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Josep Brugada - One of the best experts on this subject based on the ideXlab platform.
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present status of Brugada Syndrome jacc state of the art review
Journal of the American College of Cardiology, 2018Co-Authors: Josep Brugada, Oscar Campuzano, Elena Arbelo, Georgia Sarquellabrugada, Ramon BrugadaAbstract:AbstractThe Brugada Syndrome is an inherited disorder associated with risk of ventricular fibrillation and sudden cardiac death in a structurally normal heart. Diagnosis is based on a characteristi...
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Brugada Syndrome: clinical and genetic findings
Genetics in Medicine, 2016Co-Authors: Georgia Sarquella-brugada, Oscar Campuzano, Josep Brugada, Elena Arbelo, Ramon BrugadaAbstract:Brugada Syndrome is a rare, inherited cardiac disease leading to ventricular fibrillation and sudden cardiac death in structurally normal hearts. Clinical diagnosis requires a Brugada type I electrocardiographic pattern in combination with other clinical features. The most effective approach to unmasking this diagnostic pattern is the use of ajmaline and flecainide tests, and the most effective intervention to reducing the risk of death is the implantation of a cardioverter defibrillator. To date, 18 genes have been associated with the disease, with the voltage-gated sodium channel α type V gene ( SCN5A ) being the most common one to date. However, only 30–35% of diagnosed cases are attributable to pathogenic variants in known genes, emphasizing the need for further genetic studies. Despite recent advances in clinical diagnoses and genetic testing, risk stratification and clinical management of patients with Brugada Syndrome remain challenging. Genet Med 18 1, 3–12.
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Brugada Syndrome 2012
Circulation, 2012Co-Authors: Paola Berne, Josep BrugadaAbstract:Brugada Syndrome (BS) is a cardiac disorder characterized by typical ECG alterations, and it is associated with a high risk for sudden cardiac death (SCD), affecting young subjects with structurally normal hearts. The prevalence of this disorder is still uncertain, presenting marked geographical differences. The Syndrome has a genetic basis, and several mutations have been identified in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as in genes involved in the trafficking or regulation of these channels. Most BS patients are asymptomatic, but those who develop symptoms present with syncope and/or SCD secondary to polymorphic ventricular tachycardia and/or ventricular fibrillation. Risk stratification is still challenging, especially in cases of asymptomatic BS patients. This is a brief review of recent advances in our understanding of the genetic and molecular bases of BS, arrhythmogenic mechanisms and clinical course, as well as an update of the tools for risk stratification and treatment of the condition.
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drugs and Brugada Syndrome patients review of the literature recommendations and an up to date website www Brugadadrugs org
Heart Rhythm, 2009Co-Authors: Pieter G Postema, Vincent Probst, Martin Borggrefe, Silvia G Priori, Hanno L Tan, Christian Wolpert, Ahmad S Amin, Dan M Roden, Masayasu Hiraoka, Josep BrugadaAbstract:Background Worldwide, the Brugada Syndrome has been recognized as an important cause of sudden cardiac death in individuals at a relatively young age. Importantly, many drugs have been reported to induce the characteristic Brugada Syndrome-linked ECG abnormalities and/or (fatal) ventricular tachyarrhythmias. Objective The purpose of this study was to review the literature on the use of drugs in Brugada Syndrome patients, to make recommendations based on the literature and on expert opinion regarding drug safety, and to ensure worldwide online and up-to-date availability of this information to all physicians who treat Brugada Syndrome patients. Methods We performed an extensive review of the literature, formed an international expert panel to produce a consensus recommendation to each drug, and initiated a website (www.Brugadadrugs.org). Results The literature search yielded 506 reports for consideration. Drugs were categorized into one of four categories: (1) drugs to be avoided (n = 18); (2) drugs preferably avoided (n = 23); (3) antiarrhythmic drugs (n = 4); and (4) diagnostic drugs (n = 4). Level of evidence for most associations was C (only consensus opinion of experts, case studies, or standard-of-care) as there are no randomized studies and few nonrandomized studies in Brugada Syndrome patients. Conclusion Many drugs have been associated with adverse events in Brugada Syndrome patients. We have initiated a website (www.Brugadadrugs.org) to ensure worldwide availability of information on safe drug use in Brugada Syndrome patients.
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electrical storm in Brugada Syndrome successfully treated using isoprenaline
Europace, 2004Co-Authors: Philippe Maury, Serge Boveda, Philippe Couderc, Michael Delay, Josep BrugadaAbstract:A case of an electrical storm occurring in a patient implanted with a cardioverter-defibrillator for Brugada Syndrome is reported. Recurrent ventricular fibrillation was initiated by short-coupled isolated monomorphic ventricular premature beats probably originating from the right ventricular outflow tract, associated with a manifest electrocardiographic pattern of Brugada Syndrome. Infusion of atropine accelerated the heart rate but did not prevent ventricular fibrillation, however, low doses of isoprenaline quickly obviated any recurrence of ventricular fibrillation. This was associated with the disappearance of the short-coupled premature beats together with a normalization of the electrocardiographic pattern. Possible mechanisms are discussed according to the accepted pathophysiological hypothesis.
Vincent Probst - One of the best experts on this subject based on the ideXlab platform.
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Brugada Syndrome: Diagnosis, risk stratification and management
Archives of cardiovascular diseases, 2017Co-Authors: Jean-baptiste Gourraud, Julien Barc, Aurélie Thollet, Hervé Le Marec, Vincent ProbstAbstract:Brugada Syndrome is a rare inherited arrhythmia Syndrome leading to an increased risk of sudden cardiac death, despite a structurally normal heart. Diagnosis is based on a specific electrocardiogram pattern, observed either spontaneously or during a sodium channel blocker test. Among affected patients, risk stratification remains a challenge, despite recent insights from large population cohorts. As implantable cardiac defibrillators - the main therapy in Brugada Syndrome - are associated with a high rate of complications in this population, the main challenge is risk stratification of patients with Brugada Syndrome. Aside from the two main predictors of arrhythmia (symptoms and spontaneous electrocardiogram pattern), many risk factors have been recently suggested for stratifying risk of sudden cardiac death in Brugada Syndrome. We have reviewed these data and discuss current guidelines in light of recent progress in this complex field.
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programmed ventricular stimulation for risk stratification in the Brugada Syndrome a pooled analysis
Circulation, 2016Co-Authors: Jakub Sroubek, Vincent Probst, Andrea Mazzanti, Pietro Delise, Jesus Castro Hevia, Kimie Ohkubo, Alessandro Zorzi, Jean Champagne, Anna Kostopoulou, Xiaoyan YinAbstract:Background—The role of programmed ventricular stimulation in identifying patients with Brugada Syndrome at the highest risk for sudden death is uncertain. Methods and Results—We performed a systema...
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programmed ventricular stimulation for risk stratification in the Brugada Syndrome
Circulation, 2016Co-Authors: Jakub Sroubek, Vincent Probst, Andrea Mazzanti, Pietro Delise, Jesus Castro Hevia, Kimie Ohkubo, Alessandro Zorzi, Jean Champagne, Anna Kostopoulou, Carlo NapolitanoAbstract:Background—The role of programmed ventricular stimulation in identifying patients with Brugada Syndrome at the highest risk for sudden death is uncertain. Methods and Results—We performed a systema...
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outcome after implantation of a cardioverter defibrillator in patients with Brugada Syndrome
Circulation, 2013Co-Authors: Frederic Sacher, Vincent Probst, Philippe Maury, Jacques Mansourati, Dominique Babuty, Yuki Komatsu, Christelle Marquie, Antonio Rosa, Abou Diallo, Romain CassagneauAbstract:Background—Implantable cardioverter-defibrillator indications in Brugada Syndrome remain controversial, especially in asymptomatic patients. Previous outcome data are limited by relatively small nu...
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drugs and Brugada Syndrome patients review of the literature recommendations and an up to date website www Brugadadrugs org
Heart Rhythm, 2009Co-Authors: Pieter G Postema, Vincent Probst, Martin Borggrefe, Silvia G Priori, Hanno L Tan, Christian Wolpert, Ahmad S Amin, Dan M Roden, Masayasu Hiraoka, Josep BrugadaAbstract:Background Worldwide, the Brugada Syndrome has been recognized as an important cause of sudden cardiac death in individuals at a relatively young age. Importantly, many drugs have been reported to induce the characteristic Brugada Syndrome-linked ECG abnormalities and/or (fatal) ventricular tachyarrhythmias. Objective The purpose of this study was to review the literature on the use of drugs in Brugada Syndrome patients, to make recommendations based on the literature and on expert opinion regarding drug safety, and to ensure worldwide online and up-to-date availability of this information to all physicians who treat Brugada Syndrome patients. Methods We performed an extensive review of the literature, formed an international expert panel to produce a consensus recommendation to each drug, and initiated a website (www.Brugadadrugs.org). Results The literature search yielded 506 reports for consideration. Drugs were categorized into one of four categories: (1) drugs to be avoided (n = 18); (2) drugs preferably avoided (n = 23); (3) antiarrhythmic drugs (n = 4); and (4) diagnostic drugs (n = 4). Level of evidence for most associations was C (only consensus opinion of experts, case studies, or standard-of-care) as there are no randomized studies and few nonrandomized studies in Brugada Syndrome patients. Conclusion Many drugs have been associated with adverse events in Brugada Syndrome patients. We have initiated a website (www.Brugadadrugs.org) to ensure worldwide availability of information on safe drug use in Brugada Syndrome patients.
Charles Antzelevitch - One of the best experts on this subject based on the ideXlab platform.
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cellular mechanisms underlying the effects of milrinone and cilostazol to suppress arrhythmogenesis associated with Brugada Syndrome
Heart Rhythm, 2013Co-Authors: Tamas Szel, Istvan Koncz, Charles AntzelevitchAbstract:Background Brugada Syndrome is an inherited disease associated with vulnerability to ventricular tachycardia and sudden cardiac death in young adults. Milrinone and cilostazol, oral phosphodiesterase (PDE) type III inhibitors, have been shown to increase L-type calcium channel current (ICa) and modestly increase heart rate by elevating the level of intracellular cyclic adenosine monophosphate. Objective To examine the effectiveness of these PDE inhibitors to suppress arrhythmogenesis in an experimental model of Brugada Syndrome. Methods Action potential (AP) and electrocardiographic recordings were obtained from epicardial and endocardial sites of coronary-perfused canine right ventricular wedge preparations. The Ito agonist NS5806 (5 μM) and Ca2+ channel blocker verapamil (2 μM) were used to pharmacologically mimic Brugada phenotype. Results The combination induced all-or-none repolarization at some epicardial sites but not others, leading to ST-segment elevation as well as an increase in both epicardial and transmural dispersion of repolarization. Under these conditions, phase 2 reentry developed as the epicardial AP dome propagated from sites where it was maintained to sites at which it was lost, generating closely coupled extrasystoles and ventricular tachycardia. The addition of the PDE inhibitor milrinone (2.5 μM) or cilostazol (5–10 μM) to the coronary perfusate restored the epicardial AP dome, reduced dispersion, and abolished phase 2 reentry-induced extrasystoles and ventricular tachycardia. Conclusions Our study identifies milrinone as a more potent alternative to cilostazol for reversing the repolarization defects responsible for the electrocardiographic and arrhythmic manifestations of Brugada Syndrome. Both drugs normalize ST-segment elevation and suppress arrhythmogenesis in experimental models of Brugada Syndrome.
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the pathophysiological mechanism underlying Brugada Syndrome depolarization versus repolarization
Journal of Molecular and Cellular Cardiology, 2010Co-Authors: Arthur A.m. Wilde, Jeffrey M Fish, Jose M Di Diego, Sami Viskin, Pieter G Postema, Hiroshi Morita, Charles AntzelevitchAbstract:This Point/Counterpoint presents a scholarly debate of the mechanisms underlying the electrocardiographic and arrhythmic manifestations of Brugada Syndrome (BrS), exploring in detail the available evidence in support of the repolarization vs. depolarization hypothesis.
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empiric quinidine therapy for asymptomatic Brugada Syndrome time for a prospective registry
Heart Rhythm, 2009Co-Authors: Sami Viskin, Arthur A.m. Wilde, Charles Antzelevitch, Wataru Shimizu, Hanno L Tan, Bernard BelhassenAbstract:Our present therapeutic approach to asymptomatic Brugada Syndrome is probably causing more harm than good.1 All over the world, patients with asymptomatic Brugada Syndrome are undergoing electrophysiologic studies (EPS)2,3; depending on the aggressiveness of the EPS protocol, 20% to 80% of such patients will have inducible ventricular fibrillation (VF),2-6 and many will undergo implantation of an implantable cardioverter defibrillator (ICD).2-6 However, the rate of spontaneous VF among patients undergoing prophylactic ICD implantation for “asymptomatic Brugada Syndrome with inducible VF” seems to be only 1% per year according to a multicenter European study.7 Accordingly, ICD implantation might be unnecessary for the vast majority of patients. On the other hand, 28%7 to 32%6 of these young individuals develop very serious complications directly related to ICD implantation. Thus, the wisdom of guiding our therapeutic approach by the results of EPS has been questioned.8 Perhaps it is time to apply our experience with the long QT Syndrome (LQTS) to the Brugada Syndrome. As in Brugada Syndrome, cardiac arrest may be the presenting symptom in LQTS. Based on nonrandomized studies showing that beta-blockers dramatically reduce the arrhythmic risk, empiric drug therapy with beta-blockers has been the first line of therapy for the LQTS for more than 30 years.9 All asymptomatic LQTS patients nowadays receive beta-blocker therapy, and prophylactic ICD implantation is reserved for some of the patients with high-risk characteristics such as “genotype other than LQT1 and QTc >500 msec.”10 Of note, collecting data about the value and limitations of empiric beta-blocker therapy10-14 was possible only because the LQTS was described—and had to be treated—before the ICD became widely available.15 Numerous patients with LQTS have safely received empiric beta-blocker therapy for many years; yet, it is reasonable to assume that many of them would have undergone unnecessary ICD implantation had the LQTS been first described in the ICD era. With all the abovementioned concepts in mind, we will attempt to explain why empiric drug therapy with quinidine may be better than EPS-guided ICD implantation for the primary prevention of arrhythmic death in asymptomatic patients with Brugada Syndrome.
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Brugada Syndrome 1992 2002 a historical perspective
Journal of the American College of Cardiology, 2003Co-Authors: Charles Antzelevitch, Ramon Brugada, Josep Brugada, Pedro Brugada, Jeffreya Towbin, Kolawanee NademaneeAbstract:An intriguing new clinical entity characterized by ST-segment elevation in the right precordial electrocardiographic leads and a high incidence of sudden death in individuals with structurally normal hearts was described by Pedro and Josep Brugada in 1992. The past decade has witnessed an exponential rise in the number of reported cases and a dramatic proliferation of papers serving to define the clinical, genetic, cellular, ionic, and molecular aspects of this disease. The purpose of this brief review is to chronicle the historical highlights that have brought us to our present understanding of Brugada Syndrome.
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Brugada Syndrome a decade of progress
Circulation Research, 2002Co-Authors: Charles Antzelevitch, Ramon Brugada, Josep Brugada, Pedro Brugada, Wataru Shimizu, Ihor Gussak, A Perez R RieraAbstract:The Brugada Syndrome has gained wide recognition throughout the world and today is believed to be responsible for 4% to 12% of all sudden deaths and approximately 20% of deaths in patients with structurally normal hearts. The incidence of the disease is on the order of 5 per 10 000 inhabitants and, apart from accidents, is the leading cause of death of men under the age of 50 in regions of the world where the inherited Syndrome is endemic. This minireview briefly summarizes the progress made over the past decade in our understanding of the clinical, genetic, cellular, ionic, and molecular aspects of this disease.
Pedro Brugada - One of the best experts on this subject based on the ideXlab platform.
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SCN4A variants and Brugada Syndrome: phenotypic and genotypic overlap between cardiac and skeletal muscle sodium channelopathies
European Journal of Human Genetics, 2016Co-Authors: Véronique Bissay, Sophie Ch Van Malderen, Uschi Peeters, Dorien Daneels, Gudrun Pappaert, Kathelijn Keymolen, Anna C Jansen, Pedro Brugada, Willy Lissens, Jacques De KeyserAbstract:SCN5A mutations involving the α -subunit of the cardiac voltage-gated muscle sodium channel (NaV1.5) result in different cardiac channelopathies with an autosomal-dominant inheritance such as Brugada Syndrome. On the other hand, mutations in SCN4A encoding the α -subunit of the skeletal voltage-gated sodium channel (NaV1.4) cause non-dystrophic myotonia and/or periodic paralysis. In this study, we investigated whether cardiac arrhythmias or channelopathies such as Brugada Syndrome can be part of the clinical phenotype associated with SCN4A variants and whether patients with Brugada Syndrome present with non-dystrophic myotonia or periodic paralysis and related gene mutations. We therefore screened seven families with different SCN4A variants and non-dystrophic myotonia phenotypes for Brugada Syndrome and performed a neurological, neurophysiological and genetic work-up in 107 Brugada families. In the families with an SCN4A -associated non-dystrophic myotonia, three patients had a clinical diagnosis of Brugada Syndrome, whereas we found a remarkably high prevalence of myotonic features involving different genes in the families with Brugada Syndrome. One Brugada family carried an SCN4A variant that is predicted to probably affect function, one family suffered from a not genetically confirmed non-dystrophic myotonia, one family was diagnosed with myotonic dystrophy ( DMPK gene) and one family had a Thomsen disease myotonia congenita ( CLCN1 variant that affects function). Our findings and data suggest a possible involvement of SCN4A variants in the pathophysiological mechanism underlying the development of a spontaneous or drug-induced type 1 electrocardiographic pattern and the occurrence of malignant arrhythmias in some patients with Brugada Syndrome.
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unusual unmasking of Brugada Syndrome electrocardiographic pattern during ajmaline test by leaning forward a case report
European Heart Journal, 2010Co-Authors: Antonio Sorgente, Andrea Sarkozy, Stephan Henkens, Gianbattista Chierchia, Carlo De Asmundis, Yoshinao Yazaki, Lucio Capulzini, Stephanandreas Mullerburri, Pedro BrugadaAbstract:A 71-year-old male consulted us because of recurrent episodes of irregular paroxysmal palpitations associated with chest pain. The patient had a family history of Brugada Syndrome (the mother died suddenly at the age of 40 years and a daughter was diagnosed as a carrier of Brugada Syndrome). The cardiac evaluation revealed a structurally normal heart. A coronary angiography excluded the presence of coronary artery abnormalities. Atrial fibrillation was already diagnosed 12 years before the present consultation. He had two successful external electrical cardioversions and sinus rhythm was maintained until our consultation with the administration of sotalol, at a dosage of 240 …
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gender differences in clinical manifestations of Brugada Syndrome
Journal of the American College of Cardiology, 2008Co-Authors: Begona Benito, Ramon Brugada, Lluis Mont, Andrea Sarkozy, Stephan Henkens, Antonio Berruezo, David Tamborero, Dabit Arzamendi, Paola Berne, Pedro BrugadaAbstract:Objectives We sought to assess differences in phenotype and prognosis between men and women in a large population of patients with Brugada Syndrome. Background A male predominance has been reported in the Brugada Syndrome. No specific data are available, however, concerning gender differences in the clinical manifestations and their role in prognosis. Methods Patients with Brugada Syndrome were prospectively included in the study. Data on baseline characteristics, electrocardiogram parameters before and after pharmacological test, and events in follow-up were recorded for all patients. Results Among 384 patients, 272 (70.8%) were men and 112 (29.2%) women. At inclusion, men had experienced syncope more frequently (18%) or aborted sudden cardiac death (6%) than women (14% and 1%, respectively, p = 0.04). Men also had greater rates of spontaneous type-1 electrocardiogram, greater ST-segment elevation, and greater inducibility of ventricular fibrillation (p Conclusions Men with Brugada Syndrome present with a greater risk clinical profile than women and have a worse prognosis. Although classical risk factors identify male patients with worse outcome, conduction disturbances could be a marker of risk in the female population.
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Brugada Syndrome 1992 2002 a historical perspective
Journal of the American College of Cardiology, 2003Co-Authors: Charles Antzelevitch, Ramon Brugada, Josep Brugada, Pedro Brugada, Jeffreya Towbin, Kolawanee NademaneeAbstract:An intriguing new clinical entity characterized by ST-segment elevation in the right precordial electrocardiographic leads and a high incidence of sudden death in individuals with structurally normal hearts was described by Pedro and Josep Brugada in 1992. The past decade has witnessed an exponential rise in the number of reported cases and a dramatic proliferation of papers serving to define the clinical, genetic, cellular, ionic, and molecular aspects of this disease. The purpose of this brief review is to chronicle the historical highlights that have brought us to our present understanding of Brugada Syndrome.
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natural history of Brugada Syndrome the prognostic value of programmed electrical stimulation of the heart
Journal of Cardiovascular Electrophysiology, 2003Co-Authors: Pedro Brugada, M Ramon D Brugada, Lluis Mont, M Maximo D Rivero, Peter Geelen, Josep BrugadaAbstract:Introduction: The prognostic value of electrophysiologic studies in individuals with the Syndrome of right bundle branch block and ST segment elevation in precordial leads V1 to V3 (Brugada Syndrome) remains controversial. Our previous data from 252 individuals with the Syndrome suggested that programmed ventricular stimulation had a good overall accuracy to predict events. However, studies from independent investigators questioned our results. We report here the largest population with Brugada Syndrome ever studied by programmed electrical stimulation of the heart. Methods and Results: Four hundred forty-three individuals with an ECG diagnostic of Brugada Syndrome were studied by programmed electrical stimulation of the heart. The diagnosis was made because of the classic ECG showing a coved-type ST segment elevation in precordial leads V1 to V3. Of the 443 individuals, 180 had developed spontaneous symptoms (syncope or aborted sudden cardiac death) and 263 were asymptomatic at the time the diagnosis was made. The ventricular stimulation protocol included a minimum of two basic pacing cycle lengths with two ventricular premature beats from the right ventricular apex. A sustained ventricular arrhythmia was induced in 217 cases (49%). Symptomatic patients were more frequently inducible [126/180 (70%)] than asymptomatic individuals [91/263 (34%);P = 0.0001 ]. Males were more frequently inducible than females (54% vs 32%,P < 0.0001). Inducible individuals had a longer HV interval than noninducible patients (50 ± 12 msecvs46 ± 10 msec, P < 0.002). HV interval and number of premature beats needed to induce VF were not related to outcome. Inducibility was statistically a powerful predictor of arrhythmic events during follow-up. Sixty of 217 inducible patients (28%) had spontaneous ventricular fibrillation compared with 5 of 221 noninducible patients(2%; P = 0.0001). Conclusion: Inducibility of sustained ventricular arrhythmias during programmed ventricular stimulation of the heart is a good predictor of outcome in Brugada Syndrome.(J Cardiovasc Electrophysiol, Vol. 14, pp. 455-457, May 2003)
Arthur A.m. Wilde - One of the best experts on this subject based on the ideXlab platform.
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the pathophysiological mechanism underlying Brugada Syndrome depolarization versus repolarization
Journal of Molecular and Cellular Cardiology, 2010Co-Authors: Arthur A.m. Wilde, Jeffrey M Fish, Jose M Di Diego, Sami Viskin, Pieter G Postema, Hiroshi Morita, Charles AntzelevitchAbstract:This Point/Counterpoint presents a scholarly debate of the mechanisms underlying the electrocardiographic and arrhythmic manifestations of Brugada Syndrome (BrS), exploring in detail the available evidence in support of the repolarization vs. depolarization hypothesis.
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the Brugada ecg pattern a marker of channelopathy structural heart disease or neither toward a unifying mechanism of the Brugada Syndrome
Circulation-arrhythmia and Electrophysiology, 2010Co-Authors: Mark G Hoogendijk, Pieter G Postema, Arthur A.m. Wilde, Tobias Opthof, Jacques M T De Bakker, Ruben CoronelAbstract:In 1992, Brugada and Brugada introduced a new clinical entity characterized by right precordial ST-segment elevation followed by a negative T-wave and a high incidence of ventricular fibrillation (VF) in the absence of structural heart disease.1 The typical ECG anomaly is currently known as the Brugada ECG pattern and the conglomerate of features as the Brugada Syndrome. Over the years, the Brugada Syndrome has been recognized as an important cause of sudden cardiac death in young men, especially in Southeast Asia,2 and has attracted much attention from researchers and clinicians alike. This has led to substantial progress in identification of modulating factors of the Brugada ECG pattern, the associated ventricular arrhythmias, and in the risk stratification of patients.3 However, the development of effective therapeutic strategies has lagged behind. Currently, symptomatic treatment with implantable cardioverter-defibrillators (ICDs) is the mainstay in the prevention of sudden cardiac death,3 although it is costly and associated with a high risk of complications.4 The pathophysiological mechanism of the Brugada Syndrome remains elusive,5 and no single causal factor appears to link all patients. The Brugada ECG pattern is modulated by genetic mutations and pharmacological agents that alter the function of ion channels active during the early phases of the action potential. Furthermore, signs of right ventricular structural abnormalities are often found in patients with Brugada Syndrome. The aim of this study is to review the available literature on the Brugada Syndrome in an attempt to provide a unifying hypothesis of the mechanism of the Brugada Syndrome. This unifying hypothesis should be able to explain the ECG pattern, the arrhythmogenic mechanism, their modulation by ion channels, and the relation of structural abnormalities to the Brugada Syndrome. ### Is the Brugada Syndrome a Channelopathy? The Brugada Syndrome was introduced shortly after the first demonstration of statistical linkage between the long-QT …
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empiric quinidine therapy for asymptomatic Brugada Syndrome time for a prospective registry
Heart Rhythm, 2009Co-Authors: Sami Viskin, Arthur A.m. Wilde, Charles Antzelevitch, Wataru Shimizu, Hanno L Tan, Bernard BelhassenAbstract:Our present therapeutic approach to asymptomatic Brugada Syndrome is probably causing more harm than good.1 All over the world, patients with asymptomatic Brugada Syndrome are undergoing electrophysiologic studies (EPS)2,3; depending on the aggressiveness of the EPS protocol, 20% to 80% of such patients will have inducible ventricular fibrillation (VF),2-6 and many will undergo implantation of an implantable cardioverter defibrillator (ICD).2-6 However, the rate of spontaneous VF among patients undergoing prophylactic ICD implantation for “asymptomatic Brugada Syndrome with inducible VF” seems to be only 1% per year according to a multicenter European study.7 Accordingly, ICD implantation might be unnecessary for the vast majority of patients. On the other hand, 28%7 to 32%6 of these young individuals develop very serious complications directly related to ICD implantation. Thus, the wisdom of guiding our therapeutic approach by the results of EPS has been questioned.8 Perhaps it is time to apply our experience with the long QT Syndrome (LQTS) to the Brugada Syndrome. As in Brugada Syndrome, cardiac arrest may be the presenting symptom in LQTS. Based on nonrandomized studies showing that beta-blockers dramatically reduce the arrhythmic risk, empiric drug therapy with beta-blockers has been the first line of therapy for the LQTS for more than 30 years.9 All asymptomatic LQTS patients nowadays receive beta-blocker therapy, and prophylactic ICD implantation is reserved for some of the patients with high-risk characteristics such as “genotype other than LQT1 and QTc >500 msec.”10 Of note, collecting data about the value and limitations of empiric beta-blocker therapy10-14 was possible only because the LQTS was described—and had to be treated—before the ICD became widely available.15 Numerous patients with LQTS have safely received empiric beta-blocker therapy for many years; yet, it is reasonable to assume that many of them would have undergone unnecessary ICD implantation had the LQTS been first described in the ICD era. With all the abovementioned concepts in mind, we will attempt to explain why empiric drug therapy with quinidine may be better than EPS-guided ICD implantation for the primary prevention of arrhythmic death in asymptomatic patients with Brugada Syndrome.
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pathophysiological mechanisms of Brugada Syndrome depolarization disorder repolarization disorder or more
Cardiovascular Research, 2005Co-Authors: Paola G Meregalli, Arthur A.m. WildeAbstract:After its recognition as a distinct clinical entity, Brugada Syndrome is increasingly recognized worldwide as an important cause of sudden cardiac death. Brugada Syndrome exhibits autosomal dominant inheritance with SCN5A, which encodes the cardiac sodium channel, as the only gene with a proven involvement in 20–30% of patients. Its signature feature is ST segment elevation in right precordial ECG leads and predisposition to malignant ventricular tachyarrhythmias. The pathophysiological mechanism of ST elevation and ventricular tachyarrhythmia, two phenomena strongly related, is controversial. Here, we review clinical and experimental studies as they provide evidence to support or disprove the two hypotheses on the mechanism of Brugada Syndrome that currently receive the widest support: (1) nonuniform abbreviation of right ventricular epicardial action potentials (“repolarization disorder”), (2) conduction delay in the right ventricular outflow tract (“depolarization disorder”). We also propose a schematic representation of the depolarization disorder hypothesis. Moreover, we review recent evidence to suggest that other derangements may also contribute to the pathophysiology of Brugada Syndrome, in particular, right ventricular structural derangements. In reviewing these studies, we conclude that, similar to most diseases, it is likely that Brugada Syndrome is not fully explained by one single mechanism. Rather than adhering to the notion that Brugada Syndrome is a monofactorial disease, we should aim for clarification of the contribution of various pathophysiological mechanisms in individual Brugada Syndrome patients and tailor therapy considering each of these mechanisms.
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delay in right ventricular activation contributes to Brugada Syndrome
Circulation, 2004Co-Authors: Raymond Tukkie, Arthur A.m. Wilde, Peter Sogaard, Jim Vleugels, Irma K L M De Groot, Hanno L TanAbstract:Background— Although Brugada Syndrome revolves around reduced net depolarizing force, the electrophysiological mechanisms of its defining features (right precordial ST-segment elevation and ventric...
