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Biomedical subjects

Josep Brugada

Publications and source records attributed to Josep Brugada.

At least 55 records · Page 3Linked to original sources
PubMed2003

Dronedarone for prevention of atrial fibrillation: a dose-ranging study.

AIMS: Dronedarone, a benzofurane derivative without iodine substituents, shares the electrophysiologic properties of amiodarone. This study was designed to determine the most appropriate dose of dronedarone for prevention of atrial fibrillation (AF) after cardioversion. METHODS AND RESULTS: Patients with persistent AF were randomly allocated to 800, 1200, 1600 mg daily doses of dronedarone or placebo. The main analysis was conducted on 199/270 patients, who entered the maintenance phase following pharmacological cardioversion or, if unsuccessful, DC cardioversion. Within 6-month follow-up, the time to AF relapse increased on dronedarone 800 mg, with a median of 60 days vs 5.3 days in the placebo group (relative risk reduction 55% [95% CI, 28 to 72%] P=0.001). No significant effect was seen at higher doses. Spontaneous conversion to sinus rhythm on dronedarone occurred in 5.8 to 14.8% of patients (P=0.026). There were no proarrhythmic reactions. Drug-induced QT prolongation was only noticed in the 1600 mg group. Premature drug discontinuations affected 22.6% of subjects given 1600 mg dronedarone versus 3.9% on 800 mg and were mainly due to gastrointestinal side effects. No evidence of thyroid, ocular or pulmonary toxicity was found. CONCLUSION: Dronedarone, at a 800 mg daily dose, appears to be effective and safe for the prevention of AF relapses after cardioversion. The absence of thyroid side effects and of proarrhythmia are important features of the drug. Further studies are needed to better delineate the antiarrhythmic profile of the drug.

Aged↗
PubMed2003

[Radiofrequency ablation in the treatment of focal atrial fibrillation using circumferential mapping and segmentary disconnection of pulmonary veins].

INTRODUCTION: The treatment of paroxysmal atrial fibrillation in patients without structural heart disease using radiofrequency ablation of pulmonary veins is a recently developed procedure with a good clinical success rate, although there have only been a few published series. We analyzed our results with this technique. METHOD: The procedure was performed in 33 highly symptomatic patients with focal atrial fibrillation that had probably originated in the pulmonary veins. The electrophysiological study was carried out with a decapolar catheter inserted by transeptal catheterization. Ablation was performed using a 4-mm catheter and directed to the segments of the ostium of pulmonary veins where venous potentials with greatest precocity were recorded. Subsequent radiofrecuency applications were performed until pulmonary vein disconnection was achieved. RESULTS: Venous electrical activity was recorded in 59 of 115 pulmonary veins that were mapped (58 were disconnected). During a median follow-up of 180 days, 8 patients recurred and only 2 of these continue with repeat episodes. The success rate at short term was 74.2% and at mid-term was 93.5%. Nineteen patients continue to receive antiarrhythmic treatment innefective before the procedure. Two patients showed complications related to catheter manipulation during tansseptal catheterization, probably due to air embolism, that was resolved spontaneously without consequences. No patient showed pulmonary stenosis. CONCLUSIONS: Teatment of focal atrial fibrillation using circumferential mapping and radiofrecuency application in segments of the ostium of pulmonary veins is a highly effective procedure in selected patients and has potentially severe although infrequent complications.

Atrial Fibrillation↗
PubMed2003

Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart.

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 msec vs 46 +/- 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.

Adolescent↗
PubMed2003

Reversibility of cardiac abnormalities in adolescents with anorexia nervosa after weight recovery.

OBJECTIVE: Anorexia nervosa is a life-threatening condition, with significant risk for death due to cardiac complications. The objective of this study was to analyze the cardiac involvement in anorexia nervosa and to study the reversibility of cardiac abnormalities. METHOD: Thirty-one consecutive adolescents (aged 12 to 17 years) with a diagnosis of anorexia nervosa were evaluated from January 1998 to January 1999 at the Hospital Clínic (University of Barcelona, Catalonia, Spain). An electrocardiogram, an echocardiogram, a 24-hour Holter recording with heart rate variability, an exercise test, and a tilt test were performed at initial examination and after refeeding (3 to 18 months later). RESULTS: The basal body mass index was 15.2 +/- 2 kg/m2. Sinus bradycardia was found in 35% of patients, 93% showed a decreased left ventricular mass, and 70% had a diminished thickness of cardiac walls. The Holter recordings showed nocturnal bradycardia in 60% with an increased heart rate variability. After refeeding, a significant decrease in QT interval (p <.05) and QT dispersion (p <.01) was observed. Echocardiograms showed an increase in cardiac diameters (p <.01), left ventricular mass (p <.001), and cardiac output (p <.001). There was also an improvement in the exercise capacity (p <.05) and a normalization of the heart rate and heart rate variability (p <.05). CONCLUSION: Cardiac structural and functional abnormalities provoked by anorexia nervosa are reversible in young adolescents after refeeding.

Adolescent↗
PubMed2002

Polymorphic reentrant ventricular tachycardia in the isolated rabbit heart studied by high-density mapping.

BACKGROUND: The role of dispersion of refractoriness and reentry for the genesis of polymorphic ventricular tachycardia (VT) has recently become emphasized. We investigated the mechanisms of polymorphic arrhythmias in a 2D preparation confining an area of prolonged refractoriness. METHODS AND RESULTS: In 16 Langendorff-perfused rabbit hearts, a sheet of left ventricular epicardium was obtained by a cryoprocedure. Enhanced spatial heterogeneity in a refractory period was created by cooling a central region (diameter=12 mm). This markedly prolonged the refractory period (by 36+/-14 ms) inside but only slightly prolonged it (by 5+/-11 ms) outside the cooled area (n=6). During a control procedure, programmed stimulation with up to 3 premature stimuli induced an episode of monomorphic VT in only 1 of 10 hearts. During regional cooling, episodes of polymorphic VT with a maximum duration of 35 seconds could be induced in all hearts. High-resolution mapping (229 electrodes) of epicardial activation revealed that polymorphic VT was caused by a functional reentrant circuit located partially within the region of prolonged refractoriness. The reentrant wavefront was continuously shifting along the border of the cooled region, resulting in beat-to-beat changes in the excitation pattern. Spontaneous termination of polymorphic VT occurred either by a shift of the reentrant circuit outside the cooled region or by a block in the central common pathway during figure-of-8 reentry in the region of prolonged refractoriness. CONCLUSIONS: A shifting functional reentrant circuit was the underlying mechanism of polymorphic VT in a substrate of enhanced spatial heterogeneity of refractoriness.

Animals↗
PubMed2002

Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome.

Sudden unexplained nocturnal death syndrome (SUNDS), a disorder found in southeast Asia, is characterized by an abnormal electrocardiogram with ST-segment elevation in leads V1-V3 and sudden death due to ventricular fibrillation, identical to that seen in Brugada syndrome. We screened patients with SUNDS for mutations in SCN5A, the gene known to cause Brugada syndrome, as well as genes encoding ion channels associated with the long-QT syndrome. Ten families were enrolled, and screened for mutations using single-strand DNA conformation polymorphism analysis, denaturing high-performance liquid chromatography and DNA sequencing. Mutations were identified in SCN5A in three families. One mutation, R367H, lies in the first P segment of the pore-lining region between the DIS5 and DIS6 transmembrane segments of SCN5A. A second mutation, A735V, lies in the first transmembrane segment of domain II (DIIS1) close to the first extracellular loop between DIIS1 and DIIS2, whereas the third mutation, R1192Q, lies in domain III. Analysis of these mutations in Xenopus oocytes showed that the R367H mutant channel did not express any current and the likely effect of this mutation is to depress peak current due to the loss of one functional allele. The A735V mutant expressed currents with steady state activation voltage shifted to more positive potentials. The R1192Q mutation accelerated the inactivation of the sodium channel current. Both mutations resulted in reduced sodium channel current (I(Na)) at a time corresponding to the end of phase 1 of the action potential, as described previously in the Brugada syndrome. Based upon these observations we suggest that SUNDS and Brugada syndrome are phenotypically, genetically and functionally the same disorder.

Alleles↗
PubMed2002

Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3.

BACKGROUND: The electrocardiographic pattern of right bundle-branch block with ST-segment elevation in leads V1 to V3 is increasingly recognized among patients who have aborted sudden cardiac death, but also in asymptomatic individuals, raising questions about its prognostic significance. METHODS AND RESULTS: The clinical, electrophysiological, and follow-up data of 334 patients with the Brugada phenotype were analyzed. A total of 79 women and 255 men with a mean age at diagnosis of 42+/-16 years were studied. The abnormal ECG was recognized after a resuscitated cardiac arrest in 71 patients (group A), after a syncopal episode in 73 patients (group B), and in 190 asymptomatic individuals (group C). Sustained ventricular arrhythmias were inducible in 83%, 63%, and 33% of patients in group A, group B, and group C, respectively. During 54+/-54 and 26+/-36 months of follow-up, respectively, 62% of patients in group A and 19% of group B patients had a new arrhythmic event. Inducibility of ventricular arrhythmias was the only predictor of arrhythmia occurrence in both groups. During a mean follow-up of 27+/-29 months, 8% of group C individuals had a first arrhythmic event. In these individuals, inducibility of ventricular arrhythmias and a basal abnormal ECG were predictors of arrhythmia occurrence. CONCLUSIONS: An ECG showing right bundle-branch block and ST-segment elevation in the right precordial leads is a marker of malignant ventricular arrhythmias and sudden death. Recurrence of malignant arrhythmias is high after the occurrence of symptoms. Among asymptomatic individuals, those with a spontaneously abnormal ECG and inducible to ventricular arrhythmias have the poorer prognosis.

Adult↗
PubMed2002

[Genetics and arrhythmias].

In the last 50 years we have been very successful at prolonging survival and improving the quality of life of patients with cardiac disease. The innovations in technology and pharmacology, better preventive and diagnostic tools have provided tremendous breakthroughs. However, despite our best efforts, the majority of cardiac diseases are structural in origin and will progress to their ultimate outcome. Curative therapies are not available due in part to our poor understanding of the basic mechanisms responsible for these diseases. The new developments in molecular genetics and biology are likely to change the way we approach a cardiac patient in the future. The diseases are presently being deciphered at the most basic level, and the information obtained opens new possibilities not only for better therapeutic and diagnostic measures but also for prevention of the disease.

Arrhythmias, Cardiac↗
PubMed2002

Novel mutations in domain I of SCN5A cause Brugada syndrome.

Brugada syndrome, an autosomal dominantly inherited form of ventricular fibrillation characterized by ST-segment elevation in leads V1-V3 and right bundle-branch block on surface electrocardiogram, is caused by mutations in the cardiac sodium channel gene SCN5A. Patients with Brugada syndrome were studied using single-strand conformation polymorphism analysis, denaturing high-performance liquid chromatography, and DNA sequencing of SCN5A. Mutations were identified in SCN5A in two families and one sporadic case. In one family, a missense mutation leading to a glycine to valine substitution (G351V) in the pore region between the DIS5 and DIS6 transmembrane segments was detected. Biophysical analysis demonstrated that this mutation caused significant current reduction. In the other family, a 20-bp deletion of the exon 5 splice acceptor site was identified; as exon 5 encodes part of the intracellular loop between DIS2 and DIS3, this portion of the channel is disrupted. In the sporadic patient, a missense mutation resulting in the substitution of lysine by glutamic acid (K126E) in the intracellular loop at the boundary with DIS1 was identified. These three new SCN5A mutations in Brugada syndrome patients are all located within domain I of SCN5A, a region not previously considered important in the development of ventricular arrhythmias.

Animals↗
PubMed2002

Inappropriate tachycardia detection by a biventricular implantable cardioverter defibrillator.

This case describes "double counting" of intrinsic conduction due to the combination of intraventricular conduction delay and the merging of the electrograms from the right and left ventricle (coronary sinus) leads in a biventricular cardioverter defibrillator. This situation prompted asymptomatic antitachycardia pacing. Lengthening of AV conduction by betablocker solved the problem.

Adrenergic beta-Antagonists↗