The Cardiovascular Effects of Obesity on Ventricular Function and Mass

in Patients after Tetralogy of Fallot Repair

Mark A. Fogel, MD1,2, Thomas Pawlowski, BS1, Marc S. Keller, MD2, Meryl S. Cohen, MD1, Elizabeth Goldmuntz, MD1,
Laura Diaz, MD3, Christine Li, BS1, Kevin K. Whitehead, MD1,2, and Matthew A. Harris, MD1,2

Objectives To determine the cardiovascular effects of obesity on patients with tetralogy of Fallot (TOF) repair.
Study design Ventricular performance measures were compared between obese (body mass index [BMI]
$95%), overweight (85% #BMI <95%), and normal weight subjects (BMI <85%) in a retrospective review of pa-
tients with TOF who underwent cardiac magnetic resonance from 2005-2010. Significance was P < .05.
Results Of 260 consecutive patients with TOF, 32 were obese (12.3%), 48 were overweight (18.5%), and 180 were
normal weight (69.2%). Biventricular mass was increased in obese compared with normal weight patients with right
ventricular mass more affected than left ventricular mass. Obese patients demonstrated decreased biventricular
end-diastolic volume (EDV) and stroke volume (SV) when indexed to body surface area (BSA) with an increased
heart rate when compared with normal weight patients; cardiac index, ejection fraction, and pulmonary regurgita-
tion fraction were similar. When indexed to ideal BSA, biventricular EDV and SV were similar. EDV and SV for over-
weight patients were nearly identical to normal weight patients with ventricular mass in between the other 2 groups.
Conclusions Approximately 12% of patients after TOF repair referred for cardiac magnetic resonance in a tertiary
referral center are obese with increased biventricular mass. Obese patients and normal weight patients have similar
cardiac indices, however, when indexed to actual BSA, obese patients demonstrate decreased EDV and SV with
increased heart rate and similar cardiac indices. When indexed to ideal BSA, no differences in biventricular volumes
were noted. (J Pediatr 2015;167:325-30).

C
hildhood and adolescent obesity has reached epidemic proportions and is a leading concern in the United States1;
normal children have an obesity rate of approximately 16%.2 It not only affects individuals with normal hearts but pa-
tients with congenital heart disease (CHD) (13.8% of all patients with CHD)3; these children may even be more prone
to obesity because of physical limitations.4 The prevalence of obesity also can vary by disease state (eg, Fontan3 and transpo-
sition of the great arteries after arterial switch operation5). The National Heart, Lung, and Blood Institutes Working Group on
Obesity and Other Cardiovascular Risk Factors in Congenital Heart Disease has just recently outlined issues related to obesity.6
It is one of the few modifiable risk factors in this population.
The hearts of children with repaired tetralogy of Fallot (TOF), the most common form of cyanotic CHD, often have pulmo-
nary regurgitation and right ventricle (RV) volume overload. Multiple studies also have documented depressed RV function at
rest and with exercise.7,8 Residual outflow tract obstruction, branch pulmonary artery stenosis, RV hypertension, and
arrhythmia are also reported after repair. Superimposition of obesity on these sequelae may burden the cardiovascular
system further; it is, therefore, important to study the magnitude of the problem and the cardiovascular effects of obesity in
this patient population.
Limited data were available on the functional cardiovascular effects of obesity in pediatric patients with CHD such as TOF.
This study assessed the prevalence of overweight and obese TOF patients in a large tertiary referral center and additionally deter-
mined the effects on ventricular performance and mass compared with nonobese patients with TOF using cardiac magnetic
resonance (CMR) cine and phase encoded velocity mapping.9 It has been the noninvasive gold standard to measure ventricular
mass, volume, and function for many years.10-12 As CMR is unencumbered by adipose tissue and acoustic windows, which can
create challenges in imaging the obese individual, it is an ideal imaging modality to assess ventricular function and mass in these
patients. We hypothesized that obesity imposes a functional cardiovascular burden over and above what the normal weight
patient with TOF faces. As obesity is one of the few modifiable risk factors,

From the 1Division of Cardiology, Department of

Pediatrics, the Department of 2Radiology and the
3
BMI Body mass index iBSA Ideal BSA Division of Cardiothoracic Anesthesiology, Department
of Anesthesia and Critical Care Medicine, The Childrens
BSA Body surface area LV Left ventricle Hospital of Philadelphia, The Perelman School of
CHD Congenital heart disease RF Regurgitant fraction Medicine at The University of Pennsylvania, Philadelphia,
PA
CMR Cardiac magnetic resonance RV Right ventricle
The authors declare no conflicts of interest.
EDV End-diastolic volume SV Stroke volume
EF Ejection fraction TOF Tetralogy of Fallot 0022-3476/$ - see front matter. Copyright 2015 Published by
HR Heart rate Elsevier Inc.
http://dx.doi.org/10.1016/j.jpeds.2015.04.018

325

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THE JOURNAL OF PEDIATRICS  www.jpeds.com
establishing baseline information on its prevalence will serve
as a stepping stone to assess intervention in the future.
Methods
A search of the CMR database at our institution was per-
formed for all patients 2-18 years of age who underwent
TOF repair between 2005 and 2010 and had assessment of
ventricular performance. If a patient was evaluated more
than once, the first study was used. Patients were screened
by echocardiography as well as CMR and were excluded if
any of the following were present: RV outflow tract obstruc-
tion ($3 m per second velocity), branch pulmonary artery
stenosis evaluated by echocardiography, or CMR or pulmo-
nary hypertension as measured by the tricuspid regurgitant
jet. These criteria were used so the confounders of afterload
were not present. Patients who underwent pulmonary valve
replacement and those with pulmonary atresia or absent
pulmonary valves were excluded. This study was approved
by the institutional review board.
CMRs were performed on a Siemens 1.5 Tesla Sonata or
Avanto MRI system (Siemens Medical Solutions, Malvern,
Pennsylvania) with data analyzed using the standard
Siemens analysis package (ARGUS). Ventricular volumes,
function, and mass were calculated from the analysis of a
contiguous stack of cine steady-state free procession short
axis images from base to apex. The septum was included in
the RV mass as the RV is most affected in repaired TOF
(Figure 1; available at www.jpeds.com); trabeculations and
papillary muscles were included in the mass if contiguous
with the endocardial surface but otherwise was included in
the ventricular volume. Phase-encoded velocity mapping
across the aortic and pulmonary valves were used to
measure cardiac output and pulmonary regurgitation.
All CMR reports were examined for demographics
including sex, age, height, and weight. In addition, the
most recent clinic note (within 1 year of the CMR) was exam-
ined for blood pressures. Patients were classified as normal,
overweight, or obese according to their body mass index
(BMI) (weight/height2). For pediatric patients between
2 and 18 years of age, BMI percentile for age and sex were
determined by plotting the BMI values on the Center for Dis-
ease Control BMI-for-age growth charts.13 Patients over the
95th percentile were classified as obese, between 85th and
95th percentile as overweight, and those <85th percentile as
normal.
RV and left ventricle (LV) end-diastolic volume (EDV),
end-systolic volume, stroke volume (SV), heart rate (HR),
cardiac index, ejection fraction (EF) and myocardial mass
were collected by cine; cardiac index and regurgitant fraction
(RF) were collected by velocity mapping. Because of the
different views in the literature of how to index ventricular
volumes in obesity, data were indexed to body surface area
(BSA), BSA1.4 14 and ideal BSA (iBSA) (the height of the pa-
tients and the 50th percentile for weight at their age).15 Mass
was indexed to height2.7.16
326
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Vol. 167, No. 2
Statistical Analyses
Descriptive statistics were performed. The primary compar-
ison was between obese and normal weight patients with
TOF. Comparison between obese, overweight, and normal
weight patients were made using ANOVA with a multiple
comparison test (Tukey method) if normally distributed; if
the data were found not to be normally distributed, the
Kruskal-Wallis test was used. ANCOVA was utilized to deter-
mine differences in the regression line between 2 groups. All
values are mean
SD. P values of <.05 was considered statis-
tically significant.
Results
Two hundred sixty consecutive patients with TOF were
found; 32 were obese (12.3%), 48 were overweight (18.5%),
and 180 were normal weight (69.2%). Of the obese patients,
18 (56.3%) were male and 14 (43.7%) were female; in the
normal group, 110 (61.1%) were male and 70 (38.9%) were
female.
In the obese, overweight, and normal group, there were no
cases of systolic hypertension. Blood pressures were
111.0
10.2/69.4
8.6 mm Hg, 105.6
11.4/
66.7
7.7 mm Hg, and 107.6
12.6/68.6
10.1 mm Hg,
respectively (P = .87).
Table I lists ventricular function and mass for all groups.
BSA and BMI of obese patients were significantly higher
than those of normal patients, however, there was no
difference between the ages or height. No difference was
noted in cardiac index or EF, however, the obese group
demonstrated a significant decrease in both RV and LV
indexed EDV and SV with a concomitant significant
increase in HR. Both RV and LV mass were increased in
the obese group, however, the mass/volume ratio was
similar between the normal and obese groups in either
ventricle. No difference was noted in pulmonary RF
between groups. No significant differences were noted
between main pulmonary artery flow or aortic flow as
measured by phase contrast velocity mapping whether
comparing between normal and obese patients (Table I) or
comparing main pulmonary artery and aortic flows within
the normal group (P = .58) or within the obese group
(P = .53).
In the overweight group, as expected, BSA and BMI were
in between the obese and normal weight patients, however,
their HRs were nearly identical to the normal weight patients.
Cardiac index, RV, and LV EF and pulmonary RF were very
similar to both the obese and normal weight patients. For
both RV and LV, however, EDV and SV for overweight pa-
tients were nearly identical to normal weight patients with
measured ventricular mass in between the other 2 groups.
Another method of indexing ventricular volumes is based
on cardiac output by using BSA1.4; if this is used, no change in
the results was noted from indexing to BSA (Table II;
available at www.jpeds.com). It has been suggested that
because indexing to BSA in overweight and obese patients
will lower ventricular volumes because of the larger values
Fogel et al
August 2015 ORIGINAL ARTICLES

Table I. Ventricular function of obese and normal patients with TOF

Obese Overweight Normal P valuez
Number of patients 32 48 180
Age (y) 16.8
9.42 15.6
10.1 14.4
7.19 .37
Age at repair (y) 15.89
9.64 15.62
10.12 14.43
7.19 .895
BMI (weight/height2) 28.7
5.36 23.5
3.73 18.1
3.02 <.001
BSA (m2) 1.57
0.43 1.45
0.50 1.31
0.38 .002
Height (cm2.7) 2.94
1.01 3.03
1.37 3.06
1.20 .72
HR (beats/min) 86.3
16.4 80.0
15.2 80.1
15.9 .029
RV
EF (%) 59.8
10.0 57.6
9.24 58.8
8.79 .59
EDV/BSA (cc/m2) 106.3
26.4 123.1
49.4 121.3
37.7 .032
SV/BSA (cc/m2) 62.7
15.5 68.2
19.9 69.8
18.3 .038
Cardiac index using cine (L/min/m2)* 5.38
1.72 5.42
1.83 5.48
1.51 .44
Mass/height2.7 40.4
14.4 38.3
13.0 35.2
11.6 .046
Mass/EDV (g/cc) 0.71
0.24 0.65
0.22 0.68
0.24 .55
RF (%) 33.8
16.3 32.6
16.8 35.5
14.9 .68
MPA flow using VMAP (L/min/m2) 3.40
0.91 3.34
0.95 3.28
0.77 .43
LV
EF (%) 67.7
8.27 66.0
7.30 68.0
7.01 .97
EDV/BSA (cc/m2) 58.9
13.5 69.0
12.9 65.9
12.6 .005
SV/BSA (cc/m2) 39.4
8.70 45.8
11.1 44.5
8.16 .002
Cardiac index using cine (L/min/m2)* 3.32
0.78 3.64
1.15 3.50
0.67 .17
Mass/height2.7 24.9
4.36 21.8
5.59 19.2
5.14 .025
Mass/EDV (g/cc) 0.67
0.19 0.62
0.17 0.66
0.16 .69
Aortic flow using VMAP (L/min/m2) 3.27
0.83 3.55
1.12 3.32
0.61 .549

MPA, main pulmonary artery; VMAP, velocity mapping.

Values are mean
SD.
*Cardiac index calculated using SV and HR via cine CMR; includes both forward and regurgitant volumes and, therefore, RV and LV cardiac indices via cine will not match.
Cardiac index as measured across the semilunar valves by VMAP; this includes only the net forward flow.
zFor comparison between obese and normal weight patients.

compared with normals, iBSA should be used15; in this case,
no statistically significant difference was noted.
Figures 2 and 3 demonstrate a significant correlation
between RV and LV mass in both the normal weight and
obese groups, respectively. With the RV graphed on the
abscissa and the slope of the linear correlation being 0.26
and 0.20 for the normal weight and obese groups
respectively, RV mass increased out of proportion to LV
mass (ie, the slope of 0.20 is significantly smaller than 0.26;
P = .046). As this was an unpaired, retrospective study,
another approach to assessing the relative degree to which
the mass of each ventricle was affected by weight was to
divide RV/LV mass and compare this metric between
groups. Normal weight patients were not statistically
different from overweight patients (0.55
0.21 vs
0.57
0.20, respectively, P = .59), however, this was
significantly lower than the obese group (0.75
0.43,
P = .01), demonstrating a greater increase in RV mass
relative to LV mass as BMI increases.
Fifty-two patients underwent CMR 3.12
1.60 years after
their first study (Table III) with a number of patients in this
subset changing weight status at follow-up. In the normal
weight group, 4 became overweight and 1 became obese; in
the overweight group, 3 became normal and 6 became
obese; in the obese group, 1 became overweight and
1 became normal weight. Two patients received pulmonary
valve replacement.
Overall, for the entire group, the RV EF was lower and
EDV (indexed to BSA) was slightly higher on follow-up,
however, this did not hold true for the LV. Cardiac index
The Cardiovascular Effects of Obesity on Ventricular Function and Mass in Patients after Tetralogy of Fallot Repair
(for both LV and RV) and pulmonary RF remained the
same at both time points. Mass/height2.7 was lower for the
RV and higher for the LV with concomitant decrease in RV
mass/volume and increase in LV mass/volume.
Discussion
Our study demonstrated the prevalence of obesity in pa-
tients with TOF referred to CMR in a tertiary referral cen-
ter to be 12.3%, and the rate of overweight children to be
18.5%. Both obese and normal patients had similar cardiac
index and comparable pulmonary RF, however, when uti-
lizing actual BSA as many studies in children have
done,17,18 there was a decrease in biventricular EDV and
SV in obese patients which was seemingly compensated
for by an increased HR given the similar cardiac index.
When BSA1.4, was used, the indexing scheme based on car-
diac output,14 this result did not change, however, when
iBSA was used,15 this phenomenon did not persist, with
no difference then observed in biventricular EDV and
SV. This constellation of ventricular function measures
was accompanied by a biventricular increase in indexed
myocardial mass without systolic hypertension, with the
RV affected more than the LV. The RV and LVs of those
patients who were overweight demonstrated an intermedi-
ate amount of myocardial mass between normal and obese
patients with TOF, with HR and EDV similar to normal
weight patients with TOF.
This study demonstrated a prevalence of obesity of 12.3%
in patients with TOF referred to CMR in a tertiary referral
327

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THE JOURNAL OF PEDIATRICS  www.jpeds.com
Figure 2. LV vs RV mass in normal weight patients with TOF.
center, and the prevalence of overweight children was 18.5%.
This is slightly lower than the study by Stefan et al4 who
found 16% of 110 children with CHD obese at a mean age
of 3.9 years old; at follow-up (average age of 12.7 years),
the prevalence of obesity was 20%. In our study, of those
who returned for follow-up CMR, 14% of normal weight pa-
tients with TOF became overweight or obese, and 15% of the
nonobese patients (ie, normal weight or overweight) became
obese. Pinto et al3 found an overall incidence of obesity in
CHD of nearly 14% and a combined obese and overweight
prevalence of 26%.
When comparing the current study of TOF with individual
lesions, the prevalence of obesity is greater than those of pa-
tients undergoing Fontan (8%)16 but slightly lower than
those with transposition of the great arteries after arterial
switch operation (14%).3 There was a similar prevalence of
obesity and overweight patients in the transposition of the
great arteries after arterial switch operation group (31%). Pa-
tients with TOF, however, appear to have a similar prevalence
to obesity and overweight patients having CHD and a biven-
tricular repair reported by Pinto et al.3
Indexing ventricular volumes in patients with obesity is
complex as it may be thought that the increased BSA would
Figure 3. LV vs RV mass in obese patients with TOF.
328
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Vol. 167, No. 2
artificially lower the volumes; so, it has been suggested by
Maskatia et al15 that iBSA be used instead. When they did
so in their TOF group, they found a higher RV and LV
EDV in obese patients relative to normal. This may differ
from our findings because our patient population was not
only larger (212 obese and normal patients with TOF in
our study vs 108) but also was a purely pediatric group. Their
study included 34% who were >21 years of age. In addition,
iBSA would not appear to be a preferable approach to index-
ing; it has been demonstrated that obesity has many adverse
cardiovascular effects including increased circulating blood
volume, increased cardiac work load, and a shift of the Star-
ling curve to the left.19,20 Indexing the obese patients ventric-
ular volumes to iBSA would essentially treat this group as
normal (as their ideal body weight is used), which would
not adequately compensate for the adverse hemodynamics
that obese patients are exposed to. Indeed, when an indexing
schema based on function is used,14 BSA1.4, no difference is
seen with actual BSA data.
The current study demonstrated LV mass increased in
obese patients with TOF compared with normal weight indi-
viduals with TOF, similar to the patients with transposition
of the great arteries after arterial switch operation.5 However,
Fogel et al
August 2015 ORIGINAL ARTICLES

Table III. Follow-up data in 52 patients References

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The Cardiovascular Effects of Obesity on Ventricular Function and Mass in Patients after Tetralogy of Fallot Repair 329

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Korones SB, Ainger LE, Monif GRG, Roane J, Sever JL, Fuste F. J Pediatr 1965;67:166-81

I n vitro technique for propagation and identification of rubella virus was reported in 1962. In 1963 and 1964, isola-
tion of virus was reported from neonates with a constellation of findings already identified as the congenital rubella
syndrome (because of maternal clinical illness or exposure to others with clinical rubella or during pregnancy). The
1964 nationwide epidemic of rubella played out in Memphis, Tennessee from January through July. Collaborating
with colleagues from the National Institute of Neurological Diseases and Blindness in Bethesda, Maryland, investiga-
tors at the University of Tennessee enrolled 17 neonates born between October 1964 and January 1965 if they had
cataracts, purpura, or cardiac anomalies, singularly or in combinationsuggesting congenital rubella.
The case series of 17 infants all of whom had isolation of rubella virus in tissue culture was a first culture-proven
comprehensive report of clinical, laboratory, and pathologic findings. (Editor WE Nelson, a task master for brevity,
permitted a chunky 16 journal pages for the telling).
Some characteristic or novel findings are highlighted here. Virus was isolated from virtually all urine and throat
samplings, and frequently from serum. When biopsy or autopsy was performed, virus was isolated routinely
from lung and liver, but not from myocardiumalthough myocardial cell ballooning and necrosis without inflam-
mation was a novel finding in 4 patients reported and was associated with electrocardiographic findings suggestive of
myocardial infarction. Patent ductus occurred in all 17 neonates, with additional valvular anomalies in some. Cata-
racts were found in almost two-thirds of infants, with additional ophthalmologic abnormalities/anomalies in some.
Thrombocytopenia (not associated with increased immature platelets in bone marrow), which was present in
>90% of infants, self-resolved in most during the first few weeks. Anemia was not a featurethe reticulocytosis
and increased percentage of peripheral blood nucleated red blood cells found in most as well as hepatosplenomegaly
in many infants suggesting a compensatory mechanism to preserve hemoglobin concentrations. Regurgitative
(cholestatic) jaundice as well as pathologic features of interstitial pulmonary inflammation were additional newly
reported features of congenital rubella.
The granularity of primary data adds texture to what young doctors learn only from summaries in textbooks since
elimination of congenital rubella in the US following universal vaccination in the early 1970s. The data added much to
understanding of the pathophysiology and teratogenicity that characterized early intrauterine infection with rubella
virus as well as the incapacity of fetal immunologic processes to shut down virus proliferationan incapacity that
typically and curiously persists in affected infants for months to years after birth.

Sarah S. Long, MD
Department of Pediatrics
St. Christophers Hospital for Children
Philadelphia, Pennsylvania
http://dx.doi.org/10.1016/j.jpeds.2015.01.047

330 Fogel et al

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August 2015 ORIGINAL ARTICLES

Figure 1. Contouring the ventricular short axis for volumes

and mass. Yellow and green contours are the epicardium of
the LV and RV, respectively. Red and blue contours are the
endocardium of the LV and RV, respectively.

Table II. Other indexing schema for ventricular volumes

Normal Overweight Obese P value
BSA1.4 1.50
0.59 1.74
0.77 1.92
0.70 <.001
RV
EDV/BSA1.4 (cc/m2.8) 110.74
34.15 110.15
45.12 90.10
21.38 .002
ESV/BSA1.4 (cc/m2.8) 46.92
22.35 48.58
28.80 37.18
13.31 .05
LV
EDV/BSA1.4 (cc/m2.8) 60.23
11.65 62.43
18.05 49.86
10.57 <.001
ESV/BSA1.4 (cc/m2.8) 19.51
6.56 21.06
7.13 16.41
6.29 .02
iBSA
RV
EDV/iBSA (cc/m2) 121.30
37.67 126.25
51.70 118.15
35.23 .89
ESV/iBSA (cc/m2) 46.92
22.35 55.99
35.34 49.26
21.49 .37
LV
EDV/iBSA (cc/m2) 46.92
22.35 71.05
16.92 64.93
16.68 .25
ESV/iBSA (cc/m2) 21.38
7.47 23.83
6.37 21.49
8.95 .68

cc, cubic centimeters; ESV, end-systolic volume.

Values are displayed as mean
SD, unless otherwise indicated.

The Cardiovascular Effects of Obesity on Ventricular Function and Mass in Patients after Tetralogy of Fallot Repair 330.e1

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