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Pedro Brugada

Publications and source records attributed to Pedro Brugada.

At least 37 records · Page 2Linked to original sources
PubMed2005

Brugada syndrome: report of the second consensus conference.

Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation. The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, alpha-adrenergic agonists, beta-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity. In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred. The report of the first consensus conference, published in 2002, focused on diagnostic criteria. The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.

Arrhythmogenic Right Ventricular Dysplasia↗
PubMed2005

Electrocardiographic imaging (ECGI), a novel diagnostic modality used for mapping of focal left ventricular tachycardia in a young athlete.

We report the first clinical application of electrocardiographic imaging (ECGI), a new, noninvasive imaging modality for arrhythmias, in an athlete with focal ventricular tachycardia (VT) originating from a left ventricular (LV) diverticulum. A reconstructed map of the epicardial activation sequence during a single premature ventricular complex (PVC) of an identical QRS morphology to the clinical VT, generated from 224-electrode body surface ECGs and a chest CT (ECGI), localized the PVC to the site of the diverticulum. This correlated with subsequent maps obtained using standard techniques. We describe the first case that used ECGI to guide diagnosis and therapy of a clinical tachyarrhythmia.

Adult↗
PubMed2005

Sudden cardiac death and inherited arrhythmia syndromes.

Sudden cardiac death (SCD) at youth is rare and is often caused by inherited cardiac disorders. This review focuses on the genetic background of inherited primary electrical diseases, the so-called "channelopathies." Following a short clinical description of each syndrome, the recent findings in the genetics of long QT syndrome, short QT syndrome, isolated cardiac conduction defect, familial sick sinus syndrome, familial atrial fibrillation, cathecholaminergic polymorphic ventricular tachycardia, familial Wolff-Parkinson-White (WPW) syndrome, and Brugada syndrome are discussed. The currently proposed theoretical model of overlapping phenotypes in SCN5A sodium channel mutations is presented. The recent data indicate that advances in molecular genetics, experimental and clinical electrophysiology shed some light on the genetic background of primary electrical diseases. However, it is also becoming clear that the process from a mutation of a gene to the clinical presentation of a patient is currently only partially understood and extremely complex.

Arrhythmias, Cardiac↗
PubMed2005

Sudden cardiac death: what is inside our genes?

Although sudden cardiac death in youths is generally rare, it is estimated that 10% to 20% of these deaths occur in previously healthy infants, children, adolescents and young adults without any findings on autopsy and with devastating consequences on the family. The majority of these deaths are caused by inherited arrhythmia syndromes, the so-called 'channelopathies'. In the present paper, the recent advances in the clinical and genetic background of long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome and the overlapping phenotypes are reviewed, and the recently established connections between these syndromes and idiopathic ventricular fibrillation and sudden infant death syndrome are discussed.

Bundle-Branch Block↗
PubMed2004

Cryptic 5' splice site activation in SCN5A associated with Brugada syndrome.

The Brugada syndrome (BS) is characterized by ST segment elevation in the right precordial leads and sudden cardiac death. The disease is linked to mutations in SCN5A in approximately 20% of cases. We collected a large family with BS and have identified a novel intronic mutation. We performed the clinical, genetic, molecular and biophysical characterization of this disease-causing mutation. With direct sequencing we identified an intronic insertion of TGGG 5 bp from the end of the Exon 27 of SCN5A. For transcript analysis, we investigated Epstein-Barr-transformed lymphoblastoid cell lines from patients and controls. Total RNA was extracted and RT-PCR experiments were performed to analyze the splicing patterns in exon 27 and 28. We identified two bands, one of the expected size and the other which showed a 96 bp deletion in exon 27, leading to a 32 amino acid in-frame deletion involving segments 2 and 3 of Domain IV of the SCN5A protein. This finding indicates that the intronic mutation creates a cryptic splice site inside Exon 27. Biophysical analysis using whole-cell patch-clamp techniques showed a complete loss of function of the mutated channels when heterologously expressed. In summary, this is the first report of a dysfunctional sodium channel created by an intronic mutation giving rise to cryptic splice site activation in SCN5A in a family with the BS. The deletion of fragments of segments 2 and 3 of Domain IV leads to complete loss of function, consistent with the biophysical data found in several mutations causing BS.

Arrhythmias, Cardiac↗
PubMed2004

Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations.

BACKGROUND: The Brugada syndrome is an arrhythmogenic disease caused in part by mutations in the cardiac sodium channel gene, SCN5A. The electrocardiographic pattern characteristic of the syndrome is dynamic and is often absent in affected individuals. Sodium channel blockers are effective in unmasking carriers of the disease. However, the value of the test remains controversial. METHODS AND RESULTS: We studied 147 individuals representing 4 large families with SCN5A mutations. Of these, 104 were determined to be at possible risk for Brugada syndrome and underwent both electrocardiographic and genetic evaluation. Twenty-four individuals displayed an ECG diagnostic of Brugada syndrome at baseline. Of the remaining, 71 received intravenous ajmaline. Of the 35 genetic carriers who received ajmaline, 28 had a positive test and 7 a negative ajmaline test. The sensitivity, specificity, and positive and negative predictive values of the drug challenge were 80% (28:35), 94.4% (34:36), 93.3% (28:30), and 82.9% (34:41), respectively. Penetrance of the disease phenotype increased from 32.7% to 78.6% with the use of sodium channel blockers. In the absence of ST-segment elevation under baseline conditions, a prolonged P-R interval, but not incomplete right bundle-branch block or early repolarization patterns, indicates a high probability of an SCN5A mutation carrier. CONCLUSIONS: In families with Brugada syndrome, the data suggest that ajmaline testing is valuable in the diagnosis of SCN5A carriers. In the absence of ST-segment elevation at baseline, family members with first-degree atrioventricular block should be suspected of carrying the mutation. An ajmaline test is often the key to making the proper diagnosis in these patients.

Ajmaline↗
PubMed2004

Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue Doppler imaging echocardiography.

BACKGROUND: Cardiac resynchronization therapy was shown to reverse left ventricular (LV) remodeling in patients with congestive heart failure (CHF). However, the prediction of benefit is controversial. We aimed to investigate predictive factors of LV functional recovery and reversed remodeling after biventricular pacing. METHODS AND RESULTS: Forty-nine consecutive patients with CHF and a wide QRS complex (182+/-32 ms) were studied by echocardiography before resynchronization. Intraventricular and interventricular asynchrony and their combination were assessed by pulsed-wave tissue Doppler imaging from measurements of regional electromechanical coupling times in basal segments of the right and left ventricle. At 6-month follow-up, responders were defined by a relative increase in LV ejection fraction > or =25% compared with baseline (n=27). Receiver operating curve analysis revealed the degree of intraventricular asynchrony (area under the curve=0.77), interventricular asynchrony (area under the curve=0.69), and their combination (area under the curve=0.84) as the best predictors of functional recovery after resynchronization. In addition, the degree of intraventricular and interventricular asynchrony correlated significantly with the improvement of LV ejection fraction (r=0.73, P<0.0001), end-diastolic diameter (r=-0.59, P<0.0001), and end-systolic diameter (r=-0.48, P<0.001) at follow-up. QRS duration and conventional echo-Doppler indices were not predictive of reversed LV remodeling. CONCLUSIONS: In patients with CHF, the degree of intraventricular and interventricular asynchrony and their combination are the best predictive factors of LV functional recovery and reversed remodeling after cardiac resynchronization therapy.

Aged↗
PubMed2004

Phenotypic characterization of a large European family with Brugada syndrome displaying a sudden unexpected death syndrome mutation in SCN5A:.

INTRODUCTION: Brugada syndrome is characterized by sudden death secondary to malignant arrhythmias and the presence of ST segment elevation in leads V(1) to V(3) of patients with structurally normal hearts. This ECG pattern often is concealed but can be unmasked using potent sodium channel blockers. Like congenital long QT syndrome type 3 (LQT3) and sudden unexpected death syndrome, Brugada syndrome has been linked to mutations in SCN5A. METHODS AND RESULTS: We screened a large European family with Brugada syndrome. Three members (two female) had suffered malignant ventricular arrhythmias. Ten members showed an ECG pattern characteristic of Brugada syndrome at baseline, and eight showed the pattern only after administration of ajmaline (total 12 female). Haplotype analysis revealed that all individuals with positive ECG at baseline shared the SCN5A locus. Sequencing of SCN5A identified a missense mutation, R367H, previously associated with sudden unexpected death syndrome. Two of the eight individuals who displayed a positive ECG after the administration of ajmaline, but not before, did not have the R367H mutation, and sequencing analysis failed to identify any other mutation in SCN5A. The R367H mutation failed to generate any current when heterologously expressed in HEK cells. CONCLUSION: Our results support the hypothesis that (1) sudden unexpected death syndrome and Brugada syndrome are the same disease; (2) male predominance of the phenotype observed in sudden unexpected death syndrome does not apply to this family, suggesting that factors other than the specific mutation determine the gender distinction; and (3) ajmaline may provide false-positive results. These findings have broad implications relative to the diagnosis and risk stratification of family members of patients with the Brugada syndrome.

Adult↗
PubMed2004

Brugada syndrome: 12 years of progression.

Brugada syndrome is increasingly being recognized in clinical medicine. What started as an electrocardiographic curiosity has become an important focus of attention for individuals working in the different disciplines related to sudden cardiac death, from basic scientists to clinical cardiac electrophysiologists. In just 12 years, since the description of the disease, clinically relevant information is continuously being provided to physicians to help protect the individuals with Brugada syndrome to the best of our ability. And this information has been gathered thanks to the effort of hundreds of basic scientists, physicians and patients who continue to give their time, effort and data to help understand how the electrocardiographic pattern may cause sudden cardiac death. There are still many unanswered questions, both at the clinical and basic field. However, with the further collection of data, the longer follow-up and the continued interest from the basic science world we will have the necessary tools to the successful unraveling of the disease.

Arrhythmias, Cardiac↗
PubMed2003

Sudden death associated with short-QT syndrome linked to mutations in HERG.

BACKGROUND: Sudden cardiac death takes the lives of more than 300 000 Americans annually. Malignant ventricular arrhythmias occurring in individuals with structurally normal hearts account for a subgroup of these sudden deaths. The present study describes the genetic basis for a new clinical entity characterized by sudden death and short-QT intervals in the ECG. METHODS AND RESULTS: Three families with hereditary short-QT syndrome and a high incidence of ventricular arrhythmias and sudden cardiac death were studied. In 2 of them, we identified 2 different missense mutations resulting in the same amino acid change (N588K) in the S5-P loop region of the cardiac IKr channel HERG (KCNH2). The mutations dramatically increase IKr, leading to heterogeneous abbreviation of action potential duration and refractoriness, and reduce the affinity of the channels to IKr blockers. CONCLUSIONS: We demonstrate a novel genetic and biophysical mechanism responsible for sudden death in infants, children, and young adults caused by mutations in KCNH2. The occurrence of sudden cardiac death in the first 12 months of life in 2 patients suggests the possibility of a link between KCNH2 gain of function mutations and sudden infant death syndrome. KCNH2 is the binding target for a wide spectrum of cardiac and noncardiac pharmacological compounds. Our findings may provide better understanding of drug interaction with KCNH2 and have implications for diagnosis and therapy of this and other arrhythmogenic diseases.

Adult↗
PubMed2003

Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest.

BACKGROUND: Patients with Brugada syndrome who were resuscitated from an episode of ventricular fibrillation are at high risk for recurrent sudden death. There is general agreement about the therapeutic strategy for these patients. Conversely, the prognosis and approach in patients with a diagnostic ECG but without a previous history of sudden cardiac death is controversial. We analyzed a large cohort of patients with Brugada syndrome without previous cardiac arrest to understand the determinants of prognosis. METHODS AND RESULTS: A total of 547 patients with an ECG diagnostic of Brugada syndrome and no previous cardiac arrest were studied. The mean age was 41+/-15 years, and 408 were male. The diagnostic ECG was present spontaneously in 391 patients. In the remaining 156 individuals, the abnormal ECG was noted only after the administration of an antiarrhythmic drug. One hundred twenty-four patients had suffered from at least 1 episode of syncope. During programmed ventricular stimulation, a sustained ventricular arrhythmia was induced in 163 of 408 patients. During a mean follow-up of 24+/-32 months, 45 patients (8%) suffered sudden death or documented ventricular fibrillation. Multivariate analysis identified the inducibility of a sustained ventricular arrhythmia (P<0.0001) and a history of syncope (P<0.01) as predictors of events. Logistic regression analysis showed that a patient with a spontaneously abnormal ECG, a previous history of syncope, and inducible sustained ventricular arrhythmias had a probability of 27.2% of suffering an event during follow-up. CONCLUSIONS: Individuals with Brugada syndrome and no previous cardiac arrest have a high risk of sudden death. Inducibility of ventricular arrhythmias and a previous history of syncope are markers of a poor prognosis.

Adolescent↗
PubMed2003

Brugada syndrome: 1992-2002: a historical perspective.

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.

Bundle-Branch Block↗