Right Atrial Volume is Increased in Corrected Tetralogy of Fallot and Correlates with the Incidence of Supraventricular Arrhythmia: A CMR Study

Abstract

The aim of this study was to evaluate right atrial (RA) volume in corrected Tetralogy of Fallot (cTOF) and assess its correlation with the occurrence of supraventricular (SV) arrhythmia. Cardiac magnetic resonance imaging (CMR) and 24-h Holter were performed in n = 67 consecutive cTOF patients (age 30 ± 11.3 years). The CMR protocol included standard HASTE, SSFP cine, and blood flow measurements. Correlations between arrhythmia in ECG, heart volume, and functional parameters were investigated by negative binominal regression. Patients' characteristics (mean ± SD) included mean RA volume of 49 ± 19 ml/m(2) (HASTE sequence), mean right ventricular (RV) end-diastolic volume of 98 ± 27 ml/m(2), mean pulmonary valve regurgitation fraction (PR) of 21 ± 19 %, BMI of 25 kg/m(2), and heart rate of 75/min. Twenty-eight out of 67 patients experienced SV arrhythmia including SV couplets or bigeminus or longer non-sustained SV tachycardia (SVT) episodes. RA volume index was identified as an independent risk factor for different degrees of SV arrhythmia (SV couplets/bigeminus p < 0.001, SVT p < 0.001). Further risk factors for SV arrhythmia were male gender (p = 0.023) and decreased left ventricular (LV) ejection fraction (EF) (LV EF p < 0.001). RA volume is increased in adult patients with cTOF with larger RA volumes relating to higher incidence of SV arrhythmia. SV arrhythmia also appeared more often in male patients and those with decreased LV EF. Risk stratification according to these parameters could help to optimize early prevention and adjusted individual therapy to improve patient outcome and quality of life.

Full text

ORIGINAL ARTICLE
Right Atrial Volume is Increased in Corrected Tetralogy of Fallot
and Correlates with the Incidence of Supraventricular
Arrhythmia: A CMR Study
Jan M. Sohns
1,5
•Christina Rosenberg
1,5
•Antonia Zapf
2,5
•Christina Unterberg-Buchwald
3,5
•
Wieland Staab
1,5
•Andreas Schuster
3,5
•Johannes T. Kowallick
1,5
•
Olga Ho
¨sch
4
•Thuy-Trang Nguyen
4
•Martin Fasshauer
1,5
•Thomas Paul
4
•
Joachim Lotz
1,5
•Michael Steinmetz
4,5
Received: 22 October 2014 / Accepted: 24 March 2015
ÓSpringer Science+Business Media New York 2015
Abstract The aim of this study was to evaluate right
atrial (RA) volume in corrected Tetralogy of Fallot (cTOF)
and assess its correlation with the occurrence of
supraventricular (SV) arrhythmia. Cardiac magnetic reso-
nance imaging (CMR) and 24-h Holter were performed in
n=67 consecutive cTOF patients (age 30 ±11.3 years).
The CMR protocol included standard HASTE, SSFP cine,
and blood flow measurements. Correlations between ar-
rhythmia in ECG, heart volume, and functional parameters
were investigated by negative binominal regression. Pa-
tients’ characteristics (mean ±SD) included mean RA
volume of 49 ±19 ml/m
2
(HASTE sequence), mean right
ventricular (RV) end-diastolic volume of 98 ±27 ml/m
2
,
mean pulmonary valve regurgitation fraction (PR) of
21 ±19 %, BMI of 25 kg/m
2
, and heart rate of 75/min.
Twenty-eight out of 67 patients experienced SV arrhythmia
including SV couplets or bigeminus or longer non-sus-
tained SV tachycardia (SVT) episodes. RA volume index
was identified as an independent risk factor for different
degrees of SV arrhythmia (SV couplets/bigeminus
p\0.001, SVT p\0.001). Further risk factors for SV
arrhythmia were male gender (p=0.023) and decreased
left ventricular (LV) ejection fraction (EF) (LV EF
p\0.001). RA volume is increased in adult patients with
cTOF with larger RA volumes relating to higher incidence
of SV arrhythmia. SV arrhythmia also appeared more often
in male patients and those with decreased LV EF. Risk
stratification according to these parameters could help to
optimize early prevention and adjusted individual therapy
to improve patient outcome and quality of life.
Keywords Cardiac MRI Right atrial volume Tetralogy
of Fallot Arrhythmia Supraventricular arrhythmia
Abbreviations
BMI Body mass index
CMR Cardiac magnetic resonance
CT Computed tomography
cTOF Corrected Tetralogy of Fallot
ECG Electrocardiogram
EF Ejection fraction
HASTE Half-Fourier acquisition single-shot turbo
spin-echo
LA Left atrium
LV Left ventricle
PR Pulmonary regurgitation
RA Right atrium
RV Right ventricle
RVEDVI Right ventricular end-diastolic volume index
SSFP Steady-state free precession
Jan M. Sohns and Christina Rosenberg have contributed equally to
this work.
&Michael Steinmetz
michael.steinmetz@med.uni-goettingen.de
1
Institute for Diagnostic and Interventional Radiology, Heart
Center, University Medical Center, Georg-August-University
Go
¨ttingen, Go
¨ttingen, Germany
2
Department of Medical Statistics, Georg-August-University
Go
¨ttingen, Go
¨ttingen, Germany
3
Department of Cardiology and Pneumology, Heart Center,
University Medical Center, Georg-August-University
Go
¨ttingen, Go
¨ttingen, Germany
4
Department of Pediatric Cardiology and Intensive Care
Medicine, Heart Center, University Medical Center,
Georg-August-University Go
¨ttingen, UMG,
Robert-Koch-Str. 40, 37075 Go
¨ttingen, Germany
5
DZHK, German Center for Heart Research, Partner Site,
Go
¨ttingen, Germany
123
Pediatr Cardiol
DOI 10.1007/s00246-015-1152-2

SVES Supraventricular extrasystole
TOF Tetralogy of Fallot
VES Ventricular extrasystole
Introduction
The left atrium (LA) is known to be a source of
supraventricular (SV) arrhythmia, and the occurrence of
atrial fibrillation correlates with an increased LA volume
[17]. Tetralogy of Fallot (TOF) is the most common
cyanotic congenital cardiac defect and is associated with
pulmonary infundibular stenosis, overriding aorta, and
malalignment ventricular septal defect (VSD) [18]. After
initial surgery, a significant number of TOF patients re-
quires pulmonary valve replacement in the second or third
decade of life, due to clinically symptomatic pulmonary
regurgitation or stenosis [9]. Right ventricular (RV) size
and function can be evaluated by cardiac magnetic reso-
nance (CMR) in detail. CMR parameters such as indexed
RV end-diastolic volume (EDVi) and RV EF are important
for the optimal timing of pulmonary valve replacement.
This optimal timing for pulmonary valve replacement is
still a matter of scientific and clinical debate, different
centers use different CMR cutoff points as only one of
many markers [9,22].
A high number of corrected TOF patients (cTOF) suffer
from SV or ventricular arrhythmia (SV or V arrhythmia),
caused by recurrent heart surgery, atrial or ventricular
scarring, or possibly genetic factors, which are associated
with TOF. RV size, increased QRS duration, and my-
ocardial scars have been reported previously to correlate
with ventricular arrhythmia in TOF patients [2,4,7,20]. A
high correlation between LA volume derived from CT and
CMR and the occurrence of SV arrhythmia (e.g., atrial
fibrillation) has been reported in studies with heterogenous
patient collectives suffering from non-congenital left heart
disease [6,17], [19], [5]. CMR-derived RA volume in
cTOF patients suffering from right heart disease has not
been evaluated with regard to arrhythmia.
The aim of the present study was to assess the correla-
tion between RA volume and the occurrence of arrhythmia
in cTOF patients, using CMR measurements and 24-h
Holter ECG monitoring.
Materials and Methods
Patients’ Characteristics and Study Design
Sixty-seven consecutive cTOF patients were examined in
the outpatient clinic of the Department of Pediatric
Cardiology and Adult Congenital Heart Disease of the
University Medical Center and were recruited for the study
from 01/2009 to 10/2012. Median age was 30 ±11.3
(9–54) years, 34 were females and 33 were males. Clinical
examination included weight and height, medical history,
physical examination, gender, ECG, CMR, and 24-h Holter
monitoring for the assessment of cardiac arrhythmia (per-
formed within 2 days). Higher-grade SV arrhythmia was
divided into SV couplets/ bigeminus and non-sustained
SVT. Ventricular arrhythmia was graded according to the
Lown Classification [10]. In brief, ventricular premature
beats (VPB) or tachycardias are graded as Lown 0 =no
VPB, 1 =occasional isolated VPB, 2 =frequent VPB,
3=multiform VPB, 4 =repetitive VPB [couplets (4a) or
salvos (4b)], and 5 =early VPB. BMI and body surface
area were calculated using height and weight according to
formulas of Quetelet and DuBois. An age-matched control
group was derived from the literature. Furthermore, dif-
ferent methods of surgical correction (e.g., correction of
heart defects after birth and higher age, shunt, transannular
patch, valvuloplasty, and homograft) were registered if
present (Fig. 1; Table 1). The study was approved by the
institutional review board, and written informed consent
was obtained from each patient for clinical examination
and following research analysis. This study was conducted
in consent with the Declaration of Helsinki.
CMR Imaging Technique and Analysis
Patients undergoing CMR were placed supine with a five-
element cardiac coil system attached to the chest. Ex-
aminations were performed using a 1.5 T (Tesla) whole-
body MR scanner (Siemens Symphony). ECG-gated half-
Fourier spin turbo echo (HASTE) sequences acquired in
diastole were recorded for all patients in transversal,
coronal, and sagittal orientations (slice thickness 5 mm, TR
800, TE 48). ECG-triggered breath-hold steady-state free-
precession (SSFP) cine sequences were obtained in short-
axis orientation and standard CMR views (TR 45, TE 1,36,
flip angle 64°, slice thickness 7 mm) without any interslice
gap in both sequences. Ventricular volumes and functions
were derived from short-axis views. The procedure fol-
lowed the standardized CMR protocol of the German
Competence Network for congenital heart defects [14],
[15]. Blood flow was measured in the main pulmonary
artery with through-plane velocity-encoded phase-contrast
CMR, using standard sequence parameters and encoding
velocity.
Volume analysis was performed using semiautomatic
contour detection software (QMass, Medis, Leiden, the
Netherlands). Ventricular systole and diastole were defined
for standard ventricular volumetry, and atrial phases were
adapted based on the ventricular systole and diastole.
Pediatr Cardiol
123

Contour detection was performed, using semiautomatic
segmentation. Endocardial and epicardial ventricular were
drawn using every phase of the SSFP cine stack from apex
to base (Fig. 1b atrial, d ventricular contours). Papillary
muscles were excluded in the ventricular segmentation.
Atrial endocardial contours were drawn in transversal and
coronal HASTE sequences (Fig. 1a, c). If necessary,
manual correction of segmentation was performed. Corre-
sponding cine short-axis images were used to help deter-
mining atrioventricular borders, mitral valve planes, and
the definition of pulmonary vein ostia as described before
by Sarikouch et al. [15]. The vena cava superior and in-
ferior and the pulmonary veins were excluded from the
analysis for the right and left atrium, respectively. Atrial
appendages were included in the atrial volumetry, whereas
the coronary sinus was excluded. In order to compare the
reliability of HASTE-derived atrial volumes with those
derived from SSFP, in 23 patients, atria were also seg-
mented on SSFP sequences. In SSFP sequences, maximal
atrial volume (atrial diastole) was determined at ventricular
end systole (ES) and minimal atrial volume (atrial systole)
at ventricular end diastole (ED).
For correct segmentation, atrial wall and septum were
carefully reviewed and manual changes were adjusted if
necessary. Contours were placed independently by a junior
(CR, 1 year of CMR experience) with the help of an ex-
perienced observer (MS, more than 5 years experience in
pediatric CMR). A third reviewer (JL, long-term experi-
ence in pediatric CMR, over 10 years) reviewed all con-
tours, and consensus agreement was used to define final
contours.
Statistical Analysis
For statistical analysis, Statistica10 (StatSoft Inc., Tulsa,
OK, USA) and SAS 9.3 were used (regression analysis and
validation; SAS Institute Inc., Cary, NC, USA). Statistical
planning, consultation, and analysis were performed by
AZ, Institute for Medical Statistics, University Medical
Center, Goettingen.
Detailed descriptive analysis was performed for all
clinical data, and values were expressed as mean or median
and standard deviation as appropriate. The relationship
between CMR and 24-h Holter ECG was assessed using a
Fig. 1 Segmentation of atria
and ventricles in HASTE and
SSFP cine images: Atrial
segmentation in atransversal
and ccoronal HASTE
sequences and bin short-axis
SSFP sequences. Red left
atrium, yellow right atrium.
dSegmentation of ventricles in
short-axis SSFP sequences
(panel shown: systole). Green
left ventricle epicard. Red left
ventricle endocard. Orange and
violet papillary muscles left
ventricle. Blue right ventricle
epicard. Yellow right ventricle
endocard
Pediatr Cardiol
123

negative binomial regression analysis (as generalization of
the Poisson regression) with the number of arrhythmia as
dependent variable (separately for the different types of
arrhythmias). Baseline characteristics as well as CMR pa-
rameters were used as independent variables. A simple
regression analysis with only one independent variable was
performed initially. Subsequently, multiple regression
analysis was performed including all relevant independent
variables, which tended to significant correlation (i.e.,
p\0.05). The final model was chosen using backward
selection. Instead of r
2
of linear regression, deviance di-
vided by the degrees of freedom (df) was used as a pa-
rameter representing the goodness of fit (deviance/df =1
means a perfect model fit). Beside the pvalues, also the
estimators, which can be interpreted as relative risks, are
given. A pvalue of \0.05 was assumed to be significant
Results
Study Population
Of the 67 patients studied, 29 had higher-grade SV ar-
rhythmia as SV couplets or bigeminus and non-sustained SV
tachycardia (Table 3). Out of the 29 patients with SV
arrhythmia, 15 patients were symptomatic, i.e., com-
plained about palpitations and were aware of arrhythmias
or ectopic beats. Eight patients had paroxysmal sustained
SVT divided into five atrial flutters and three intra-atrial
reentrant tachycardias (IARTR). Mean values for CMR-
derived measures of ventricular function and volumes
were RVEDVi 98 ±27 SD ml/m
2
; pulmonary valve re-
gurgitation fraction 21 ±19 %; RV EF 46 ±11 %; LV
EF 60 ±7 %; and mean heart rate on 24-h Holter ECG
75/min, ranging from 43/min to 105/min (Table 1). Tri-
cuspid regurgitation obtained from last echocardiography
report was none in 10, mild in 31, moderate in 24, and
severe in 2 patients.
Atrial Volume
Mean RA volumes in atrial systole were 50 ml/m
2
(±15 ml/m
2
, transversal HASTE), 47 ml/m
2
(±15 ml/m
2
,
coronal HASTE), and 41 ml/m
2
(±13 ml/m
2
, SSFP, i.e.,
minimal volume) as well as 59 ml/m
2
(±16 ml/m
2
, SSFP
cine atrial diastole, i.e., maximal volume; Table 2). To
assess the reliability of atrial volume measurements in
HASTE sequences compared to SSFP cine sequences,
minimal and maximal RA volumes were obtained from
SSFP cine and were compared to HASTE sequences in 23
patients. In the interest of scan time and patient comfort,
not all cTOF scans included atrial coverage in short-axis
stacks. Bland–Altman plots were calculated for both SSFP
atrial systole (minimal volume) and diastole (maximal
volume) in comparison with volumes of transversal and
coronal HASTE sequences (Fig. 2a, b). Bland–Altman
analysis confirmed a good correlation of RA volumes from
SSFP cine and HASTE sequences with a minor overesti-
mation of RA volumes in HASTE sequences. Atrial vol-
umes from HASTE sequences obtained in ventricular
diastole (i.e., atrial systole) corresponded well with SSFP
atrial systole (Table 2; Fig. 2).
Table 1 Patients’ characteristics
Patient groups Total numbers
(n±SD)
Patients 67
Female 34
Male 33
Age at study inclusion (years) 30 ±11.3
BMI (kg/m
2
)25±4.4
Age at corrective surgery 4.2 ±3.2
Heart beat/min 75 ±11
Surgical correction
Ventricular septal defect patch closure 67
Previous a–p shunt 38
RV PA conduit or homograft 40
Transannular patch 27
Myectomy 24
Pulmonary artery plasty 22
RVOT plasty 19
Commissurotomy 12
Atrial septal defect patch closure 4
Mechanical pulmonary valve 2
Total number ±SD (standard deviation) or absolute numbers (for
surgery numbers); previous a–p shunt, previous aorto-pulmonal shunt;
RV PA conduit, right ventricular pulmonal artery conduit; RVOT
plasty, right ventricular outflow tract plasty
Table 2 Atrial volumes in SSFP cine and HASTE sequences
SSFP cine Haste trans Haste coro
Right atrium
End-diastole index (ml/m
2
)41±13 50 ±16 47 ±15
End-systole index (ml/m
2
)60±16
Left atrium
End-diastole index (ml/m
2
)20±924±825±8
End-systole index (ml/m
2
)40±10
Values mean ±SD (Standard deviation), end diastole =ventricular
end diastole, end systole =ventricular end systole, end-diastole and
end-systole index =volume indexed to body surface area (ml/m
2
)
SSFP cine steady-state free precession, HASTE half-Fourier acquisi-
tion single-shot turbo spin-echo, Trans transversal, Coro coronal
Pediatr Cardiol
123

Supraventricular Arrhythmia
In multiple regression analysis, RA volume index correlated
with the occurrence of higher-grade SV arrhythmia, such as
SV couplets or bigeminus (p=0.001, estimator 1.15;
Table 3). Additional correlations were found for male gender
(p=0.023, estimator 11.49), previous shunt (p=0.015,
estimator 28.474), myectomia (p=0.001, estimator 0.048),
and LV EF (p\0.001, estimator 0.814; Table 4). Moreover,
RA volume index correlated also with the occurrence of non-
sustained SV tachycardia (p\0.001, estimator 1.18;
Table 4). No significant correlation was found for RA vol-
umes with age, age at shunt or at TOF repair or type of TOF
repair, PV replacement, TR, PR, RVEDVi, or RV EF.
Ventricular Arrhythmia
We also analyzed whether any of the measured parameters
correlated with the occurrence of ventricular arrhythmias.
Statistical analysis revealed a negative correlation of Lown
I with status after myectomia (p=0.040). The study
population did not include patients with Lown II. Only two
patients exhibited Lown III, and consequently, no mean-
ingful statistical results could be constructed. Lown IV was
correlated to myectomia (p=0.002), age (p=0.001), and
negatively to LV EF (p=0.014).
Discussion
This is the first CMR study that demonstrates that RA
volume, measured by different CMR sequences (HASTE
and SSFP), is increased in cTOF patients and correlates
with the occurrence of SV arrhythmia, consistently and
independent of other confounding factors such as age, age
at repair, PV replacement, TR, PR, RV EF, or RV
volume.
Not only ventricular arrhythmias, as the major cause of
late sudden death in patients after surgical repair of TOF,
but also SV arrhythmia affects the quality of life and
morbidity in patients after TOF repair [7], [2]. Khairy et al.
analyzed the arrhythmia burden in adults with cTOF and
demonstrated that 11.5 % suffer from SV arrhythmia. In
our study, 29 out 67 cTOF suffered from higher-grade SV
arrhythmia. Of these, eight had paroxysmal SV tachycardia
as atrial flutter and IART (i.e., 11.9 %). CMR is crucial to
plan treatment and identify risk factors for mortality and
morbidity in TOF patients such as decreased RV function,
scars, and pulmonary regurgitation [18]. The present study
demonstrates that it may be helpful to evaluate the risk of
SV arrhythmia in cTOF patients by incorporating RA
volumes from CMR in the risk stratification process.
Table 3 Arrhythmia in TOF patients
Type of arrythmia Number of
patients
Number of arrhythmias
per patient mean value
Supraventricular
SV couplets/bigeminus 21 40 ±200
SV tachycardia 8 1 ±5
Ventricular
Lown 0 10
Lown I 27
Lown II 0
Lown III 2
Lown IV 23
Values are mean ±SD (standard deviation). Ventricular arrhythmia
according to the Lown classification: Lown 0: no ventricular ex-
trasystoles (VES); Lown I: occasionally, few VES; Lown II: frequent
VES; Lown III: polymorph VES single or bigeminus; Lown IV:
repetitive VES such as couplets or salves
TOF Tetralogy of Fallot, SVES supraventricular extrasystoles, SV
supraventricular
Fig. 2 Bland–Altman plots of the difference between RAEDVi (from
SSFP cine) and RAEDVi from HASTE sequences: atransversal
orientation and bcoronal orientation. RAEDVi =right atrial volume
index in ventricular systole in ml/m
2
Pediatr Cardiol
123

Previous CMR studies have established reference values
for atrial volumes in healthy children and adults [15], [16].
The present study shows markedly higher RA volumes in
cTOF patients compared to those reported for healthy
volunteers in the literature (Table 5).
Smaller studies have reported some RA volumes in
cTOF patients and demonstrated only slightly enlarged RA
volumes compared to healthy volunteers. In contrast, RA
volumes from our study in 67 patients are remarkably
larger than the values of the Riesenkampff et al.’s [12]
study group. This may be due to sample size (only 20
patients), to only mild TR in that study, while our patients
exhibited different degrees of also moderate and higher
degree TR, and to a slight overestimation of RA volumes
from the HASTE sequences in our protocol.
To the best of our knowledge, this is the first study that
describes increased RA volumes in cTOF patients and their
correlation with SV arrhythmia. Other methods to asses RA
and SV arrhythmia have been reported. Bonello et al. [1]
demonstrated RA area in 4CV SSFP cine sequences from
CMR as a predictor of SV arrhythmia. Another study by
Rosinau et al. [13] reported RA diameters from echocar-
diography in conjunction with SV arrhythmia. Unlike these
studies, we focused on RA volumes from CMR easily ac-
quired from HASTE sequences, since the strength of CMR
is that it can deliver three-dimensional volumes rather than
two-dimensional areas. This has been proven to be ad-
vantageous for RV volume assessment, which is prob-
lematic in standard echocardiography. Our data together
with the findings of Bonello and Rosinau support the
Table 4 Correlation of CMR
and biometric data with
supraventricular arrhythmia in
TOF (binominal negative
regression analysis)
Arrhythmia Correlating independent
variable
Pvalue Exp
(estimator)
Coefficient
(95 % Cl)
SV couplets/bigeminus
CoroEDVi RA 0.001 1.146 1.061; (1.237)
Gender (m vs. f) 0.023 11.485 1.399; (94.255)
Shunt (0 vs. 1) 0.015 28.474 1.906; (424.962)
Myectomia (0 vs. 1) 0.001 0.048 0.008; 0.298
LV EF \0.001 0.814 0.730; 0.908
SV tachycardia
Trans EDVi RA \0.001 1.176 1.109; 1.247
Only significant correlations are displayed. Exp: Estimator for a one-unit change in the predictor variable;
the difference in the logs of expected counts of the responsive variable is expected to change by the
respective regression coefficient, given the other predictor variables in the model are held constant. For
example, if a patient has a RA volume one unit larger, the expected counts are on average 1.18 times
(12 %) higher for SV tachycardia. The coefficient gives the interval in which the real value is included in
95 %, SVES deviance/df =1.279, SV couplets deviance/df =0.617, SV tachycardia deviance/df =0.619,
coro EDVi RA =end-diastolic volume of the right atrium measured in coronal HASTE slices and indexed
to body surface area
ASD patch Atrial septal patch, BMI body mass index, mmale, ffemale, LV EF left ventricular ejection
fraction, Trans EDVi RA end-diastolic volume of the right atrium measurement in transversal HASTE and
indexed to body surface area
Table 5 Right atrial volumes of cTOF patients compared to values from the literature
Present Study Riesenkampff et al. [12] Sievers et al. [16]
n672070
Characteristics cTOF patients cTOF patients Healthy volunteers
Age, years 30.9 ±11.3 19.5 ±8.9 51.8 ±15.6
MRI sequence/orientation SSFP cine SA HASTE trans HASTE coro SSFP cine SA SSFP cine SA
End diastole, ml/m
2
41 ±13 50 ±16 47 ±15 30 ±12 27 ±10
End systole, ml/m
2
60 ±16 51 ±17 53 ±17
cTOF =Patients with surgically corrected Tetralogy of Fallot, age years ±SD (standard deviation), SSFP cine SA =Steady-state free-
precession cine short-axis sequence. HASTE trans =Half-Fourier acquisition single-shot turbo spin-echo sequence transversal orientation,
HASTE coro =Half-Fourier acquisition single-shot turbo spin-echo sequence coronal orientation, end diastole =ventricular end diastole, end
systole =ventricular end systole
Pediatr Cardiol
123

notion that RA size plays an important role in the devel-
opment of SV arrhythmia in cTOF patients.
Increased RA volume and subsequently reduced RA
function may be one reason for an increased risk of ar-
rhythmia in TOF patients as observed in our study. Other
groups have reported that atrioventricular interaction and
coordination is of importance in TOF patients. Moderate
systolic and diastolic RV dysfunction is associated with
impaired RA function [12]. However, RV function was
only slightly decreased in our study group, and we cannot
comment on atrial function reliably, since quantification of
RA function has not been established in CMR routine.
Newer techniques such as CMR feature tracking may help
to quantify atrial function better in the future [8].
For cTOF patients, CMR examinations have been rec-
ommended by the ESC and AHA guidelines for adult
congenital heart disease [11,21]. We suggest that on CMR
RA, volumes should always be measured from either
HASTE or SSFP sequences in clinical follow-up. In case of
high RA volumes especially in male patients, those with
previous shunt or an increase in RA volume over time,
clinicians should rigorously search for SV arrhythmia by
24-h Holter monitoring and history taking and refer
tachycardia-positive patients to an electrophysiology study.
MRI Sequences
The present results also demonstrate that atrial volumes can
be calculated from segmentation of ECG-gated HASTE
sequences obtained in ventricular diastole in different
planes in CMR. Compared to SSFP cine sequences, HASTE
sequences slightly overestimated minimal atrial size com-
pared to SSFP sequences. However, volumes of HASTE
sequences were reproducible and comparable to those ob-
tained from SSFP cine images. The advantage of measuring
atrial volumes in HASTE sequences is that it can be per-
formed in a single breath-hold of the patient as opposed to
multiple breath-holds in multiplanar SSFP cine loops.
Gender-Specific Correlations
Apart from RA volume, gender was an important inde-
pendent factor increasing the risk of SV arrhythmia. Male
TOF patients had a higher risk for SV arrhythmia than
female patients (gender m vs. f p=0.023, estimator 11.46;
Table 4). Former studies underline differences in cardiac
volumes and function for women and man. Sievers et al.
[16] reported slightly higher CMR-derived RA volumes for
male compared to female healthy volunteers. Sarikouch
et al. [14] reported differences in ventricular function:
decreased RV EF in female, but decreased RV and LV EF
in male TOF patients. Our study underlines the importance
of sex differences also in congenital heart disease.
Ventricles
Risk factors for ventricular arrhythmia in our patient cohort
were status after myectomia and decreased LV EF, which
is in concordance with observations from studies on re-
duced LV function or with non-congenital cardiac disease.
These patients exhibit an increased risk of sudden cardiac
death due to ventricular arrhythmia (e.g., status after my-
ocardial infarction) and reduced LV EF of \35 % [23].
Unlike other groups, we could not detect a correlation
between RV dysfunction, RVEDVi or RV ESVi, and
ventricular arrhythmia, which may be due to, first, a
relatively small number of patients with ventricular ar-
rhythmia in our study population and, second, to an only
moderately increased RVEDVi. Mean RVEDVi and ESVi
were lower in our study compared to the study of Dav-
louros et al. [3] that compared RV function in TOF patients
with healthy individuals. Values of pulmonary regurgita-
tion fraction (21.38 ml/m
2
±19.8 SD %) are similar to
values reported by former studies.
Study Limitations
Our study is limited by the fact that the data were evaluated
in a single-center study. The follow-up period and incor-
poration of additional clinical parameters should probably
include a longer time span (e.g., decades) for all cases, and
more patients should be analyzed preferably in a multi-
center, prospective study. Due to the small sample size, it is
not feasible to calculate a reliable cutoff value for an RA
volume that confers a definite risk for SV tachycardia.
Larger studies, preferably multicenter, would be needed to
calculate a reliable cutoff value for RA volumes.
Moreover, a follow-up correlation of CMR and 24-h
Holter ECG should be performed, to evaluate whether
further increased RA volumes in the same patients are
associated with a higher incidence of arrhythmia in the
future. Additionally, some results (e.g., atrial volumes)
should possibly be compared with RA pressures from
cardiac catheterization or atrial function derived from
CMR feature tracking. Our control group, though age-
matched, was derived from the literature.
Conclusion
This is the first study to elucidate the importance of RA
volumes from CMR in conjunction with SV arrhythmia.
RA volumes are increased and can be reliably measured in
HASTE sequences in cTOF patients. The larger the RA
volume was measured in our study population, the higher
the incidence of SV arrhythmia. This correlation was in-
dependent of patients’ age, pulmonary valve replacement,
Pediatr Cardiol
123

RV volume and function, and tricuspid regurgitation or
pulmonary valve regurgitation. CMR-derived RA volumes
may contribute valuable information to assess the risk of
arrhythmia in cTOF patients.
Acknowledgments This study was supported by DFG, Project
Number LO 1773/1-1.
Conflict of interest The author(s) declare that they have no com-
peting interests.
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