Journal of the American College of Cardiology 2014 by the American College of Cardiology Foundation Published by Elsevier Inc.
Vol. 63, No. 20, 2014 ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2014.01.072
Heart Rhythm Disorders
Electrocardiographic Parameters and Fatal Arrhythmic Events in Patients With Brugada Syndrome Combination of Depolarization and Repolarization Abnormalities Koji Tokioka, MD,* Kengo F. Kusano, MD, PHD,y Hiroshi Morita, MD, PHD,* Daiji Miura, PHD,* Nobuhiro Nishii, MD, PHD,* Satoshi Nagase, MD, PHD,* Kazufumi Nakamura, MD, PHD,* Kunihisa Kohno, MD, PHD,* Hiroshi Ito, MD, PHD,* Tohru Ohe, MD, PHDz Okayama and Osaka, Japan Objectives
This study aimed to determine the usefulness of the combination of several electrocardiographic markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS).
Background
Detection of high-/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several electrocardiographic markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear.
Methods
Baseline characteristics of 246 consecutive patients (236 men; mean age, 47.6 13.6 years) with a Brugada-type electrocardiogram, including 13 patients with a history of VF and 40 patients with a history of syncope episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in 1 patient were observed. Clinical/genetic and electrocardiographic parameters were compared with VF/SCD events.
Results
On univariate analysis, a history of VF and syncope episodes, paroxysmal atrial fibrillation, spontaneous type 1 pattern in the precordial leads, and electrocardiographic markers of depolarization abnormalities (QRS duration 120 ms, and fragmented QRS [f-QRS]) and those of repolarization abnormalities (inferolateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. On multivariable analysis, a history of VF and syncope episodes, inferolateral ER pattern, and f-QRS were independent predictors of documented VF and SCD (odds ratios: 19.61, 28.57, 2.87, and 5.21, respectively; p < 0.05). Kaplan-Meier curves showed that the presence/absence of inferolateral ER and f-QRS predicted a worse/better prognosis (log-rank test, p < 0.01).
Conclusions
The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high- and low-risk BrS patients. (J Am Coll Cardiol 2014;63:2131–8) ª 2014 by the American College of Cardiology Foundation
Brugada syndrome (BrS) is a distinct form of idiopathic ventricular fibrillation (VF). BrS is characterized by a unique electrocardiographic pattern consisting of a right bundle branch blocklike morphology and ST-segment elevation in precordial leads. Results of many studies (1–10) have
From the *Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; yDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; and the zSakakibara Heart Institute of Okayama, Okayama, Japan. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received October 9, 2013; revised manuscript received January 7, 2014, accepted January 14, 2014.
suggested that patients with syncope, particularly patients with a spontaneous type 1 electrocardiographic pattern, have a significant risk of sudden cardiac death (SCD) or VF. See page 2139
In the remaining population of asymptomatic subjects, the risk is lower, but not negligible (1,5). Therefore, assessment of the risk of SCD and VF in patients with a Brugada-type electrocardiogram (ECG) is clinically important, especially when sporadic cases are detected during routine medical checkups. Many markers for the development of VF in BrS have been reported, including clinical markers of a family history
2132
Tokioka et al. ECG Markers in High-Risk Brugada Syndrome
of SCD (11), syncope with nonprodromal episodes (12), episodes of paroxysmal atrial fibrillation BrS = Brugada syndrome (PAF) (13), electrocardiographic CI = confidence interval markers of a spontaneous type 1 ECG = electrocardiogram electrocardiographic pattern, exEP = electrophysiological istence of late potential (14), fragmented QRS (f-QRS) (15), ER = early repolarization T-wave alternans after sodium f-QRS = fragmented QRS channel blocker injection (16), an HR = hazard ratio inferolateral early repolarization ICD = implantable (ER) pattern (17,18), a genetic cardioverter-defibrillator marker of SCN5A, a gene encodPAF = paroxysmal atrial ing the cardiac sodium channel fibrillation (19), electrophysiological markers SCD = sudden cardiac death of VF inducibility by programmed VF = ventricular fibrillation electrical stimulation, abnormal restitution properties, and ventricular effective refractory period 440 ms (7 of 24, 29.2% vs. 28 of 222, 12.6%; p ¼ 0.036), and inferolateral ER pattern (8 of 24, 33.3% vs. 17 of 222, 7.7%; p < 0.001) were observed more often in patients with VF/SCD than in those without VF/SCD. Multivariate analysis showed that the following 4 parameters were independent risk factors for arrhythmic events: f-QRS (hazard ratio [HR]: 5.21; 95% confidence interval [CI]: 1.69 to 16.13; p ¼ 0.004), inferolateral ER pattern (HR: 2.87; 95% CI: 1.16 to 7.14; p ¼ 0.023), a history of VF episodes (HR: 19.61; 95% CI: 4.12 to 90.91; p < 0.001), and a history of syncope episodes (HR: 28.57; 95% CI: 6.14 to 142.86; p < 0.001) (Table 2). Patient characteristics with f-QRS. On multivariate analysis, depolarization abnormalities of f-QRS were an independent risk factor for arrhythmic events. Therefore, clinical, genetic, and electrocardiographic data for patients with and without f-QRS were analyzed again (Table 3). There were no significant differences in age, family history of SCD, and incidence of the SCN5A gene mutation between patients with and without f-QRS. However, a history of syncope episodes, a history of VF episodes, and VF inducibility during EP study were more frequently observed in patients with f-QRS than in those without f-QRS (p ¼ 0.002, p ¼ 0.005, and p ¼ 0.002, respectively). PQ
2134
Tokioka et al. ECG Markers in High-Risk Brugada Syndrome
Table 2
JACC Vol. 63, No. 20, 2014 May 27, 2014:2131–8
Characteristics of Patients With and Without VF/SCD During Follow-Up Univariate Analysis VF/SCD þ
VF/SCD
OR
213/9
1.029
0.125–8.490
95% CI
Multivariate Analysis p Value
HR
95% CI
p Value
Clinical/genetic parameters Male/female
23/1
Age (yrs), median (IQR)
47 (15)
48 (21)
History of syncope episodes
13 (54.2)
27 (12.2)
8.535
3.477–20.955
Vol. 63, No. 20, 2014 ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2014.01.072
Heart Rhythm Disorders
Electrocardiographic Parameters and Fatal Arrhythmic Events in Patients With Brugada Syndrome Combination of Depolarization and Repolarization Abnormalities Koji Tokioka, MD,* Kengo F. Kusano, MD, PHD,y Hiroshi Morita, MD, PHD,* Daiji Miura, PHD,* Nobuhiro Nishii, MD, PHD,* Satoshi Nagase, MD, PHD,* Kazufumi Nakamura, MD, PHD,* Kunihisa Kohno, MD, PHD,* Hiroshi Ito, MD, PHD,* Tohru Ohe, MD, PHDz Okayama and Osaka, Japan Objectives
This study aimed to determine the usefulness of the combination of several electrocardiographic markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS).
Background
Detection of high-/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several electrocardiographic markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear.
Methods
Baseline characteristics of 246 consecutive patients (236 men; mean age, 47.6 13.6 years) with a Brugada-type electrocardiogram, including 13 patients with a history of VF and 40 patients with a history of syncope episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in 1 patient were observed. Clinical/genetic and electrocardiographic parameters were compared with VF/SCD events.
Results
On univariate analysis, a history of VF and syncope episodes, paroxysmal atrial fibrillation, spontaneous type 1 pattern in the precordial leads, and electrocardiographic markers of depolarization abnormalities (QRS duration 120 ms, and fragmented QRS [f-QRS]) and those of repolarization abnormalities (inferolateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. On multivariable analysis, a history of VF and syncope episodes, inferolateral ER pattern, and f-QRS were independent predictors of documented VF and SCD (odds ratios: 19.61, 28.57, 2.87, and 5.21, respectively; p < 0.05). Kaplan-Meier curves showed that the presence/absence of inferolateral ER and f-QRS predicted a worse/better prognosis (log-rank test, p < 0.01).
Conclusions
The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high- and low-risk BrS patients. (J Am Coll Cardiol 2014;63:2131–8) ª 2014 by the American College of Cardiology Foundation
Brugada syndrome (BrS) is a distinct form of idiopathic ventricular fibrillation (VF). BrS is characterized by a unique electrocardiographic pattern consisting of a right bundle branch blocklike morphology and ST-segment elevation in precordial leads. Results of many studies (1–10) have
From the *Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; yDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; and the zSakakibara Heart Institute of Okayama, Okayama, Japan. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received October 9, 2013; revised manuscript received January 7, 2014, accepted January 14, 2014.
suggested that patients with syncope, particularly patients with a spontaneous type 1 electrocardiographic pattern, have a significant risk of sudden cardiac death (SCD) or VF. See page 2139
In the remaining population of asymptomatic subjects, the risk is lower, but not negligible (1,5). Therefore, assessment of the risk of SCD and VF in patients with a Brugada-type electrocardiogram (ECG) is clinically important, especially when sporadic cases are detected during routine medical checkups. Many markers for the development of VF in BrS have been reported, including clinical markers of a family history
2132
Tokioka et al. ECG Markers in High-Risk Brugada Syndrome
of SCD (11), syncope with nonprodromal episodes (12), episodes of paroxysmal atrial fibrillation BrS = Brugada syndrome (PAF) (13), electrocardiographic CI = confidence interval markers of a spontaneous type 1 ECG = electrocardiogram electrocardiographic pattern, exEP = electrophysiological istence of late potential (14), fragmented QRS (f-QRS) (15), ER = early repolarization T-wave alternans after sodium f-QRS = fragmented QRS channel blocker injection (16), an HR = hazard ratio inferolateral early repolarization ICD = implantable (ER) pattern (17,18), a genetic cardioverter-defibrillator marker of SCN5A, a gene encodPAF = paroxysmal atrial ing the cardiac sodium channel fibrillation (19), electrophysiological markers SCD = sudden cardiac death of VF inducibility by programmed VF = ventricular fibrillation electrical stimulation, abnormal restitution properties, and ventricular effective refractory period 440 ms (7 of 24, 29.2% vs. 28 of 222, 12.6%; p ¼ 0.036), and inferolateral ER pattern (8 of 24, 33.3% vs. 17 of 222, 7.7%; p < 0.001) were observed more often in patients with VF/SCD than in those without VF/SCD. Multivariate analysis showed that the following 4 parameters were independent risk factors for arrhythmic events: f-QRS (hazard ratio [HR]: 5.21; 95% confidence interval [CI]: 1.69 to 16.13; p ¼ 0.004), inferolateral ER pattern (HR: 2.87; 95% CI: 1.16 to 7.14; p ¼ 0.023), a history of VF episodes (HR: 19.61; 95% CI: 4.12 to 90.91; p < 0.001), and a history of syncope episodes (HR: 28.57; 95% CI: 6.14 to 142.86; p < 0.001) (Table 2). Patient characteristics with f-QRS. On multivariate analysis, depolarization abnormalities of f-QRS were an independent risk factor for arrhythmic events. Therefore, clinical, genetic, and electrocardiographic data for patients with and without f-QRS were analyzed again (Table 3). There were no significant differences in age, family history of SCD, and incidence of the SCN5A gene mutation between patients with and without f-QRS. However, a history of syncope episodes, a history of VF episodes, and VF inducibility during EP study were more frequently observed in patients with f-QRS than in those without f-QRS (p ¼ 0.002, p ¼ 0.005, and p ¼ 0.002, respectively). PQ
2134
Tokioka et al. ECG Markers in High-Risk Brugada Syndrome
Table 2
JACC Vol. 63, No. 20, 2014 May 27, 2014:2131–8
Characteristics of Patients With and Without VF/SCD During Follow-Up Univariate Analysis VF/SCD þ
VF/SCD
OR
213/9
1.029
0.125–8.490
95% CI
Multivariate Analysis p Value
HR
95% CI
p Value
Clinical/genetic parameters Male/female
23/1
Age (yrs), median (IQR)
47 (15)
48 (21)
History of syncope episodes
13 (54.2)
27 (12.2)
8.535
3.477–20.955
