Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome

OBJECTIVES: The purpose of this study was to compare the effect of intravenous flecainide and ajmaline with respect to their ability to induce or accentuate the typical ECG pattern of Brugada syndrome. BACKGROUND: Brugada syndrome is associated with a high incidence of sudden cardiac death. The typical ECG pattern of ST-segment elevation in the right precordial leads often is concealed, but it can be unmasked with sodium channel blockers such as flecainide and ajmaline. Little is known about the relative effectiveness of these provocative agents in unmasking Brugada syndrome. METHODS: Intravenous pharmacologic challenge with flecainide and ajmaline was performed. Whole-cell patch clamp techniques were used to assess the relative potency of ajmaline and flecainide to inhibit the transient outward current (I(to)). RESULTS: A coved-type ST-segment elevation in the right precordial leads was induced or enhanced in 22 of 22 patients following ajmaline administration. Among the 22 patients, only 15 patients showed positive response to flecainide, resulting in a positive concordance of 68%. Both drugs produced equivalent changes in QRS and PQ intervals, suggesting similar effects on sodium channel current. Whole-cell patch clamp experiments revealed a reduction of the total charge provided by I(to) with an IC(50) of 216 and 15.2 microM for ajmaline and flecainide, respectively. CONCLUSIONS: Our data demonstrate disparate response of Brugada patients to flecainide and ajmaline, with a failure of flecainide in 7 of 22 cases (32%). Greater inhibition of I(to) by flecainide may render it less effective. These observations have important implication for identification of patients at risk for sudden death.     

Brugada pattern masquerading as ST-segment elevation myocardial infarction in flecainide toxicity

Flecainide (a class 1c antiarrhythmic) produces a dose-dependent decrease in intracardiac conduction. Its well known common electrocardiographic effects are prolongation of PR and QT intervals and the QRS complex duration. We report a case of flecainide toxicity in an elderly female who presented with a type 1 Brugada pattern who essentially had a previously normal ECG pattern on therapeutic dose of flecainide therapy. The case describes a rare electrocardiographic abnormality induced by flecainide toxicity which otherwise could be easily misinterpreted as a ST-segment elevation myocardial infarction (STEMI) without lack of expertise and high clinical suspicion.     

Unusual response to the ajmaline test in a patient with Brugada syndrome.

We present a Brugada syndrome patient who suffered an aborted sudden death. The ajmaline test (1 mg/kg body weight) induced accentuated alternans ST-segment elevation in V1-V2 without ventricular arrhythmias. It could represent silent ischaemia not detected before, failure of myocardial regions to repolarize in alternate beats due to transmural dispersion of conduction and refractoriness in the right ventricular outflow tract or a rate dependent sodium channel block by ajmaline. We need more studies to know whether this electrocardiographic sign is a risk factor for life-threatening ventricular arrhythmias in Brugada syndrome patients.     

国人Brugada综合征临床特征的Meta分析

目的了解国人Brugada综合征的主要临床特征。方法对1998～2002年国内期刊报道的26例Brugada综合征的临床和心电图资料的临床特征作Meta分析。结果患者主要见于青壮年男性,猝死发生时记录到可救治的心室颤动和多形性室性心动过速;心电图呈类右束支传导阻滞型,V1、V2导联以ST段下斜型抬高、T波倒置为主,有家族史者在心律失常发生前出现先兆者明显低于无家族史者(30%比62.5%,P<0.05)。结论国人Brugada综合征以青壮年男性为主,心电图表现与文献资料相似。有家族史者比无家族史者病情凶险。     

The hyperkalemic Brugada sign

Background

A few case reports have indicated that hyperkalemia can induce a Brugada pattern in the electrocardiogram. The specific clinical and electrocardiographic features of the hyperkalemic Brugada sign, however, have not been previously described.

Methods

A case series was collected from hospitalized hyperkalemic patients with a type I Brugada pattern in the electrocardiogram, and a literature review was performed. Electrocardiograms were examined for rhythm and morphology, and clinical characteristics were analyzed.

Results

Nine new cases with the hyperkalemic Brugada sign were identified with an additional 15 cases found in the literature. Of the 9 cases, 8 were male patients, and all were critically ill; 5 of the 9 died within 48 hours. The mean (±SD) serum potassium level was 7.8 ± 0.5 mEq/L. The mean QRS width was 144 ± 31 milliseconds, and all had abnormal QRS axis. In 6 cases, there was a wide complex rhythm without visible P waves. The clinical and electrocardiographic characteristics of 15 cases found in the literature were remarkably similar to those in our series.

Conclusions

The hyperkalemic Brugada pattern differs in substantial ways from the electrocardiogram of patients with the genetic Brugada syndrome. Many patients have wide complex rhythms without visible P waves, marked QRS widening, and an abnormal QRS axis. Most patients are male, and many are critically ill. Prompt recognition of this clinical and electrocardiographic entity may expedite the initiation of appropriate treatment for hyperkalemia.     

1 065例健康汉族人Brugada心电图征发生率的初步调查

目的通过调查健康体检者Brugada心电图征的发生率,获得中国人Brugada综合征的流行病学资料。方法对连续1069例参加年度健康体检的公务员进行病史、家庭史询问、体检、X线胸片和标准12导联心电图检查,按照欧洲心脏病学会推荐标准筛选出Brugada心电图征。结果排除4例器质性心脏病患者后,共1065例(男性805例,女性260例)入选,年龄18～83平均(38.58±15.26)岁。其中39例有黑史,36例有晕厥史,7例有猝死家族史。共8份心电图符合阳性标准,占总例数7.5‰。所有携带者均为男性,心电图均呈鞍型,其中符合Ⅱ型和Ⅲ型者各4例,1例(N7)有黑和晕厥史。结论Brugada心电图征在中国健康汉族人中并不少见,男性多见,其临床意义有待于进一步随访研究证实。     

药物激发试验在Brugada综合征中的应用

目的探讨药物激发试验在隐匿性Brugada综合征中的应用。方法将高度怀疑为Brugada综合征的9例患者分成两组,分别用缓脉灵(ajmaline)1mg/kg和氟卡尼(flecainide)2mg/kg进行激发试验。以2002年欧洲心脏病协会心律失常组提出的阳性标准为判断标准。结果两组中各有1例患者诱发呈阳性反应。结论药物激发试验有助于隐匿性Brugada综合征的发现。     

Low-dose isoproterenol for repetitive ventricular arrhythmia in patients with Brugada syndrome.

AIMS: Arrhythmic storm or repetitive ventricular arrhythmia (VA) has been occasionally observed in Brugada syndrome (BS). A beta-adrenergic stimulator [isoproterenol (ISP)] has been reported to suppress this arrhythmic storm in sporadic cases. Accordingly, we investigated the antiarrhythmic effects of ISP infusion in consecutive BS patients with arrhythmic storm or repetitive VA. METHODS AND RESULTS: Seven BS patients with arrhythmic storm were studied. Intravenous ISP was administered as a bolus injection (1-2 microg), followed by continuous infusion (0.15 microg/min). Arrhythmic storm or repetitive VA was suppressed immediately after the bolus administration of ISP, which was followed by continuous infusion of low-dose ISP for 1-3 days. In all patients, ST-elevation decreased in right precordial leads. In six of the seven patients, VA subsided after the discontinuance of ISP. RR interval was shortened and ST-elevation in right precordial leads was decreased after ISP bolus injection. ST-elevation in right precordial leads remained decreased during continuous ISP infusion, whereas the RR interval returned to the control level. CONCLUSION: Continuous administration of low-dose ISP may be effective for the suppression of repetitive VA occurrence in patients with BS.     

Diagnostic value of flecainide testing in unmasking SCN5A-related Brugada syndrome

INTRODUCTION: Provocation tests with sodium channel blockers are often required to unmask ECG abnormalities in Brugada syndrome (BrS). However, their diagnostic value is only partially established, while life-threatening ventricular arrhythmias during these tests were reported. We aimed to establish sensitivity, specificity, and safety of flecainide testing, and to predict a positive test outcome from the baseline ECG. METHODS AND RESULTS: We performed 160 tests with flecainide in subjects determined to be at risk for BrS. P wave width, PQ duration, QRS width, S wave amplitude and duration in leads II-III, in addition to ST morphology and J point elevation in V1-V3 were measured before and after flecainide administration. Moreover, leads were positioned over the third intercostal space (V1(IC3)-V2(IC3)). Flecainide tests were considered positive if criteria from the First Consensus Report on BrS were fulfilled. In 64 cases, the test was positive, while 95 were negative (1 test was prematurely interrupted). The sensitivity and specificity, calculated in SCN5A-positive probands and their family members, were 77% and 80%, respectively. Baseline ECGs exhibited significant group differences in P, PQ, and QRS duration, J point elevation (leads V1-V2 and V1(IC3)-V2(IC3)), and S duration in II, but an attempt to predict the outcome of flecainide testing from these baseline ECG parameters failed. No malignant arrhythmias were observed. CONCLUSION: Flecainide testing is a valid and safe tool to identify SCN5A-related BrS patients. Baseline ECGs do not predict test outcomes, but point to conduction slowing as a core mechanism in BrS.     

Heart rate variability in patients with Brugada syndrome in Thailand.

AIMS: Since patients with Brugada syndrome usually have symptoms at nighttime, we hypothesize that changes in autonomic modulation have an important role in the occurrence of the ventricular fibrillation episodes. The objective of this study was to determine the changes in heart rate variability (HRV) in patients with Brugada syndrome compared to asymptomatic subjects with Brugada ECG and controls. METHODS AND RESULTS:We studied 17 patients with Brugada syndrome, 10 asymptomatic subjects with Brugada ECG and 45 controls. Patients with Brugada syndrome and asymptomatic subjects with Brugada ECG underwent echocardiography, exercise stress testing, 24-h Holter monitoring, signal-averaged ECG. Patients with Brugada syndrome also underwent coronary angiography and electrophysiologic study. Time domain and frequency domain HRV analysis were performed at daytime and nighttime. The results of this study showed that patients with Brugada syndrome had lower HRV or lower vagal tone at night compared to the controls. They also had lower heart rate during the day and higher during the night compared to asymptomatic subjects and the controls. CONCLUSION: Patients with Brugada syndrome had low heart rate variability at night which may predispose to the occurrence of VF episodes.     

Type 1 electrocardiographic burden is increased in symptomatic patients with Brugada syndrome

Background

Spontaneous type 1 electrocardiographic (ECG) is a risk factor for arrhythmic events in Brugada patients but the importance of the proportion of time with a type 1 ECG is unknown.

Patients and Methods

Thirty-four Brugada patients (15 symptomatic) underwent a 24-hour 12-lead ECG recording. One-minute averaged waveforms displaying ST-segment elevation above 200 μV, with descending ST-segment and negative T-wave polarity on leads V₁-V₃ were considered as type 1 Brugada ECG. The burden was defined as the percentage of type 1 Brugada waveforms.

Results

Type 1 ECG on lead V2 was more frequent in symptomatic patients (median 80.6% [15.7-96.7] vs 12.4% [0.0-69.7], P = .05). Patients with a permanent type 1 pattern on lead V₂ were more likely to be symptomatic (5/6) than patients without type 1 ECG during a 24-hour period (2/9) (P < .05).

Conclusion

Type 1 pattern is more prevalent across a 24-hour period in symptomatic Brugada patients.     

Site-specific arrhythmogenesis in patients with Brugada syndrome

INTRODUCTION: It has been believed that electrophysiologic abnormality of the epicardial region of the right ventricular free wall may play an important role in arrhythmogenesis of phase 2 reentry in Brugada syndrome, but clinical evidence of the occurrence of ventricular arrhythmias at the right ventricular free wall has not been evaluated. In this study, we evaluated the site-specific inducibility of ventricular fibrillation (VF) and the origin of spontaneous premature ventricular contractions (PVCs) in patients with Brugada syndrome. METHODS AND RESULTS: Forty-five patients with Brugada-type ECG were enrolled in this study. Spontaneous PVCs were recorded in 9 patients. Programmed electrical stimulation (PES) was performed at the right ventricular apex (RVA), the free wall and septal region of the right ventricular outflow tract (RVOT), and the left ventricle (LV). The inducibility of PVT/VF was evaluated at each ventricular site, and the origin of PVC was determined by pace mapping. Sustained VF was induced in 17 patients. VF was induced in all 17 patients by PES at RVOT. Although PES at the septal region of the RVOT induced VF in only 5 patients (29%), PES at the free-wall region of the RVOT induced PVT/VF in 13 patients (76%). PES at RVA induced VF in only 2 patients (12%), and PES at LV failed to induce any arrhythmic events. Ventricular pace mapping showed that 64% of PVCs occurred at the free-wall region of the RVOT, 18% at the septal region of the RVOT, 9% at RVA, and 9% at LV. CONCLUSION: VF in patients with Brugada syndrome frequently is induced at the free-wall region of the RVOT area. The origin of PVC appears to be related to the site of PVT/VF induction by PES.     

Brugada综合征室性心律失常发作的时间特征及其临床意义

目的运用Holter和置入式心脏复律除颤器(ICD)研究Brugada综合征(BrS)患者室性心律失常发作的时间特征。方法8例BrS患者和6例特发性BrS心电图征者均为男性,平均年龄(41.07±11.49)岁,根据临床表现分为心室颤动(室颤)组和无室颤组各7例,行Holter检查比较两组间室性早搏(室早)发作的时间特征。根据ICD的随访资料,分析室颤发作的时间特征。结果Holter显示,多数患者室早总数在0~74(9.61±17.23)个/24h,两组间室早的数量差异无统计学意义[(108±269)个/24h与(8±19)个/24h,P>0.05]。室颤组的98.67%的室早发作集中在夜间2200至凌晨700,而无室颤组为44.14%,室颤组明显高于无室颤组(χ2=1480,P<0.01)。5例患者ICD置入后随访9~54(23.80±17.96)个月,75次室颤发作中93.3%集中在夜间2200至凌晨700。结论高危的BrS患者的室早具有夜间和凌晨集中发作的特征,可能是新的无创性危险分层指标。BrS患者的室颤发作多集中在夜间和凌晨,可据此设计给药方案以减少副作用。     

Brugada syndrome in patients with acute febrile illness

BackgroundBrugada syndrome (BrS) is an inherited electroclinical syndrome and can be occasionally precipitated by fever. The prevalence of Brugada-type electrocardiographic patterns (BTEP) due to febrile illnesses have not been previously studied in India.Materials and methodsBetween June 2014 and December 2015, 525 consecutive patients admitted to a government hospital with acute febrile illness were retrospectively enrolled. In addition to their investigations for workup of fever, ECGs were analyzed and BTEP types 1 and 2 were noted. Daily ECGs if available were perused to document reversal.ResultsBTEP was seen in 23 (4% 95%CI: 2.9–6.5%): BTEP type 1 (Brugada syndrome) in 11 patients (2%; 95%CI 1.2–3.7%) and BTEP type 2 in 12. All patients with BrS (BTEP type1) were males; mean age and temperature were 37.7 years (SD: 17.6) and 38.8 °C (SD: 0.6), respectively. There were no significant differences in age, temperature or ECG parameters between patients with BTEP and those without. These patients neither had cardiac symptoms nor family history of sudden cardiac deaths. Bacterial infections were the commonest cause of fever in patients with BrS. All BTEP changes resolved with defervesence of fever except in one.ConclusionThe prevalence of the fever induced BrS is higher in our study group and is comparable to estimates in Southeast Asian populations. An ECG should be considered in all febrile patients. Further studies are required for better characterization and risk stratification of these patients.     

Brugada electrocardiographic pattern induced by fever

Brugada syndrome is a major cause of sudden death in young adults.Fever has been described to induce a Brugada-type electrocardiogram in asymptomatic patients with a negative family history,to disclose Brugada syndrome and to increase the risk of death and induce T wave alternans in patients with diagnosed Brugada syndrome.Risk stratification is challenging and demands a careful evaluation.Here we present 2 case reports and review the literature.     

Brugada综合征伴发的室上性心律失常

目的：报道Brugada综合征伴发的多种室上性心律失常。方法：对符合Brugada综合征诊断标准的46例患者行动态心电图检查，记录心律失常发作类型，部分行电生理检查与射频消融治疗。结果：男性39例，女性7例。21例有家族史，23例有晕厥史，其中3例经心肺复苏。46例中5例并发阵发性室上性心动过速（阵发性室上速，4例为显性预激综合征）；3例室上速与心房扑动（房扑）并存；2例室上速与室性心动过速（室速）并存；14例房性心动过速（房速）、房扑和心房颤动（房颤）；2例房速伴三度房室阻滞；1例房速与室速并存；11例多形室速；5例单形室速；1例室颤电风暴并三度房室阻滞；1例室速与三度房室阻滞并存；1例室速与三度房室阻滞、房颤并存。39例行射频消融治疗成功32例，4例并发三度房室阻滞者植入心脏永久起搏器，4例植入心律转复除颤器。结论：除室速、室颤外，Brugada综合征可发生房颤、房扑、室上速、三度房室阻滞等多种心律失常，且两种以上心律失常可以共存。Brugada综合征心脏钠通道基因变异引起细胞膜钠通道功能异常不仅存在于希氏一浦肯野系统和心室肌，亦可存在于心房肌及房室结，引发多种类型心律失常。     

Electrocardiographic findings typical of Brugada syndrome unmasked by cocaine consumption

Brugada syndrome is characterized by the presence of right bundle branch block on electrocardiography and by ST-segment elevation in the right precordial leads (V1-V3), by the absence of structural cardiac abnormalities, and by episodes of syncope or sudden death. On occasion, diagnosis is made difficult by temporary normalization of the ECG. The condition can be unmasked by potent sodium channel blockers, such as flecainide. Our patient presented with a Brugada syndrome-type ECG after intake of a large amount of cocaine.