Biomedical subjects

Josep Brugada

Publications and source records attributed to Josep 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

Diphenhydramine overdose and Brugada sign.

We report a case of electrocardiographic signature of the Brugada syndrome in a 39-year-old patient with an overdose of diphenhydramine. He was found unconscious and hypotensive. His serum potassium concentration was 8.3 mEq/L and the ECG revealed a coved-type ST-segment elevation in leads V2-V3. These repolarization abnormalities neither normalize with the correction of the hyperkalemia nor with an intravenous infusion of isoproterenol. When he regained consciousness, he was admitted the toxic ingestion of diphenhydramine and progressively the ECG normalized. A negative flecainide test confirmed that the transient ECG abnormalities were the consequence of the drug overdose and ruled out the Brugada syndrome.

Adult↗

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

Electrocardiographic recognition of the epicardial origin of ventricular tachycardias.

BACKGROUND: Some ventricular tachycardias (VTs) originating from the epicardium are not suitable for endocardial radiofrequency ablation and require an epicardial approach. The aim of this study was to define the ECG characteristics that may identify an epicardial origin of VTs. METHODS AND RESULTS: We analyzed the 12-lead ECG recordings during epicardial and endocardial left ventricular pacing in 9 patients to verify the hypothesis that the epicardial origin of the ventricular activation widens the initial part of the QRS complex. Then, we analyzed the ECG pattern in 14 VTs successfully ablated from the epicardium after a failed endocardial approach (group A), in 27 VTs successfully ablated from the endocardium (group B), and in 28 additional VTs that could not be ablated from the endocardium (group C). Four distinct intervals of ventricular activation were defined and measured: (1) the pseudodelta wave, (2) the intrinsicoid deflection time in V2, (3) the shortest RS complex, and (4) the QRS complex. VTs from groups A and C showed a significantly longer pseudodelta wave, intrinsicoid deflection time, and RS complex duration compared with VTs of group B. There was no difference between groups A and C. A pseudodelta wave of > or =34 ms has a sensitivity of 83% and a specificity of 95%, an intrinsicoid deflection time of > or =85 ms has a sensitivity of 87% and a specificity of 90%, and an RS complex duration of > or =121 ms has a sensitivity of 76% and a specificity of 85% in identifying an epicardial origin of the VTs. CONCLUSIONS: ECG suggests VTs originating from the epicardium and those with an unsuccessful radiofrequency ablation from the endocardium.

Cardiac Pacing, Artificial↗

PubMed2004

Value of the implantable loop recorder for the management of patients with unexplained syncope.

AIM: Recurrent syncope often remains unexplained despite extensive multidisciplinary screening. The implantable loop recorder (ILR) may be a tool to define the cardiac arrhythmias underlying syncope. METHODS AND RESULTS: The study population consisted of 43 consecutive patients with unexplained syncope who underwent extensive cardiological screening and were followed with an ILR. During follow-up, 5 patients had only presyncope, 4 had palpitations, and 15 had a true recurrence of syncope. In all patients with palpitations, 3 with presyncope, and 7 with a recurrence of syncope, the ILR excluded arrhythmias. In the patients with a true recurrence, 1 had symptomatic paroxysmal atrial fibrillation (PAF) treated with drugs, 1 had polymorphic ventricular tachycardia (VT) and received an implantable cardioverter defibrillator (ICD), and 7 had asystole and received a pacemaker. Two patients with presyncope received a pacemaker for Mobitz II block and PAF with brady-tachycardia syndrome. One asymptomatic patient received a pacemaker for significant nocturnal asystole recorded by ILR. Abnormalities in the cardiac screening were observed both in patients with and without syncope, but none of these had a predictive value. CONCLUSION: The ILR is a valuable and effective tool to establish an arrhythmic cause for unexplained syncope. The results of head-up tilt testing (HUTT) and electrophysiological study (EPS) are neither sufficiently sensitive nor specific enough in this patient group.

Adolescent↗

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

Orthodromic pacemaker-mediated tachycardia in a biventricular system without an atrial electrode.

Pacemaker-mediated tachycardia is a well-known complication of dual-chamber devices. In this report, we describe for the first time a case of orthodromic pacemaker-mediated tachycardia in a patient in whom a biventricular system without an atrial electrode had been implanted. Retrograde atrial activation was directly produced by the dislodged coronary vein electrode in the AV groove, resulting in simultaneous capture of the left atrium and left ventricle. During tachycardia, AV nodal conduction was via the anterograde pathway of the circuit and limited the ventricular response. Subsequently, right ventricular activation was sensed by the right ventricular electrode that triggered biventricular pacing and left atrial capture, perpetuating the tachycardia. Because the left atrial threshold was higher than the left ventricular threshold, the problem could be resolved easily by lowering the output of the coronary vein electrode.

Aged↗

PubMed2004

Radiofrequency catheter ablation for arrhythmic storm in patients with an implantable cardioverter defibrillator.

The aim of the study was to analyze the usefulness of RFA in controlling arrhythmic storm due to hemodynamically stable VT in a cohort of patients with an ICD and to evaluate the incidence of arrhythmic storm among patients with an ICD. A group of 13 (3%) of 403 consecutive ICD recipients were submitted to RFA of VT during an arrhythmic storm. Two additional patients were referred from other institutions. Standard criteria were used for VT endocardial ablation. A transcatheter epicardial approach was required in three patients. A total of 18 procedures were performed in 15 patients. A mean of 13.2 +/- 9.7 pulses of RF were delivered. Clinical tachycardia was successfully ablated in 12 (80%) patients. One patient died in incessant VT, 1 patient underwent heart transplant, and 1 was treated with direct current ablation. During a mean follow-up of 12 +/- 17 months, only two patients suffered a single episode of VT. Arrhythmic storm requiring VT ablation was uncommon among patients with an ICD and occurred late after ICD implantation. The arrhythmic episode was successfully controlled in the majority of patients with endocardial or epicardial RFA.

Adolescent↗

PubMed2004

Short head-up tilt test potentiated with oral nitroglycerine: comparison with a conventional test using isoproterenol.

Conventional tilt test protocols are time consuming and there is no consensus regarding the optimal duration of the test and the provocative drug to be used. This study evaluated the diagnostic power of a short nitroglycerine test against a conventional isoproterenol protocol. A cohort of 128 patients with unexplained syncope was studied. A group of 64 consecutive patients were tilted with a short nitroglycerine test consisting of a passive phase of 15 minutes and if this proved negative, 400 microg of sublingual nitroglycerin spray for a further 15 minutes. The control group consisted of 64 patients tilted with a conventional isoproterenol protocol with a passive phase of 30 minutes and a drug-challenge phase of 20 minutes. In the nitroglycerine protocol 39 (60.9%) patients showed a positive response versus 27(42.2%) in the isoproterenol group (P = 0.034). The duration of the protocol was 23.2 +/- 7.2 minutes in the nitroglycerine group versus 41.1 +/- 15.5 minutes with isoproterenol (P = 0.001). The time until syncope was 18.87 +/- 6.1 versus 29 +/- 18, respectively (P = 0.002). For evaluating unexplained syncope the short tilt test protocol with nitroglycerine is less time consuming, easier to perform, and has a higher rate of positive response than a conventional isoproterenol protocol.

Female↗

PubMed2004

T wave oversensing by a cardioverter defibrillator implanted in a patient with the Brugada syndrome.

Oversensing of electrical signals in recipients of ICDs is a common complication causing the delivery of inappropriate therapy. The Brugada syndrome has a characteristic ECG pattern with dynamic temporal changes in response to various physiological or environmental conditions. This case report presents a patient with the Brugada syndrome and intermittent T wave oversensing by an ICD due to changes in T wave amplitude which could not be resolved by device reprogramming and required repositioning of the electrode.

Aged↗

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↗

PubMed2004

[Predictors of lack of clinical improvement at mid-term follow-up with cardiac resynchronization therapy].

INTRODUCTION: About 30% of all patients do not respond to cardiac resynchronization therapy for heart failure. The objective of the study was to analyze the variables that may predict the lack of response. PATIENTS AND METHOD: We analyzed the results in a series of 63 patients who received cardiac resynchronization with a biventricular device. Clinical and left ventricular function parameters were evaluated at the beginning of the study and at 6 months. Responders were defined as those who were alive, had not received a heart transplant, and who achieved more than a 10% increase in distance in the 6-minute walking test. RESULTS: Mean age was 68.3 (8) years, 51 patients (81%) were men, and NYHA functional class was III-IV in 79.4%. Mean left ventricular ejection fraction was 22.4% (6)%, QRS width was 177 (25) ms, and 77.8% were in sinus rhythm. Almost half (46%, n=29) had ischemic heart disease. At 6-month follow-up, 69.8% of the patients were responders. Ischemic heart disease, sustained monomorphic ventricular tachycardia and a degree of mitral regurgitation >II/IV before implantation were associated with lack of response. No association was found for any of the other baseline variables. Logistic regression analysis identified all three of the aforementioned variables as independent predictors of lack of response: ischemic heart disease OR=4.8, 95% CI, 1.2-18.3, P=.023; ventricular tachycardia OR=8.7, 95% CI, 1.8-41.3, P=.007; and mitral regurgitation OR=8.03, 95% CI, 1.7-37.1, P=.008. CONCLUSION: The likelihood of responding to resynchronization therapy is lower in patients with ischemic heart disease, significant mitral regurgitation, or sustained monomorphic ventricular tachycardia.

Aged↗

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

Comparison of effectiveness of implantable cardioverter defibrillator in patients with idiopathic dilated cardiomyopathy versus those with proved coronary heart disease.

This study analyzes the effectiveness of the implantable cardioverter defibrillator in a group of 40 consecutive patients with idiopathic dilated cardiomyopathy and sustained ventricular arrhythmia; these patients were compared with a control group of 80 consecutive patients with proved coronary artery disease. There were no differences in the type and probability of recurrences at follow-up. Most recurrences were due to sustained monomorphic ventricular tachycardia, and the efficacy of the defibrillator in treating the arrhythmia was the same in both groups.

Aged↗

PubMed2003

Nonsurgical transthoracic epicardial radiofrequency ablation: an alternative in incessant ventricular tachycardia.

OBJECTIVES: The purpose of this study was to analyze the feasibility, efficacy, and safety of epicardial radiofrequency (RF) ablation in patients with incessant ventricular tachycardia (VT). BACKGROUND: Management of patients with incessant VT is a difficult clinical problem. Drugs and RF catheter ablation are not always effective. A nonsurgical transthoracic epicardial RF ablation can be an alternative in patients refractory to conventional therapy. METHODS: Epicardial RF ablation was performed in 10 patients who presented with incessant VT despite the use of two or more intravenous antiarrhythmic drugs. RESULTS: In eight patients, endocardial ablation (EdA) failed to control the tachycardia. In the remaining two patients, epicardial ablation (EpA) was first attempted because of left ventricular thrombus and severe artery disease, respectively. Eight patients had a diagnosis of coronary artery disease with healed myocardial infarction. One patient had dilated cardiomyopathy, and one patient had idiopathic, incessant VT. In patients with structural heart disease, the mean ejection fraction was 0.28 +/- 0.10%. Four patients previously received an implantable defibrillator. The EpA effectively terminated the incessant tachycardia in eight patients, which represents a success rate of 80%. In them, after a follow-up of 18 +/- 18 months, a single episode of a different VT was documented in one patient. No significant complications occurred related to the procedure. CONCLUSIONS: In patients with incessant VT despite the use of drugs or standard EdA, the epicardial approach was very effective and should be considered as an alternative in this life-threatening situation.

Aged↗

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↗