Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
Eur Heart J ; 45(14): 1255-1265, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38445836

RESUMO

BACKGROUND AND AIMS: Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes. METHODS: A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years. RESULTS: During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients [18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P = .001] and age >50 years (HR 1.7, P = .016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P < .001) was a predictor of VAs. CONCLUSIONS: ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation.


Assuntos
Síndrome de Brugada , Desfibriladores Implantáveis , Marca-Passo Artificial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Síndrome de Brugada/complicações , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , Eletrocardiografia/métodos , Eletrocardiografia Ambulatorial/métodos , Adulto
2.
JACC Clin Electrophysiol ; 9(8 Pt 1): 1296-1306, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37227348

RESUMO

BACKGROUND: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype. OBJECTIVES: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes. METHODS: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (P+), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA). RESULTS: Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence. CONCLUSIONS: In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.


Assuntos
Testes Genéticos , Fibrilação Ventricular , Humanos , Estudos Retrospectivos , Arritmias Cardíacas/complicações
3.
Europace ; 24(5): 845-854, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-34499723

RESUMO

AIMS: Ajmaline challenge can unmask subcutaneous implantable cardioverter-defibrillator (S-ICD) screening failure in patients with Brugada syndrome (BrS) and non-diagnostic baseline electrocardiogram (ECG). The efficacy of the SMART Pass (SP) filter, a high-pass filter designed to reduce cardiac oversensing (while maintaining an appropriate sensing margin), has not yet been assessed in patients with BrS. The aim of this prospective multicentre study was to investigate the effect of the SP filter on dynamic Brugada ECG changes evoked by ajmaline and to assess its value in reducing S-ICD screening failure in patients with drug-induced Brugada ECGs. METHODS AND RESULTS: The S-ICD screening with conventional automated screening tool (AST) was performed during ajmaline challenge in subjects with suspected BrS. The S-ICD recordings were obtained before, during and after ajmaline administration and evaluated by the means of a simulation model that emulates the AST behaviour with and without SP filter. A patient was considered suitable for S-ICD if at least one sensing vector was acceptable in all tested postures. A sensing vector was considered acceptable in the presence of QRS amplitude >0.5 mV, QRS/T-wave ratio >3.5, and sense vector score >100. Of the 126 subjects (mean age: 42 ± 14 years, males: 61%, sensing vectors: 6786), 46 (36%) presented with an ajmaline-induced Brugada type 1 ECG. Up to 30% of subjects and 40% of vectors failed the screening during the appearance of Brugada type 1 ECG evoked by ajmaline. The S-ICD screening failure rate was not significantly reduced in patients with Brugada ECGs when SP filter was enabled (30% vs. 24%). Similarly, there was only a trend in reduction of vector-failure rate attributable to the SP filter (from 40% to 36%). The most frequent reason for screening failure was low QRS amplitude or low QRS/T-wave ratio. None of these patients was implanted with an S-ICD. CONCLUSION: Patients who pass the sensing screening during ajmaline can be considered good candidates for S-ICD implantation, while those who fail might be susceptible to sensing issues. Although there was a trend towards reduction of vector sensing failure rate when SP filter was enabled, the reduction in S-ICD screening failure in patients with Brugada ECGs did not reach statistical significance. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov Unique Identifier NCT04504591.


Assuntos
Síndrome de Brugada , Desfibriladores Implantáveis , Adulto , Ajmalina/efeitos adversos , Arritmias Cardíacas , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , Eletrocardiografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
4.
J Cardiovasc Electrophysiol ; 32(6): 1704-1711, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33928706

RESUMO

BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICDs) avoid complications secondary to transvenous leads, but inappropriate shocks (ISs) are frequent. Furthermore, IS data from patients with Brugada syndrome (BrS) with an S-ICD are scarce. OBJECTIVE: We aimed to establish the frequency and predictors of IS in this population. METHODS: We analyzed the clinical and electrocardiographic characteristics, automated screening test data, device programming, and IS occurrence in adult patients with BrS with an S-ICD. RESULTS: Thirty-nine patients were enrolled (69% male, mean age at diagnosis 46 ± 13 years, mean age at implantation 48 ± 13 years). During a mean follow-up of 26 ± 21 months, 18% patients experienced IS. Patients with IS were younger at the time of diagnosis (36 ± 8 vs. 48 ± 13 years, p = .018) and S-ICD implantation (38 ± 9 vs. 50 ± 23 years, p = .019) and presented with spontaneous type 1 Brugada electrocardiogram pattern more frequently at diagnosis or during follow-up (71% vs. 25%, p = .018). During automated screening tests, patients with IS showed lower QRS voltage in the primary vector in the supine position (0.58 ± 0.26 vs. 1.10 ± 0.35 mV, p = .011) and lower defibrillator automated screening score in the primary vector in the supine (123 ± 165 vs. 554 ± 390 mV, p = .005) and standing (162 ± 179 vs. 486 ± 388 mV, p = .038) positions. Age at diagnosis was the only independent predictor of IS (hazard ratio = 0.873, 95% confidence interval: 0.767-0.992, p = .037). CONCLUSION: IS was a frequent complication in patients with BrS with an S-ICD. Younger age was independently associated with IS. A more thorough screening process might help prevent IS in this population.


Assuntos
Síndrome de Brugada , Desfibriladores Implantáveis , Adulto , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis/efeitos adversos , Eletrocardiografia , Feminino , Seguimentos , Coração , Humanos , Masculino , Tela Subcutânea , Resultado do Tratamento
5.
J Cardiovasc Electrophysiol ; 32(4): 1187-1190, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33586167

RESUMO

A 52-year-old male was admitted with unstable angina and three-vessel coronary artery disease. Electrocardiography (ECG) changes consistent with type-1 Brugada ECG pattern were noted during admission. The patient was asymptomatic for syncope and had no family history of sudden cardiac death, ICD implantation, and Brugada syndrome. After coronary by-pass graft the Brugada ECG pattern resolved, and ajmaline test did not elicit type-1 ECG pattern, confirming the suspicion of Brugada phenocopy.


Assuntos
Síndrome de Brugada , Doença da Artéria Coronariana , Angina Instável/diagnóstico , Angina Instável/etiologia , Síndrome de Brugada/diagnóstico , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Síncope
6.
J Interv Cardiol ; 2019: 6704031, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772541

RESUMO

OBJECTIVES: The aim of this study was to investigate the outcomes of left atrial appendage occlusion (LAAO) in high bleeding risk patients suffering atrial fibrillation (AF) and to analyze the different antithrombotic therapies following the intervention. BACKGROUND METHODS: This monocentric study included 68 patients with nonvalvular AF with an absolute contraindication to OAT or at high bleeding risk. Follow-up was done with a clinical visit at 3-6-12 months. RESULTS: Successful LAAO was achieved in 67/68 patients. At discharge, 32/68 patients were on dual antiplatelet therapy (APT), 34/68 were without any antithrombotic therapy or with a single antiplatelet drug, and 2/68 were on anticoagulant therapy. At three-month follow-up visit, 73.6% of the patients did not receive dual APT, of whom 14.7% had no thrombotic therapy and 58.9% were on single antiplatelet therapy. During a follow-up of 1.4 ± 0.9 years, 3/62 patients had late adverse effects (2 device-related thrombus without clinical consequences and 1 extracranial bleeding). The device-related thrombosis was not related to the antithrombotic therapy. CONCLUSIONS: LAAO is feasible and safe and prevents stroke in patients with AF with contraindication to oral anticoagulant therapy. After LAAO, single antiplatelet therapy seems to be a safe alternative to dual antiplatelet therapy, especially in patients at high bleeding risk. No benefit has been observed with dual APT.


Assuntos
Apêndice Atrial/cirurgia , Fibrilação Atrial , Fibrinolíticos/efeitos adversos , Hemorragia/prevenção & controle , Implantação de Prótese , Dispositivo para Oclusão Septal , Acidente Vascular Cerebral , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Contraindicações de Medicamentos , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Itália/epidemiologia , Masculino , Implantação de Prótese/efeitos adversos , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos , Risco Ajustado/métodos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
7.
J Invasive Cardiol ; 31(9): E280-E281, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31478900

RESUMO

This case emphasizes the need to use intravascular imaging to optimize stent implantation in the left main coronary artery. Despite recommendations, intravascular imaging is still widely under-utilized. The recently developed stent apposition OCT software (OPTIS Stent Optimization Software; Abbott Vascular) confirmed its usefulness in optimizing stent implantation in unprotected left main PCI.


Assuntos
Estenose Coronária/cirurgia , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Tomografia de Coerência Óptica/métodos , Idoso , Angiografia Coronária , Estenose Coronária/diagnóstico , Vasos Coronários/cirurgia , Feminino , Humanos , Desenho de Prótese , Falha de Prótese , Reoperação , Ultrassonografia de Intervenção
8.
Europace ; 21(11): 1670-1677, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504477

RESUMO

AIMS: To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]. CONCLUSION: Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences.


Assuntos
Desfibriladores Implantáveis , Eletrocardiografia , Parada Cardíaca Extra-Hospitalar/etiologia , Sistema de Registros , Fibrilação Ventricular/complicações , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia , Valores de Referência , Estudos Retrospectivos , Fatores de Tempo , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/fisiopatologia , Adulto Jovem
9.
Card Electrophysiol Clin ; 11(2): 315-331, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31084853

RESUMO

Electrocardiogram (ECG) analysis trying to understand the mechanisms of QRS widening is often problematic. During WCTs, identification of P waves and atrioventricular relationship is often difficult and increasingly so if the number of recording leads available for examination is limited. For this reason, it is necessary to use every information available in an ECG tracing. The goal of this article is to focus on the reasons for QRS variations occurring during tachycardia. Correct interpretation of these data can offer the key to understand the arrhythmia mechanism.


Assuntos
Arritmias Cardíacas , Eletrocardiografia , Arritmias Cardíacas/classificação , Arritmias Cardíacas/diagnóstico , Eletrocardiografia/classificação , Eletrocardiografia/métodos , Medicina de Precisão
10.
J Cardiovasc Med (Hagerstown) ; 20(1): 1-9, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30431481

RESUMO

: Atrial fibrillation is the most common cardiac arrhythmia and its prevalence is constantly increasing. The main complications related to atrial fibrillation are death and major stroke. Oral anticoagulant therapy is the cornerstone of management of atrial fibrillation patients at increased stroke risk. Unfortunately, a significant proportion of patients do not receive adequate anticoagulant therapy due to increased or prohibitive hemorrhagic risk. The observation that most thrombi are generated in the left atrial appendage (LAA) had led to the consideration of surgical or percutaneous occlusion as an alternative. During recent years, the WATCHMAN percutaneous occlusion device has proven to be not inferior to anticoagulant therapy for the prevention of thromboembolic events, with the added benefit of a lower rate of hemorrhagic events. Numerous data showed the same results for the AMPLATZER cardiac plug and Amulet devices. Left atrial appendage occlusion (LAAO) often represents the only therapeutic strategy in this group of patients. We describe the current state of the art of percutaneous LAAO in atrial fibrillation patients with a high hemorrhagic risk.


Assuntos
Anticoagulantes/efeitos adversos , Apêndice Atrial , Fibrilação Atrial/terapia , Cateterismo Cardíaco , Hemorragia/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Apêndice Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Tomada de Decisão Clínica , Contraindicações de Medicamentos , Humanos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Tromboembolia/diagnóstico , Tromboembolia/epidemiologia , Tromboembolia/fisiopatologia , Resultado do Tratamento
11.
Proteomics Clin Appl ; 12(6): e1800065, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29956481

RESUMO

PURPOSE: The Brugada syndrome (BrS) is a severe inherited cardiac disorder. Given the high genetic and phenotypic heterogeneity of this disease, three different "omics" approaches are integrated in a synergic way to elucidate the molecular mechanisms underlying the pathophysiology of BrS as well as for identifying reliable diagnostic/prognostic markers. EXPERIMENTAL DESIGN: The profiling of plasma Proteome and MiRNome is perfomed in a cohort of Brugada patients that were preliminary subjected to genomic analysis to assess a peculiar gene mutation profile. RESULTS: The integrated analysis of "omics" data unveiled a cooperative activity of mutated genes, deregulated miRNAs and proteins in orchestrating transcriptional and post-translational events that are critical determining factors for the development of the Brugada pattern. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides the basis to shed light on the specific molecular fingerprints underlying BrS development and to gain further insights on the pathogenesis of this life-threatening cardiac disease.


Assuntos
Biomarcadores/sangue , Proteínas Sanguíneas/genética , Síndrome de Brugada/sangue , Proteoma/genética , Síndrome de Brugada/genética , Síndrome de Brugada/patologia , Feminino , Genoma Humano/genética , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Mutação
15.
J Am Coll Cardiol ; 70(16): 1991-2002, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29025556

RESUMO

BACKGROUND: Implantable cardioverter-defibrillator (ICD) indications for primary prevention in Brugada syndrome (BrS) are still debated. OBJECTIVES: The authors investigated the long-term outcome after ICD implantation in a large cohort of BrS patients. METHODS: Of a total of 370 patients with BrS in follow-up (age 43 ± 14 years; 74% male), 104 patients (28.1%) were treated with ICDs. The authors analyzed the long-term incidence of shocks and complications. RESULTS: An ICD was implanted for secondary prevention in 10 patients (9.6%) and for primary prevention in 94 patients (90.4%). After a follow-up of 9.3 ± 5.1 years, 21 patients (20.2%) experienced a total of 81 appropriate shocks (incidence rate 2.2 per 100 person-years). The rate of appropriate shocks was higher in secondary prevention patients (p < 0.01). However, 4 of the 45 asymptomatic patients (8.9%) experienced appropriate ICD therapy, all with a spontaneous type 1 electrocardiogram and inducible ventricular arrhythmias. In the multivariable analysis, type 1 electrocardiogram with syncope (hazard ratio: 4.96; 95% confidence interval: 1.87 to 13.14; p < 0.01) and secondary prevention indication (hazard ratio: 6.85; 95% confidence interval: 2.29 to 20.50; p < 0.01) were significant predictors of appropriate therapy. Nine patients (8.7%) experienced 37 inappropriate shocks (incidence rate 0.9 per 100 person-years). Twenty-one patients (20.2%) had other ICD-related complications (incidence rate 1.4 per 100 person-years). Three patients (2.9%) died (1 electrical storm and 2 noncardiovascular deaths). CONCLUSIONS: ICD therapy is an effective therapy in high-risk patients with BrS. However, it is also associated with a significant risk of device-related complications. Special care during ICD implantation, adequate device programming, and regular follow-up may allow reducing the number of adverse events.


Assuntos
Síndrome de Brugada/fisiopatologia , Síndrome de Brugada/terapia , Desfibriladores Implantáveis/tendências , Eletrocardiografia/tendências , Adulto , Síndrome de Brugada/diagnóstico , Estudos de Coortes , Desfibriladores Implantáveis/efeitos adversos , Estimulação Elétrica/efeitos adversos , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Fatores de Tempo
16.
J Am Coll Cardiol ; 68(6): 614-623, 2016 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-27491905

RESUMO

BACKGROUND: A proband of Brugada syndrome (BrS) is the first patient diagnosed in a family. There are no data regarding this specific, high-risk population. OBJECTIVES: This study sought to investigate the Brugada probands diagnosed from 1986 through the next 28 years. METHODS: We included 447 probands belonging to families with a diagnostic type 1 electrocardiogram Brugada pattern. The database was divided into 2 periods: the first period identified patients who were part of the initial cohort that became the consensus document on BrS in 2002 (early group); the second period reflected patients first diagnosed from 2003 to January 2014 (latter group). RESULTS: There were 165 probands in the early group and 282 in the latter group. Aborted sudden death as the first manifestation of the disease occurred in 12.1% of the early group versus 4.6% of the latter group (p = 0.005). Inducibility during programmed electrical stimulation was achieved in 34.4% and 19.2% of patients, respectively (p < 0.001). A spontaneous type 1 electrocardiogram pattern at diagnosis was present in 50.3% early versus 26.2% latter patients (p = 0.0002). Early group patients had a higher probability of a recurrent arrhythmia during follow-up (19%) than those of the latter group (5%) (p = 0.007). The clinical suspicion and use of a sodium-channel blocker to unmask BrS has allowed earlier diagnoses in many patients. CONCLUSIONS: Since being first described, the presentation of BrS has changed. There has been a decrease in aborted sudden cardiac death as the first manifestation of the disease among patients who were more recently diagnosed. These variations in initial presentation have important clinical consequences. In this setting, the value of inducibility to stratify individuals with BrS has changed.


Assuntos
Síndrome de Brugada/diagnóstico , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Previsões , Medição de Risco/métodos , Adulto , Bélgica/epidemiologia , Síndrome de Brugada/complicações , Síndrome de Brugada/fisiopatologia , Morte Súbita Cardíaca/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Taxa de Sobrevida/tendências
17.
J Cardiovasc Electrophysiol ; 27(5): 563-70, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26799774

RESUMO

INTRODUCTION: The diagnosis of Brugada syndrome based on the ECG is hampered by the dynamic nature of its ECG manifestations. Brugada syndrome patients are only 25% likely to present a type 1 ECG. The objective of this study is to provide an ECG diagnostic criterion for Brugada syndrome patients that can be applied consistently even in the absence of a type 1 ECG. METHODS AND RESULTS: We recorded 67-lead body surface potential maps from 94 Brugada syndrome patients and 82 controls (including right bundle branch block patients and healthy individuals). The spatial propagation direction during the last r' wave and the slope at the end of the QRS complex were measured and compared between patients groups. Receiver-operating characteristic curves were constructed for half of the database to identify optimal cutoff values; sensitivity and specificity for these cutoff values were measured in the other half of the database. A spontaneous type 1 ECG was present in only 30% of BrS patients. An orientation in the sagittal plane < 101º during the last r' wave and a descending slope < 9.65 mV/s enables the diagnosis of the syndrome with a sensitivity of 69% and a specificity of 97% in non-type 1 Brugada syndrome patients. CONCLUSION: Spatiotemporal characteristics of surface ECG recordings can enable a robust identification of BrS even without the presence of a type 1 ECG.


Assuntos
Potenciais de Ação , Síndrome de Brugada/diagnóstico , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Adulto , Área Sob a Curva , Síndrome de Brugada/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Processamento de Sinais Assistido por Computador , Espanha , Fatores de Tempo
18.
PLoS One ; 10(7): e0132888, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26173111

RESUMO

BACKGROUND: Brugada syndrome (BrS) is a rare genetic cardiac arrhythmia that can lead to sudden cardiac death in patients with a structurally normal heart. Genetic variations in SCN5A can be identified in approximately 20-25% of BrS cases. The aim of our work was to determine the spectrum and prevalence of genetic variations in a Spanish cohort diagnosed with BrS. METHODOLOGY/PRINCIPAL FINDINGS: We directly sequenced fourteen genes reported to be associated with BrS in 55 unrelated patients clinically diagnosed. Our genetic screening allowed the identification of 61 genetic variants. Of them, 20 potentially pathogenic variations were found in 18 of the 55 patients (32.7% of the patients, 83.3% males). Nineteen of them were located in SCN5A, and had either been previously reported as pathogenic variations or had a potentially pathogenic effect. Regarding the sequencing of the minority genes, we discovered a potentially pathogenic variation in SCN2B that was described to alter sodium current, and one nonsense variant of unknown significance in RANGRF. In addition, we also identified 40 single nucleotide variations which were either synonymous variants (four of them had not been reported yet) or common genetic variants. We next performed MLPA analysis of SCN5A for the 37 patients without an identified genetic variation, and no major rearrangements were detected. Additionally, we show that being at the 30-50 years range or exhibiting symptoms are factors for an increased potentially pathogenic variation discovery yield. CONCLUSIONS: In summary, the present study is the first comprehensive genetic evaluation of 14 BrS-susceptibility genes and MLPA of SCN5A in a Spanish BrS cohort. The mean pathogenic variation discovery yield is higher than that described for other European BrS cohorts (32.7% vs 20-25%, respectively), and is even higher for patients in the 30-50 years age range.


Assuntos
Síndrome de Brugada/genética , Predisposição Genética para Doença/genética , Hispânico ou Latino/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Rearranjo Gênico/genética , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Subunidade beta-2 do Canal de Sódio Disparado por Voltagem/genética , Adulto Jovem
19.
Heart Rhythm ; 12(7): 1636-43, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25814417

RESUMO

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a difficult-to-diagnose cause of sudden cardiac death (SCD). We identified a family of 1400 individuals with multiple cases of CPVT, including 36 SCDs during youth. OBJECTIVES: We sought to identify the genetic cause of CPVT in this family, to preventively treat and clinically characterize the mutation-positive individuals, and to functionally characterize the pathogenic mechanisms of the mutation. METHODS: Genetic testing was performed for 1404 relatives. Mutation-positive individuals were preventively treated with ß-blockers and clinically characterized with a serial exercise treadmill test (ETT) and Holter monitoring. In vitro functional studies included caffeine sensitivity and store overload-induced calcium release activity of the mutant channel in HEK293 cells. RESULTS: We identified the p.G357S_RyR2 mutation, in the cardiac ryanodine receptor, in 179 family members and in 6 SCD cases. No SCD was observed among treated mutation-positive individuals over a median follow-up of 37 months; however, 3 relatives who had refused genetic testing (confirmed mutation-positive individuals) experienced SCD. Holter monitoring did not provide relevant information for CPVT diagnosis. One single ETT was unable to detect complex cardiac arrhythmias in 72% of mutation-positive individuals, though the serial ETT improved the accuracy. Functional studies showed that the G357S mutation increased caffeine sensitivity and store overload-induced calcium release activity under conditions that mimic catecholaminergic stress. CONCLUSION: Our study supports the use of genetic testing to identify individuals at risk of SCD to undertake prophylactic interventions. We also show that the pathogenic mechanisms of p.G357S_RyR2 appear to depend on ß-adrenergic stimulation.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Morte Súbita Cardíaca , Desfibriladores Implantáveis , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Taquicardia Ventricular , Adolescente , Adulto , Criança , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia Ambulatorial/métodos , Teste de Esforço/métodos , Feminino , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Medição de Risco , Espanha , Taquicardia Ventricular/complicações , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/genética , Taquicardia Ventricular/terapia , Resultado do Tratamento
20.
J Card Fail ; 21(3): 217-25, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25498755

RESUMO

BACKGROUND: Dilated cardiomyopathy (DCM), a cardiac heterogeneous pathology characterized by left ventricular or biventricular dilatation, is a leading cause of heart failure and heart transplantation. The genetic origin of DCM remains unknown in most cases, but >50 genes have been associated with DCM. We sought to identify the genetic implication and perform a genetic analysis in a Spanish family affected by DCM and sudden cardiac death. METHODS AND RESULTS: Clinical assessment and genetic screening were performed in the index case as well as family members. Of all relatives clinically assessed, nine patients showed clinical symptoms related to the pathology. Genetic screening identified 20 family members who carried a novel mutation in LMNA (c.871 G>A, p.E291K). Family segregation analysis indicated that all clinically affected patients carried this novel mutation. Clinical assessment of genetic carriers showed that electrical dysfunction was present previous to mechanical and structural abnormalities. CONCLUSIONS: Our results report a novel pathogenic mutation associated with DCM, supporting the benefits of comprehensive genetic studies of families affected by this pathology.


Assuntos
Cardiomiopatia Dilatada/genética , Morte Súbita Cardíaca , Lamina Tipo A/genética , Mutação/genética , Adulto , Sequência de Aminoácidos , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/mortalidade , Pré-Escolar , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...