RESUMO
Brugada syndrome has been linked to mutations in SCN5A. Agents that dissociate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome electrocardiogram and precipitate ventricular tachycardia/fibrillation. Lidocaine, an agent with rapid dissociation kinetics, has previously been shown to exert no effect in patients with Brugada syndrome. We characterized a novel double mutation of SCN5A (V232I in DI-S4+L1308F in DIII-S4) identified in a rare case of lidocaine (1 mg/kg)-induced Brugada syndrome. We studied lidocaine blockade of I(Na) generated by wild-type and V232I+L1308F mutant cardiac sodium channels expressed in mammalian TSA201 cells using patch clamp techniques. Despite no significant difference in steady-state gating parameters between V232I+L1308F and wild-type sodium currents at baseline, use-dependent inhibition of I(Na) by lidocaine was more pronounced in V232I+L1308F versus wild-type (73.0+/-0.1% versus 18.23+/-0.04% at 10 micromol/L measured at 10 Hz, respectively). A dose of 10 micromol/L lidocaine also caused a more negative shift of steady-state inactivation in V232I+L1308F versus wild-type (-14.1+/-0.3 mV and -4.8+/-0.3 mV, respectively). The individual mutations produced a much less accentuated effect. We report the first case of lidocaine-induced Brugada electrocardiogram phenotype. The double mutation in SCN5A, V232I, and L1308F alters the affinity of the cardiac sodium channel for lidocaine such that the drug assumes Class IC characteristics with potent use-dependent block of the sodium channel. Our results demonstrate an additive effect of the 2 missense mutations to sensitize the sodium channel to lidocaine. These findings suggest caution when treating patients carrying such genetic variations with Class I antiarrhythmic drugs.
Assuntos
Anestésicos Locais/efeitos adversos , Síndrome de Brugada/genética , Lidocaína/efeitos adversos , Proteínas Musculares/genética , Mutação de Sentido Incorreto/genética , Canais de Sódio/genética , Síndrome de Brugada/fisiopatologia , Eletrocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.5 , FenótipoRESUMO
OBJECTIVES: The aim of this study was to develop a hybrid approach-specific model to predict chronic total coronary artery occlusion (CTO) percutaneous coronary intervention success, useful for experienced but not ultra-high-volume operators. BACKGROUND: CTO percutaneous coronary intervention success rates vary widely and have improved with the "hybrid approach," but current predictive models for success have major limitations. METHODS: Data were obtained from consecutively attempted patients from 7 clinical sites (9 operators, mean annual CTO volume 61 ± 17 cases). Angiographic analysis of 21 lesion variables was performed centrally. Statistical modeling was performed on a randomly designated training group and tested in a separate validation cohort. The primary outcome of interest was technical success. RESULTS: A total of 436 patients (456 lesions) met entry criteria. Twenty-five percent of lesions had prior failed percutaneous coronary interventions at the site. The right coronary artery was the most common location (56.4%), and mean occlusion length was 24 ± 20 mm. The initial approach was most often antegrade wire escalation (70%), followed by retrograde (22%). Success was achieved in 79.4%. Failure was most closely correlated with presence of an ambiguous proximal cap, and in the presence of an ambiguous proximal cap, specifically defined collateral score (combination of Werner and tortuosity scores) and retrograde tortuosity. Without an ambiguous proximal cap, poor distal target, occlusion length >10 mm, ostial location, and 1 operator variable contributed. Prior failure, and Werner and tortuosity scores alone, were only weakly correlated with outcomes. The basic 7-item model predicted success, with C statistics of 0.753 in the training cohort and 0.738 in the validation cohort, the later superior (p < 0.05) to that of the J-CTO (Multicenter CTO Registry of Japan) (0.55) and PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) (0.61) scores. CONCLUSIONS: Success can be reasonably well predicted, but that prediction requires modification and combination of angiographic variables. Differences in operator skill sets may make it challenging to create a powerful, generalizable, predictive tool.
Assuntos
Angiografia Coronária , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Técnicas de Apoio para a Decisão , Intervenção Coronária Percutânea , Idoso , Canadá , Doença Crônica , Competência Clínica , Tomada de Decisão Clínica , Oclusão Coronária/fisiopatologia , Feminino , Hospitais com Alto Volume de Atendimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Seleção de Pacientes , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Estados Unidos , Carga de TrabalhoAssuntos
Falso Aneurisma/complicações , Aneurisma Roto/complicações , Aneurisma Cardíaco/complicações , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/cirurgia , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Angiografia Coronária , Ecocardiografia Transesofagiana , Eletrocardiografia , Evolução Fatal , Aneurisma Cardíaco/diagnóstico por imagem , Aneurisma Cardíaco/cirurgia , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Recusa do Paciente ao TratamentoRESUMO
Cardiac tamponade is a common cardiac emergency requiring prompt diagnosis and intervention. A thorough understanding of the spectrum of clinical and hemodynamic changes in patients with pericardial effusion is vital for interventional cardiologists. This review discusses pathophysiology of cardiac tamponade with emphasis on hemodynamic aberrations. Specific clinical situations that lead to atypical hemodynamic presentations of cardiac tamponade are emphasized with a review of various diagnostic and therapeutic procedures.
Assuntos
Tamponamento Cardíaco/fisiopatologia , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/terapia , Diagnóstico Diferencial , Ecocardiografia , Eletrocardiografia , Hemodinâmica/fisiologia , HumanosRESUMO
Cocaine use has been associated with a significant risk of myocardial ischemia and myocardial infarction (MI). The previous approach to the treatment of cocaine-induced MI focused on medical treatment with verapamil, nitroglycerine and thrombolytics. Percutaneous revascularization for the cocaine-associated MI has been reported and is the preferred treatment modality. Identification of culprit vessel in the patients presenting with acute myocardial infarction associated with cocaine use is problematic owing to the frequent presence of baseline electrocardiogram (ECG) changes. Chronic cocaine use predisposes to diffuse coronary vasculopathy and may cause systemic alteration of coagulation parameters. Multivessel coronary thrombosis presenting as myocardial infarction associated with cocaine use has not been previously reported. This study describes a case of multivessel coronary thrombosis caused by cocaine ingestion successfully treated with multivessel primary angioplasty.