical activity pattern was studied comprehensively in our participants using 7-day activity monitoring (pedometer and diary) and a questionnaire on physical activity and participation. We combined the approach of
exercise testing and activity monitoring in an attempt to
determine whether (1) the aerobic capacity is indeed reduced in children with TGA compared to that of healthy
peers, and (2), if true, whether this resulted from reduced
physical activity or cardiac restriction. The results of the
present study might aid in the preparation of specific recommendations regarding participation in daily physical activity functioning, sports, and therapy for children with
TGA that could improve their quality of life.
a
Department of Integrative Physiology, Radboud University Nijmegen
Medical Centre, Nijmegen, The Netherlands; bDepartment of Pediatric
Cardiology, Radboud University Nijmegen Medical Centre, Nijmegen,
The Netherlands. Manuscript received July 9, 2009; revised manuscript
received and accepted September 11, 2009.
*Corresponding author: Tel: (⫹31) 0-24-361-3676; fax: (⫹31) 0-24354-0535.
E-mail address: [email protected] (P. de Groot).
0002-9149/10/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjcard.2009.09.048
Methods
Children eligible for participation in the present study
were selected from a database of the Department of Pediatric Cardiology that includes patients with TGA who
underwent surgery from 1990 to 1999 at the Radboud
University Nijmegen Medical Centre (Nijmegen, The
Netherlands). Patients with metabolic, neurologic, muscular, or orthopedic anomalies were excluded. Also, syndromes with congenital heart defects as one of the features,
heart failure (New York Heart Association class ⱖI), cyanosis at rest (oxygen saturation ⬍90%), and severe cardiac
arrhythmia were considered exclusion criteria. A total of 35
children were contacted by letter and invited to participate
in the study. The siblings of these children were asked to
participate in the control group. Of the 35 children, 5 could
not be traced because of invalid address data. In total, 17
children with TGA aged 10 to 17 years and 20 gendermatched control subjects were included in the present study.
The local ethical committee of the Radboud University
Nijmegen approved the study, and the children and their
parents provided written informed consent.
Anthropometric measurements were taken and included
height, weight, abdominal girth, and skin fold thickness. For
each participant, body mass index was calculated. The abdominal girth was assessed to estimate the amount of abdominal fat and was measured 1 cm above the level of the
iliac crest. A 4-site (biceps, triceps, subscapular, and suprailiac) skin fold thickness measurement of the nondominant body site was performed (Ponderal, Zoetermeer, The
Netherlands). The sum of the 4 skin folds was used to
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Congenital Heart Disease/Exercise in Children With TGA
399
Table 1
Demographic and anthropometric values of both groups
Variable
Control Group
(n ⫽ 20)
TGA Group
(n ⫽ 17)
Gender
Male
13
12
female
7
5
Age (years)
12.8 ⫾ 2.4 (10–17)
12.1 ⫾ 2.0 (10–17)
Weight (kg)
49.5 ⫾ 10.6 (33.1–70.7) 47.3 ⫾ 14.1 (28.5–76.8)
Length (cm)
159.9 ⫾ 12.2 (141–186) 156.2 ⫾ 14.6 (138–186)
Body mass index
19.2 ⫾ 2.3 (16.4–23.8)
19.1 ⫾ 2.4 (14.8–23.5)
(kg/m2)
Lean body mass (kg) 40.9 ⫾ 9.4 (26.4–59.8)
38.5 ⫾ 11.5 (23.3–65.4)
Systolic blood
110 ⫾ 11 (85–132)
119 ⫾ 13 (90–154)
pressure
(mm Hg)
Diastolic blood
76 ⫾ 8 (60–114)
72 ⫾ 9 (60–90)
pressure
(mm Hg)
Data are presented as mean ⫾ SD (minimum to maximum range).
Table 2
Cardiac co-morbidities in children with transposition of the great arteries
(TGA) treated by arterial switch operation (ASO)
Deficiency
Complete right bundle branch block
Incomplete right bundle branch block
First-degree atrioventricular block
Homograft stenosis
Pulmonary stenosis
Pulmonary insufficiency
Neoaortic insufficiency
Aortic valve stenosis
Pulmonary valve stenosis
Tricuspid valve insufficiency
Mitral valve insufficiency
Narrowing of left ventricular outflow tract
Enlarged neoaortic root diameter
Figure 1. Peak aerobic capacity (ml/kg/min) in children with TGA after
ASO (n ⫽ 15) and controls (n ⫽ 15). Values are presented as mean ⫾ SD.
*p ⬍0.05.
Patients (n)
1
5
1
1
13
1
5
1
1
1
1
1
2
determine the age- and gender-adjusted body fat percentage.
Using the tables provided by Deurenberg et al6 and this
information, the lean body mass was calculated. The blood
pressure at rest was measured with a manual sphygmomanometer (Welch Allyn Max-Stabil 3, Jungingen, Germany).
To measure cardiovascular fitness and exercise capacity,
all children performed an incremental exercise test on a
half-supine, electronically braked, cycle ergometer (Sensormedics BV, Bilthoven, The Netherlands) adhering to a standardized ramp protocol.7 During cycling, the workload was
gradually increased by 10, 15, or 20 W/min (depending on
the subject’s weight, age, gender, and exercise habits), and
the cycling speed was maintained at approximately 65 rpm.
The exercise was terminated at the subjects’ request, because of electrocardiographic changes associated with myocardial ischemia, physical exhaustion, dyspnea, or calf/thigh
pain. To prevent decreases in systolic blood pressure from
venous pooling after test termination, the subjects were
instructed to continue cycling for 3 additional minutes at 30
rpm against a workload of 20 W.8 A 12-lead electrocardiogram was obtained during each minute of exercise and
recovery. The heart rate and rhythm were monitored continuously (GEMS IT Cardiosoft V4.2, Freiburg, Germany),
and blood pressure was measured with 2-minute intervals.
Gas exchange parameters were obtained throughout the
exercise test and during the first 2 minutes of recovery on a
breath-by-breath basis using a metabolic cart (Vmax Spectra 29, SensorMedics, Yorba Linda, California). The oxygen
consumption and respiratory quotient were measured every
20 seconds. The peak oxygen uptake (VO2peak) was defined
as the mean of the last 40 seconds of the ergometer test. The
exercise test results were considered valid when the following criteria were met: (1) observed exhaustion of the child,
(2) VO2peak leveling off, and (3) respiratory quotient
⬎1.00.9 The subjects were asked to repeat the cycle ergometer test 1 week later if the respiratory quotient had
remained ⬍1.00. Only data meeting these criteria were
analyzed.
The daily physical activity level was assessed using an
electronic pedometer (Yamax SW-200 DigiWalkers,
Yamax, Japan) and an activity diary for 7 days, including 2
weekend days. The pedometer was clipped to the waistline
at the right side according to the manufacturer’s instructions. The activity diary consisted of 7 timelines, 1 for each
day. Each day was divided into 48 U, with 1 U representing
30 minutes. The activities were indicated using numbers
drawn from a previously devised legend. Arrows were used
to indicate the child’s waking hours. The activities were
computed to the metabolic equivalent (MET) values (1
MET ⫽ 1 kcal/kg/hr) using the Compendium of Physical
Activities, a coding scheme that classifies specific physical
activity by the rate of energy expenditure.10
To obtain a questionnaire concerning physical fitness and
participation in sports for children with coronary heart disease (CHD), the Haemophilia and Physical Fitness Questionnaire (Department of Paediatric Physical Therapy, Rad-
400
The American Journal of Cardiology (www.AJConline.org)
Table 3
Exercise test results in both groups
Variable
VO2peak (ml/kg/min)
VO2peak lean body mass (ml/kg/min)
VO2peak (% of predicted)
Respiratory quotient
Peak workload (W)
Peak workload (W/kg)
Peak heart rate (beats/minute)
Heart rate after 1 min (beats/minute)
Heart rate after 3 min (beats/minute)
Control Group
(n ⫽ 15)
TGA Group
(n ⫽ 15)
p Value
47.4 ⫾ 6.4 (39.3–58.4)
58.2 ⫾ 10.0 (46.1–85.4)
94.6 ⫾ 12.1 (75.6–111.5)
1.04 ⫾ 0.03 (0.98–1.09)
179.3 ⫾ 60.5 (96–320)
3.7 ⫾ 0.5 (2.7–4.7)
189 ⫾ 9 (168–200)
153 ⫾ 17 (113–178)
120 ⫾ 16 (83–146)
41.1 ⫾ 6.6* (32.1–55.5)
50.5 ⫾ 7.1* (32.1–55.5)
81.4 ⫾ 10.9* (63.0–103.8)
1.03 ⫾ 0.04 (0.98–1.12)
154.1 ⫾ 61.6 (80–312)
3.1 ⫾ 0.6* (2.5–4.2)
180 ⫾ 14 (155–202)
149 ⫾ 16 (126–179)
118 ⫾ 14 (89–146)
0.013
0.021
0.004
0.46
0.27
0.005
0.045
0.40
0.80
Data are presented as mean ⫾ SD (minimum to maximum range).
* p ⬍0.05.
Figure 2. Peak workload (W/kg) in children with TGA after ASO (n ⫽ 15)
and controls (n ⫽ 15). Values are presented as mean ⫾ SD. *p ⬍0.05.
boud University Nijmegen Medical Centre, Nijmegen, The
Netherlands) was modified to suit our study purposes. This
CHD and physical fitness questionnaire was used to acquire
information on co-morbidities, the number of hours of
sports participation at school and during leisure time, recreational exercise, other leisure activities, type of transport
to and from school, self-rated fitness and health and physical
activity, and overprotection.
The results are expressed as the mean ⫾ SD, with the
range. For comparison of the anthropometric measurements,
exercise testing parameters, pedometer and activity measurements, unpaired Student’s t tests were applied. For
comparison of frequencies, chi-square tests were administered. For intergroup comparison of ordinal variables, the
nonparametric Mann-Whitney U test was used. Descriptive
statistics were used for questions concerning overprotection. For all tests, a level of significance of p ⬍0.05 was
used. All statistical analyses were performed with Statistical
Package for Social Sciences for Windows, version 16.0
(SPSS, Chicago, Illinois).
Figure 3. Peak heart rate (beats/min) during exercise testing in children
with TGA after ASO (n ⫽ 15) and controls (n ⫽ 15). Values are presented
as mean ⫾ SD. *p ⬍0.05.
Results
Two subjects in the TGA group could not perform the
cycle test because of practical problems. One child had a
cold and difficulties breathing through the mask and one
was too small and could not reach the pedals properly. The
remaining children (n ⫽ 15) met the criteria for a valid
exercise test, and physical exhaustion was the reason for test
termination. Because the predicted VO2peak values were
greater for the male children than for the female children,
the exercise test results of the 15 TGA subjects who were
able to complete the test were compared with the results of
15 gender- and age-matched control subjects. The pedometer, diary, and questionnaire results of the entire TGA
group were compared with the results of 17 age- and gender-matched subjects. The data from 20 control subjects
were used. No significant differences were found in age,
Congenital Heart Disease/Exercise in Children With TGA
401
Table 4
Activity monitoring in both groups
Variable
Number of steps/day
Metabolic equivalent score (without sleep)
Metabolic equivalent score/hour awake
Metabolic equivalent/hour/day
Greatest metabolic equivalent score/hour
Time awake (hour)
Control Group
(n ⫽ 17)
TGA Group
(n ⫽ 17)
p Value
11,794 ⫾ 2,326 (9,024–16,629)
36.8 ⫾ 7.1 (26.0–54.4)
2.5 ⫾ 0.5 (1.3–3.5)
1.9 ⫾ 0.3 (1.4–2.6)
5.5 ⫾ 1.1
14.4 ⫾ 0.7 (13.3–15.6)
11,016 ⫾ 4,560 (5,598–26,227)
32.3 ⫾ 5.1* (25.5–43.2)
2.3 ⫾ 0.3 (1.9–2.9)
1.7 ⫾ 0.2 (1.5–2.1)
5.5 ⫾ 1.6
14.0 ⫾ 0.9 (12.7–15.8)
0.54
0.044
0.16
0.56
0.99
0.13
Values are presented as mean ⫾ SD (minimum to maximum range).
* p ⬍0.05.
Table 5
Congenital heart disease and physical fitness questionnaire results for
both groups
Variable
Control Group
(n ⫽ 17)
TGA Group
(n ⫽ 17)
Self-rated health (scale 1–10)
8.5 ⫾ 1.2 (7–10)
8.4 ⫾ 1.2 (5–10)
Self-rated fitness (scale 1–10) 7.6 ⫾ 0.9 (6–9)
7.2 ⫾ 1.2 (5–9)
Participation in sports (hours/ 3.5 ⫾ 1.7 (0.5–7.5) 4.8 ⫾ 0.8 (0–11)
week)
Participation in sports
27.0 ⫾ 14.2 (3–47) 37.0 ⫾ 23.1 (4–75)
(metabolic equivalent/
week)
Participation in physical
17/17 (100%)
15/17 (88%)
education class*
Overprotection by self†
0/17 (0%)
1/17 (6%)
Overprotection in past by
0/17 (0%)
4/17 (23%)
environment‡
Overprotection in present by
0/17 (0%)
3/17 (18%)
environment
Data are presented as mean ⫾ SD (range), unless otherwise indicated.
* Percentage of subjects who always participate in physical education
class and do not stop during exercises.
†
Subject considers physical activity harmful.
‡
Environment considers physical activity harmful.
weight, length, body mass index, lean body mass, or blood
pressure between the TGA and control groups (Table 1).
The mean age at surgery was 7.6 ⫾ 10.8 days. Of the 17
subjects with TGA, 15 underwent ASO during the first 2
months of life, with closure of an atrial septal defect and/or
ventricular septal defect, if necessary. One subject with
partial anomalous pulmonary venous return and left atrial
isomerism underwent an ASO with correction of the partial
anomalous pulmonary venous return. At 11 years of age, an
atrial inhibited rate modulated pacemaker was implanted
with a lower rate of 70 beats/min and an upper center rate of
180 beats/min because of an abnormal chronotropic response to exercise. One patient had TGA with a large
subaortic ventricular septal defect and pulmonary stenosis.
For this patient, a Blalock-Taussig shunt was placed as a
palliative procedure 3 days after birth, followed by a Rastelli procedure 2 years later. Four patients required cardiac
catheterization with balloon dilation to treat stenosis at the
site at which the pulmonary artery was reconnected during
the ASO. One subject underwent repeat surgery to close the
remainder of an atrial septal defect at 6 and 8 years of age.
The residual postoperative cardiac co-morbidities are listed
in Table 2.
The VO2peak (ml/kg/min) and the adjusted per kilogram
lean body mass were significantly lower in the TGA group
than in the controls (Figure 1, Table 3). In addition, the peak
workload (Figure 2) and peak heart rate (Figure 3) were
significantly lower in the TGA subjects than in the controls
(Table 3).
No significant differences were evident between the
TGA and control group in the total number of steps or MET
scores per hour (Table 4). The MET score during awakening
was significantly lower for the TGA children than for the
controls (p ⫽ 0.044). However, the MET score per hour
awake did not differ between the 2 groups.
No differences were observed regarding self-rated fitness
and health, participation in sports and activities at and after
school, physical activity level, or overprotection between
the TGA and control groups (Table 5).
Discussion
This is the first study to compare children with TGA to
their healthy peers regarding both the physical activity pattern and fitness late after the ASO. Our findings have demonstrated that the VO2peak, peak heart rate, and peak workload were significantly lower in the TGA group than in the
control group. In contrast, the physical activity patterns
were not different between the 2 groups, suggesting that
physical hemodynamic restrictions are more important
causal factors for the lower exercise capacity levels than
reduced physical activity.
Our findings demonstrated that VO2peak (ml/kg/min) adjusted for lean body mass and VO2peak, expressed as a
percentage of the predicted, were significantly lower in the
TGA group (81%) than in the controls (95%). Subnormal
values of maximal heart rate during exercise (chronotropic
impairment) and subnormal exercise capacity in children
after ASO have been previously reported,1,2 although
VO2peak values within the normal range have also been
reported.3 Pasquali et al1 determined the maximal exercise
capacity in 53 children after ASO. Variant coronary artery
patterns were present in 30%, and the investigators reported
that VO2peak was lower than predicted in subjects with usual
and variant coronary artery patterns (89 ⫾ 20% and 80 ⫾
17%, respectively).1 Furthermore, multivariate analyses revealed that a variant coronary artery pattern and ventricular
septal defect were predictors of chronotropic impairment
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The American Journal of Cardiology (www.AJConline.org)
and associated with a trend toward lower a VO2peak (p ⬍
0.09). However, we did not have this information for our
participants and were unable to sort the data in a similar
matter. The physical activity pattern in daily living, as
indicated by the total number of steps or MET score did not
differ between TGA group and the age- and gender-matched
controls. A lower total MET score during awaking hours
was found for the TGA group. However, it is important to
correct this score for the actual hours that the children were
awake. Because the TGA children in the present study spent
more hours sleeping than did the controls, this difference
was no longer evident when the MET score was expressed
per hour awake (p ⫽ 0.16). Previous studies of children
with CHD, including TGA, have indicated that these children were significantly less active than controls. Massin et
al4 investigated the activity patterns of 52 children with
TGA 7 to 14 years after ASO using 24-hour heart rate
monitoring and compared the results to those from 127
age-matched healthy peers. The TGA group emerged as
significantly less active than the control group regarding
moderate and vigorous activities. However, because chronotropic impairment can be present in TGA, continuous
heart rate monitoring does not seem to be the most suitable
method to assess exercise intensity and physical activity
patterns in these children. In the present study, exercise
intensity was calculated as the average greatest MET score
per hour, and this outcome was similar in both groups.
Apparently, children with TGA are as physically active as
healthy control children and do not refrain from physically
demanding tasks.
Self-perceived restrictions, overprotection by parents, or
altered self-perception are factors that might explain the
observed lower physical activity levels of children with
CHD as reported in previous studies.11–13 Although overprotection by parents is often described as an explanation
for the lower physical activity levels in children with cardiac defects,12 our findings have not supported this assumption. Four children with TGA (24%) reported overprotection by their environment in the past, 3 (18%) reported
overprotection by the environment in the present, and 1
(6%) considered physical activity to be harmful. However,
the person being overprotective for the child with CHD was
never a parent or sibling.
Using the outcomes of the questionnaires completed by
our subjects, no differences in participation in sports and
leisure activities between the TGA group and healthy peers
were present.
Furthermore, physical fitness and general health status
were rated equally in both groups, suggesting that an altered
self-perception is not present. These results are in concordance with the absence of any differences in physical activity as recorded in the diary and by the pedometer between
the 2 study groups.
Cardiac/hemodynamic restrictions that can adversely affect exercise capacity in children with TGA include chronotropic impairment, which emerged during peak exercise
in the present study. These subnormal maximal heart rate
values can be caused by partial cardiac sympathetic denervation after transection of the great arteries during ASO.3,14
From exercise studies in the spinal cord-injured population
with cervical lesions, it is known that substantially lower
peak heart rates (ie, 120 to 140 beats/min) occur during
exercise.15 Also, it has been shown previously that patients
who underwent surgery ⬎55 days after birth had a lesser
amount of reinnervation, which might have affected their
exercise tolerance years after surgery.14 A subnormal maximal heart rate could also be caused by conduction defects
secondary to cardiopulmonary bypass.16 Other potential
mechanism that could relate to cardiac/hemodynamic restrictions and compromised physical capacity in children
with TGA include residual hemodynamic defects, such as a
mild to moderate degree of supravalvular pulmonary stenosis, which was present in all but 2 of the 15 children with
TGA completing the cycle test. Also, decreased right and
left ventricular ejection fractions in patients with TGA
could equally contribute to reduced exercise capacity.17
Finally, an abnormal coronary flow reserve caused by manipulation of the coronary arteries during the ASO could
alter the balance between myocardial oxygen supply and
demand, thereby reducing exercise capacity. A previous
study documented a prevalence of coronary lesions in 6.8%
of 324 patients, 7 years after ASO.18 The long-term development of coronary circulation in these patients, including
the evolution of atherosclerosis and coronary flow reserve,
is still unknown.19
In conclusion, the findings of the present study have
demonstrated that the exercise capacity of children with
TGA after ASO is significantly reduced compared to that of
their age- and gender-matched healthy peers. The daily life
activity pattern and sport participation did not differ between the 2 groups. Hence, it appears that the decrease in
exercise capacity in children with TGA mainly results from
compromised hemodynamic restrictions rather than a reduced physically active lifestyle. Future studies on the clinical consequences for cardiovascular health of altered hemodynamics in children with congenital heart diseases are
recommended.
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