RESUMO
BACKGROUND: Although QT prolongation following myocardial infarction (MI) is generally moderate, cases with marked QT prolongation leading to life-threatening torsades de pointes (TdP) have been described. OBJECTIVE: To investigate the genetic substrate of this phenomenon. METHODS: We studied 13 patients who developed TdP in the subacute phase of MI (2-11 days) and a group of 133 ethnically matched controls with uncomplicated MI. Long QT syndrome genes and the KCNH2-K897T polymorphism were screened by using denaturing high-performance liquid chromatography plus direct sequencing and a specific TaqMan assay, respectively. RESULTS: Two of the 13 patients (15%) who presented with QT prolongation and TdP were found to carry long QT syndrome mutations (KCNH2-R744X and SCN5A-E446K). Nine of the remaining 11 patients (82%) carried the KCNH2-K897T polymorphism, which was present in 35% of the controls (P = .0035). Thus, patients with an acute MI carrying the KCNH2-K897T polymorphism had an 8-fold greater risk of experiencing TdP compared with controls (95% confidence interval = 2-40). CONCLUSIONS: Our data suggest that the common K897T polymorphism is associated with an increased risk of TdP developing in the subacute phase of MI. Our findings support the concept that the electrical remodeling associated with this healing phase of MI may unmask a genetic substrate predisposing to a time-limited development of life-threatening arrhythmias. They also provide the first line of evidence in support of the hypothesis that a common polymorphism, previously described as a modifier of the severity of LQTS, may increase the risk of life-threatening arrhythmias in a much more prevalent cardiac disease such as myocardial infarction.
Assuntos
Infarto do Miocárdio/complicações , Infarto do Miocárdio/genética , Torsades de Pointes/etiologia , Torsades de Pointes/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Morte Súbita Cardíaca , Canal de Potássio ERG1 , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Canais de Potássio Éter-A-Go-Go/genética , Feminino , Técnicas de Genotipagem , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Síndrome do QT Longo/genética , Masculino , Pessoa de Meia-Idade , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIMS: The present study assessed the role of programmed ventricular stimulation (PVS) in risk stratification of patients with ischaemic cardiomyopathy (ICM), candidates for implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: Consecutive patients with ICM and LVEF < or = 40% (n = 106, age 61 +/- 7 years, LVEF 27 +/- 7%) underwent PVS. This was considered positive in case of inducibility of monomorphic ventricular tachycardia (VT) with < or =3 extrastimuli; polymorphic VT, ventricular fibrillation (VF), and fast monomorphic VT (CL < or = 230 ms) with < or =2 extrastimuli. Primary end-point was the combination of arrhythmic death and VF requiring ICD shock. Forty-nine patients (46%) were inducible at PVS; 74 (70%) were implanted with ICD. During a 24-month follow-up, the primary end-point occurred more frequently in positive PVS patients among the overall population, among patients with LVEF < or = 30% (n = 80) and among patients with an ICD. The negative predictive value of PVS was 96% in each group. In the overall population, both PVS (HR 7.32, 95% CI 1.6-32) and LVEF (HR 4.59, 95% CI 1.6-13) predicted the primary end-point. CONCLUSION: PVS may still have a role in predicting the arrhythmic risk in patients with ICM. A negative PVS identifies a subgroup with a very low risk of arrhythmic events even in patients with LVEF < or = 30%.
Assuntos
Desfibriladores Implantáveis , Terapia por Estimulação Elétrica/métodos , Ventrículos do Coração/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Seleção de Pacientes , Idoso , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/terapia , Valor Preditivo dos Testes , Fatores de Risco , Volume Sistólico/fisiologia , Análise de Sobrevida , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/terapia , Disfunção Ventricular Esquerda/fisiopatologia , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/terapiaRESUMO
It is well known that both atrial and ventricular arrhythmias play a key role in morbidity and overall mortality among patients with heart failure. In addition to pharmacological treatment, up-to-date and evidence-based use of invasive electrophysiology, including implantable cardioverter defibrillator implantation, is recommended in the global management of patients with heart failure. This article will review current clinical indications for invasive electrophysiology, either acknowledged or under evaluation, focusing on the scientific background and some technical and practical aspects. The discussion is organized in an arrhythmia-based manner so that ventricular-, atrial-, and heart transplant-related arrhythmias will be discussed separately.