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Prevalence of spontaneous Type I ECG pattern, syncope and other risk markers
in sudden cardiac arrest survivors with Brugada Syndrome
Kevin MW Leong MRCP1,2; Fu Siong Ng MRCP PhD1,2; Sian Jones RN2; Ji-Jian Chow MRCP1,2,
Norman Qureshi MRCP PhD2; Michael Koa-Wing MRCP PhD2; Nicholas WF Linton MRCP PhD1,2;
Zachary I Whinnett MRCP PhD1,2; David C Lefroy MRCP MD2; D Wyn Davies MRCP MD2; Phang
Boon Lim MRCP PhD1,2; Nicholas S Peters MRCP MD 1,2; Prapa Kanagaratnam MRCP PhD 1,2;
Amanda M Varnava MRCP MD 2
1National Heart & Lung Institute, Imperial College London, UK
2Imperial College Healthcare NHS Trust, London, UK
Address for correspondence:
Dr Amanda Varnava
Consultant Cardiologist
Imperial College Healthcare NHS Trust
Hammersmith Hospital
London, W12 0HS
Tel: 020 33131000
Email: [email protected]
Manuscript word count: 4861 words
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Abstract
Introduction
A spontaneous type I ECG pattern and/or unheralded syncope are conventionally used as risk
markers for primary prevention of sudden cardiac arrest/death (SCA/SCD) in Brugada
Syndrome (BrS). In this study, we determine the prevalence of conventional and newer
markers of risk in those with and without previous aborted SCA events.
Methods
All patients with BrS were identified at our institute. History of symptoms were obtained
from medical or from interview. Other markers of risk were also obtained:- presence of
i)spontaneous Type I pattern ii)fractionated QRS(fQRS); iii)early-repolarisation(ER) pattern;
iv)late potentials on signal-averaged ECG(SAECG); v)response to programmed electrical
stimulation.
Results
In 133 patients with BrS, 10 (7%) patients (mean age 39±11 yrs; 9 males) were identified
with a previous VF/VT episode (n=8) or requiring CPR (n=2). None of these patients had a
prior history of syncope before their SCA event. Only 2 (20%) reported a history of
palpitations or dizziness. None had apnoeic breathing and 3 (30%) had a family history of
SCA.
From their ECGs, a spontaneous pattern was only found in 1 (10%) of these patients. 10%
had fQRS; 17% late potentials on signal-averaged ECG; 20% deep S waves in lead I and 10%
ER pattern in the peripheral leads. No significant differences were observed with the non-
SCA group.
Conclusion:
Majority of BrS patients with previous aborted SCA events did not have a spontaneous Type
I and/or or prior history of syncope. Conventional and newer markers of risk appear to only
have limited ability to predict SCA.
Keywords: Brugada Syndrome, Risk Stratification, Sudden Cardiac Arrest
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Introduction
Survival data from registries and other studies have consistently shown that a spontaneous
type I ECG pattern and/or history of unexplained syncope confers a higher risk of sudden
cardiac arrest/death (SCA/SCD) 1–3. Accordingly, presence of both these factors would
warrant consideration of an implantable cardioverter defibrillator (ICD) based on current
guidelines (Class IIA recommendation)4,5,6. Yet, in those who have had an ICD implanted for
primary prevention purposes, only a minority have required therapy suggesting that such
criteria have limited discriminating ability 7.
In individuals who present with an aborted SCA event, an ICD is mandated given that SCA
recurrence is the highest in this group2. Whilst these group of individuals have been
stochastically fortunate to have survived their presenting event, and gained an ICD for life
long protection, it is unclear if current risk markers would have identified such individuals for
an ICD had they been assessed before their presenting event. In a post mortem analysis of 50
SCA probands with a familial diagnosis of Brugada Syndrome (BrS), fewer than 25% had a
prior history of syncope or spontaneous Type I pattern on ECG8. This introduces an important
observation that a substantial number of truly high risk BrS patients do not have the
conventional markers of risk employed by current guidelines. Other ECG based parameters,
such as i) presence of late potentials on signal averaged ECG (SAECG) ii) fractionated QRS
(fQRS) iii) a deep or wide S wave or iv) early repolarization (ER) pattern, have been shown
to be associated with a more malignant course in BrS but it remains unclear if these
parameters can improve on current risk stratification9,10.
In a retrospective analysis of our BrS cohort, we determine the prevalence of conventional
and newer ECG risk markers in those with and without previous aborted SCA events and
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evaluate the performance of current guidelines to detect the high risk. Based on previous data
reported in the literature, we hypothesize a low prevalence of conventional risk markers in
those with an aborted SCA event and a limited discriminating ability using current criteria.
Methods
Study population and design
The study population consisted of patients with BrS aged above 18 years under follow up at
our centre. The diagnosis of BrS was based on the finding of a spontaneous or a
pharmacologically induced Type I BrS pattern with coved ST segment elevation ≥2mm in ≥1
right precordial leads as defined previously 4. The diagnosis of BrS was also validated with
the Shanghai scoring system 11. The risk profile of each patient was ascertained following a
retrospective review of clinical records and ECG data for each patient. Clinical and ICD data
ranging from date of first contact to most recent follow up were reviewed for the occurrence
of SCA events. This was until the study’s censure date set as the 1st of May 2017. Patients
with a prior history of an aborted SCA event were also included in the analysis.
Clinical data and risk factors obtained
Demographic data including age at initial assessment, gender and reason for referral were
obtained for all patients. The main risk factors used in current guidelines were obtained
which included i) history of unexplained syncope and ii) the presence of a spontaneous type I
pattern on ECG. In those with a history of an aborted SCA event, an interview was conducted
with each to ascertain the circumstances surrounding the SCA event and to determine if there
was any prior history of symptoms. A personal history of syncope was only considered a risk
factor if it was present prior to their SCA event. Other clinical data obtained included a
family history of BrS or SCA (<40 years in age) and outcome of programmed electrical
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stimulation (PES) study where available. PES previously performed in these patients
consisted of 2 drive cycles (600ms and 400ms) with up to 3 extrastimuli in the RV apex and
outflow tract at twice the diastolic threshold. The minimum coupling interval of extrastimuli
was set to 200 ms for S2 and S3 and to refractoriness for S4. A positive PES was defined as
inducible VF, sustained polymorphic ventricular tachycardia (>30s duration) or requiring
direct current cardioversion.
We also collected data of other ECG based risk markers previously shown to be an
independent predictor of SCA on multi-variate analysis in at least one prospective follow up
study9,10. These included 1) the presence of fQRS1 2) the presence of late potentials on
SAECG12 3) presence of a significant S wave in lead I13 and 4) presence of an ER pattern14.
ST segment augmentation following exercise has been shown to be an independent predictor
of risk15 but was not included as exercise tolerance test data was not performed or available
for majority of the cohort.
Electrocardiographical measurements
Standard 12-lead ECGs were recorded at paper speed of 25 mm/s and a standard gain of 1
mV/cm. I examined and interpreted all tracings obtained previously at baseline evaluation.
Where this was not available, the next available 12 lead ECG at follow up was used. A
spontaneous type I pattern was defined as the presence of a type I pattern in the absence of a
class I antiarrhythmic drug, and if found on any 12 lead or high RV lead ECG during the
follow up period. The presence of the following risk markers were based on the ECG
obtained closest to baseline.
The presence of fQRS was defined as abnormal fragmentation within the QRS complex as ≥2
spikes in V1, V2 or V3 as described previously4. An ER pattern was defined as an elevation
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of the J-point (≥1mm) above baseline in at least 2 consecutive leads, either as QRS interval
slurring or notching in the inferior (II, III, and aVF) or lateral (I, aVL, and V4 to V6) leads 14.
The presence of a significant S wave in lead I was examined. The amplitude from the
isoelectric line to the nadir of the S-wave and duration were assessed and considered
significant if it were deep (≥0.1mV) or wide (≥40ms) as defined previously13.
Presence of a late potential was evaluated by a SAECG (ART 1200 EPX [Arrhythmia
Research Technology Inc, Fitchburg, Massachusetts], using a noise level of <0.3 mV, and
high-pass filtering of 40Hz with a bidirectional 4-pole Butterworth). A late potential was
considered present if the following 2 criteria were met: root mean square voltage of the
terminal 40 ms in the filtered QRS complex of <20 mV and a duration of low amplitude
signals <40 mV in the terminal filtered QRS complex of >38 ms12.
SCA event and ICD therapy
An aborted SCA or equivalent event was considered to be i) successful cardio-pulmonary
resuscitation from cardiac arrest or ii) having received an appropriate ICD discharge in
response to ventricular fibrillation or fast ventricular tachycardia (>200bpm) as documented
by interrogation of stored electrocardiographic data. ICD discharges in response to an
accelerated ventricular rhythm caused by anti-tachycardic pacing (ATP) were excluded
Statistical analysis
Categorical variables are presented as percentages and continuous data as mean±standard
deviation. Differences between groups were performed using student t-test for continuous
variables and χ2 test for categorical variables. A P value of <0.05 was considered statistically
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significant. Graphpad PRISM (v5) statistical software package was used for statistical
analysis.
Results
Clinical characteristics of BrS cohort
A total of 133 patients with BrS were identified (mean age 45±15 years; 79 males (61%). 33
(25%) had a spontaneous Type I BrS pattern on ECG, with the remainder having an inducible
Type I pattern following an Ajmaline challenge. The mean Shanghai score for this cohort was
3.8±1.2. In our cohort of patients, the commonest reason for initial assessment was for
symptoms (53%). This included out of hospital cardiac arrest (n=9), syncope (n=31), pre-
syncope or palpitations (n=61) often in combination with a family history of sudden cardiac
arrest/death and/or an ECG suggestive of the Brugada phenotype. The second most common
reason for initial assessment was family screening (33%), followed by an incidental finding
on ECG during clinical care (14%). Following initial assessment, 27 (20%) patients
proceeded to have ICDs implanted for primary prevention and 9 (7%) for secondary
prevention. Mean follow up for the entire cohort was 42±25 months.
BrS patients with aborted SCA events
Ten patients experienced an aborted SCA or equivalent event (mean age 38±12 years, 9
males) (Table 1). This comprised of nine individuals whose initial presentation was an out of
hospital cardiac arrest (documented VF (n=6), polymorphic VT in (n=1) and pulseless
electrical activity (n=2)) from which they were successfully resuscitated and one who
received an appropriate ICD shock therapy for VF. In this patient, an ICD was implanted for
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primary prevention on the basis of older guidance set by the Second Consensus Conference
Report16, after a finding a spontaneous Type I pattern and a strong family history of BrS and
sudden cardiac death. PES was performed in this individual which did not induce any
sustained ventricular arrhythmias. All patients were found to have structurally normal hearts
on echocardiography and cardiac MRI. No significant coronary artery disease was detected in
any of these patients on clinical work up with coronary angiography or functional stress
testing.
Review of clinical history in these patients revealed none had prior syncope before their
aborted SCA event. Only two (20%) had a history of palpitations or dizziness and three
(30%) with a family history of SCA. On review of all ECGs taken over the course of follow
up, a spontaneous Type I pattern was only found to be present in one individual (10%). In
one other (10%), a Type 2 pattern was present at resting baseline. With regard to other ECG
risk markers, there was a low prevalence of fQRS (10%), a significant S wave (20%), or an
ER pattern in any lead (10%) in these patients. Table 1 provides a summary of the clinical
characteristics and ECG findings of these ten patients. SAECG was available for six
individuals and evidence of late potentials found only in one (17%). A PES study was
performed in four, with one having inducible VF (25%).
Activity at the time of cardiac arrest or ventricular arrhythmia varied between individuals. In
three patients, occurrence was during sleep. In four individuals, the event occurred shortly
after finishing a meal (n=2), and immediately after exertional activity (running n=1,
gardening n=1). In the remaining three, there did not seem to be a clear precipitating factor
(n=2) or complete recollection of the event (n=1).
BrS patients without SCA events and ICD therapy
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One hundred and twenty-three BrS patients (mean age 45±15, 70 male) had not experienced a
previous SCA event or any ICD therapy during the duration of follow up with the service.
Mean follow up time was 42±26 months. 26% had a spontaneous Type I pattern, 25% a
history of syncope, and 31% a family history of SCA. In comparison to the SCA group, there
was a smaller male to female ratio (p=0.04). No significant differences between the SCA and
non-SCA group were found for age or in the frequency of individuals with a history syncope,
spontaneous Type I pattern or family history of SCA (Table 2). Other baseline ECG patterns
included a Type II/III BrS ECG (n=38), RSR’ pattern (n=12), ER (n=4), fQRS (n=7),
significant S wave in lead I (n=30) and an entirely normal ECG in 32%. SAECG was
available for seventy-eight individuals, with 38% fulfilling criteria for presence of late
potentials. Fifty-nine underwent a PES study and eleven (19%) were found to be inducible.
In the non-SCA group, twenty-seven (22%) individuals received an ICD for primary
prevention. Five (19%) patients had a history of syncope and Type I ECG, with the remaining
twenty-two (81%) having either a type I ECG or previous syncope with an additional minor
risk factor(s) which included a positive PES study, abnormal SAECG and/or family history of
SCA.
Presence of syncope and/or Type I ECG to predict risk
Current guidance recommends consideration of an ICD (class IIA) for primary prevention in
BrS patients with both a spontaneous Type I pattern and a history of prior syncope4,5. Based
on the presence of these two factors, only six would have been considered for an ICD in this
cohort of BrS patients. None of these individuals suffered an SCA event during the follow up
period. There were also no patients with a previously aborted SCA event who had both these
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risk factors (Figure 1). For the majority of patients in the SCA and non-SCA groups, there
was an absence of both these factors (90% and 54% respectively).
44% of BrS individuals in our cohort had either one of these risk factors present. Using either
a spontaneous Type I pattern or the presence of prior syncope as a risk discriminator would
provide a sensitivity of 10% and specificity of 54% (positive predictive value of 2%; negative
predictive value of 88%) in our cohort.
Presence of newer ECG based markers of risk
There was a low prevalence of fQRS (6%; n=8) and ER pattern (4%; n=5) in our cohort of
BrS patients. A significant S wave was found in 26% of patients and late potentials in 37% of
individuals who underwent the test. No significant differences were observed in the
proportion of any of the ECG risk markers between the SCA and non-SCA groups (Table 2).
For each risk marker, its presence was predominantly found in those without SCA events and
generally had a poor positive predictive value overall (3-20%) (Figure 2). fQRS had a
sensitivity of 10% and specificity of 94%; late potentials a sensitivity of 17% and specificity
of 62%; a significant S wave sensitivity of 20% and specificity of 76%; and an ER pattern a
sensitivity of 10% and specificity of 97% (Table 3). An aggregate analysis of fQRS, ER
pattern and deep S wave was performed as these were assessed in all patients. No patient had
all three of these newer risk markers, and the addition of ≥1 of these risk markers did not
improve the sensitivity or specificity when combined with a spontaneous Type I pattern
and/or syncope (Table 3). Presence of any 1 of these markers on their own improved
sensitivity to 30% but had a low positive predictive value (Table 3).
Discussion
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Conventional markers of risk
In our cohort of BrS patients, a history of syncope and/or a spontaneous Type I ECG would
not have pre-emptively identified the majority of patients before their aborted SCA event.
Data to support the current risk stratification strategy of BrS patients has been based on short
and medium term prospective cohort studies of those identified in life1–3. The largest of these
cohort studies came from the FINGER registry, comprising of 1,029 BrS patients, with
follow up indicating that a prior cardiac arrest, spontaneous type I ECG and syncope were the
only independent predictors of arrhythmic risk2.
In our SCA survivor cohort none had a prior history of a syncope, as determined by reported
symptoms from each of these individuals during interview. The notion that the majority of
sudden deaths in BrS occurred in asymptomatic individuals came from a post mortem
analysis of 50 SCA probands and their families with BrS8. Following extensive review of past
medical records and interview with relatives, Raju and colleagues had found a prior history of
syncope only in 9 of 50 (18%) of these individuals. An obvious limitation of this work is that
the determination of a history of syncope in the deceased individual is based on written
record and the assumption that such symptoms would have been relayed to family members.
However, it is also possible that significant ventricular arrhythmias can occur in the absence
of reported symptoms. Antzelevitch and colleagues had reported on the circadian pattern of
VF episodes based on ICD interrogations in 19 BrS patients with an aborted SCA event14. 26
of the 64 documented episodes of ventricular fibrillation were asymptomatic by virtue of
these having occurred during sleep and requiring no device therapy as they were self-limiting.
Whilst these findings limit the sensitivity of reported symptoms as a marker of ventricular
arrhythmias, the specificity of syncope to indicate prior ventricular arrhythmias may be also
limited by the preponderance of other co-existing causes of syncope, such as of a vasovagal
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aetiology17. Individuals without a spontaneous Type I pattern are thought to be at low risk for
SCA events. From 15 lead ECGs obtained following the aborted SCA event and during
follow up (average 1 per year) in all ten patients, the majority did not have a spontaneous
Type I pattern (90%). Similarly, Raju et al found an absence of a spontaneous Type I pattern
in the majority of patients (80%) for whom ECGs were available8. In the FINGER registry,
only half of the individuals who presented with an aborted SCA had a spontaneous Type I
ECG2. Whilst one may be cautious about interpreting such findings given the dynamicity of
the BrS ECG and if high RV leads were used for assessment in the other studies18,19, the data
calls into question if the absence of a spontaneous Type I ECG may really be considered as a
marker of low risk.
Use of other risk markers
The role of the PES during an electrophysiological catheter study to predict risk continues to
be debated, although a recent meta-analysis suggests that a positive PES provided further
discrimination in the intermediate risk groups where either syncope or a spontaneous Type I
ECG was present20. It did not provide any significant discriminating value for those without
previous syncope or a spontaneous Type I pattern. A secondary finding of the study was that
PES could not be used on its own to accurately identify low and high risk patients, as non-
inducible individuals still exhibited a 1% per year risk of ventricular arrhythmias20. Whilst a
PES study was not performed in everyone in our cohort, it is noteworthy that it was negative
in the one individual with a spontaneous Type I ECG who subsequently received an
appropriate ICD shock for VF.
An ICD was recommended in this case given the background of a malignant family history of
multiple SCA in accordance with the 2005 consensus criteria used at the time14. Whilst a
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family history of SCA in 1 or more family members has not consistently shown to be an
independent predictor of risk2,21,22, and hence its non-inclusion from current guidance5, the
specificity or role of multiple SCA in family members has yet to be explored.
Non-conventional or newer risk markers which include the presence of late potentials on
SAECG, fQRS, ER pattern or deep S wave may have some specificity in predicting
ventricular arrhythmias but are hampered as useful screening parameters given their poor
sensitivity. Interestingly, the presence of certain newer markers of risk such as fQRS or an
ER pattern have a higher specificity in identifying these high risk individuals compared to
PES. In addition, the presence of 2 or more of these newer markers of risk appeared to have
comparable specificity to the presence of syncope and Type I pattern. This effect could still
be observed even in the absence of syncope and a spontaneous type I pattern, suggesting that
the presence of 2 or more newer markers of risk may warrant consideration for an ICD. These
findings will need to be validated with a larger cohort study before this can be translated into
clinical practice. Accordingly, their absence is not an indicator of low risk as evidenced by
the findings in our cohort of SCA patients. Although these parameters have been selected to
detect electrophysiological abnormalities in conduction and repolarisation within the heart,
they are based on a limited number of body surface electrodes which would limit their
accuracy.
Role of autonomic triggers
In our cohort of patients with aborted SCA events, activities at the time of event initially
appear to be quite varied. On analysis, majority of the events occurred during situations
where a heightened vagal tone may be invoked. Studies have previously reported
augmentation of the BrS pattern and increased incidence of ventricular arrhythmias during
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sleep14,23, following exercise15,24 and after meals25,26. As the BrS pattern has been anecdotally
observed to manifest or be augmented prior to the onset of ventricular arrhythmias18,27 it is
implied that such autonomic stimuli have a pro-arrhythmic effect on the electrophysiological
substrate.
Our findings together with that previous reported in the literature highlight the importance of
studying the electrophysiological properties of the heart during such autonomic stimuli. Many
of these activities are routine and are likely to have been undertaken by BrS patients in the
non-SCA group as well. Given that such routine activities have not yet triggered an
arrhythmic event in these patients, it suggests that differences are likely to exist in their
electrophysiological substrate which are not identifiable with current ECG based parameters.
One plausible reason for this is that current ECG based parameters lack the spatial resolution
to identify the arrhythmogenic substrate during such autonomic stimuli. This is suggested by
other studies employing non-invasive electrocardiographical imaging, that employs >250
surface electrodes, which have augmented spatial heterogeneities in conduction and
repolarisation following autonomic and pharmacological stimuli28,29.
Limitations
This study is limited by the relative small numbers of SCA patients and findings are therefore
prone to a type one error on statistical analysis. However, findings from other studies support
our observation that a significant number of high risk individuals do not have prior syncope
or the presence of a spontaneous type I pattern2,8. This is an important consideration given the
current criteria used in risk stratification. In the diagnosis of BrS, we acknowledge that an
ajmaline challenge carries a small false positive rate (1-8%)30,31. This however is small and
should not significantly alter the main findings. In addition, we also employed the Shanghai
risk scoring system to support the diagnosis of BrS in this cohort of patients. Another issue
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relates to the dynamic nature of the Type I pattern. It is plausible that there may have been
periods in between ECG recordings on follow up where the pattern is manifest. Whilst
previous studies have linked the presence of a fixed spontaneous Type I pattern with SCA 1-3,
it is unclear if those with a dynamic Type I pattern carry a similar level of risk. However,
only one of our SCA patients showed evidence of a type 1 pattern immediately after their
event, or on multiple subsequent ECGs. It should also be highlighted that the follow up time
of ICD recipients was relatively limited, although it was comparable to the FINGER study. It
is probable with longer follow up more SCA equivalent events would occur altering the
predictive value of these markers.
Conclusion
A spontaneous Type I and/or syncope prior to their SCA event was not present in most of our
BrS patients with SCA events. Conventional and newer markers of risk appear to only have
limited ability to predict SCA, highlighting the need for better risk stratification techniques.
Funding Sources: KL was supported by a British Heart Foundation Grant
(PG/15/20/31339), The Dan Bagshaw Memorial Trust Fund and the Coronary Flow Trust of
Imperial College Healthcare NHS.
Authorship contribution and acknowledgements
The drafting of the manuscript and data analysis were performed by KL Data collection and
interpretation of clinical investigations were performed by KL, JC, SJ, AV. Recruitment of patients
and critical revision of the manuscript for its content were provided by NL, ZW, MKW, NQ, PBL,
DWD, NSP, FSN, AV and PK
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Figure Legends
Figure 1 - Proportional representation of SCA and non-SCA patients by conventional risk
factor profiles:- i) Syncope and spontaneous Type I pattern, ii) Syncope only, iii)
Spontaneous Type I pattern only, iv) absence of syncope and spontaneous Type I pattern
Figure 2 - Proportional representation of SCA and non-SCA patients by the presence of other
and newer types of risk markers: i) Late potentials on signal-averaged ECG, ii) Significant S
wave in lead I, iii) fQRS, iv) ER pattern
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Figure 1
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Figure 2
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Table 1 Characteristics of patients with previous aborted SCA event
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SCA group(n=10)
Non-SCA group(n=123)
P value
Age at diagnosis (years)
38±12 45±15 ns
Male:Female ratio 9:1 2:1 0.04Clinical ParametersSpontaneous Type I ECG and Syncope
0 6 (5%) ns
Spontaneous Type I BrS ECG only
1 (10%) 32 (26%) ns
Syncope only 0 31 (25%) nsFamily history of sudden cardiac death
3 (30%) 38 (31%) ns
Family history of BrS 2 (22%) 44 (36%) nsECG parametersfQRS 1 (10%) 7 (6%) nsLate potentials on SAECG
1/6 (17%) 30/78 (38%) ns
Significant S wave (lead I)
2 (20%) 30 (24%) ns
ER pattern 1 (10%) 4 (3%) nsPES study 1/4 (25%) 11/59 (19%) ns
Table 2 Risk profile of SCA and non-SCA groups. ns – not significant
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Individual risk markers NPV PPV Sens. Spec
.
A Spontaneous Type I 91% 3% 10% 74%
B Syncope 90% 0% 0% 75%
C Fractionated QRS 93% 13% 10% 94%
D Early repolarisation 93% 20% 10% 97%
E Deep S wave 92% 6% 20% 76%
F Signal averaged ECG (SAECG)* 91% 3% 17% 62%
G Programmed electrical stimulation (PES)* 92% 8% 20% 81%
Aggregate of risk markers NPV PPV Sens. Spec
.
1 A+B 92% 0% 0% 95%
2 A or B 88% 2% 10% 54%
3 A or B + any 1 other risk marker (C/D/E) 91% 0% 0% 86%
4 A or B + any 2 other risk markers (C/D/E) 92% 0% 0% 98%
5 Presence of any 1 of other risk markers (C/D/E) 92% 8% 30% 70%
6 Presence of any 2 of other risk markers (C/D/E) 93% 20% 10% 97%
7 Presence of any 2 of other risk markers (C/D/E) in
the absence of A+B
89% 33% 11% 97%
Table 3 Negative predictive value (NPV), positive predictive value (PPV), sensitivity
(sens.) and specificity (spec.) of conventional and newer risk markers and on aggregate.
No patient had all 3 of the non-conventional risk markers (C/D/E) *SAECG and PES
not included in aggregate analysis as not performed in all patients.
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