Brugada Syndrome (brugada + syndrome)
Increased Right Ventricular Repolarization Gradients Promote Arrhythmogenesis in a Murine Model of Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2010
CLAIRE A. MARTIN M.R.C.P.
Repolarization Gradients in Brugada Syndrome.,,Introduction: Brugada syndrome (BrS) is associated with loss of Na+ channel function and increased risks of a ventricular tachycardia exacerbated by flecainide but reduced by quinidine. Previous studies in nongenetic models have implicated both altered conduction times and repolarization gradients in this arrhythmogenicity. We compared activation latencies and spatial differences in action potential recovery between different ventricular regions in a murine Scn5a+/, BrS model, and investigated the effect of flecainide and quinidine upon these. Methods and Results: Langendorff-perfused wild-type and Scn5a+/, hearts were subjected to regular pacing and a combination of programmed electrical stimulation techniques. Monophasic action potentials were recorded from the right (RV) and left ventricular (LV) epicardium and endocardium before and following flecainide (10 ,M) or quinidine (5 ,M) treatment, and activation latencies measured. Transmural repolarization gradients were then calculated from the difference between neighboring endocardial and epicardial action potential durations (APDs). Scn5a+/, hearts showed decreased RV epicardial APDs, accentuating RV, but not LV, transmural gradients. This correlated with increased arrhythmic tendencies compared with wild-type. Flecainide increased RV transmural gradients, while quinidine decreased them, in line with their respective pro- and antiarrhythmic effects. In contrast, Scna5+/, hearts showed slowed conduction times in both RV and LV, exacerbated not only by flecainide but also by quinidine, in contrast to their differing effects on arrhythmogenesis. Conclusion: We use a murine genetic model of BrS to systematically analyze LV and RV action potential kinetics for the first time. This establishes a key role for accentuated transmural gradients, specifically in the RV, in its arrhythmogenicity. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1153-1159) [source]
Ionic Basis of Pharmacological Therapy in Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2007
MANLIO F. MÁRQUEZ M.D.
An implantable cardioverter-defibrillator is considered the only effective therapy to terminate ventricular arrhythmias in symptomatic patients with Brugada syndrome. However, it does not prevent future arrhythmic episodes. Only antiarrhythmic drug therapy can prevent them. There have been several reports of a beneficial effect of oral quinidine in both asymptomatic and symptomatic patients. Other possible beneficial oral agents could be Ito blockers. Intravenous isoproterenol has been reported to be especially useful in abolishing arrhythmic storms in emergency situations. Also, isolated case reports on the usefulness of cilostazol, sotalol, and mexiletine have been described. The present article reviews the mechanisms by which these drugs may act and their possible role in the pharmacotherapy of this disease. [source]
Brugada Syndrome with ST-Segment Elevation in the Lateral LeadsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2006
MAARTEN P. VAN DEN BERG M.D., Ph.D.
No abstract is available for this article. [source]
Diagnostic Value of Flecainide Testing in Unmasking SCN5A-Related Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2006
PAOLA G. MEREGALLI M.D.
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 (V1IC3 -V2IC3). 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 V1IC3 -V2IC3), 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. [source]
The Full Stomach Test as a Novel Diagnostic Technique for Identifying Patients at Risk of Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2006
F.A.C.C., Ph.D., TAKANORI IKEDA M.D.
Introduction: Autonomic modulation, particularly high vagal tone, plays an important role in the occurrence of ventricular tachyarrhythmias in the Brugada syndrome. Food intake modulates vagal activity. We assessed the usefulness of a novel diagnostic technique, the "full stomach test," for identifying a high-risk group in patients with a Brugada-type electrocardiogram (ECG). Methods and Results: In 35 patients with a Brugada-type ECG, we assessed 12-lead ECGs before and after a large meal, a pilsicainide pharmacological test, spontaneous ST-segment change, late potentials by signal-averaged ECG, microvolt T-wave alternans, and four other ECG parameters. These patients were divided into two groups (i.e., high-risk group [n = 17] and indeterminate risk group [n = 18]). The full stomach test was defined as positive when augmentation of characteristic ECG abnormalities was observed after meals. Thirteen patients had a prior history of life-threatening events such as aborted sudden death and syncope, with a total of 30 episodes. These episodes had a circadian pattern, at night and after meals. The full stomach test was positive in 17 of the study patients (49%). A positive test outcome was characterized by a higher incidence of a history of life-threatening events than a negative test outcome (P = 0.015, odds ratio = 7.1). In comparison between the two groups, the incidence (82%) of positive outcomes in the high-risk group was significantly higher than that (17%) in the indeterminate risk group (P = 0.0002). Conclusions: Characteristic ECG changes diagnostic of Brugada syndrome are augmented by a large meal. These data are associated with a history of life-threatening events in Brugada syndrome. [source]
Electrophysiological Basis and Genetics of Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2005
AUGUSTUS O. GRANT M.B.Ch.B., Ph.D.
Brugada syndrome is a primary arrhythmic syndrome arising in the structurally normal heart. Any proposed mechanism should account for the major features of the syndrome: localization of the ST segment and T-wave changes to the right precordial leads, association of conduction slowing at several levels, precipitation or aggravation of the major ECG changes by sodium channel-blocking drugs and the occurrence of ventricular fibrillation. Heterogeneity of repolarization across the ventricle wall plays a major role. Any agency that shifts the net current gradient during phase I outward would exaggerate the normal heterogeneity of repolarization and result in the ST segment and T-wave changes characteristic of the syndrome. When the outward current shift is marked, premature repolarization may occur in epicardial zone and the resulting gradient may precipitate reentry. The syndrome is inherited as an autosomal dominant. However, 75% of clinically affected individuals are males. In 20% of cases, the syndrome is associated with mutations of the cardiac sodium channel gene SCN5A. The mutations result in a loss-of-function as a result of the synthesis of a non-functional protein, altered protein trafficking, or change in gating. Agencies that reduce the sodium current may precipitate the characteristic ECG changes, for example, sodium channel blockers and membrane depolarization by hyperkalemia. Sympathetic stimulation may reverse the ECG changes and reduce arrhythmia recurrence. By its nonspecific potassium channel blocking action, quinidine may also reduce arrhythmia recurrence. We still do not know the basis for defect in the majority of patients with Brugada syndrome. [source]
Defibrillation in the Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2005
ALAN KADISH M.D.
No abstract is available for this article. [source]
An Autopsy Case of Brugada Syndrome with Significant Lesions in the Sinus NodeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2005
SHIN-ICHIRO MORIMOTO M.D.
A 30-year-old man with Brugada syndrome died suddenly. The heart weighed 380 g. The left ventricular wall showed mild thickening, and marked fatty tissue deposition was noted in the right ventricular outflow tract. Neither ventricle was enlarged. Contraction band necrosis was diffuse in both ventricles. In the ventricles no cardiac muscle cell hypertrophy or atrophy, or significant interstitial fibrosis was observed. In the sinus node the number of nodal cells was reduced by half, with fatty tissue and fibrosis prominent. But no lesions were evident in the right bundle branch. [source]
Propranolol Intoxication Revealing a Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2005
PHILIP AOUATE M.D.
This is the first report of Brugada syndrome revealed by beta-blocker intoxication. A 24-year-old healthy man ingested propranolol (2.28 g) to commit suicide. After early gastric lavage, electrolytes, cardiac enzymes, chest X-ray, and echocardiography were normal. Dosages of psychotropic drugs were negative. ECG showed a typical coved-type pattern of Brugada syndrome. Follow-up showed partial ECG normalization of the discrete saddleback-type pattern. The ajmaline- test confirmed Brugada syndrome. These ECG modifications may be explained by the stabilizing membrane effect of high concentration of propranolol and/or inhibition of ICaL. This case illustrates the possible deleterious effects of beta-blockers in patients with Brugada syndrome. [source]
Assessment of Markers for Identifying Patients at Risk for Life-Threatening Arrhythmic Events in Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2005
YOUICHI AJIRO M.D.
Introduction: Risk stratification for life-threatening arrhythmic events in Brugada syndrome is not yet established. The aim of the present study was to examine the usefulness of various markers in predicting life-threatening arrhythmic events in the Brugada syndrome. Methods and Results: Forty-six patients with Brugada-type ECGs were categorized into the symptomatic (n = 28) and asymptomatic (n = 18) groups. Statistical analyses were performed with respect to the usefulness of the following markers: SCN5A mutation, pharmacologic challenge, ventricular fibrillation (VF) inducibility by programmed electrical stimulation, and late potential (LP) by signal-averaged ECG (SAECG). Comparison between the two groups revealed a significant difference only in LP positivity (92.6% vs 47.1%, P = 0.0004). The symptomatic group had significantly lower RMS40, longer LAS40, and longer fQRSd compared with the asymptomatic group. A significant difference was noted, especially RMS40. The positive predictive value, negative predictive value, and predictive accuracy when setting a cutoff value of 15 ,V were 92.0%, 78.9%, and 86.4%, respectively. Furthermore, patients with an RMS40 value <15 ,V (n = 25) showed significantly higher rates of VF recurrence compared with patients with an RMS40 value , 15 ,V (n = 19, P = 0.047). Conclusion: Regarding risk stratification for identifying high-risk patients in Brugada syndrome, only LP by SAECG was shown to be useful, suggesting the importance of RMS40 in predicting the history of life-threatening arrhythmic events and the recurrence of VF. [source]
Site-Specific Arrhythmogenesis in Patients with Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2003
HIROSHI MORITA M.D.
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.(J Cardiovasc Electrophysiol, Vol. 14, pp. 373-379, April 2003) [source]
Site-Specific Arrhythmogenesis in Brugada Syndrome?JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2003
BERNARD BELHASSEN M.D.
No abstract is available for this article. [source]
Pilsicanide-Induced Marked T Wave Alternans and Ventricular Fibrillation in a Patient with Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002
MASAHIKO TAKAGI M.D.
Prevention of Ventricular Fibrillation by Cilostazol, an Oral Phosphodiesterase Inhibitor, in a Patient with Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2002
TAKESHI TSUCHIYA M.D.
Cilostazol and Brugada Syndrome. We report the case of 67-year-old man with Brugada syndrome, in whom daily episodes of ventricular fibrillation (VF) occurred every early morning for 4 days. The episodes of VF were completely prevented by an oral administration of cilostazol, a phosphodiesterase inhibitor. This effect was confirmed by the on-and-off challenge test, in which discontinuation of the drug resulted in recurrence of VF and resumption of the drug again prevented VF. This effect may be related to the suppression of Ito secondary to the increase in heart rate and/or to an increase in Ca2+ current (ICa) due to an elevation of intracellular cyclic AMP concentration via inhibition of phosphodiesterase activity. This drug might have an anti-VF potential in patients with Brugada syndrome. [source]
Brugada Syndrome Mimicked by Tricyclic Antidepressant OverdoseJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2001
HIROSHI TADA M.D.
Transient ST Segment Elevation in Right Precordial Leads Induced by Psychotropic Drugs: Relationship to the Brugada SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2001
FREDERIC ROULEAU M.D.
Psychotropic Drugs and ST Segment Elevation. Transient ST segment elevation in right precordial leads with use of psychotropic drugs is reported in two cases of overdose and one case of therapeutic administration. Flecainide did not reproduce ST segment elevation. The relationship of these abnormalities to the Brugada syndrome and the electrophysiologic hypothesis are discussed. [source]
Hypercalcemia Due to Rhabdomyolysis Mimicking Brugada SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 11 2009
SAHIL MEHTA M.D.
No abstract is available for this article. [source]
The Spectrum of Electrocardiographic Manifestations of Brugada SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2009
PEDRO BRUGADA M.D., Ph.D.
No abstract is available for this article. [source]
Abnormal Nocturnal Heart Rate Variability and QT Dynamics in Patients with Brugada SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2007
BERTRAND PIERRE M.D.
Background: In Brugada syndrome (BSY), most of the ventricular arrhythmic events are nocturnal, suggesting an influence of the autonomic nervous system. Methods: In 46 patients (mean age = 41 ± 14 years, 43 men) with electrocardiograms (ECG) consistent with BSY and structurally normal hearts, we measured heart rate variability (HRV) and QT dynamics (QT/RR slopes) on 24-hour ambulatory ECG. Type 1 BSY-ECG was spontaneous in 23 (50%) and induced in 23 patients. Results: History of syncope was present in 23 patients (50%). Programmed ventricular stimulation induced ventricular tachyarrhythmias (VTA) in 13 patients (28%). A single patient developed ventricular tachycardia during a mean follow-up of 34 months. Compared to a control group matched for age and sex, HRV was decreased over 24 hours and during nighttime in patients with BSY (SDNN 122 ± 44 vs 93 ± 36 ms, P = 0.0008 and SDANN 88 ± 39 vs 54 ± 24 ms, P < 0.0001). QTend /RR slopes were decreased over 24 hours in patients with BSY (0.159 ± 0.05 vs 0.127 ± 0.05, P = 0.003) and particularly at night (0.123 ± 0.04 vs 0.089 ± 0.04, P = 0.0001). QTend /RR slopes were significantly decreased during nighttime in patients with spontaneous versus provoked BSY-ECG patterns. By contrast, HRV and QT/RR slopes were similar in symptomatic and asymptomatic patients, whether VTA were induced or not. Conclusions: Patients with a BSY-ECG pattern had lower HRV and QT/RR slopes than control subjects during nighttime. High-risk patients with spontaneous BSY-ECG patterns had the lowest nocturnal QTend/RR slopes. These unique repolarization dynamics might be related to the frequent nocturnal occurrence of VTA in BSY. [source]
Arrhythmic Storm Responsive to Quinidine in a Patient with Brugada Syndrome and Vasovagal SyncopePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 8 2005
MANLIO F. MÁRQUEZ
A 37-year-old man with Brugada syndrome (BrS) and arrhythmic storm is described. One month after implantation of a cardioverter-defibrillator he presented with recurrent appropriate shocks for spontaneous ventricular fibrillation (VF). Because of this arrhythmic storm, quinidine therapy was initiated with total suppression of all spontaneous arrhythmias. He had remained free of arrhythmias for 22 months since quinidine initiation. Two episodes of VF occurred after the patient stopped taking the medication. The patient resumed quinidine and has been free of VF for the last 3 months. This response to quinidine in a patient with symptomatic BrS supports its role in the prophylaxis of arrhythmic events in BrS. [source]
Sudden Cardiac Death with Left Main Coronary Artery Occlusion in a Patient Whose Presenting ECG Suggested Brugada SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 11 2003
This article describes a patient who died suddenly during Holter ECG monitoring. A ventricular premature systole with an extremely short coupling interval of 240 ms was immediately followed by torsades de pointes, soon degenerating into ventricular fibrillation. Retrospective survey of the patient's medical records revealed an incomplete right bundle branch block (iRBBB) configuration with fluctuating saddle back-type ST elevation in leads V1 and V2, these suggesting Brugada syndrome. Autopsy showed complete thrombotic occlusion of the left main coronary artery. (PACE 2003; 26:2175,2177) [source]
ST Segment and T Wave Alternans in a Patient with Brugada SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2000
We describe a patient with Brugada syndrome in whom J point and ST-segment elevation in leads V1 and V2 were augmented by atrial pacing and intravenous administration of propranolol or cibenzoline. Significant T wave alternans with a 2:1 appearance of terminal negative T wave was observed in the absence and presence of atrial pacing after the administration of cibenzoline. The cellular mechanism responsible for T wave alternans. beat-to-beat appearance of terminal negative T wave and augmented J point and ST-segment elevation is discussed [source]
Epsilon-Like Electrocardiographic Pattern in a Patient with Brugada SyndromeANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2009
Ozcan Ozeke M.D.
Both Brugada syndrome (BrS) and arrhythmogenic right ventricle dysplasia/cardiomyopathy (ARVD/C) can cause repolarization abnormalities in right precordial leads and predispose to sudden cardiac death (SCD) due to ventricular arrhythmias. Although there is controversy over whether BrS is distinct from ARVD/C, it is believed that both are different clinical entities with respect to both the clinical presentation and the genetic predisposition. The coexistence of these two relatively rare clinical entities is also reported, but, some hypothesized that it is more possible that disease of the right ventricular muscle might accentuate the Brugada electrocardiographic pattern. In clinic practice, there may be cases where the dividing line is not so clear. We report a 33-year-old male presenting with recurrent syncope, who has a peculiar pattern of coved-type ST-segment elevation (ST-SE) with epsilon-like wave in right precordial leads. [source]
Sodium Channel Blockers Enhance the Temporal QT Interval Variability in the Right Precordial Leads in Brugada SyndromeANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2008
Tetsuzou Kanemori M.D.
Background: Temporal QT interval variability is associated with sudden cardiac death. The purpose of this study was to evaluate temporal QT interval variability in Brugada syndrome (BS). Methods: We measured QT and RR intervals in precordial leads (V1,V6) based on 12-beat resting ECG recordings from 16 BS patients (B group) with spontaneous ST elevation in right precordial leads (V1,V2) and from 10 patients with normal hearts (C group). We measured the response in B group before and after administration of pilsicainide (1 mg/kg). The standard deviation (QT-SD, RR-SD) of the time domain and total frequency power (QT-TP, RR-TP) were calculated for all precordial leads, and the latter was to analyze the frequency domain. Results: The right precordial leads in BS exhibited an additional and prominent ST elevation (coved-type) after pilsicainide administration. Both QT-SD and QT-TP values were significantly more increased in B, than in C (5.1 ± 1.2 vs 3.6 ± 0.2 and 23.4 ± 2.9 vs 12.3 ± 1.7 msec2, P < 0.01, respectively) and after pilsicainide administration in B. (5.1 ± 0.4 vs 3.9 ± 0.3, 25.8 ± 3.4 vs 16.3 ± 2.6 msec2, P < 0.01, respectively) However, QT-SD and QT-TP did not significantly change in any of other leads (V3,V6) and RR-SD and RR-TP were similar for both groups, as well as after intravenous pilsicainide administration in B. Conclusions: The temporal QT interval variability was identified in BS. Moreover, sodium channel blocker induced temporal fluctuation in QT interval and it may possibly provide a substrate for ventricular arrhythmia in BS patients. [source]
Antiarrhythmic Induced Electrical Storm in Brugada Syndrome: A Case ReportANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2007
Sandeep Joshi M.D.
Brugada syndrome (BS) may be "unmasked" by several pharmacological and/or physiological agents in an otherwise normal electrocardiogram. Once diagnosed the possibility of persistent ventricular tachycardia/fibrillation exists. Although this is treated with various antiarrhythmic agents, there remains a cohort of patients who fail to respond to conventional antiarrhythmic therapy therefore, amplifying the electrical storm. We report a case of a BS diagnosed via procainamide challenge, the resultant near fatal electrical storm aggravated by amiodarone and the eventual resolution with isoproterenol. [source]
Brugada Syndrome: Current Clinical Aspects and Risk StratificationANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2002
Ph.D., Takanori Ikeda M.D.
Brugada syndrome is a primary electrical disease of the heart that causes sudden cardiac death or life-threatening ventricular arrhythmias, especially in younger men. Genetic analysis supports that this syndrome is a cardiac ion channel disease. A typical electrocardiographic finding consists of a right bundle branch block pattern and ST-segment elevation in the right precordial leads. The higher intercostal space V1 to V3 lead electrocardiogram could be helpful in detecting Brugada patients. Although two types of the ST-segment elevation are present, the coved type is more relevant to the syndrome than the saddle-back type. These patterns can be present permanently or intermittently. Recent data suggest that the Brugada-type electrocardiogram is more prevalent than the manifest Brugada syndrome. Asymptomatic individuals have a much lower incidence of future cardiac events than the symptomatic patients. Although risk stratification for the Brugada syndrome is still incomplete, the inducibility of sustained ventricular arrhythmias has been proposed as a good outcome predictor in this syndrome. In noninvasive techniques, some clinical evidence supports that late potentials detected by signal-averaged electrocardiography are a useful index for identifying patients at risk. The available data recommend prophylactic implantation of an imptantabie cardioverter defibrillator to prevent sudden cardiac death. This review summarizes recent information of the syndrome by reviewing most of new clinical reports and speculates on its risk stratification. A.N.E. 2002;7(3):251,262 [source]
Concomitant-Acquired Long QT and Brugada Syndromes Associated with Indapamide-Induced Hypokalemia and HyponatremiaPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2008
NGAI-SHING MOK M.B.B.S.
Electrolyte disturbances are known to cause acquired Long QT syndrome (LQTS) and Brugada syndrome. While a reduction in INa due to SCN5A mutation is implicated as the underlying mechanism in Brugada syndrome, hyponatremia, which can give rise to a reduced INa, has never been reported in literature as a cause or precipitating factor in this syndrome. We detailed a case in which concomitant-acquired LQTS and Brugada syndrome were associated with severe hypokalemia and hyponatremia following indapamide use for treatment of hypertension and highlighted the potential role of hyponatremia in the pathogenesis of the acquired form of Brugada syndrome. [source]
Non-SCN5A Related Brugada Syndromes: Verification of Normal Splicing and Trafficking of SCN5A Without Exonic MutationsANNALS OF HUMAN GENETICS, Issue 1 2007
Summary Recently, it has been reported that under 20% of Brugada syndrome cases are linked to SCN5A mutations. The purpose of this study was to clarify whether abnormalities other than exonic mutations, such as splicing disorders, decreased mRNA expression levels, or membrane transport abnormalities of SCN5A, play a role in the pathogenesis of Brugada syndrome. We analyzed all SCN5A exons and splice sites using genomic DNA from 23 Brugada syndrome patients. We also analyzed the mRNA obtained from RV cardiomyocytes using real time PCR and sequencing, to study the expression levels and splicing patterns of SCN5A. The localization of SCN5A was examined by immunofluorescence analysis. A de novo heterozygous G to A transversion in a 5, splice junction of the intron between exons 21 and 22 was detected in 1 patient. In the mRNA analysis of Brugada syndrome patients without a mutation of SCN5A no splicing abnormalities were detected, and the SCN5A mRNA levels were similar to those of normal controls. Immunofluorescence analyses revealed that SCN5A is located on the surface membrane not only in the RV cardiomyocytes of normal controls but also in those with Brugada syndrome. We can confirm that some Brugada syndrome patients without exonic mutations in SCN5A had no other SCN5A abnormalities, including any involving the location of the SCN5A protein. These results suggest the involvement of other proteins in the pathogenesis in Brugada syndrome. [source]
Regional variations in action potential alternans in isolated murine Scn5a+/, hearts during dynamic pacingACTA PHYSIOLOGICA, Issue 2 2010
G. D. K. Matthews
Abstract Aim:, Clinical observations suggest that alternans in action potential (AP) characteristics presages breakdown of normal ordered cardiac electrical activity culminating in ventricular arrhythmogenesis. We compared such temporal nonuniformities in monophasic action potential (MAP) waveforms in left (LV) and right ventricular (RV) epicardia and endocardia of Langendorff-perfused murine wild-type (WT), and Scn5a+/, hearts modelling Brugada syndrome (BrS) for the first time. Methods:, A dynamic pacing protocol imposed successively incremented steady pacing rates between 5.5 and 33 Hz. A signal analysis algorithm detected sequences of >10 beats showing alternans. Results were compared before and following the introduction of flecainide (10 ,m) and quinidine (5 ,m) known to exert pro- and anti-arrhythmic effects in BrS. Results:, Sustained and transient amplitude and duration alternans were both frequently followed by ventricular ectopic beats and ventricular tachycardia or fibrillation. Diastolic intervals (DIs) that coincided with onsets of transient (tr) or sustained (ss) alternans in MAP duration (DI*) and amplitude (DI,) were determined. Kruskal,Wallis tests followed by Bonferroni-corrected Mann,Whitney U -tests were applied to these DI results sorted by recording site, pharmacological conditions or experimental populations. WT hearts showed no significant heterogeneities in any DI. Untreated Scn5a+/, hearts showed earlier onsets of transient but not sustained duration alternans in LV endocardium compared with RV endocardium or LV epicardium. Flecainide administration caused earlier onsets of both transient and sustained duration alternans selectively in the RV epicardium in the Scn5a+/, hearts. Conclusion:, These findings in a genetic model thus implicate RV epicardial changes in the arrhythmogenicity produced by flecainide challenge in previously asymptomatic clinical BrS. [source]
Differences in sino-atrial and atrio-ventricular function with age and sex attributable to the Scn5a+/, mutation in a murine cardiac modelACTA PHYSIOLOGICA, Issue 1 2010
Abstract Aim:, To investigate the interacting effects of age and sex on electrocardiographic (ECG) features of Scn5a+/, mice modelling Brugada syndrome. Methods:, Recordings were performed on anaesthetized wild-type (WT) and Scn5a+/, mice and differences attributable to these risk factors statistically stratified. Results:,Scn5a+/, exerted sex-dependent effects upon sino-atrial function that only became apparent with age. RR intervals were greater in old male than in old female Scn5a+/,. Atrio-ventricular (AV) conduction was slower in young female mice, whether WT and Scn5a+/,, than the corresponding young male WT and Scn5a+/,. However, PR intervals lengthened with age in male but not in female Scn5a+/, giving the greatest PR intervals in old male Scn5a+/, compared with either old male WT or young male Scn5a+/, mice. In contrast, PR intervals were similar in old female Scn5a+/, and in old female WT. QTc was prolonged in Scn5a+/, compared with WT, and female Scn5a+/, compared with female WT. Age-dependent alterations in durations of ventricular repolarization relative to WT affected male but not female Scn5a+/,. Thus, T-wave durations were greater in old male Scn5a+/, compared with old male WT, but indistinguishable between old female Scn5a+/, and old female WT. Finally, analysis for combined interactions of genotype, age and sex demonstrated no effects on P wave and QRS durations and QTc intervals. Conclusion:, We demonstrate for the first time that age, sex and genotype exert both independent and interacting ECG effects. The latter suggest alterations in cardiac pacemaker function, atrio-ventricular conduction and ventricular repolarization greatest in ageing male Scn5a+/,. [source]