Author + information
- Received January 8, 2016
- Revision received March 31, 2016
- Accepted April 7, 2016
- Published online January 16, 2017.
- Takeshi Kitamura, MDa,∗ (, )
- Seiji Fukamizu, MDa,
- Iwanari Kawamura, MDa,
- Rintaro Hojo, MDa,
- Yuya Aoyama, MD, PhDa,
- Mitsuhiro Nishizaki, MD, PhDb,
- Masayasu Hiraoka, MD, PhDc and
- Harumizu Sakurada, MD, PhDd
- aDepartment of Cardiology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan
- bDepartment of Cardiology, Yokohama Minami Kyosai Hospital, Yokohama, Japan
- cTokyo Medical and Dental University, Yushima, Tokyo, Japan
- dTokyo Metropolitan Health and Medical Treatment Corporation, Ohkubo Hospital, Tokyo, Japan
- ↵∗Reprint requests and correspondence:
Dr. Takeshi Kitamura, Department of Cardiology, Tokyo Metropolitan Hiroo Hospital, 2-34-10 Ebisu, Shibuya-ku, Tokyo, Japan.
Objectives This study investigated clinical characteristics and prognosis of Brugada syndrome (BrS) in patients older than 60 years of age during a long-term follow-up period.
Background Clinical characteristics and prognosis of senior patients with BrS have not been clearly elucidated.
Methods A total of 181 patients with BrS were divided into 2 groups by age at the time of diagnosis: the younger group was <60 years of age (n = 123), and the senior group was ≥60 years of age (n = 58).
Results Mean ages were 42.7 ± 11 years and 68.6 ± 7.1 years, respectively. Prevalence of spontaneous type 1 electrocardiogram (ECG) was lower in the senior group (22 of 58; 37.9%) than in the younger group (64 of 123; 51.9%) (p = 0.027). Among various ECG parameters, the senior group had a lower incidence of prolonged r-J intervals in V2 ≥90 ms than the younger group (34 of 58; 58.6% vs. 90 of 123; 73.1%, p = 0.049) and day-to-day variation of Brugada ECG patterns (3 of 58; 5.2% vs. 23 of 123; 18.7%, p = 0.032). During a mean follow-up period of 7.6 ± 5.8 years, no senior patients experienced documented fatal ventricular arrhythmias, but 11 younger patients did. Kaplan-Meier analysis revealed a better prognosis in the senior group than in the younger group (log-rank, p = 0.011).
Conclusions Senior BrS patients, ≥60 years of age, had a better prognosis than those <60 years of age. Implantable cardioverter-defibrillator insertion for senior patients with BrS needs careful consideration.
Brugada syndrome (BrS) is characterized by unique electrocardiogram (ECG) patterns on the right precordial leads (V1 to V3) and increased risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF) in the absence of major structural heart disease (1). Although various risk factors for future development of VF have been proposed by large numbers of reports, no consensus has been reached to predict fatal cardiac events, especially in BrS patients without a history of documented VF or aborted SCD. The only available therapeutic option is insertion of an implantable cardioverter-defibrillator (ICD), but the role and indication for ICD implantation remain controversial, particularly in the elderly population. The mean age of patients with BrS has been reported to be in the fourth to fifth decade (2–4). Brugada type 1 ECGs are observed less frequently in elderly patients than in the younger patients (4). Recently, 2 studies have indicated a benign prognosis of elderly BrS patients (5,6). Those studies, however, do not clarify differences in clinical and ECG characteristics underlying prognostic factors between the senior and younger patients. Moreover, the indication for ICDs in senior patients, according to the latest consensus statement, has not been verified. Because the United Nations classification defined people at ≥60 years of age as senior, we classified BrS patients with diagnoses at ≥60 years of age as the senior group and those <60 years of age as the younger group in our study and investigated their clinical characteristics and prognostic variables. In addition, we reclassified all patients in classes of ICD indication according to the latest consensus statement and then evaluated the distribution and incidence of fatal ventricular arrhythmia during a long-term follow-up period.
The study included 181 consecutive patients whose BrS was diagnosed and followed at the Tokyo Metropolitan Hiroo Hospital from 1992 to 2014. Diagnosis of BrS was defined by the 2 consensus reports in 2002 (7) and 2005 (8). This retrospective observational study protocol was approved by the Institutional Review Board of Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan. Patients were divided into 2 groups according to their age at the time of diagnosis: the younger group (<60 years of age) and the senior group (≥60 years of age). Clinical histories and 12-lead ECG findings, including those from leads V1 to V3 placed at the 2nd, 3rd, or 4th intercostal space were accessed in all patients.
Organic heart diseases were excluded by examinations using ultrasound cardiography, coronary angiography, right and left ventriculography, and cardiac magnetic resonance imaging. Acetylcholine provocation test was performed to exclude vasospastic angina in 74 patients. ECGs for BrS were classified according to the 2002 and 2005 consensus reports (7,8), with or without provocation test by sodium-channel blockers. Patients with syncope of unknown cause, family history of SCD or atrial fibrillation (AF) (to avoid a possible risk of unexpected lethal ventricular arrhythmia to be provoked by sodium channel blockers) were screened by sodium channel provocation test if their ECG revealed type 2 or type 3 Brugada ECG. All baseline and drug-induced 12-lead ECG records were obtained at a paper speed of 25 mm/s and with amplitude of 10 mm/mV with the right precordial leads positioned at the 2nd, 3rd, and 4th intercostal spaces. All ECGs were analyzed by 3 independent experienced electrophysiologists. Early repolarization pattern was defined in the presence of J-point elevation ≥1 mm in ≥2 contiguous inferior and lateral leads of ECG, according to the 2013 consensus statement (9). Fragmented QRS was defined in the presence of abnormal fragmentation within the QRS complex as 4 spikes in 1 or 8 spikes in all of leads V1, V2, and V3 (10). Day-to-day variation in Brugada ECGs was positive if a type 1 Brugada ECG was present on one day but spontaneously disappeared or changed to type 2 or type 3 ECG on another day during the follow-up period. We acquired ECGs during the initial follow-up and at each scheduled follow-up, and any unscheduled visits and during any in-hospital stays. The alterations in the ECG were evaluated at rest (commonly 2 h before or after meal) and excluded the ECGs recorded with any stress (during exercise test, drug challenge test, full stomach, and in febrile illness). Significant augmentation of ST-segment elevation during recovery phase in treadmill exercise testing was defined as ST-segment amplitude increase >0.05 mV in at least 1 of leads V1 to V3 at early recovery (1 to 4 min at recovery) compared with the baseline level (pre-exercise) (11). The presence of late potentials (LPs) was evaluated with a signal-averaged ECG (noise level: 0.3 V, filtered with a high-pass filter by 40 Hz). Three parameters were assessed using a computer algorithm: the filtered QRS duration (f-QRS); the root-mean-square voltage of the terminal 40 ms in the filtered QRS complex (RMS40); and the duration of low-amplitude signals, 40 mV in the terminal filtered QRS complex (LAS40). LPs were considered positive when 2 of 3 criteria (f-QRS >114 ms; RMS40 <20 mV; and LAS40 >38 ms) were met (12,13). Electrophysiological study (EPS) findings were evaluated among 115 of 181 patients for diagnosis or risk stratification or both. Those patients underwent programmed electrical stimulation to assess ventricular tachycardia (VT) or VF inducibility. Our method for EPS and protocol of ventricular stimulation for induction of VT/VF was described previously (14). In short, EPS was performed using 3 multielectrode catheters introduced percutaneously through the femoral vessels. Programmed ventricular stimulation was performed with the use of a maximum of 3 ventricular extra-stimuli from the right ventricle apex and outflow tract. Minimum coupling interval was effective refractory period during single ventricular extra-stimulus, 180 ms during 2 ventricular extra-stimuli, 200 ms during 3 ventricular extra-stimuli. Patients with VF lasting for more than 30 s or who required electrical cardioversion were classified as inducible. Informed consent was obtained from all patients. Indication for ICD implantation was determined according to the 2002 or 2008 American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) guideline (15), the Japanese guideline (16), or 2013 HRS/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society (HRS/EHRA/APHRS) consensus statement (9). Because our study period spanned 1992 to 2014 and the guidelines for ICD therapy were modified several times during the entire period, we reclassified all patients by the indication for ICD implantation according to the latest consensus statement of the 2013 HRS/EHRA/APHRS (9). Fourteen patients were registered in the Japan idiopathic ventricular fibrillation study (17).
Patients with ICD implantation underwent regular follow-up of the device and clinical symptoms, at least, every 3 to 4 months at our outpatient clinic. Patients without ICD implantation were followed every 6 or 12 months with a visit to our outpatient clinic for checking clinical status and examinations of resting ECG and signal averaged ECG (SAECG).
Data are mean ± SD or absolute values and percentages where appropriate. The chi-square test and Fisher exact test were used to compare categorical variables. Continuous variables between the 2 groups were analyzed using the unpaired Student t test or Mann-Whitney U test as appropriate. Survival curves were constructed by using the Kaplan-Meier method and compared using the log-rank test. Univariate Cox proportional hazards models were used to assess the effect of each variable on VF during follow-up. A p value <0.05 was considered statistically significant. Statistical analyses were conducted using SPSS version 19.0 software (SPSS Inc., Chicago, Illinois).
Clinical and electrophysiological characteristics of the 2 groups
The senior group, ≥60 years of age, consisted of 58 cases (32%), and the younger group, <60, was 123 cases (68%). Mean ages were 68.6 ± 7.1 years in the former and 42.7 ± 11 years in the latter group. The age distribution at diagnosis in all patients is shown in Figure 1. The youngest patient was 16 years of age, and the oldest was 91 years of age. In the senior group, there were 35 patients 60 years of age, 19 patients in their 70s, and 4 patients in their 80s. In the younger group, there were 38 patients in their 50s, 39 patients in their 40s (the highest number of cases), 29 patients in their 30s, and 17 patients less than 29 years of age.
Clinical characteristics of the 2 groups are shown in Table 1. The proportion of patients with spontaneous type 1 ECG was lower, and that of drug-induced type 1 was higher in the senior group than in the younger group. Other clinical parameters, except for their ages, were not significantly different between the 2 groups. Male predominance was similar in the 2 groups. Rates of patients with history of syncope, documented VF, and vasospastic angina were not different. There were 5 patients in the younger group who had a family history of BrS, but all patients in the senior group were probands without family history. No differences were noted between the 2 groups with regard to incidence of ICD implantation and inappropriate ICD therapy. During follow-up, coronary angiography was required to identify the cause of chest pain in 10 patients. Six patients developed de novo coronary stenosis, which was treated by percutaneous coronary intervention (mean: 60 ± 11 years of age; range: 42 to 74 years). The mean duration from diagnosis of BrS to diagnosis of newly developed coronary stenosis was 10.5 ± 6.2 years (range: 3.8 to 16.5 years). Three patients underwent coronary angiography to determine the cause of VF and appropriate therapy; however, there was no case of newly developed coronary stenosis. Other patients with recurrence of VF during follow-up were also screened for development of ischemic heart disease by using noninvasive examinations. No positive findings of ischemic events by exercise test or myocardial perfusion scintigraphy were detected among other patients.
Parameters of various ECG findings and electrophysiological studies of 2 groups are shown in Table 2. The number of ECGs recorded per patient per year was 4.2 ± 2.8/patient/year. P-wave duration, PQ interval, QRS duration, and QTc intervals were not different among them. Patients showing r-J interval ≥90 ms and day-to-day variation of type 1 ECG had significantly higher ratios in the younger group than those in the senior group. However, there were no differences in percentages of patients with fragmented QRS, inferolateral ER pattern, AF, positive LP by SAECG, and positive T-wave alternans in the 2 groups.
After a mean follow-up period of 7.6 ± 5.8 years (91 ± 69 months), 11 patients developed VT/VF episodes (cardiac events), and all of the events belonged to the younger group but none to the senior group. Figure 2 shows age distributions of VF events at or before the age of diagnosis (VF history) (Figure 2A) and of VT/VF recurrences during follow-up period (Figure 2B). Details of senior patients with VF events at diagnosis are shown in Table 3. The patient’s age at VF history ranged between 19 and 68 years of age, and the range of age at VT/VF recurrences during follow-up period was between 19 and 49 years of age. No patients over 50 years of age had recurrences, despite history of VF in 7 patients. Kaplan-Meier analysis revealed a better prognosis for the senior group than the younger group (log-rank p = 0.011) (Figure 3). Univariate Cox regression analysis of each risk factor is shown in Table 4. Patients younger than 60 years of age (p = 0.042; hazard ratio [HR]: 2.82; 95% confidence interval [CI]: 1.695 to 50.74), documented VF (p < 0.01; HR: 22.1; 95% CI: 10.22 to 54.33), ER pattern (p < 0.01; HR: 17.43; 95% CI: 4.597 to 66.1), fragmented QRS (p < 0.01; HR: 8.574; 95% CI: 2.614 to 28.12), and day-to-day variations of type 1 ECG (p < 0.01; HR: 9.617; 95% CI: 2.43 to 38.06) had a correlation with VF recurrence. In addition, we also evaluated combinations of risk factors for prediction of VF recurrences (Table 4). Although several risk factors could not singly predict VF events, combinations of age <60 years and risk factors (syncope, spontaneous type 1 ECG, induced VF, VF induction by single or double extra-stimuli) might predict a VF event. Five combinations with highest HR among all combinations are described at the bottom of Table 4. In addition, we evaluated alteration, especially attenuation with age, in several parameters during follow-up. There were no changes in r-J interval >90 and fragmented QRS during follow-up. On the other hand, 2 of 42 patients had day-to-day variations in ER pattern (ER was not documented regularly). Six of 125 patients had a change from positive to negative LP. According to the definition of day-to-day variations in type 1 ECG, spontaneous alterations from type 1 to type 2 or 3 were observed in 14 of 26 cases. Among the 14 patients, 10 (of 26) had their ECGs reidentified as spontaneous type 1 ECG. There were only 4 patients with type 1 ECG who alternated to persistent type 2 or 3 ECG. The prevalence of attenuating LP and day-to-day variations was low (LP: 6 of 125 [4.8%]; day-to-day variation in type 1 ECG: 4 of 26 [15.3%]).
Figure 4A shows the number of ICD indication category modified to the latest guideline among all patients and those with implanted ICD. There were 24 of 181 cases (13.2%) classified as Class 1; 21 of 181 (11.6%) as Class 2a; 86 of 181 (47.5%) as Class 2b; and 5 as Class 3 and 45 as others (e.g., spontaneous type 1 ECG and family history of SCD) in all patients (Figure 4A, left bar). Regarding the numbers of patients who received ICD implantation (Figure 4A, right bar), 23 patients were in Class 1, 6 in Class 2a, and 44 in Class 2b. No patients in Class 3 or other received ICD implantation. Figure 4B compares patient numbers classified by ICD indication and patients with implanted ICDs between the younger and senior groups. In the senior group, there were 5 patients in Class 1, 6 patients in Class 2a, and 32 patients in Class 2b. Among senior patients with ICD, there were 5 patients in Class 1, 3 patients in Class 2a, and 19 patients in Class 2b.
Complications associated with the ICD
Table 5 presents details of complications such as inappropriate shocks and other ICD complications. A total of 18 patients with ICD implantation had inappropriate therapy (18 of 73; 24.7%). The cause was AF in 10 cases, paroxysmal supraventricular tachycardia in 4, lead fractures in 2, sinus tachycardia in 1, and T-wave oversensing in 1. The incidence of inappropriate therapy due to AF was not statistically different between the 2 groups. Other complications (14 events) were found in 14 patients who received ICD (14 of 73; 19.2% [10 lead fractures, 3 ICD infections, and 1 hematoma at ICD replacement]). Kaplan-Meier analyses of all complications and lead fracture are shown in Figure 5.
Clinical characteristics of senior patients with Brugada syndrome in comparison to those in the younger group
BrS is generally characterized by male predominance with a middle-aged onset of cardiac events or diagnosis at 40 to 50 years of age, or both. There are, however, certain numbers of patients in whom BrS is diagnosed at ≥60 years of age in the clinical setting. In the present study, 32% (58 of 181 subjects) of our BrS cohort represented the senior group. Recent reports indicated that the senior BrS patients had benign prognosis compared with the younger age populations in general BrS cohort as well as in high-risk patients (5,6). Our study also confirmed their results with a benign prognosis of the senior group ≥60 years of age. Furthermore, the results indicated certain clinical characteristics suggestive of better prognostic signs that were not indicated in the previous reports.
Many clinical variables have been proposed as risk factors with which to predict cardiac events in patients with BrS. Among these variables, symptomatic patients including a history of VT/VF, syncope of unknown origin, and spontaneous type 1 ECG were assumed to be important predictors (2). Furthermore, whether other symptoms or clinical signs could be applicable to predict cardiac events in senior BrS patients is not known. Conte et al. (5) reported a better prognosis of the senior BrS patients with significantly less frequent prevalence in family history of SCD than in the younger patients. Our study did not show a difference in prevalence of family history of SCD between the senior and younger groups. The discrepant results may be due to differences in the subjects’ backgrounds, as their study population included a relatively high prevalence of family members of BrS (49% in 58 cases), and our cases represented 21.1% to 25.7% of the family history in both groups. The report by Conte et al. (5) also indicated fewer numbers of patients with induced VT/VF during programmed ventricular stimulation in the senior group than the younger group, but we could not observe a difference in the ratio of induced VT/VF between the 2 groups. As to the induced VT/VF by EPS, its positive predictive value for cardiac events has been in intense dispute and a consensus has been reached (2,3,9,18–20). Different outcomes by EPS might be attributed to differences in stimulation protocol, but a prospective study by a fixed stimulation protocol could not demonstrate a predictive value of VT/VF induction for cardiac events (20).
In the present study, spontaneous type 1 ECG and day-to-day variations in Brugada ECG patterns were significantly less prevalent in the senior group than in the younger group. Type 1 ECG and day-to day variations of Brugada ECG pattern are thought to be risks factor for fatal ventricular arrhythmia depending on different ethnic groups and population of the study subjects, values, and timing of ECG recordings, and selections of ECG lead placements at different intercostal spaces (21–23). Therefore, the lower frequency of those findings might contribute to a better prognosis in the senior group. Among other conditions supposed to predict cardiac events, there were fewer patients with r-J interval >90 ms (17) in the senior group than in the younger group. However, other parameters including positive LP by SAECG (12,24), fragmented QRS (10), history of AF (17,25,26), ER patterns (22,27,28), augmented ST elevation during recovery phase after exercise (11), and ventricular effective refractory period <200 ms (20) were not different between the 2 groups.
Possible Reasons for Better Prognosis in Senior Patients With Brugada Syndrome
Our results indicated that BrS patients ≥60 years of age had a better prognosis than those <60 years of age over 7-year follow-up, confirming the results of previous reports (5,6). Five patients with a history of VF at the age of diagnosis older than 60 years of age did not experience any recurrence of VF events during the follow-up (11.7 ± 3.2 years). Furthermore, patients including the younger group older than 50 years of age had no recurrences of VF. As to the mechanism of ST-segment elevation and development of VT, repolarization theory (29) and depolarization theory (30) have been proposed without reaching a firm consensus. The results that spontaneous type 1 ECG were less frequently observed in the senior group with better prognosis might be explained by decreased hormonal influence of testosterone with age (31,32). In addition, a prolonged r-J interval of ≥90 ms, which might indicate conduction abnormality and day-to-day variations of Brugada ECG patterns, which might indicate autonomic tone disorder as markers of the proposed risk (13,29), were less frequent in the senior group. Moreover, attenuation or disappearance of several risk factors with age during follow-up were observed in a small number of patients. Therefore, the true reason why the senior patients showed a better prognosis than the younger group <60 years of age was not clarified by the present study, and further exploration should be continued. In addition, in our case series, there were no VF events after 5-year follow-up, contrary to our expectations. We anticipated that there would be events in the late period of follow-up, as reported in other studies (18,20). Therefore, we also expected that there would be patients with VF events during later follow-up period in future. One possible reason could be that the patients had more time to receive education at outpatient clinics to avoid being exposed to circumstances such as high-grade fever, taking medication worsening BrS ECG (Na channel blockers, calcium channel blockers, and so forth) (33,34), or hyperactivated parasympathetic tone as the follow-up duration became longer. However, we do not have evidence or data in support of this.
Age as a prognostic factor
A number of clinical prognostic factors have been shown to predict VF in patients with BrS, as mentioned above. In our case series, younger patients, <60 years of age, had worse prognosis than senior patients based on the log-rank test and univariate Cox regression analysis. In the Cox regression model, documented VF, fragmented QRS, ER pattern, and day-to-day variation in type 1 ECG could also predict VF events. Moreover, although several risk factors (syncope, spontaneous type 1 ECG, induced VF, VF induction mode single or double) do not alone statistically predict VF events, combinations of age <60 years and those factors (syncope, spontaneous type 1 ECG, induced VF, VF induction mode single or double) may predict VF events. Recently, a combination of risk factors has been proposed to predict VF in patients with BrS (35,36). Age <60 years might be helpful not only as a simple prognostic factor but also as one of the reasonable risk factors in combination with other risk factors to stratify VF recurrence risk. However, we could not conduct a multivariate analysis because of an insufficient number of VF events. Therefore, a study with a larger sample size with enough VF events to conduct multivariate analysis is warranted to confirm the results.
ICD indication for the senior patients with Brugada syndrome
In the present study, all patients were reclassified by ICD indication according to the latest consensus statement (9). Figure 4 shows the distribution of reclassified patients. Patients with ICD insertion were reclassified into class 1, 2a, or 2b, but none in class 3 or other. There were 5 patients reclassified into class 1, and 6 patients into class 2a in senior group. There was no VT/VF in those patients during the long-term follow-up period. The indication for ICD implantation has not been clarified in senior BrS patients. In the consensus statements for BrS (9), a specific consideration of ICD implantation for senior BrS patients was not described. Although ICD implantation is supposed to be the only therapeutic means to protect against SCD at the present time, there are factors associated with device complications after the implantation (6). Therefore, the risk stratification of cardiac events and a better prognosis of the senior patients must be carefully considered for the selection of ICD implantation. However, it should be emphasized that 5 senior patients in their 60s already had VF episodes at the time of diagnosis in the present study. Results further indicate that patients with BrS over 60 years of age have the potential to develop VF and that ICD indication should not be avoided simply because of advanced age at the time of diagnosis; the decision should be made by weighing the risks and benefits of implantation in each individual.
Complications associated with the ICD
In the present study, there were no statistical differences between the 2 groups in the prevalence of total number of inappropriate therapies or inappropriate therapy due to AF and other supraventricular tachycardias (SVT). However, during the follow-up period, complications or lead fracture incidence gradually increased, which is a finding in line with that of a previous study (6). Kamakura et al. (6) reported that numbers of SVT and inappropriate shocks increased with age. In our study, this did not achieve statistical significance; however, the prevalence of inappropriate therapy due to AF was slightly higher in the senior group than in the younger group. Therefore, considering the increasing accumulation of complications and inappropriate therapy due to SVT including AF in senior patients, careful decision making for ICD implantation may be necessary in senior patients with BrS, particularly in patients with Class 2b indication.
Our study has several limitations: it is a single-center study with retrospective analysis with heterogeneous clinical characteristics. The numbers of the study subjects were rather small. In addition, a direct correlation between cardiac events during follow-up and the positive findings (i.e., type 1 ECG, day-to-day variation, or prolonged R-J interval) was not confirmed. Furthermore, there were only 11 events during the follow-up period in the present study, which contributed to several risk factors with large hazard ratios and large confidence intervals in Cox regression analysis. Therefore, we might have overestimated the impact of those risk factors, and the results in Table 4 should be interpreted carefully. Moreover, because a multivariate analysis needs at least 10 events per risk factor, we could not conduct a multivariate Cox regression analysis to confirm the independence of each risk factor. A large-scale prospective study is needed to confirm these results and to clarify the mechanism.
Senior BrS patients ≥60 years of age at diagnosis seem to have a better prognosis than younger patients. ICD implantations for BrS patients ≥60 years of age should be carefully evaluated.
COMPETENCY IN MEDICAL KNOWLEDGE: Senior BrS patients ≥60 years of age at diagnosis have a better prognosis than the younger age group. ICD implantations for BrS patients ≥60 years of age should be carefully evaluated.
TRANSLATIONAL OUTLOOK: A study with a larger population and a longer follow-up period, specifically a span lasting until the end of life in senior patients, is needed.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors' institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- Brugada syndrome
- implantable cardioverter-defibrillator
- signal averaged electrocardiogram
- sudden cardiac death
- ventricular fibrillation
- ventricular tachycardia
- Received January 8, 2016.
- Revision received March 31, 2016.
- Accepted April 7, 2016.
- 2017 American College of Cardiology Foundation
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