RESUMO
BACKGROUND: Long QT syndrome (LQT) is a pro-arrhythmogenic condition with life-threatening complications. Fifteen genes have been associated with congenital LQT, however, the genetic causes remain unknown in more than 20% of cases. MATERIALS AND METHODS: Eighteen patients with history of palpitations, pre-syncope, syncope and prolonged QT were referred to the Yale Cardiovascular Genetics Program. All subjects underwent whole-exome sequencing (WES) followed by confirmatory Sanger sequencing. Mutation burden analysis was carried out using WES data from 16 subjects with no identifiable cause of LQT. RESULTS: Deleterious and novel SCN10A mutations were identified in 3 of the 16 patients (19%) with idiopathic LQT. These included 2 frameshifts and 1 missense variants (p.G810fs, p.R1259Q, and p.P1877fs). Further analysis identified 2 damaging SCN10A mutations with allele frequencies of approximately 0.2% (p.R14L and p.R1268Q) in 2 independent cases. None of the SCN10A mutation carriers had mutations in known arrhythmia genes. Damaging SCN10A mutations (p.R209H and p.R485C) were also identified in the 2 subjects on QT prolonging medications. CONCLUSION: Our findings implicate SCN10A in LQT. The presence of frameshift mutations suggests loss-of-function as the underlying disease mechanism. The common association with atrial fibrillation suggests a unique mechanism of disease for this LQT gene.
Assuntos
Arritmias Cardíacas/genética , Síndrome do QT Longo/genética , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Síncope/genética , Adulto , Idoso , Arritmias Cardíacas/fisiopatologia , Análise Mutacional de DNA , Feminino , Mutação da Fase de Leitura , Frequência do Gene , Predisposição Genética para Doença , Testes Genéticos , Humanos , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Síncope/fisiopatologiaRESUMO
Because there is controversy regarding the clinical relevance of exercise-induced ventricular arrhythmias, we analyzed their significance in 383 patients who had undergone both exercise thallium-201 stress-testing and cardiac catheterization. Two-hundred twenty-one patients (58%) had no exercise-induced ventricular arrhythmias while 162 (42%) did. There was no difference between patients with and without exercise-induced ventricular arrhythmias in terms of previous myocardial infarction (p = 0.61), incidence of fixed thallium-201 defects (0.06), number of diseased vessels (p = 0.09) and resting left ventricular ejection fraction (p = 0.06). In contrast, evidence of provocable ischemia (redistribution on thallium-201 and ST-segment depression on the electrocardiogram) were more likely (p less than 0.02) to be seen in patients with exercise-induced ventricular arrhythmias. Discriminant function analysis revealed that these 2 variables best separated patients with and without exercise-induced ventricular arrhythmias. In a 4- to 8-year follow-up, 89 patients had adverse cardiac events. Of these 89, there were 41 deaths, 9 nonfatal myocardial infarctions and 39 coronary revascularization procedures performed later than 3 months after catheterization. Patients with exercise-induced ventricular arrhythmias were more likely (p = 0.01) to have these events than those without these arrhythmias. Moreover, these arrhythmias provided independent prognostic information beyond that provided by the thallium-201 stress test and coronary angiography. We conclude that exercise-induced ventricular arrhythmias are associated with exercise-induced ischemia and provide prognostic information which adds marginally to that provided by other noninvasive and invasive parameters in ambulatory patients being evaluated for chest pain.
Assuntos
Arritmias Cardíacas/etiologia , Doença das Coronárias/complicações , Exercício Físico , Cateterismo Cardíaco , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/mortalidade , Doença das Coronárias/fisiopatologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , CintilografiaRESUMO
We postulated that because the first step in the management of critically ill patients with hypotension, pulmonary edema, or both is to determine whether the cause is cardiac or noncardiac, direct visualization of the heart with two-dimensional echocardiography would be useful for determining the basis of hemodynamic compromise in such patients. Accordingly, 49 consecutive patients (33 men and 16 women; mean age 61 +/- 15 years) underwent two-dimensional echocardiography within 2 hours of placement of a pulmonary artery flotation catheter for determining the reason for hypotension, pulmonary edema, or both. To discriminate between cardiac and noncardiac causes, hemodynamic and two-dimensional echocardiographic data were evaluated independently by two to three blinded interpreters based on predetermined criteria. There was complete agreement between pulmonary artery catheter and two-dimensional echocardiographic data in 36 (86%) of the 42 patients in whom interpretable data were available in terms of cardiac versus noncardiac causes. The two modalities agreed in all patients with hypotension alone and disagreed in 2 of the 20 patients with pulmonary edema alone and 4 of the 14 patients with combined hypotension and pulmonary edema. In cases of discordance, the two tests provided complimentary information, particularly in patients with sepsis in whom the stroke volume may be normal to high but left ventricular systolic function may be depressed. The time taken for pulmonary artery catheter placement was 63 +/- 45 minutes versus 19 +/- 7 minutes for two-dimensional echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Ecocardiografia , Cardiopatias/diagnóstico por imagem , Hipotensão/diagnóstico por imagem , Edema Pulmonar/diagnóstico por imagem , Cateterismo de Swan-Ganz , Estudos de Avaliação como Assunto , Feminino , Cardiopatias/complicações , Humanos , Hipotensão/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Artéria Pulmonar , Edema Pulmonar/etiologia , Pressão Propulsora Pulmonar , Fatores de TempoRESUMO
The inability to perform telemetry on an ICD may have many potential causes. We report three recently identified cases where such a finding was indicative of unexpected device failure. Two of these cases involved identical failure mechanisms resulting from arcing of current within the high voltage hybrid. This placed the device into a high current state that caused rapid and complete battery depletion. There were no company alerts issued regarding this systematic problem. A multicenter arrhythmia device/lead database would be extremely useful in providing timely and unbiased information concerning device problems.
Assuntos
Desfibriladores Implantáveis , Telemetria , Idoso , Bases de Dados Factuais , Desfibriladores Implantáveis/estatística & dados numéricos , Remoção de Dispositivo , Fontes de Energia Elétrica , Falha de Equipamento/estatística & dados numéricos , Feminino , Humanos , Masculino , Estados Unidos , United States Food and Drug AdministrationRESUMO
Ocular changes during treatment with amiodarone are almost universal but are rarely serious. In this article we describe three patients from a single electrophysiology practice in whom optic neuropathy developed during treatment with amiodarone. All three patients were more than 65 years of age. The doses of amiodarone ranged from 100 to 400 mg/day, and the time intervals between the initiation of the amiodarone therapy and the appearance of first symptoms of optic neuropathy were 5 to 19 months. Two patients had bilateral involvement, and one had only unilateral involvement. Whether this result was due solely to amiodarone therapy, to the underlying poor health of these patients, or to the combination of these two factors is uncertain. These findings prompt us to recommend that all patients who receive amiodarone undergo complete ophthalmologic examinations, including careful evaluation of the ocular fundus regularly during such therapy. No randomized study had been undertaken to determine the true incidence of complications associated with this medication.
Assuntos
Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Atrofia Óptica/induzido quimicamente , Drusas do Disco Óptico/induzido quimicamente , Papiledema/induzido quimicamente , Idoso , Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Relação Dose-Resposta a Droga , Seguimentos , Humanos , Masculino , Atrofia Óptica/diagnóstico , Drusas do Disco Óptico/diagnóstico , Papiledema/diagnóstico , Acuidade Visual/efeitos dos fármacos , Campos Visuais/efeitos dos fármacosRESUMO
This case describes another example of inappropriate implantable defibrillator shock. We also show that this phenomenon resulted from electromagnetic current traveling down a coronary wire during coronary angioplasty.
Assuntos
Angioplastia Coronária com Balão , Desfibriladores Implantáveis , Fibrilação Ventricular/diagnóstico , Angioplastia Coronária com Balão/instrumentação , Artefatos , Impedância Elétrica , Eletrocardiografia , Fenômenos Eletromagnéticos , Desenho de Equipamento , Falha de Equipamento , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Ventricular/terapiaRESUMO
Advances in technology have enabled the implantation of defibrillators in the pectoral region. Complications encountered with pacemakers may also be observed with defibrillators. We describe two cases of twiddler's syndrome in patients with defibrillators implanted subcutaneously in the left pectoral region.
Assuntos
Desfibriladores Implantáveis/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Movimento , Obesidade/complicações , Síndrome , Taquicardia Ventricular/complicações , Taquicardia Ventricular/terapiaRESUMO
Although the potential for transcutaneous electronic nerve stimulation (TENS) units to interfere with appropriate function of cardiac pacemakers is well documented, an adverse interaction between a TENS unit and an ICD has never been reported. We describe a patient in whom a TENS unit created an electrical artifact that was interpreted by a transvenous ICD as ventricular fibrillation, leading to the delivery of inappropriate therapy. TENS units should be used with caution in patients with ICDs.