incidence and clinical significance of brugada syndrome

Circulation Journal Vol.79, December 2015

2568 WADA T et al.Circulation JournalOfficial Journal of the Japanese Circulation Societyhttp://www.j-circ.or.jp

occasionally induces fatal ventricular tachyarrhythmia, SCB test should be avoided in patients with type 1 ECG under baseline conditions, but it is difficult to identify type 1 in BrS patients with CRBBB.

The prevalence and clinical significance of the combination of CRBBB and BrS has not been well investigated. Therefore, the present study evaluated the incidence and clinical signifi-cance of BrS with CRBBB, especially BrS masked by CRBBB.

MethodsSubjectsA total of 326 consecutive BrS patients (mean age, 47.4±13.6 years; male, 95.4%) and 20 control subjects were enrolled in this study. All BrS patients were diagnosed as having BrS based on HRS/EHRA/APHRS expert consensus statement.1 Type 1 ECG was documented spontaneously or was provoked by SCB test (pilsicainide, at a dose of 1 mg/kg for 5–10 min) in all BrS patients. Echocardiography was performed to exclude

rugada syndrome (BrS) is characterized by ST-segment elevation at the J point in the right precordial electro-cardiographic (ECG) leads and sudden cardiac death

caused by polymorphic ventricular tachycardia/ventricular fibrillation (PVT/VF). This ST-segment elevation is the most important characteristic for diagnosis of BrS,1,2 and spontane-ous ST-segment elevation is reported to be a high risk for PVT/VF.3–5

Aizawa et al reported that BrS can coexist with complete right bundle-branch block (CRBBB), and that CRBBB can completely mask BrS on ECG.6 Recently, a typical BrS-type ECG pattern was observed on spontaneous or mechanical relief of CRBBB: what is called “BrS masked by CRBBB”.7–9 The arrhythmogenic significance of CRBBB in patients with idio-pathic VF (IVF) has also been reported.10 These reports suggest that CRBBB might also have a prognostic association with BrS and IVF.

Sodium-channel blocker (SCB) can provoke type 1 ECG in BrS patients and is useful to unmask BrS. Because SCB test

B

Received June 7, 2015; revised manuscript received September 2, 2015; accepted September 3, 2015; released online October 8, 2015 Time for primary review: 15 days

Department of Cardiovascular Medicine (T.W., K. Nakagawa, N.N., K. Nakamura, K.K., H.I.), Department of Cardiovascular Therapeutics (H.M.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama; Department of Cardio-vascular Medicine, National Cerebral and Cardiovascular Center, Suita (S.N., K.F.K.); and Department of Cardiology, Sakakibara Heart Institute of Okayama, Okayama (T.O.), Japan

Mailing address: Tadashi Wada, MD, Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. E-mail: [email protected]

ISSN-1346-9843 doi: 10.1253/circj.CJ-15-0618All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected]

Incidence and Clinical Significance of Brugada Syndrome Masked by Complete Right Bundle-Branch BlockTadashi Wada, MD; Satoshi Nagase, MD; Hiroshi Morita, MD; Koji Nakagawa, MD;

Nobuhiro Nishii, MD; Kazufumi Nakamura, MD; Kunihisa Kohno, MD; Hiroshi Ito, MD; Kengo F. Kusano, MD; Tohru Ohe, MD

Background: Brugada syndrome (BrS)-type electrocardiogram (ECG) is concealed by complete right bundle-branch block (CRBBB) in some cases of BrS. Clinical significance of BrS masked by CRBBB is not well known.

Methods and Results: We reviewed an ECG database of 326 BrS patients who had type 1 ECG with or without pilsicainide. “BrS masked by CRBBB” was defined on ECG as <2-mm elevation of the J point at the time of CRBBB in the right precordial leads, and BrS-type J-point elevation ≥2 mm at the time of normalized QRS complex on relieved CRBBB. We identified 25 BrS patients (7.7%) with persistent (n=12) or intermittent CRBBB (n=13). Relief of CRBBB by pacing was performed in patients with persistent CRBBB. The prevalence of BrS masked by CRBBB was 3.1% (10/326 patients). Three patients had type 1 ECG, and 7 patients had type 2 or 3 ECG on relief of CRBBB. Two of these 10 patients had lethal arrhythmic events during the follow-up period (mean, 86.4±57.2 months). There was no prognostic difference between BrS masked by CRBBB and other BrS.

Conclusions: In a small BrS population, CRBBB can completely mask typical BrS-type ECG. BrS masked by CRBBB is associated with the same risk of fatal ventricular tachyarrhythmia as other BrS. (Circ J 2015; 79: 2568 – 2575)

Key Words: Brugada syndrome; Complete right bundle-branch block; Extrastimulus; Ventricular fibrillation

ORIGINAL ARTICLEArrhythmia/Electrophysiology


2569BrS Masked by RBBB

last beat in all ECG recordings as the persistent CRBBB group. During follow-up, 2 patterns of ECG changes in CRBBB were found. In the first, originally normal QRS complex developed into CRBBB; and in the second, CRBBB had a temporal change into normalized QRS complex. These patients were defined as the intermittent CRBBB group.

Definition of BrS Masked by CRBBBSome studies on BrS masked by CRBBB have reported that distinctive ST-elevation with BrS can be concealed by CRBBB,7–9 but that there is no definition of “BrS masked by CRBBB”. In BrS masked by CRBBB, the typical BrS-type ECG pattern is completely buried within CRBBB, being unmasked only when the CRBBB is relieved. In the present study, “BrS masked by CRBBB” was defined on ECG as <2-mm elevation of the J point at the time of CRBBB in the right precordial leads at the fourth intercostal space. The ECG then showed BrS-type J-point elevation ≥2 mm at the time of a normalized QRS complex with relieved CRBBB.

Pacing From the Right Ventricle to Resolve CRBBBPacing from the right ventricle can normalize QRS complexes in patients with CRBBB, and this is one of the interventions for resolving CRBBB in patients with BrS.6–8 In the present study, a similar procedure was attempted in patients with per-manent CRBBB. In an electrophysiology study, 2 catheters were positioned at high right atrium (HRA) and right ventricu-lar apex (RVA). A single extrastimulus from RVA was deliv-ered in the same cardiac cycle as the HRA potential in which the pacing trigger was set up. A single extrastimulus was repeated every 4 ms until the ECG indicated RVA-pacing morphology. In patients with implantable cardioverter defi-brillator (ICD), atrioventricular delay was gradually prolonged by 10 ms until the ECG indicated pacing morphology during recording of the 12-lead ECG. This method was carried out in as many of the CRBBB patients as possible.

structural heart disease and repeated 12-lead ECG was recorded at the current institution and at other hospitals. We obtained all 12-lead ECG in the study patients and reviewed this ECG database. Written informed consent regarding the data acquisi-tion was obtained from all individuals. The study conformed to the 1975 Declaration of Helsinki, as reflected by approval from the relevant Institutional Review Board.

ECG AnalysisTwelve-lead ECG was recorded during sinus rhythm at a paper speed of 25 mm/s with an amplification of 10 mm/mV in each patient. The ST amplitude at the J point in the right pre-cordial lead (V1 and V2) was measured. The J point was determined as the endpoint of the QRS interval in lead V5. The presence of fragmented QRS and infero-lateral early repolarization (ER) pattern were also evaluated. Fragmented QRS was defined as abnormal fragmentation within the QRS complex ≥4 spikes in 1 lead or ≥8 spikes in leads V1, V2, and V3.11 The amplitude of the J wave or J-point elevation had to be ≥1 mm above the baseline level.12

Definitions of CRBBBIn the present study, the ECG criteria for the diagnosis of CRBBB were based on AHA/ACCF/HRS recommendations13 as follows. The first criterion is QRS duration ≥120 ms. The second criterion is rsr’, rsR’, or rSR’ in leads V1 or V2. The R’ or r’ deflection is usually wider than the initial R wave. In the minority of patients, a wide and often notched R wave pattern may be seen in lead V1 and/or V2. The third criterion is S wave of greater duration than the R wave or >40 ms in leads I and V6. The fourth criterion is normal R peak time in leads V5 and V6, but this time is >50 ms in lead V1. Of these criteria, the first 3 should be present to make a diagnosis. When a pure dominant R wave with or without a notch is pres-ent in V1, criterion 4 should be satisfied. We defined patients whose ECG consistently showed CRBBB from the first to the

Table 1. Baseline Patient Characteristics vs. Presence of CRBBB

Patients with CRBBB (n=25)

Patients without CRBBB (n=301) P-value

Age, years 54.2±14.5 46.8±13.4 0.01

Male 24 (96) 286 (95.3) 0.87

FH of SCD 7 (28) 84 (27.9) 0.9　　Symptoms

VF 2 (8) 16 (5.3)

Syncope 13 (52) 79 (26.2) 0.01

Asymptomatic 10 (40) 206 (68.4)

Signal-averaged ECG

LP positive 11 (47.8) 182 (60.5) 0.11

Filtered QRS, ms 139.5±30.4　　 118.4±13.2　　 0.001

LAS40, ms 50±20.8 44±12.9 0.19

RMS40, μV 15.5±11.6 16.2±11.7 0.48

EPS 19 (76) 163 (54.2) 0.02

Inducible VF at PES 10/19 (52.6) 73/163 (44.8) 0.52

SCN5A mutation 3/17 (17.6) 21/139 (15.1) 0.78

ICD implantation 11 (44) 59 (19.6) 0.005

Data given as mean ± SD or n (%). CRBBB, complete right bundle-branch block; ECG, electrocardiogram; EPS, elec-trophysiology study; FH, family history; ICD, implantable cardioverter defibrillator; LAS40, duration of low-amplitude signal <40 μV in the terminal filtered QRS complex; LP, late potential; PES, programmed electrical stimulation; RMS40, root-mean-square voltage of terminal 40 ms in the filtered QRS complex; SCB, sodium-channel blocker; SCD, sudden cardiac death; VF, ventricular fibrillation.


2570 WADA T et al.

underwent regular health examinations and had normal phys-ical and laboratory examinations, except for CRBBB. Sudden cardiac death was ruled out in all family members. In all of the 7 patients with persistent CRBBB, the same pacing interven-

Control CRBBB SubjectsIn 20 control subjects without structural heart disease, we iden-tified 13 patients whose ECG showed intermittent CRBBB and 7 patients with persistent CRBBB. All of these patients

Figure 1. Representative cases of Brugada syndrome (BrS) with complete right bundle-branch block (CRBBB). (A) BrS not masked by CRBBB in the intermittent CRBBB group. Twelve-lead ECG of a 34-year-old man. Electrocardiogram (ECG) in October 2004 at first hospital visit showed type 1 BrS without CRBBB. ECG developed into CRBBB in August 2008. The J points in V1 and V2 were elevated ≥2 mm at both times with and without CRBBB. (B) BrS masked by CRBBB in the intermittent CRBBB group. Twelve-lead ECG of a 59-year-old man. ECG shows spontaneous changes from CRBBB to non-CRBBB at the third and fifth beat in precordial leads (intermittent CRBBB). Type 1 BrS ECG in V1 and type 2 ECG in V2 were unmasked. J-point elevations in V1 and V2 were completely unmasked compared with that at CRBBB. This patient is listed as no. 10 in Table 2. (C) BrS not masked by CRBBB in the persistent CRBBB group. Twelve-lead ECG of a 62-year-old man. This ECG shows CRBBB with ≥2-mm elevation of the J point in the right precordial leads. A change in the ECG on pacing intervention is also shown. The second beat shows relief of CRBBB. Type 1 BrS ECG in V1 and type 2 ECG in V2 were unmasked, but ST levels in V1 and V2 were already elevated ≥2 mm before CRBBB was relieved. (D) BrS masked by CRBBB in the persistent CRBBB group. Twelve-lead ECG of a 47-year-old man. ECG already showed CRBBB at on first hospital visit. A change in the ECG on pacing intervention is also shown. Type 1 BrS ECG in V1 and type 2 ECG in V2 with ≥2 mm J-point elevation were completely unmasked. This patient is listed as no. 1 in Table 2.



with CRBBB. There were 13 patients (4.0%) in the intermit-tent CRBBB group and 12 (3.7%) in the persistent CRBBB group. In 6 patients in the intermittent CRBBB group, ECG subsequently developed into CRBBB during follow-up. In these patients, a normalized QRS complex without CRBBB was observed at the first ECG examination. In the other 7 patients, the ECG showed temporary changes between normalized QRS complex and CRBBB. In these patients with temporary ECG change, 5 patients had spontaneous ECG changes and the other 2 patients had temporary ECG changes on mechani-cal contact of the catheter during electrophysiology study.

Patient Characteristics vs. Presence of CRBBBBaseline characteristics between patients with and those with-out CRBBB are listed in Table 1. BrS patients with CRBBB were significantly older than BrS patients without CRBBB. In patients with CRBBB, filtered QRS was longer than that in those without CRBBB. Patients with CRBBB had more symp-toms of BrS and ICD implantation compared with patients without CRBBB. There were no significant differences in clin-ical and ECG characteristics between intermittent and persis-tent CRBBB.

Presence and Prevalence of BrS Masked by CRBBBAmong a total of 13 patients with intermittent CRBBB, 5 were correspondent with unmasked BrS due to ≥2-mm elevation of the J point at the time of CRBBB. Among a total of 12 patients

tion during the electrophysiology study was performed to resolve CRBBB. In all these patients, indications for electro-physiology study for recurrent episodes of unknown syncope or faintness were met sufficiently.14

Follow-upAll of the patients were followed up at outpatient clinics. Lethal arrhythmic events during follow-up included sudden cardiac death, documented and detected PVT, or VF. We evaluated the occurrence of arrhythmic events between study patients.

Statistical AnalysisContinuous variables are expressed as mean ± SD. Means between the 2 groups were analyzed using Student’s t-test or Mann-Whitney U-test. Discontinuous variables and nominal variables are expressed as frequencies and percentages. Dif-ferences between the 2 groups were analyzed using chi-squared test or Fisher’s test. Survival and event rates were determined using the Kaplan-Meier method and compared between the groups with 2-sample log-rank test. P<0.05 was considered statistically significant. JMP7 (SAS Institute, Cary, NC, USA) was used for analysis.

ResultsPrevalence of CRBBB in BrSAmong a total of 326 BrS patients, we identified 25 (7.7%)

Table 2. Clinical Characteristics of BrS Masked by CRBBB

Patient ID no. Age (years) Sex Symptom FH Induced VF ICD Fragmented

QRS ER SCN5A Arrhythmic event

1 47 M Syncope − + + + − Negative VF

2 23 M Asymptomatic − − − − − Negative −

3 43 M Syncope − − − − − Negative −

4 61 M Asymptomatic − − − − − Negative −

5 58 M Asymptomatic − ND − + − ND −

6 55 M Asymptomatic − + − + − Negative −

7 50 M VF − − + + − Negative VF

8 43 M Syncope − − − − − ND −

9 74 M Asymptomatic − − − − − ND −

10 59 M Syncope − ND − + − ND −

BrS, Brugada syndrome; ER, early repolarization; ND, not done. Other abbreviations as in Table 1.

Table 3. ECG Characteristics of BrS Masked by CRBBB

Patient ID no. Type of CRBBB

ECG

4th ICS 3rd ICS

With CRBBB Without CRBBB With CRBBB Without CRBBB

1 Persistent Non-BrS Type 1 Type 1 ND

2 Intermittent Non-BrS Type 2 Non-BrS Type 2


4 Intermittent Non-BrS Type 2 Type 1 Type 1

5 Intermittent Non-BrS Type 2 Type 1 Type 1


7 Persistent Non-BrS Type 1 Non-BrS ND

8 Intermittent Non-BrS Type 3 ND Type 2


10 Intermittent Non-BrS Type 1 ND Type 1

ICS, intercostal space. Other abbreviations as in Tables 1,2.


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(patient 7) had a history of VF, and 4 patients (patients 1,3,8,10) had a history of syncope. Five patients had asymp-tomatic BrS masked by CRBBB. Two patients had ICD implantation based on symptoms or VF induction in an elec-trophysiology study. None of the patients had a family history of sudden cardiac death or positive SCN5A mutation. Frag-mented QRS was identified in 50% of patients (5/10) and none of the patients had ER. Eight patients (patients 1–8) were diagnosed with BrS based on SCB test. The other 2 patients (patients 9,10) were diagnosed with BrS based on ECG at a high intercostal space. Two patients (patients 1,7) had recur-rence of VF. Patient 1 had VF recurrence at 1 month and patient 7 had recurrence at 28 months after ICD implantation.

Electrocardiographic characteristics of BrS masked by CRBBB are listed in Table 3. Eight patients had intermittent CRBBB and 2 patients had persistent CRBBB. On ECG at the fourth intercostal space, all of the 10 patients had non-BrS ECG and <2-mm elevation of the J point at the time of CRBBB, and then had BrS-type J-point elevation ≥2 mm at the time of normalized QRS complex with relieved CRBBB. Three patients had type 1 ECG, and 7 patients had type 2 or 3 ECG ony relief of CRBBB at the fourth intercostal space.

BrS Masked by CRBBB vs. Other BrSBaseline characteristics of patients with BrS masked by CRBBB and the other BrS patients are shown in Table 4. Patients with BrS masked by CRBBB had significantly more symptoms than the other BrS patients. There were no other significant differences between the 2 groups, except for family history.

On Kaplan-Meier analysis of the new occurrence of arrhyth-mic events between patients with BrS masked by CRBBB and other BrS patients, no prognostic difference was seen between the 2 groups (log-rank test; Figure 2).

Control Subject ECG CharacteristicsIn the control subjects, 13 with intermittent CRBBB (mean age, 71.0±4.9 years; male, 80.0%) and 7 with persistent CRBBB (mean age, 59.3±20.1 years; male, 85.7%) were evaluated. A representative control subject with intermittent CRBBB is shown in Figure 3A and one with persistent CRBBB is shown

with persistent CRBBB, 10 already had ≥2-mm elevation of the J point at the time of CRBBB. The other 2 patients had unmasked type 1 or type 2 ECG when CRBBB was relieved. Finally, there were 8 patients with BrS masked by CRBBB who had intermittent CRBBB and 2 patients with BrS masked by CRBBB who had persistent CRBBB. The prevalence of BrS masked by CRBBB was 3.1% (10/326 patients). Repre-sentative cases of BrS with CRBBB are shown in Figure 1 (intermittent CRBBB, n=2, Figures 1A,B; persistent CRBBB, n=2, Figures 1C,D).

Clinical and ECG Characteristics of BrS Masked by CRBBBThe clinical characteristics of BrS masked by CRBBB are listed in Table 2. All 10 patients with BrS masked by CRBBB were male and the mean age was 51.3±13.7 years. One patient

Table 4. Baseline BrS Patient Characteristics vs. Presence of CRBBB Masking

BrS masked by CRBBB (n=10)

Other BrS (n=316) P-value

Age, years 51.3±13.7 47.3±13.6 0.2738

Male 10 (100) 300 (94.9) 0.4798

Family history of SCD 0 (0)　　 91 (28.8) 0.0447

Symptom

VF 1 (10) 17 (5.4)

Syncope 4 (40) 88 (27.9) 0.01　　　　 Asymptomatic 5 (50) 211 (66.8)

Signal-averaged ECG

LP positive 3 (30) 190 (60.1) 0.0545

Filtered QRS, ms 127.1±19.9　　 119.8±16.0　　 0.3416

LAS40, ms 38.5±15.3 44.7±13.6 0.2351

RMS40, μV 22.3±12.1 15.9±11.6 0.065　　 EPS 8 (80) 186 (58.9) 0.18　　　　 Inducible VF at PES 2/8 (25) 81/186 (43.5) 0.2187

SCN5A mutation 0/6 (0) 24/150 (16) 0.1524

ICD implantation 2 (20) 68 (21.5) 0.9076

Data given as mean ± SD or n (%). Abbreviations as in Tables 1,2.

Figure 2. Kaplan-Meier analysis of the new occurrence of arrhythmic events in Brugada synrome (BrS) masked by com-plete right bundle-branch block compared with other BrS.



DiscussionNew ObservationsIn the present study the prevalence of CRBBB in patients with BrS was 7.7%. Additionally, there were a few patients with BrS masked by CRBBB in whom CRBBB completely con-cealed BrS on ECG. The prevalence of BrS masked by CRBBB was 3.1% in patients with BrS. In BrS masked by CRBBB, typical ST-segment elevation was confirmed on spontaneous or mechanical relief of CRBBB. This change was never observed in control subjects. Patients with BrS masked by CRBBB have the same risk of fatal ventricular tachyarrhyth-mia as other BrS patients. To the best of our knowledge, the present study is the first to demonstrate the clinical signifi-cance of BrS masked by CRBBB.

CRBBB in the General PopulationThe prevalence of CRBBB in the general population is reported to be 1–5%.15 CRBBB is strongly correlated with age, and is common at older ages.16 In the present study, patients with

in Figure 3B. There was no significant J-point elevation with or without CRBBB in the control subjects. In all control sub-jects with intermittent or persistent CRBBB, no BrS-type ECG was observed on relief of CRBBB.

Comparison of ECG characteristics between CRBBB patients with BrS and control subjects (CRBBB patients without BrS) is given in Table S1. PR interval was longer in CRBBB patients with BrS than without BrS (176±48 ms vs. 149±26 ms; P=0.0275). And ST level at the J point in right precordial lead (V1 and V2) was higher in CRBBB patients with BrS than in those without BrS (V1, 0.21±0.20 mV vs. 0.02±0.06 mV; P=0.0001; V2, 0.23±0.23 mV vs. 0.05±0.08 mV; P=0.0014).

Follow-upDuring the follow-up period (mean, 86.4±57.2 months), there was no sudden cardiac death in 25 patients with CRBBB. In the patients with BrS masked by CRBBB, 2 of 10 patients had lethal arrhythmic events during follow-up (Table 2). There was no prognostic difference between BrS masked by CRBBB and other BrS (Figure 2).

Figure 3. (A) Representative control sub-ject with intermittent complete right bun-dle-branch block (CRBBB). Twelve-lead electrocardiogram (ECG) of a 67-year-old man. ECG shows spontaneous change from non-CRBBB to CRBBB at the third beat. All ECG show no J-point elevation in the right precordial leads. (B) Representa-tive control subject with persistent CRBBB. Twelve-lead ECG of a 73-year-old man who received catheter ablation for parox-ysmal atrial fibrillation. ECG shows no J-point elevation in the right precordial leads. Change in ECG on pacing interven-tion in electrophysiology study is also shown. The third beat shows relief of CRBBB. No Brugada syndrome-type ECG pattern was found.


2574 WADA T et al.

ing SCB test. Another method for unmasking BrS involves deep inspiration on ECG.25 Pacing intervention for resolving CRBBB, however, is the most useful method to detect BrS-type ECG safely in patients who have had an episode of unknown syncope or cardiopulmonary arrest with ECG showing CRBBB. And, given that BrS masked by CRBBB has the same risk of fatal ventricular tachyarrhythmia as other BrS, detection of BrS masked by CRBBB is also important. CRBBB does not necessarily indicate a benign ECG finding, but the possibility of BrS masked by CRBBB should be considered.

Study LimitationsThe present study has several limitations. First, this study was conducted at a single medical institution and the study group was small. Second, the control subjects were sex matched but not age matched with BrS patients. The control subjects were older than patients with BrS. Third, we could not perform pac-ing intervention in all of the BrS patients with persistent CRBBB. All of the patients in whom pacing intervention was not performed, however, had ≥2-mm elevation of the J point on ECG. None of the patients in the control group had masked BrS.

ConclusionsIn a small BrS population, CRBBB can completely mask typical BrS-type ECG. Patients with BrS masked by CRBBB have the same risk of fatal ventricular tachyarrhythmia as other BrS patients.

DisclosuresThe authors declare no conflicts of interest.

References 1. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al.

Executive summary: HRS/EHRA/APHRS expert consensus state-ment on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Europace 2013; 15: 1389 – 1406.

2. Antzelevitch C, Brugada P, Borggrefe M, Brugada J, Brugada R, Corrado D, et al. Brugada syndrome: Report of the second consensus conference: Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation 2005; 111: 659 – 670.

3. Priori SG, Gasparini M, Napolitano C, Della Bella P, Ottonelli AG, Sassone B, et al. Risk stratification in Brugada syndrome: Results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol 2012; 59: 37 – 45.

4. Probst V, Veltmann C, Eckardt L, Meregalli PG, Gaita F, Tan HL, et al. Long-term prognosis of patients diagnosed with Brugada syn-drome: Results from the FINGER Brugada Syndrome Registry. Circulation 2010; 121: 635 – 643.

5. Murakoshi N, Aonuma K. Epidemiology of arrhythmias and sudden cardiac death in Asia. Circ J 2013; 77: 2419 – 2431.

6. Aizawa Y, Takatsuki S, Sano M, Kimura T, Nishiyama N, Fukumoto K, et al. Brugada syndrome behind complete right bundle-branch block. Circulation 2013; 128: 1048 – 1054.

7. Aizawa Y, Kimura T, Takatsuki S. A case of Brugada syndrome showing augmentation of electrocardiogram phenotype by complete right bundle branch block. Europace 2013; 15: 1525.

8. Chiale PA, Garro HA, Fernandez PA, Elizari MV. High-degree right bundle branch block obscuring the diagnosis of Brugada electrocar-diographic pattern. Heart Rhythm 2012; 9: 974 – 976.

9. Tomita M, Kitazawa H, Sato M, Okabe M, Antzelevitch C, Aizawa Y. A complete right bundle-branch block masking Brugada syn-drome. J Electrocardiol 2012; 45: 780 – 782.

10. Aizawa Y, Takatsuki S, Kimura T, Nishiyama N, Fukumoto K, Tanimoto Y, et al. Ventricular fibrillation associated with complete right bundle branch block. Heart Rhythm 2013; 10: 1028 – 1035.

11. Morita H, Kusano KF, Miura D, Nagase S, Nakamura K, Morita ST, et al. Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. Circulation 2008; 118: 1697 – 1704.

CRBBB were older than those without CRBBB. Although CRBBB is generally considered a benign finding in healthy individuals,17 a recent cohort study of 18,441 participants showed that RBBB is associated with increased cardiovascu-lar risk and all-cause mortality.18 An association of CRBBB with arrhythmic events in patients with IVF has also been reported.10 This suggests that CRBBB is related to arrhythmo-genicity, despite patient background.

Combination of BrS and CRBBBIn BrS, true CRBBB is uncommon, and its prevalence has not been well evaluated. In a previous report on BrS, CRBBB was included as part of the ECG diagnosis.19 The ECG in approxi-mately one-third of BrS patients, however, does not have the wide final S waves in the left leads (I, aVL, V5, and V6) nec-essary for CRBBB.20 No systematic studies on CRBBB in BrS have been conducted. Maury et al, however, recently studied the prevalence of various conduction disturbances in patients with BrS, and noted that CRBBB was present in 23% of BrS patients.21 This proportion is larger than that in the present study (7.7%). Some cases of BrS have been reported in which ECG changed into CRBBB with ST segment elevation after SCB test.22 ECG after SCB test were not evaluated in the pres-ent study, but Maury et al did include ECG after SCB test in their analysis. This is one of the reasons for the difference in proportion between the studies.

In CRBBB in healthy subjects, the ST segment is usually not elevated in the right precordial leads. In the present study (Table S1), control patients (CRBBB patients without BrS) had no significant ST-segment elevation, but higher ST-seg-ment elevation at the J point was seen in CRBBB patients with BrS. Also, longer PR interval was noted in CRBBB patients with BrS. One of the hypotheses for the arrhythmogenesis in BrS involves the presence of delayed conduction in the right ventricle, and the other involves ER of the right ventricular epicardium. These differences in the morphology of the ECG pattern suggest that diverse conduction disturbances and early repolarization seem to be present and important in Brugada ECG.

Manifestation of BrS Masked by CRBBBAizawa et al reported that CRBBB can completely mask BrS.6 Cases of BrS masked by CRBBB have been recently reported,7–9 but the prevalence and clinical significance of BrS masked by CRBBB have not been well studied. The present study is the first to evaluate the prevalence of BrS masked by CRBBB (3.1%). Given that significant ST elevation at the J point is not always found in BrS with CRBBB, even experienced cardi-ologists sometimes find it difficult to distinguish BrS from CRBBB on ECG alone. Some of the patients with CRBBB had <2-mm ST elevation (Figures 1B,D). In such cases in which BrS-type ECG is completely masked by CRBBB, evaluation of the ST level at spontaneous or mechanically relief of CRBBB is useful.

SCB treatment can provoke type 1 ECG in BrS patients and is useful to unmask BrS. In equivocal or suspected cases of BrS, SCB test is frequently used in the diagnostic approach. Because SCB test occasionally induces fatal ventricular tachyar-rhythmia,23 SCB test should be avoided in patients with dis-tinct type 1 ECG under baseline condition.24 Administration of SCB to patients in whom CRBBB completely masks type 1 ECG may induce further conduction disturbance (fatal antio-ventricular conduction disturbance) or VF storm. Therefore, SCB test should be performed carefully in patients with CRBBB. In the present subjects, 5 (1.9%; 5/265) had induced VF dur-



aspects. J Am Coll Cardiol 1999; 33: 5 – 15.21. Maury P, Rollin A, Sacher F, Gourraud JB, Raczka F, Pasquie JL, et

al. Prevalence and prognostic role of various conduction distur-bances in patients with the Brugada syndrome. Am J Cardiol 2013; 112: 1384 – 1389.

22. Fujiki A, Usui M, Nagasawa H, Mizumaki K, Hayashi H, Inoue H. ST segment elevation in the right precordial leads induced with class IC antiarrhythmic drugs: Insight into the mechanism of Brugada syndrome. J Cardiovasc Electrophysiol 1999; 10: 214 – 218.

23. Chinushi M, Komura S, Izumi D, Furushima H, Tanabe Y, Washizuka T, et al. Incidence and initial characteristics of pilsic-ainide-induced ventricular arrhythmias in patients with Brugada syndrome. Pacing Clin Electrophysiol 2007; 30: 662 – 671.

24. Rolf S, Bruns HJ, Wichter T, Kirchhof P, Ribbing M, Wasmer K, et al. The ajmaline challenge in Brugada syndrome: Diagnostic impact, safety, and recommended protocol. Eur Heart J 2003; 24: 1104 – 1112.

25. Yamawake N, Nishizaki M, Shimizu M, Fujii H, Sakurada H, Hiraoka M. Unmasking Brugada-type electrocardiogram on deep inspiration. Circ J 2014; 78: 360 – 365.

Supplementary FilesSupplementary File 1

Table S1. ECG characteristics of CRBBB patients vs. presence of BrS

Please find supplementary file(s);http://dx.doi.org/10.1253/circj.CJ-15-0618

12. Haissaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008; 358: 2016 – 2023.

13. Surawicz B, Childers R, Deal BJ, Gettes LS, Bailey JJ, Gorgels A, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram. J Am Coll Cardiol 2009; 53: 976 – 981.

14. JCS Joint Working Group. Guidelines for clinical cardiac electro-physiologic studies (JCS 2011): Digest version. Circ J 2013; 77: 497 – 518.

15. Eriksson P, Wilhelmsen L, Rosengren A. Bundle-branch block in middle-aged men: Risk of complications and death over 28 years: The primary prevention study in Goteborg, Sweden. Eur Heart J 2005; 26: 2300 – 2306.

16. Jeong JH, Kim JH, Park YH, Han DC, Hwang KW, Lee DW, et al. Incidence of and risk factors for bundle branch block in adults older than 40 years. Korean J Intern Med 2004; 19: 171 – 178.

17. Fahy GJ, Pinski SL, Miller DP, McCabe N, Pye C, Walsh MJ, et al. Natural history of isolated bundle branch block. Am J Cardiol 1996; 77: 1185 – 1190.

18. Bussink BE, Holst AG, Jespersen L, Deckers JW, Jensen GB, Prescott E. Right bundle branch block: Prevalence, risk factors, and outcome in the general population: Results from the Copenhagen City Heart Study. Eur Heart J 2013; 34: 138 – 146.

19. Brugada P, Brugada J. Right bundle branch block, persistent ST seg-ment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome: A multicenter report. J Am Coll Cardiol 1992; 20: 1391 – 1396.

20. Gussak I, Antzelevitch C, Bjerregaard P, Towbin JA, Chaitman BR. The Brugada syndrome: Clinical, electrophysiologic and genetic

incidence and clinical significance of brugada syndrome

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