CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 1, January/February 2013
178
AFRICA
estimated to be 65%. The frequency of various form of CHD in MDS
patients has not been established.
Methods:
Records of patients diagnosed with MDS and CHD
between 2008 and 2012 at our institutions were reviewed. A litera-
ture review included searching MEDLINE and Google Scholar.
Inclusion criteria included a clinical or genetic diagnosis of MDS
and a specific CHD diagnosis. Cases with ambiguous descriptions
of cardiac anatomy and infants with only a PFO and/or PDA, which
could be physiological, were excluded from the analysis.
Results:
We report four new cases of CHD in MDS. Their cardiac
diagnoses were TAPVR, VSD, VSD and pulmonary stenosis (PS)
and TOF. The literature review identified 16 cases of CHD in MDS:
TOF-PA (four), TOF (three), PS (two), and one each of Ebstein
anomaly, PA/IVS, ASD and DORV.
Conclusions:
This is the first report of TAPVR in a patient with
MDS. In addition, this study found that among MDS patients with
CHD, right-sided lesions were common. TOF-PA was particularly
frequent. Genes in the region of chromosome 17 associated with
MDS have not previously been reported to be involved in CHD. The
results of this study highlight the need for further study of the impact
of genes from this region on cardiac development.
644: CARDIACAUTONOMIC FUNCTION INADOLESCENTS
OPERATED BY ARTERIAL SWITCH SURGERY
Cecilia Falkenberg
1
, Ingegerd Östman-Smith
1
, Thomas Gilljam
1
,
Gavin Lamberg
2
, Peter Friberg
3
1
Institute of Clinical Sciences, Sahlgrenska University Hospital,
Sweden
2
Monash University, Australia
3
Sahlgrenska University Hospital, Sweden
Background
: Children with transposition of the great arteries, in
whom an arterial switch
operation (ASO) is performed, have been
shown to have an increased incidence of sudden death, which may be
due to cardiac autonomic imbalance and repolarisation instability. We
hypothesised that (1) cardiac norepinephrine (NE)
kinetics, and (2)
arterial baroreflex sensitivity (BRS), reflecting sympathetic activity
and vagal function, respectively, are altered in this group.
Methods and Results:
Seventeen children (15.8
±
1.6 years) with
ASO surgery in the neonatal period were
studied; 17 had cardiac
BRS assessed by spontaneous fluctuations of systolic
blood pres-
sure and RR interval, and repolarisation was measured as QT
vari-
ability index. Matched healthy subjects were controls. Cardiac vagal
function
and repolarisation pattern were unchanged following ASO
surgery. At cardiac
catheterisation, we infused tritiated
[3H]
NE into
eight of these children to examine total body and cardiac sympathetic
function at baseline and following five minutes of adenosine infusion
to induce reflex sympathetic activation. Blood was sampled simulta-
neously from the aorta and coronary sinus. Cardiac fractional extrac-
tion of
[3H]
NE was substantially lower in operated children, being 56
±
10 vs 82
±
9% (
p
=
0.0001). Following i.v. adenosine in the operated
group, NE total body spillover doubled vs baseline (
p
<
0.002) and
the coronary venous–arterial concentration of
[3H]
dihydroxyphenylg-
lycol increased four-fold (
p
=
0.04).
Conclusions:
The
arterial switch operation performed neonatally
appeared to leave cardiac vagal
function intact and, although cardiac
sympathetic activation in response to
adenosine occurred, cardiac
neuronal NE re-uptake was impaired. This may have been pro-
arrhythmic by reducing removal capacity of NE from the cardiac
synaptic cleft.
654: PRENATAL RISK FACTORS ASSOCIATED WITH
CONGENITAL HEART DISEASE
Katie Lee, Alan Fung, Ashok Kumar Manickaraj, Lisa D’Alessandro,
Seema Mital
Hospital for Sick Children, Toronto, Canada
Background:
Congenital heart disease (CHD) affects 1% of live
births. We previously identified advanced parental age, maternal
smoking and medication use during pregnancy to be associated with
risk for CHD in offspring.
Objective:
To assess the interactions between prenatal risk factors
and CHD risk.
Methods:
Patients with CHD and healthy controls enrolled in the
Heart Centre Biobank were studied. Prenatal exposure data and CHD
anatomical subtypes were obtained from questionnaires and medical
records. The cardiac phenotype was compared by prenatal risk-factor
exposure using chi-squared analysis.
Results:
The study cohort included 2 345 CHD patients and 193
control patients; 19% reported advanced maternal age, 11% advanced
paternal age, 21% maternal smoking, 31% non-fertility medication
use, and 6% fertility medication use during pregnancy; 53.6% had
no risk factor, 18.8% had one risk factor, and 27.5% had
≥
two risk
factors. Advanced paternal age was associated with lower frequency
of left heart lesions (LHL) (
p
=
0.003). Medication exposure during
pregnancy was associated with higher frequency of septal defects (
p
=
0.003), endocardial cushion defects (
p
=
0.009), right heart lesions
(
p
<
0.001), and thoracic vessel anomalies (
p
=
0.001), and a lower
frequency of LHL (
p
=
0.018). Other prenatal risk factors did not
show a predilection for specific CHD subtypes.
Conclusions:
There is a high burden of environmental risk factors in
CHD causation. Advanced paternal age and non-fertility medications
were associated with specific CHD phenotypes. Additional stud-
ies will evaluate whether genetic factors increase the susceptibility
to development of foetal CHD in pregnancies with environmental
exposures.
659: GENETIC ASSOCIATIONS WITH ANTHRACYCLINE
CARDIOTOXICITY IN PAEDIATRIC CANCER PATIENTS
Roslyn Cheung, Ashok Kumar Manickaraj, Lisa D’Alessandro, Luc
Mertens, Paul Nathan, Seema Mital
Hospital for Sick Children, Canada
Background
: Anthracycline cardiotoxicity (ACT) is the third leading
cause of death in cancer patients and is associated with left ventricu-
lar (LV) wall thinning and dysfunction. Several genetic variants that
regulate anthracycline pharmacokinetics have been identified and
variants in pharmacodynamic pathways on ACT require further study.
Objective:
To study the relative contribution of genetic variants
involved in ACT.
Methods:
One hundred and thirty-nine paediatric cancer patients
were prospectively enrolled through the Heart Centre Biobank; 77
patients were genotyped for three hypoxia-inducible factor 1-alpha
(HIF1A) SNPs, rs11549465 (1744C
>
T), rs2057482 (45T
>
C) and
rs10873142 (-145C
>
T). Serial echocardiograms were reviewed
to obtain markers of LV function and wall thinning, including LV
ejection fraction (LVEF), end-diastolic dimension and posterior wall
thickness (LVPWT), and these were compared with patient genotype.
Results:
Of the 139 anthracycline-exposed patients, 59% were male,
64.7% white, 26.6% Asian, and 8.6% other. Mean age at enrolment
was 12.7 years. Mean duration of follow up was 5.8 years; 14% of
patients had at least one abnormal measure (
≤
55%) of LVEF at any
time point. All three SNPs were in Hardy–Weinberg equilibrium. For
-145C
>
T (rs10873142), the LVPWT
z
-scores were significantly
lower in patients with the CT+CC genotype compared with the TT
genotype (–0.78 vs –0.03,
p
=
0.008).
Conclusions:
The HIF1A-145CT/CC genotype was associated with
LV posterior wall thinning during follow up. Additional candidate
SNPs are being genotyped and will help for early identification of
patients with a genetic susceptibility to ACT that can guide pre-
emptive risk-reduction measures.
663: GENETIC VARIANTS ASSOCIATED WITH PROGRES-
SIVE RIGHT VENTRICULAR REMODELLING IN TETRAL-
OGY OF FALLOT
Ashok Kumar Manickaraj, Brian Choi, Luc Mertens, Seema Mital
Hospital for Sick Children, Toronto, Canada
