DOI: 10.1161/CIRCEP.113.000636
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Fragmented QRS Complex in Adult Patients with Ebstein’s Anomaly and Its Association with Arrhythmic Risk and the Severity of the Anomaly
Running title: Park et al.; Fragmented QRS in Ebstein’s Anomaly
Seung-Jung Park, MD, PhD1; Seungmin Chung, MD1; Young Geun On, MD, PhD1;
June Soo Kim, MD, PhD1; Ji-Hyuk Yang, MD, PhD2; Tae-Gook Jun, MD, PhD2;
Shin Yi Jang, RN, PhD1; Ok Jung Lee, MD3; Jinyoung Song, MD, PhD3;
I-Seok Kang, MD3; June Huh, MD, PhD3
Department of 1Medicine, 2Thoracic and Cardiovascular Surgery, and 3Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence:
June Huh, MD, PhD
Associate Professor
Grown-Up Congenital Heart Disease Clinic,
Department of Pediatrics, Cardiac and Vascular Center,
Samsung Medical Center, Sungkyunkwan University School of Medicine,
50 Irwon-dong, Gangnam-gu
Seoul 135-710
Korea
Tel: +82-2-3410-3526
Fax: +82-2-3410-0043
E-mail: [email protected]
Journal Subject Code: [171] Electrocardiology
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DOI: 10.1161/CIRCEP.113.000636
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Abstract:
Background - Fragmented QRS complex (fQRS) on 12-lead ECG, a marker of myocardial scar,
is a predictor of arrhythmic events in patients with ischemic and non-ischemic cardiomyopathy.
We investigated whether the presence of fQRS is associated with the severity of the anomaly and
with increased arrhythmic events in adult patients with Ebstein’s anomaly (EA).
Methods and Results - In 51 consecutive adult EA patients (median age, 37 years; 18 males), the
severity index of EA calculated from echocardiographic data and clinical arrhythmic events were
analyzed. The extent of fQRS in each patient was measured by counting the number of ECG
leads showing fQRS. There were 35 (68.6%) patients with fQRS (fQRS group) and 16 (31.4%)
patients without fQRS (non-fQRS group). fQRS was observed more frequently in the inferior
(n=26) and precordial (n=25) leads versus the lateral leads (n=5). The patients in the fQRS group
had a worse functional class, greater cardiothoracic ratios, more severe tricuspid regurgitation,
larger atrialized right ventricular (aRV) areas, higher EA severity scores, and more frequent
arrhythmic events compared to those in the non-fQRS group. The aRV area showed a positive
correlation with the fQRS extent (r=0.51, P<0.001). In multivariable Cox regression models, the
presence of fQRS was independently associated with arrhythmic events (P=0.036).
Conclusions - Fragmented QRS on 12-lead ECG was associated with larger aRV area and an
increased risk of arrhythmic events in adult patients with EA.
Key words: ECG, Ebstein's anomaly, adult congenital heart disease, arrhythmia, fragmented QRS complex
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Ebstein’s anomaly (EA) is a congenital malformation of the tricuspid valve (TV) and the right
ventricle (RV). The most prominent morphological feature of EA is the varying degree of apical
displacement of the TV into the RV, dividing the RV into a proximal chamber of “atrialized RV
(aRV)” and distal portion of “functional RV”. This abnormality often causes tricuspid
regurgitation (TR), progressive dilatation and dysfunction of the right atrium (RA) and RV.1
Therefore, the most common clinical presentations in adolescents and adults with this
malformation are arrhythmic events and right-sided heart failure.2-5 Moreover, these
complications are expected to become more frequent with the improvement in long-term survival
of patients5,6 However, there have been very few studies investigating the risk factors for
arrhythmic complications, especially in adults with EA.
Fragmented QRS complexes (fQRS) on 12-lead ECG, which represent conduction delay
caused by myocardial scar, have been identified as a predictor of arrhythmic events in patients
with ischemic or non-ischemic heart disease7,8 Recently, the fQRS found in adults with repaired
tetralogy of Fallot (TOF) was reported to represent more extensive RV scarring and dilatation.9
In this study, we evaluated whether the presence of fQRS reflects a greater risk of
arrhythmic events and more severe abnormalities of the right-sided chambers in adult patients
with EA.
Methods
Patient Population
Fifty-one adult patients (>18 years old) diagnosed consecutively with EA at the Samsung
Medical Center from November 1994 to April 2011 were enrolled for the present study. EA was
diagnosed by echocardiography when the apical displacement of the septal leaflet of the TV
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relative to the insertion of the anterior leaflet of the mitral valve was measured at least 20 mm or
8 mm/m2 body surface area (BSA). Patients with failed ablation of accessory pathways (AP),
paced ventricular rhythms, and a previous cardiac surgery were excluded because these
conditions could affect the QRS morphology. Demographic, electrocardiographic, and
echocardiographic data were analyzed retrospectively. The study protocol was approved by our
institutional review board, and the requirement for written informed consent was waived.
Definition of fQRS and Measurement of ECG Parameters
Standard 12-lead ECGs were obtained with an optimal low-pass filter setting (filter range 0.15 to
100 Hz, alternating current filter 60 Hz, 25 mm/s, 10mm/mV; GE Marquette, Milwaukee, WI,
USA). To assess the correlation between fQRS and the severity of the structural abnormality in
EA, we analyzed the index electrocardiogram recorded closest in time to the echocardiographic
examination performed during the first visit to our institute. The time interval between
electrocardiographic and echocardiographic study ranged from 0 to 105 days (median 1 day).
QRS complexes were defined t ') or notch on the
R/S waves were present in narrow QRS complexes (<120ms), or when >2 notches on the R/S
waves were noted in wide QRS complexes ( .7-9 This fragmentation should be observed
in at least two contiguous leads representing anterior (V1–V5), inferior (II, III, aVF), or lateral (I,
aVL, V6) myocardial segments (Figure 1). The extent of the fQRS in each patient was estimated
by counting the number of ECG leads showing fQRS.9 In the presence of delta-waves in the
QRS complex, electrocardiograms obtained after accessory pathway (AP) ablation were used
because pre-excitation of the ventricle through the AP could alter the QRS morphology,
mimicking fQRS. All ECG tracings were analyzed by two independent cardiologists who were
blinded to clinical outcome data. There was a 97% and 95% intra- and interobserver agreement
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for the presence of fQRS, respectively. Electrocardiographic parameters such as
PR/QRS/corrected QT/corrected JT intervals and QRS/QT/JT dispersion were also measured
manually.
Echocardiographic Parameters and Severity Grading of Ebstein’s Anomaly
Comprehensive transthoracic echocardiography was performed using 2.5 to 4 MHz transducers
(Vivid 7, GE Medical System, Milwaukee, WI or Acuson 512, Siemens Medical Solution,
Mountain View, CA, USA). Maximal apical displacement of the TV was measured from the
hinge point of TV septal leaflet to the insertion point of the MV anterior leaflet. The severity
index of EA was estimated using the Great Ormond Street Score (GOSE), an echocardiographic
method described previously.10 The GOSE was calculated as the ratio of the combined area of
the RA and aRV divided by the combined area of the RV proper, left atrium (LA), and left
ventricle (LV) in a four-chamber view at the end of diastole (Figure 2). Four grades of increasing
severity were defined: grade 1, ratio<0.5; grade 2, ratio 0.5 to 0.99; grade 3, 1 to 1.49; and grade
-quantitative measurement depending on
vena contracta width, proximal isovelocity surface area, hepatic vein flow reversal, RV or RA
enlargement, and the plethora of the inferior vena cava.11 The LV ejection fraction was
calculated using Simpson's biplane method.
Clinical Outcomes
Clinical arrhythmias were defined as spontaneous episodes associated with palpitation, dizziness,
or syncope with ECG documentation. Occurrence of clinical arrhythmias has been investigated
since the index electrocardiograms were taken. The index electrocardiograms were obtained
during the first visit as mentioned above. Regular clinical and electrocardiographic follow-up (3
to 6 month interval) was performed in all patients. If a patient reported symptoms suggesting
or leaflet. The seveveveveririrr t
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ere defined: grade 1, ratio<0.5; grade 2, ratio 0.5 to 0.99; grade 3, 1 to 1.49; and
q antitati e meas rement depending
scrrrribibbibedededed ppprererer vivv ouououuslss y.10 The GOSE was callllccuc llated as the rrratiooo ooof the combined area
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tntitit tatii tt dde dndiin
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arrhythmia at any time, ECG and 24-hour Holter monitoring were repeated. Ventricular
tachyarrhythmia included ventricular fibrillation (VF), ventricular tachycardia (VT), appropriate
implantable cardioverter-defibrillator (ICD) shock, and nonsustained VT ( 3 consecutive
ventricular beats at a rate of 100 beats/min with a duration of <30 seconds). Atrial
tachyarrhythmia included atrial tachycardia (AT), atrial fibrillation (AF), atrial flutter (AFL), and
atrioventricular reentrant tachycardia (AVRT) using AP. For the present study, tachycardia
episodes caused by AVRT using AP were not included when analyzing the relationship between
fQRS and arrhythmic events. Since fQRS is a marker of myocardial fibrosis, we focused on
specific relationships between fQRS and arrhythmias more directly related to myocardial
dysplasia/degeneration. Therefore, the AVRT with a bypass tract was analyzed separately. Open
heart surgery and cardiac death were also investigated.
Statistical Analysis
Continuous variables were expressed as medians (25th and 75th percentiles) and were compared
using the Mann-Whitney test. The results for categorical variables were described as percentages
and the Fisher’s exact test was performed to compare these results. Correlations between QRS
duration or fragmentation and the severity of disease were assessed by the Spearman rank
correlation coefficient. Crude survival in each group was assessed using the Kaplan–Meier
method and the log-rank test was applied. Hazard ratios (HR) with 95% confidence intervals (CI)
were computed using Cox regression models after the proportional hazards assumption was
tested based on correlations between survival rankings and Schoenfeld residuals. The overall C-
index was calculated using Cox survival methods to evaluate the discriminatory accuracy of
several electrocardiographic variables (see supplemental Table) for the occurrence of arrhythmic
events (12). All analyses were performed using SAS software version 9.2 (SAS Institute, Cary,
brosis, we focuseed d d d onooo
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North Carolina, USA). All p values were two-sided and results with a p value less than 0.05 were
considered statistically significant.
Results
Patient Demographics
Baseline characteristics of the 51 patients are summarized in Table 1. Median (25th and 75th
percentiles) age was 37 (31-45) years, and the median (25th and 75th percentiles) cardiothoracic
(CT) ratio was 0.55 (0.50-0.62). About half of the patients (27/51, 52.9%) were in New York
Heart Association functional class III-IV. Atrial septal defects were the most common associated
cardiac defect (n=19, 37.3%). In most of the patients (48/51, 94.1%), the right-sided chamber
was much larger than the left, with a combined RA and RV area of 53 (43-75) cm2 compared to a
combined LA and LV area of 37 (32-44) cm2 (P<0.001). The median (25th and 75th percentiles)
value of the EA severity index was 0.79 (0.63-0.94).
Comparison Between the fQRS and Non-fQRS Groups
Approximately two-thirds of the patients (35/51, 68.6%) showed
(fQRS group). fQRS occurred primarily in the inferior (26 patients) and precordial (25 patients)
leads. fQRS in the lateral leads was observed in only 5 patients. The detailed distribution of
fQRS complexes is presented in Figure 3.
The fQRS group had a worse functional class, a greater CT ratio, a longer PR interval, a
longer QRS duration, more frequent right bundle branch blocks (RBBB), and more frequent right
axis deviations compared to the non-fQRS group (Table 1 and 2). On echocardiographic
examination, apical displacement and regurgitation of the TV were more severe in patients with
fQRS versus those without (Table 2). Functional RV, LV, and LA areas indexed to BSA showed
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no significant differences between the two groups. However, aRV and RA enlargements were
more prominent in the fQRS group; therefore, the fQRS group showed a greater severity index
compared to the non-fQRS group (P<0.001). The indexed aRV area (Spearman’s r=0.51,
P<0.001), indexed RA areas (Spearman’s r=0.60, P<0.001), and Ebstein severity index
(Spearman’s r=0.58, P<0.001) were positively correlated with the extent of the fQRS (see
supplemental Figure 1).
Associations Between fQRS Complexes and Arrhythmic Complications
Table 3 summarizes clinical outcomes. Median follow-up duration (25th and 75th percentiles)
was 49 (25-116) months with no significant difference between the fQRS and non-fQRS groups
[49 (29-112) versus 51 (1-126) months, P=0.699]. Compared to the non-fQRS group, a greater
proportion of patients in the fQRS group underwent TV replacement/repair or a Fontan operation
due to severe TR and right heart failure. The incidence of AVRT with AP was not significantly
different between the two groups (fQRS versus non-fQRS group, 5/35 versus 4/16, P=0.436).
However, ventricular tachyarrhythmia (9/35, 25.7%), unexplained syncope (4/35, 11.4%), and
cardiac death due to right heart failure (1/35, 2.9%) were only found in patients with fQRS.
Sustained VT, appropriate shock for VF, and non-sustained VT episodes occurred in five, one,
and three patients with fQRS, respectively. The atrial tachyarrhythmic event (AF, AFL, and AT)
rate was also higher in the fQRS group (48.6% versus 18.8%, P=0.064). In addition, permanent
pacemaker implantation was performed only in patients with fQRS due to complete (n=2) or
advanced (n=1) AV block. Overall, total arrhythmic events occurred more frequently in the
fQRS group compared to the non-fQRS group during the follow-up (Figure 4). The presence of
fQRS in Cox regression analysis was independently associated with total arrhythmic events,
even after adjusting for relevant clinical, radiographic, echocardiographic, and
5th and 75th pep rcenenenntititt l
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electrocardiographic parameters (Table 4).
Discussion
New findings
The present study is the first to reveal a significant relationship between the presence of fQRS
and an increased risk of ventricular or atrial arrhythmic events. We also found fQRS to be
associated with poorer functional class, more severe TR, a larger right-sided chamber, and
greater severity of EA in adult patients with this cardiac defect.
Recently published data suggests that the fQRS detected in patients with EA reflects the
presence of RV dysfunction with greater aRV volume13. However, arrhythmic risk was not
evaluated in that study. Additionally, adult patients (>18 years old) accounted for only 60% of
their study population. Although there have been some studies dealing with arrhythmic
complications in adult patient groups, they only described the prevalence of a few types of
arrhythmias in a limited number of patients.2-5 Most of the previous data focused primarily on the
characteristics or management of AVRT with a bypass tract.14-16
In contrast, we evaluated the association between fQRS and arrhythmic risk as well as
the severity of the structural abnormality. Moreover, we tried to identify predictors for
arrhythmic events more directly associated with dysplasia/degenerative changes in the
atrial/ventricular myocardium; these arrhythmic complications will pose greater challenges to
clinicians than AVRT using bypass tracts especially in adult EA patients because of recent
advances in their long-term survival and in ablation technology. Our data show that
approximately 50% of adult patients with EA experienced arrhythmic complications, which is
consistent with previous studies.2,4,5,16 In addition, we found the presence of fQRS to be
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independently associated with overall arrhythmic events, even after adjusting for relevant clinical
and echocardiographic parameters.
fQRS Complexes and Risk of Ventricular Tachyarrhythmias
Fragmentation of QRS morphology on surface ECG reflects inhomogeneous ventricular
activation caused by myocardial scar in patients with a prior myocardial infarction.7,17 As the
myocardium is replaced by scar tissue following an infarction, myocardial conduction slows or
becomes blocked around the infarcted zone, resulting in a ‘zigzag’ course of activation.18 fQRS
was also associated with an increased risk of arrhythmic events in nonischemic dilated
cardiomyopathy patients.8
Several histopathologic studies on EA demonstrated that the atrialized portion of the RV
becomes disproportionately dilated and has extensive fibrosis with reduced numbers of
myocytes.19,20 Additionally, the abnormal signal observed during endocardial mapping of the
aRV was related to the bizarre configuration of the widened QRS complexes on surface ECG.21,22
They also showed that the aRV was particularly irritable, and therefore, could serve as a
substrate for VF.21,23 Indeed, in our study, patients in the fQRS group had significantly larger
aRV area and more frequent ventricular arrhythmic complications compared to the non-fQRS
group. Moreover, the extent of fQRS complexes was positively correlated with the aRV area
(Spearman’s r=0.51, P<0.001). Therefore, fQRS in adults with EA might signify a higher burden
of arrhythmogenic substrate. We previously reported that in adults with repaired tetralogy of
Fallot (TOF), myocardial fibrosis was predominant in the RV outflow tract, and that fQRS was
found at least twice as frequently in the right to mid precordial leads than in the inferior lead
showing a good spatial concordance between the fQRS and RV scarring.9 In the present study,
however, the most common locations of fQRS were the inferior and precordial leads, and fQRS
ischemic dilated
veral histopathologic studies on EA demonstrated that the atrialized portion of th
i
h
elated to the bizarre configuration of the widened QRS complexes on surface EC
sho ed that the aRV as partic larl irritable and therefore co ld ser e as a
verralalal hhhhisisisi tototoopappathhhololologic studies on EA demmmonononsstrated that tttheh aaaatrtrtrtrialized portion of th
isssps rrror portionattelly dddilllateddd andddd hhhhasss eextenennsiveve fibbbbrorooosisisiis wiiithhh redduucededede nummmmbbeb rsrs of f
99,20002000 AAAAdddddddititititiiionalllllly, ttthhhe abnorororormmmal siiiigngngngnalalal obsbbb ervedddd dududud riririring eeee ddnddocardididiialalala mmapappiiing fffof ttth
elateddd to thhhe bibibiizarre confffigigigurattiiion ffoff the widididden dded QQQRSRSRSRS ccccomplplpllexes on surffffacacaca eee e EC
hsh ded tthhatt thth RaRVV trtiic ll ll ii itit bablle dd thth fef ldld
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were negligible in the lateral leads. In EA, the aRV, or the inlet component, is the main site of
congenital dysplasia and subsequent degeneration. With further enlargement, the aRV could
occupy a greater proportion of the inferior wall of the heart, making fQRS complexes in the
inferior leads as frequent as that in precordial leads. Repolarization parameters such as QTc and
QRS/QT dispersions were measured worse in the fQRS group compared to the non-fQRS group.
Repolarization parameters therefore might also be associated with an increased susceptibility to
ventricular arrhythmia.
fQRS Complexes and Risk of Atrial Tachyarrhythmias
The degree of apical displacement, regurgitation of the TV, and RA enlargement were more
severe in the fQRS group than the non-fQRS group. The indexed RA areas were positively
correlated with the extent of the fQRS. These abnormalities could make patients with fQRS more
vulnerable to atrial tachyarrhythmias related to degenerative changes in the atria, such as AF,
AFL, and AT. As mentioned above, atrial tachyarrhythmias including AF, AFL, and AT tended
to occur more frequently in the fQRS group than in the non-fQRS group (48.6% versus 18.8%,
P=0.064).
fQRS Complexes and Risk of Bradyarrhythmias
The AV conduction system in EA, especially the right bundle branch traveling over the
dysplastic aRV portion, is abnormally formed and shows marked fibrosis. The AV node is also
compressed due to enlargement of the right-sided chambers.1,24,25 Additionally, chronic
hemodynamic stress in adult EA patients can aggravate right-sided chamber dilatation,
dysfunction, and fibrosis.1,2 All of these factors could predispose the development of
bradyarrhythmia. The longer PR intervals and more frequent RBBB observed in the fQRS group
might suggest more fibrosis within the right-sided chambers and in the right bundle branch and
nlargegemementnttt wwerere e momomomorr
h y
w S
to atrial tachyarrhythmias related to degenerative changes in the atria, such as A
A n
ore freq entl in the fQRS gro p than in the non fQRS gro p (48 6% ers s 18
he fQfQQfQRSRSRR ggggrorroupppp tthan the non-fQRS grouppp. ThTTT e indexed RAAA aaaareas were positively
wwwwitttth h the extennt of thththe fQQQRRSRR . TThTT eseese abbnnnormmalititittieieiesss cooulllddd maakee pppatattientttts wiwithh fQRQRQRS
to attttririrrialalal ttttachyhhh arrhhhh ttythhhhmias sss rererelated ddd totototo ddddeggeneratattativivivve chchchchannngggeg s iiin tttthe aaaatrtrtrtriiia, su hhchh as AAAA
AT. AAAs mentioioioonneddd d bbabove, atrialll tachhhhyayy rrhyhyhy hthhh iimias iiinclullul dididid nggg AFAFAFAF, AFAFAFFLL,L andndndnd AAAATTTT ten
ff ttll ii thth fQfQRSRS tthha iin tthhe ffQRQRSS (4(488 6%6% 1818
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more adverse hemodynamic impact on these structures. Although not statistically significant,
first degree AV block (24% versus 13%, P=0.464) was more prevalent in the fQRS group, and
permanent pacemakers were implanted only in patients showing fQRS due to advanced or
complete AV block.
Clinical Implications
In our study, lower functional class at the time of presentation, a greater CT ratio, more advanced
grade of EA, and a higher rate of corrective surgery were found in the fQRS group, which had a
larger average aRV area. These results are in agreement with previous studies that showed aRV
volume to be independently related to aerobic capacity, and that the volume of the aRV is a
novel CMR measure which may describe the severity of disease in adults with unrepaired
EA.12,26 On the other hand, QRS duration is considered a good surrogate marker for severity of
disease. The wider the QRS complex and the greater the degree of TR and RV enlargement, the
worse the clinical course.12, 27 Our data also showed that QRS duration was as good as QRS
fragmentation in predicting RV structural remodeling (see supplemental Figures 2) and
arrhythmic risks (see supplemental Figures 3).
Therefore, further investigation might be worthwhile in order to ascertain whether fQRS,
independently or in combination with QRS duration, could be a potential marker of worsening
right-sided heart dysplasia/dysfunction (see supplemental Figures 4 and supplemental Table).
Also, it would be useful to further investigate the association between fQRS and increased
vulnerability to atrial and/or ventricular tachyarrhythmia as well as bradyarrhythmia in larger
adult cohorts with this anomaly.
Study Limitations
This study has several limitations. Firstly, comparisons from this analysis are limited by their
studies that showewewewed ddd
olumme e ooffff ththththee RRaRaRV VVV isisisis a
R
n t
h t
c S
ion in predicting RV str ct ral remodeling (see s pplemental Fig res 2) and
R memememeasasasa ururreeee whwhwhicicich may describe the severrritititityy of disease in nn adddduuults with unrepaired
n thhhhe other handnd, QRQRQRS dududuurationon iiis consnssidereed aaa ggggoooooooodd suurrrroggatte d mamm rkeererr fofof r sevvverrrit
he wididididererer tttthhheh QQQQRSRSRSS complexxxx aaand thehehehe grerere tatter ttthehhh ddddeeegrerereree ofofofof TRTRTRTR and RRRRVVV V enlal rgementRRR
cliniciii alll course.ee 1222 2727712222, 272727 OOOur dddatta allllso shhhoh weddd hthhatt QQQQRSRSRSR dddurratatata ioii n nn wwwaw s as gggoodd d asasasas QQQQRS
iio iin didi tctiin RVRV ttr tt ll ddelili ((s lpl ttall FiFi 2)2) dnd
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retrospective design, in which unmeasured confounders may preclude any definite conclusion.
Therefore, prospective studies on a larger scale are needed to and to show
the clinical implications of fQRS complexes more definitely. Secondly, the study population was
relatively small, and the follow-up duration was short. Although, our cohort is one of the largest
adult-only groups. Thirdly, the extent of the cardiac fibrosis and the volumetric measurements
were not confirmed by biopsy or cardiac magnetic resonance (CMR) imaging. However, we
adopted a grading system to quantify the severity of EA, and our data correspond well to those
acquired from CMR examination.13
Conclusions
Fragmented QRS complexes on 12-lead ECG were found in approximately two-thirds of adult
patients with Ebstein’s anomaly. fQRS complexes were associated with larger atrialized right
ventricle, a more severe anomaly, and an increased risk of arrhythmic events in this patient group.
Conflict of Interest Disclosures: None.
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WAAAA, EnEnEnEn iriququez-SaSSS rano MMMM, FFoFoF sterr EEEE, GGGrGrayaybbburnnn PPPPAAAA, KKKKrafafafafttt CDCDCDD, Levivivivinnnen RRRRAAA,opouuulolololosss PPP,,,, OtOtOtttototoo CCCMMMM, QuQuQuQuininininononono essss MMMMAAAA,,, RaRR kokokoowswswsskikikik HHHH, StStStStewewewewararara ttt WJWJWJWJ,,, WaWaWaW ggggggg onononnerererer AAA,,,,NJ; AmAA ericii anannn SSSSociiietytyty off f EEEcE hoca drddioiii grgg appphyhyhy. ReRR commeneee dadd tititiooono s fffor ev laluauauauatititit ooono onative valalalvuvuvuvulalalar rrr rererer gugugugurgrgrgrgititiitataata ioioion nn wiwiwiwithththth ttwowowowo-d-d-d-dimmimimeneee sisisionononnalalalal aaanddndnd DDDDopopopopplplpplerererer eeeechchchchococococara diographh didi 20200303 1;166:777777 808022
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E. Morbid anatomymyyy iiiinnggggicicicic aaaandndndnd cccclilililininininicacacacal lll
JA, Goldreyer BN, Josephson ME, Perloff JK, Scharf DL, Manchester JH, Shelbeld JW Jr. Electrophysiologic characteristics of Ebstein's anomaly of the tricuspic
ara T, Tsuchiya T, Takahashi N, Saikawa T, Yoshimatsu H. The characteristics oe Pr
a Ng O Millie P Richardson A Pittaro M Josephson ME Ventric lar
JA,A,A,A, GGGGolololo drdrdrd eyeeyererrr BBBN, Josephson ME, Perlooooffffffff JK, Scharf DLDD , MMaMM nchester JH, Shelbelllldd dd JJWJJ Jr. EEEEleeectctctctrorophphphp ysysysy ioiiiololologigigigicccc chhharararacccteteterir stticcs ofofof EEEEbsbbsb teeeinininin'sss aanononoomalyyyly oooofff the e e trtrtrt icicicusuusu picuuuulaaaation. 1975;552:9998887-999595959 .
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Table 1. Comparison of clinical characteristics between the fQRS group and the non-fQRS group
Total
(n=51)
fQRS (+)
(n =35)
fQRS (-)
(n =16 ) P value*
Demographics
Age†, years 37 (31-45) 36 (31-45) 41 (27-45) 0.604
Male gender, n (%) 18(35.3) 11(31.4) 7 (43.8) 0.529
Diabetes mellitus, n (%) 2 (3.9) 2 (5.7) 0 (0.0) 1.000
Hypertension, n (%) 6 (11.8) 6 (17.1) 0 (0.0) 0.159
NYHA class III~IV, n (%) 27(52.9) 23(65.7) 4 (25.0) 0.014
CT ratio† 0.55 (0.50-0.62) 0.58 (0.53-0.66) 0.49 (0.45-0.52) <0.001
8 (15.7) 8 (22.9) 0 (0.0) 0.045
Associated anomaly
Atrial septal defect, n (%) 19 (37.3) 16 (44.4) 3 (20.0) 0.123
Patent foramen ovale, n (%) 5 (9.8) 5 (13.9) 0 (0.0) 0.305
Mitral valve prolapse, n (%) 1 (2.0) 0 (0.0) 1 (6.7) 0.294
Ventricular septal defect, n (%) 1 (2.0) 1 (2.8) 0 (0.0) 1.000
*The P value is based on the Mann-Whitney test for continuous variables and the Fisher’s exact test for categorical variables.†Data represented as the median (25th and 75th percentiles).CT ratio, cardiothoracic ratio; NYHA, New York Heart Association
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Table 2. Comparison of electrocardiographic and echocardiographic variables
Variable Total(n=51)
fQRS (+)(n=35)
fQRS (-)(n=16 ) P value*
Electrocardiographic variables
PR interval†, msec 176 (162-193) 182 (163-200) 166 (138-182) 0.030
RBBB, n (%) 15(29.4) 15(42.9) 0 (0.0) 0.002
Right axis deviation, n (%) 26 (51.0) 23 (65.7) 3 (18.8) 0.003
QRS duration†, msec 119 (107-148) 135 (118-156) 99 (94-112) <0.001
Corrected QT†, msec 441 (416-486) 472 (428-498) 414 (406-444) 0.003
Corrected JT†, msec 314 (297-330) 311 (285-330) 299 (282-326) 0.422
QRS dispersion†, msec 26(20-40) 40(22-40) 20(15-36) 0.006
QT dispersion†, msec 40(28-80) 55(40-80) 35(20-74) 0.106
JT dispersion†, msec 60(28-80) 60(46-100) 33(20-60) 0.011
QRS preexcitation, n (%) 9 (17.6) 5 (14.3) 4 (25.0) 0.436
Echocardiographic variables
RA area†‡, cm2/m2 14.5(10.9-21.5) 17.1(12.3-24.3) 11.6(8.7-14.1) 0.004
Atrialized RV area†‡, cm2/m2 9.04(7.4-13.1) 9.7(8.0-14.5) 7.4(6.1-9.3) 0.013
Functional RV area†‡, cm2/m2 8.2(6.3-12.8) 9.1(6.2-13.8) 6.9(6.3-10.2) 0.204
LV area†‡, cm2/m2 15.0(12.3-18.6) 14.8(12.1-17.6) 17.7(12.4-19.2) 0.369
LA area†‡, cm2/m2 7.5(6.1-9.2) 7.4(6.1-9.5) 7.6(6.3-8.8) 0.958
LV ejection fraction†, % 60(54-65) 59(54-66) 60(53-64) 0.911
TV displacement†, mm/m2 1.9(1.3-2.6) 1.9(1.4-2.8) 1.5(1.1-2.1) 0.072
Severe TR, n (%) 25(49.0) 22(62.9) 3 (18.8) 0.006
Ebstein severity index† 0.79(0.63-0.94) 0.87(0.67-1.07) 0.63(0.44-0.74) 0.001 Ebstein severity grade, n (%) 0.030
1 5 (12.5) 1 (3.6) 4 (33.3)
2 28 (70.0) 20 (71.4) 8 (66.7)
3 4 (10.0) 4 (14.3) 0 (0.0)
4 3 (7.5) 3 (10.7) 0 (0.0)*The P value is obtained as described in Table 1. †Data represented as the median (25th and 75th percentiles).‡Each value is indexed to body surface area. RBBB, right bundle branch block; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; TR, tricuspid regurgitation; TV, tricuspid valve
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ioooogrgrgrgraphic variaablles
cmmm2/m/m/m/m2 1414144.5.5.5(1(1(1(10.9-9-9-21212121.5.5.55)))) 17171717.1.1.1.1(1(1(1(12.2.2.2 3-3-3-3-2424244.3.3.33))) 1111.6.6.6.6(8(8(8(8 77.77-11114.44.1)1)1)1
RV arararareaeaea†‡†‡††‡, cmcmcmm2222/m/m/m/ 2222 9.9..0404040 (7777.4.4.4.4-1-1-13.3.3.3 1)1)1)1 9.9.9.9.7(7(7(7(8.888 0-0-0-14141414.5.5.5) ) )) 7.777 4(4(4(4(6.6.6.6 1-1-1-9.9.9.9 3)3)3)3)
lll RRRVVV area†‡†‡,, cm22///m22 888.2(2(2(666.3-3-3-121212 88.8) )) 999.1(1(1(666.222-131313 88.8) ) ) 666.9(9(9(666.333-101010 22.2))) 222// 222 1515 00(1(122 33 1818 66)) 1414 88((1212 11 1177 6)6) 1717 77(1(122 44 1919 22))
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DOI: 10.1161/CIRCEP.113.000636
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Table 3. Comparison of clinical outcomes
Total
(n=51)
fQRS (+)
(n =35)
fQRS (-)
(n =16 ) P value*
Total Arrhythmic events, n (%) 26 (51.0) 23 (65.7) 3 (18.8) 0.003
Bradyarrhythmia requiring PPM, n (%) 3 (5.9) 3 (8.6) 0 (0.0) 0.227
Tachyarrhythmia, n (%) 26 (51.0) 23 (65.7) 3 (18.8) 0.003
Atrial tachyarrhythmia, n (%) 20 (39.2) 17 (48.6) 3 (18.8) 0.064
Ventricular tachyarrhythmia, n (%) 9 (17.6) 9 (25.7) 0 (0.0) 0.043
Unexplained syncope, n (%) 4 (7.8) 4 (11.4) 0 (0.0) 0.295
Tricuspid valve repair/replacement, n (%) 27 (52.9) 22 (62.9) 5 (31.3) 0.036
Fontan operation, n (%) 1 (2.0) 1 (2.9) 0 (0.0) 1.000
Cardiac death, n (%) 1 (2.0) 1 (2.9) 0 (0.0) 1.000
*The P value is based on the Fisher’s exact test.PPM, permanent pacemake
r
3333 (1(1(1(18.8.88 8)8)8)8) 00.0 06006064444
0 (0(0(00 0000)))) 0000 04040 3y y ( ) ( ) ( ) ( )
e 5
v 6
e 0
y y ( ) ( ) ( ) ( )
eeddd d sssys ncope, n (%(%(%(%) 4 (7(7(7(7.8) 4 444 (1(1(1(11.11 4)4)4)) 0 0 0 (0(0(0(0 00.00) ) ) 0.000 2922 5
valvvvveeee rerererepapapaairiririr///repepepeplalalacececec mememementnnn , n nnn (%(%(%(%)))) 2727277 (5(5(5( 2222.99.9))) 22222222 (6(6(6( 2.222 9)9)9)9 5 (3(3(331.1.1.1.3)3)3)3) 0.00.0 030303036
eratioiii n, n (((%)%)%) 111 (2(2(2( .0) ))) 111 (2(2(2( .999)))) 0000 (0(0(0.0000)) 1.111 000
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Table 4. Predictors for arrhythmic events in univariate and multivariable Cox regression analyses
CharacteristicsUnivariate analysis Multivariable analysis model 1 Multivariable analysis model 2*
HR (95% CI) P value HR (95% CI) P value HR (95% CI) P value
NYHA class III~IV 1.72(0.76-3.90) 0.194 1.53(0.54-4.34) 0.421
2.13(0.85-5.34) 0.108 1.04(0.35-3.10) 0.951
LV ejection fraction 1.01(0.96-1.05) 0.876 1.01(0.95-1.07) 0.815
Severe tricuspid regurgitation 1.48(0.67-3.25) 0.335 1.46(0.56-3.82) 0.446
Atrialized RV area index 1.05(0.97-1.14) 0.200 1.02(0.92-1.13) 0.751
Ebstein’s anomaly severity index 1.45(0.41-5.07) 0.565 0.25(0.03-1.84) 0.809
QRS duration 1.01(1.01-1.03) 0.015 1.00(0.98-1.02) 0.844 1.01(0.99-1.02) 0.444
Corrected QT interval 1.01(0.99-1.01) 0.254 1.01(0.99-1.02) 0.527
fQRS 5.05(1.50-16.9) 0.009 5.91(1.07-32.6) 0.041 4.13(1.09-15.6) 0.036
* Multivariable analysis model 2 incorporated parameters attaining a P value<0.05 in univariate analysis. Abbreviations as in the Table 1 and 2.
1.111 07070707)))) 0.0.0.0.8181811
1 48(0 67 3 25) 0 335 1 46(0 56 3 82) 0.44
5
0
4
1.48888(0(0(0( ..67676767-3.3.3.3 22225) 0.335 1.46(0.56----3.333 82) 0.44
11.1 00050 (0.97-1.114)))) 00.00 202000 1.1.1.1.02020202(00..92--111.1313131 ) 000.75
1.4555((((00.41111-5.07077)))) 0.565 0.0.25(0((( .0333-1.8444)))) 0.80
11.0101(1(1.0.001111-1.1.11.030303)))) 0.0.00 00001515155 1.1.1..00000000(0(0((0.9.999888-1.1.1.1.00002222)))) 00.8484
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Figure Legends:
Figure 1. Fragmented QRS complexes observed in adult patients with Ebstein’s anomaly.
Dashed arrows indicate fragmentation of QRS complexes in precordial and inferior leads.
Figure 2. Measurement of the severity of Ebstein’s anomaly. Planimetry was performed in the
apical four-chamber view at end-diastole. In this case, the ratio of the combined area of the RA
and atrialized RV divided by the combined area of the RV proper, LA, and LV was 0.82, which
falls under severity grade 2.
RV, functional right ventricle; aRV, atrialized RV; RA, right atrium; LV, left ventricle; LA, left
atrium.
Figure 3. Detailed distribution of fQRS complexes. fQRS complexes occurred primarily in
inferior and precordial leads.
Figure 4. Arrhythmic event-free survival curves depending on the presence of fQRS
, and LV was 0.82222,, , , ww
onal right ventricle; aRV, atrialized RV; RA, right atrium; LV, left ventricle; LA, l
Detailed distribution of fQRS co lexes. fQRS co lexes occurred rimarily in
d precordial leads
onallalal rrrrigigigi hththtt vvvene trtrtriciii le; aRV, atrialized RV; RARARA, right atrium; LVLVLVLV, left ventricle; LA, l
Detaaaailililledededd ddddissstrtrtribibibbututututioioionn n ofofoff ffffQRQRQRRS cocococ mpmpmplelelel xexexesss. ffffQRQRQRQRS SSS cococoompmpmpplelelel xexexex sss ocococccucucucurrrrrredededd pppriririimamamamariririllylyl in
ddd pprerecocordrdrdiaiaialll leleleadadadss
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Shin Yi Jang, Ok Jung Lee, Jinyoung Song, I-Seok Kang and June HuhSeung-Jung Park, Seungmin Chung, Young Geun On, June Soo Kim, Ji-Hyuk Yang, Tae-Gook Jun,
Arrhythmic Risk and the Severity of the AnomalyFragmented QRS Complex in Adult Patients with Ebstein's Anomaly and Its Association with
Print ISSN: 1941-3149. Online ISSN: 1941-3084 Copyright © 2013 American Heart Association, Inc. All rights reserved.
Dallas, TX 75231is published by the American Heart Association, 7272 Greenville Avenue,Circulation: Arrhythmia and Electrophysiology
published online November 14, 2013;Circ Arrhythm Electrophysiol.
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Supplemental Table. C-index calculated using Cox survival methods
C-index Lower 95% CI Upper 95% CI
QRS duration 0.784 0.387 0.999
Wide QRS 0.814 0.422 0.999
fQRS 0.841 0.455 0.999
Combined parameter* 0.751 0.348 0.999
C-index was computed to evaluate the discriminatory accuracy of several
electrocardiographic variables (QRS duration, wide QRS, fQRS, and combination of QRS
duration and fragmentation) for predicting the occurrence of arrhythmic events.
* Combined parameter refers to categorized electrocardiographic variable determined by
QRS duration and fragmentation; narrow non-fragmented (normal), narrow fragmented, wide
non-fragmented, and wide fragmented.
SUPPLEMENTAL MATERIAL
0
20
40
60
80
Lowest Tertile Mid Tertile Highest Tertile
(%)
QRS duration
* P for trend (total arrhythmic events)=0.004 † P for trend (ventricular arrhythmic events)=0.050
*
†
Total Arrhythmic Events
Ventricular Arrhythmic Events
Supplemental Figure 3
(%)
Total Arrhythmic Events
Ventricular Arrhythmic Events
*
†
* P for trend (total arrhythmic events)=0.002 † P for trend (ventricular arrhythmic events)=0.025
0
20
40
60
80
Normal QRS Narrow fQRS Wide fQRS
Supplemental Figure 4
Supplemental Figure Legends
Supplemental Figure 1. The extent of fQRS and the severity of Ebstein's Anomaly
QRS fragmentation shows a significant positive correlation with the severity of Ebstein's anomaly.
Supplemental Figure 2. QRS duration and the severity of Ebstein's Anomaly
QRS duration seems to represent quite well the severity of Ebstein's anomaly. The degree of QRS widening
showed a significant positive correlation with the aRVAi (A) as well as with the Ebstein severity index (B). The Ebstein
severity index was calculated as described in the method section.
Supplemental Figure 3. QRS duration and arrhythmic burden
When our patients were divided into 3 groups depending on the degree of QRS widening, a clear trend
toward more frequent arrhythmic events (total and ventricular tachyarrhythmias) was noted in patients with longer QRS
duration.
Supplemental Figure 4. Combined QRS morphologic markers (duration & fragmentation) and arrhythmic burden.
The risk of arrhythmic events tended to rise as the abnormal features of QRS morphology (prolongation and
fragmentation) were added (P for trend = 0.002 and 0.025 in total and ventricular arrhythmic events, respectively).