RESUMEN
Calcium regulation plays a central role in cardiac function. Several variants in the calcium channel Cav1.2 have been implicated in arrhythmic syndromes. We screened patients with Brugada syndrome, short QT syndrome, early repolarisation syndrome, and idiopathic ventricular fibrillation to determine the frequency and pathogenicity of Cav1.2 variants. Cav1.2 related genes, CACNA1C, CACNB2 and CACNA2D1, were screened in 65 probands. Missense variants were introduced in the Cav1.2 alpha subunit plasmid by mutagenesis to assess their pathogenicity using patch clamp approaches. Six missense variants were identified in CACNA1C in five individuals. Five of them, A1648T, A1689T, G1795R, R1973Q, C1992F, showed no major alterations of the channel function. The sixth C-terminal variant, Cavα1c-T1787M, present mostly in the African population, was identified in two patients with resuscitated cardiac arrest. The first patient originated from Cameroon and the second was an inhabitant of La Reunion Island with idiopathic ventricular fibrillation originating from Purkinje tissues. Patch-clamp analysis revealed that Cavα1c-T1787M reduces the calcium and barium currents by increasing the auto-inhibition mediated by the C-terminal part and increases the voltage-dependent inhibition. We identified a loss-of-function variant, Cavα1c-T1787M, present in 0.8% of the African population, as a new risk factor for ventricular arrhythmia.
Asunto(s)
Arritmias Cardíacas/genética , Síndrome de Brugada/genética , Canales de Calcio Tipo L/genética , Canales de Calcio/genética , Paro Cardíaco/genética , Fibrilación Ventricular/genética , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etnología , Arritmias Cardíacas/fisiopatología , Bario/metabolismo , Población Negra , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/etnología , Síndrome de Brugada/fisiopatología , Calcio/metabolismo , Canales de Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Cationes Bivalentes , Estudios de Cohortes , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Paro Cardíaco/diagnóstico , Paro Cardíaco/etnología , Paro Cardíaco/fisiopatología , Humanos , Transporte Iónico , Masculino , Persona de Mediana Edad , Mutación Missense , Técnicas de Placa-Clamp , Linaje , Factores de Riesgo , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/etnología , Fibrilación Ventricular/fisiopatología , Población BlancaRESUMEN
BACKGROUND: Current data on the risk of sudden arrhythmic death (SAD) and ventricular tachyarrhythmias (VTs) after acute coronary syndrome (ACS) in the Asian population are limited. OBJECTIVE: The purpose of this study was to investigate the incidence and predictors of SAD or VT after ACS in a contemporary cohort of Chinese patients in the era of early revascularization. METHODS: Consecutive patients admitted to our unit for ACS from 2010 to 2015 were retrospectively reviewed. RESULTS: A total of 918 patients (74.8% male, mean age 65.9 ± 13.4 years) were included in the study. Of these patients, 864 (94.1%) survived to discharge. After a mean of 34.1 ± 21.8 months, 42 (4.9%) had SAD or VT. The event rate was 0.46% in month 1, 0.26% per month in the months 2 to 6, 0.15% per month in months 6 to 12, and 1.23% per year from the second year onward. In multivariate analysis, early VT (hazard ratio [HR] 5.78, 95% confidence interval [CI] 2.63-12.72, P < .01), left ventricular ejection fraction ≤35% (HR 1.96, 95% CI 1.03-3.73, P = .04), prior coronary artery disease (HR 2.50, 95% CI 1.29-4.82, P < .01), triple-vessel disease (HR 3.69, 95% CI 1.81-7.54, P < .01), and chronic kidney disease (HR 2.43, 95% CI 1.21-4.92, P = .01) independently predicted SAD or VT. CONCLUSION: This study reports the rate of SAD or VT among Asian patients after ACS in the era of early revascularization and optimal medical therapy. Aggressive preventive measures should be considered for patients with multiple risk factors for SAD or VT, especially in the initial period after ACS.
Asunto(s)
Síndrome Coronario Agudo/mortalidad , Muerte Súbita Cardíaca/epidemiología , Taquicardia Ventricular/mortalidad , Fibrilación Ventricular/mortalidad , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/etnología , Síndrome Coronario Agudo/terapia , Distribución por Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Muerte Súbita Cardíaca/etnología , Femenino , Hong Kong/epidemiología , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Distribución por Sexo , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etnología , Taquicardia Ventricular/terapia , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/etnología , Fibrilación Ventricular/terapiaRESUMEN
BACKGROUND: Early repolarization (ER) with a horizontal ST segment (ST-h) and high-amplitude J waves in the inferior leads is associated with an increased risk of cardiac arrhythmic death. The effect of ethnicity and athletic status on this increased-risk ER pattern has not been established. Aboriginal Australian/Torres Strait Islander and Pacific Islander/Maori (non-Caucasian [non-C]) subjects are well represented in Australian sport; however, the patterns and prevalence of ER in these populations are unknown. OBJECTIVE: The purpose of this study was to assess the prevalence and effect of athletic activity on ER patterns in young non-C and Caucasian (C) subjects. METHODS: Twelve-lead ECGs of 726 male athletes (23.8% non-C) and 170 male controls (45.9% non-C) aged 16-40 years were analyzed for the presence of ER, defined as J-point elevation (J wave, QRS slur, or discrete ST elevation) ≥0.1 mV in ≥2 inferior (II, III, aVF) or lateral (I, aVL,V4-V6) leads. ST morphology was coded as horizontal (ST-h) or ascending (ST-a). "Increased-risk ER" was defined as inferior ER with ST-h and J waves >2 mV. RESULTS: Regardless of athletic status, ER and increased-risk ER were more prevalent in non-C than in C subjects (53.8% vs 32% and 7.6% vs 1.2%, respectively, P <.0001). Whereas lower heart rate, larger QRS voltage, and shorter QRS duration were predictors of ER, non-C ethnicity was the only independent predictor of increased-risk ER (odds ratio 17.621, 95% confidence interval 4.98-62.346, P < .0001). CONCLUSION: ER patterns associated with increased arrhythmic risk are more common in young non-C than C subjects and were not influenced by athletic status. The long-term clinical significance of ER in these populations is yet to be determined.
Asunto(s)
Atletas/estadística & datos numéricos , Muerte Súbita Cardíaca , Fibrilación Ventricular , Adolescente , Adulto , Rendimiento Atlético/fisiología , Australia/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Electrocardiografía/métodos , Técnicas Electrofisiológicas Cardíacas , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Masculino , Nativos de Hawái y Otras Islas del Pacífico , Prevalencia , Pronóstico , Medición de Riesgo , Fibrilación Ventricular/complicaciones , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/etnología , Fibrilación Ventricular/fisiopatologíaRESUMEN
INTRODUCTION: Survival from cardiac arrest is associated with having a shockable presenting rhythm (VF/pulseless VT) upon EMS arrival. A concern is that several studies have reported a decline in the incidence of VF/PVT over the past few decades. One plausible explanation is that contemporary cardiovascular therapies, such as increased use of statin and beta blocker drugs, may shorten the duration of VF/PVT after arrest. As a result, EMS response time would become an increasingly important factor in the likelihood of a shockable presenting rhythm, and consequently, cardiac arrest survival. OBJECTIVE: To develop a model describing the likelihood of shockable presenting rhythm as a function of EMS response time. METHODS: We conducted a retrospective observational study of cardiac arrest using the North Carolina Prehospital Care Reporting System (PreMIS). Inclusionary criteria consisted of adult patients suffering nontraumatic cardiac arrests witnessed by a layperson between January 1 and June 30, 2012. Patients defibrillated prior to EMS arrival were excluded. Chi-square and t-tests were used to analyze the relationship between shockable presenting rhythm and patient age, gender, and race; response time measured as elapsed minutes between 9-1-1 call receipt and scene arrival; and bystander CPR. Logistic regression was used to calculate the adjusted odds ratio (OR) of shockable presenting rhythm as a function of response time while controlling for statistically significant covariates. RESULTS: A total of 599 patients met inclusion criteria. Overall, VF/PVT was observed in 159 patients (26.5%). VF/PVT was less likely with increasing EMS response time (OR 0.92, 95% CI = 0.87-0.97, p < 0.01) and age (OR 0.98, 95% CI = 0.97-0.99, p < 0.01), while males (OR 1.98, 95% CI = 1.29-3.03, p < 0.01) and Caucasians (OR 1.86, 95% CI = 1.17-2.95, p < 0.01) were more likely to have shockable presenting rhythm. Bystander CPR was not associated with shockable presenting rhythm, although EMS response time was longer among patients with bystander CPR compared to those without (9.83 vs. 8.83 minutes, p < 0.01). CONCLUSIONS: We found that for every one minute of added ambulance response time, the odds of shockable presenting rhythm declined by 8%. This information could prove useful for EMS managers tasked with developing EMS system response strategies for cardiac arrest management.
Asunto(s)
Cardioversión Eléctrica/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Paro Cardíaco Extrahospitalario/terapia , Taquicardia Ventricular/terapia , Tiempo de Tratamiento , Fibrilación Ventricular/terapia , Distribución por Edad , Anciano , Servicios Médicos de Urgencia/organización & administración , Servicios Médicos de Urgencia/normas , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Salud de las Minorías/estadística & datos numéricos , North Carolina/epidemiología , Oportunidad Relativa , Paro Cardíaco Extrahospitalario/etnología , Paro Cardíaco Extrahospitalario/mortalidad , Probabilidad , Estudios Retrospectivos , Distribución por Sexo , Análisis de Supervivencia , Taquicardia Ventricular/etnología , Taquicardia Ventricular/mortalidad , Fibrilación Ventricular/etnología , Fibrilación Ventricular/mortalidad , Población Blanca/estadística & datos numéricosRESUMEN
OBJECTIVE: Studies evaluating a possible survival advantage from sudden cardiac arrest (SCA) in women have produced mixed results possibly due to a lack of comprehensive analyses. We hypothesized that race, socioeconomic status (SES), and elements of the lifetime clinical history influence gender effects and need to be incorporated within analyses of survival. METHODS: Cases of SCA were identified from the ongoing, prospective, multiple-source Oregon Sudden Unexpected Death Study (population approximately one million). Subjects included were age ≥18 years who underwent attempted resuscitation by EMS providers. Pearson's chi-square tests and independent samples t tests or analysis of variance were used for univariate comparisons. We evaluated gender and race differences in survival adjusted for age, circumstances of arrest, disease burden, and socioeconomic status using a logistic regression model predicting survival. RESULTS: A total of 1,296 cases had resuscitation attempted (2002-2007; mean age 65 years, male 67%). Women were older than men (68 vs. 63 years, p < 0.0001) and were more likely to have return of spontaneous circulation (41% vs. 33%, p = 0.004). Women were more likely to present with pulseless electrical activity (PEA) and asystole (p < 0.0001), and overall, PEA was more common among African Americans (p = 0.04). Higher survival to hospital discharge was observed in women compared to men presenting with ventricular fibrillation/tachycardia (34% vs. 24%, p = 0.02) or with PEA (10% vs. 3%, p = 0.007). In a multivariate model adjusting for age, race, presenting arrhythmia, arrest circumstances, arrest location, disease burden, and SES, women were more likely than men to survive to hospital discharge [odds ratio 1.85; 95% confidence interval (1.12-3.04)]. CONCLUSIONS: Despite older age, higher prevalence of SCA in the home, and higher rates of PEA, women had a survival advantage from ventricular fibrillation and pulseless electrical activity.
Asunto(s)
Paro Cardíaco/mortalidad , Fibrilación Ventricular/mortalidad , Factores de Edad , Anciano , Análisis de Varianza , Reanimación Cardiopulmonar , Distribución de Chi-Cuadrado , Femenino , Paro Cardíaco/etnología , Humanos , Modelos Logísticos , Masculino , Oregon/epidemiología , Estudios Prospectivos , Factores Sexuales , Factores Socioeconómicos , Análisis de Supervivencia , Fibrilación Ventricular/etnologíaRESUMEN
BACKGROUND: Racial disparities in survival after out-of-hospital cardiac arrest have been reported, but their causes remain uncertain. We sought to determine if hospital racial composition accounted for survival differences for patients hospitalized after cardiac arrest. METHODS: We evaluated hospitalizations of white and black Medicare beneficiaries (2000-2007) admitted from the emergency department to the intensive care unit with a diagnosis of cardiac arrest or ventricular fibrillation. We examined unadjusted survival rates and developed a multivariable logistic regression model that included patient and hospital factors. RESULTS: We analyzed 68,115 cardiac arrest admissions. Unadjusted survival to hospital discharge was worse for blacks (n = 7,942) compared with whites (n = 60,173) (30% vs 33%, P < .001). In multivariate analyses accounting for patient and hospital factors, adjusted probability of survival was worse for black patients at hospitals with higher proportions of black patients (31%, 95% CI 29%-32%) compared with predominately white hospitals (46%, 95% CI 36%-57%; P = .003). Similarly, whites had worse risk-adjusted survival at hospitals with higher proportions of black patients (28%, 95% CI 27%-30%) compared with predominately white hospitals (32%, 95% CI 31%-33%, P = .006). Blacks were more likely to be admitted to hospitals with low survival rates (23% vs 15%, P < .001). CONCLUSION: Hospitals with large black patient populations had worse cardiac arrest outcomes than predominantly white hospitals, and blacks were more likely to be admitted to these high-mortality hospitals. Understanding these differences in survival outcomes may uncover the causes for these disparities and lead to improved survival for all cardiac arrest victims.
Asunto(s)
Paro Cardíaco/etnología , Paro Cardíaco/mortalidad , Hospitalización , Fibrilación Ventricular/etnología , Fibrilación Ventricular/mortalidad , Negro o Afroamericano , Anciano , Anciano de 80 o más Años , Femenino , Paro Cardíaco/terapia , Humanos , Masculino , Tasa de Supervivencia , Fibrilación Ventricular/terapia , Población BlancaRESUMEN
BACKGROUND: Although implantable cardioverter defibrillator (ICD) therapy is widely endorsed for preventing sudden cardiac death (SCD), prior research documented a large black-white disparity in ICD therapy among the elderly. No studies have examined this disparity among nonelderly adults or over time as ICD therapy became widely diffused. OBJECTIVE: This study compares disparity in use of ICD therapy for 1996-1998 to 1999-2001 between African Americans and other adults. METHODS: The National Hospital Discharge Survey is used to compare ICD utilization between black and other adults diagnosed with ventricular tachycardia, ventricular fibrillation or cardiac arrest. RESULTS: Adjusting for patient and hospital characteristics, ICD use per 100 at-risk patients rose from 11.0 to 27.3 among African Americans and from 24.0 to 37.5 among other adults between 1996-1998 and 1999-2001. Although the disparity was evident throughout the study period, it declined by 40%. Compared with their nonblack counterparts, black adults at risk for SCD were five years younger on average (p < 0.01) and more likely to be female (p < 0.01). CONCLUSIONS: As ICD therapy became more widely available, use of this technology increased faster for black versus other adults, and the disparity in use declined but was not eliminated. Policymakers and clinicians should focus on increasing access among underserved populations to promising new technologies. Research focusing only on the elderly may miss important racial disparities when there is a race difference in the age distribution of disease risk. Further research should explore the relationship of technology diffusion to disparities in health service use.
Asunto(s)
Negro o Afroamericano , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables/estadística & datos numéricos , Difusión de Innovaciones , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Fibrilación Ventricular/terapia , Población Blanca , Adulto , Anciano , Muerte Súbita Cardíaca/etnología , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Clase Social , Estados Unidos , Fibrilación Ventricular/etnologíaRESUMEN
BACKGROUND: Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death. METHODS AND RESULTS: Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals < or = 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits. CONCLUSIONS: This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.
Asunto(s)
Canales de Calcio Tipo L/genética , Muerte Súbita Cardíaca , Electrocardiografía , Taquicardia Ventricular/genética , Fibrilación Ventricular/genética , Adulto , Animales , Células CHO , Canales de Calcio/genética , Canales de Calcio/fisiología , Canales de Calcio Tipo L/fisiología , Cricetinae , Cricetulus , Salud de la Familia , Femenino , Ligamiento Genético , Humanos , Masculino , Mutagénesis Sitio-Dirigida , Mutación Missense , Técnicas de Placa-Clamp , Fenotipo , Sistema de Registros , Taquicardia Ventricular/etnología , Taquicardia Ventricular/fisiopatología , Fibrilación Ventricular/etnología , Fibrilación Ventricular/fisiopatología , Población Blanca/genéticaRESUMEN
OBJECTIVES: We performed a meta-analysis of prognostic studies of patients with a Brugada ECG to assess predictors of events. BACKGROUND: The Brugada syndrome is an increasingly recognized cause of idiopathic ventricular fibrillation; however, there is wide variation in the prognosis of patients with the Brugada ECG. METHODS AND RESULTS: We retrieved 30 prospective studies of patients with the Brugada ECG, accumulating data on 1,545 patients. Summary estimates of the relative risk (RR) of events (sudden cardiac death [SCD], syncope, or internal defibrillator shock) for a variety of potential predictors were made using a random-effects model. The overall event rate at an average of 32 months follow-up was 10.0% (95% CI 8.5%, 11.5%). The RR of an event was increased (P < 0.001) among patients with a history of syncope or SCD (RR 3.24 [95% CI 2.13, 4.93]), men compared with women (RR 3.47 [95% CI 1.58, 7.63]), and patients with a spontaneous compared with sodium-channel blocker induced Type I Brugada ECG (RR 4.65 [95% CI 2.25, 9.58]). The RR of events was not significantly increased in patients with a family history of SCD (P = 0.97) or a mutation of the SCN5A gene (P = 0.18). The RR of events was also not significantly increased in patients inducible compared with noninducible by electrophysiologic study (EPS) (RR 1.88 [95% CI 0.62, 5.73], P = 0.27); however, there was significant heterogeneity of the studies included. CONCLUSIONS: Our findings suggest that a history of syncope or SCD, the presence of a spontaneous Type I Brugada ECG, and male gender predict a more malignant natural history. Our findings do not support the use of a family history of SCD, the presence of an SCN5A gene mutation, or EPS to guide the management of patients with a Brugada ECG.
Asunto(s)
Síndrome de Brugada/complicaciones , Desfibriladores Implantables/efectos adversos , Adulto , Pueblo Asiatico , Síndrome de Brugada/etnología , Síndrome de Brugada/terapia , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores Sexuales , Síncope/etiología , Síncope/terapia , Síndrome , Fibrilación Ventricular/etnología , Fibrilación Ventricular/etiología , Fibrilación Ventricular/prevención & control , Población BlancaRESUMEN
OBJECTIVES: To determine whether case fatality rates in South Asian (Bangladeshi, Indian and Pakistani) patients with acute myocardial infarction have shown similar declines to those reported for white patients during the past 15 years. DESIGN: Cross-sectional, observational study. SETTING: Coronary care unit in east London. PATIENTS: 2640 patients-29% South Asian-admitted with acute myocardial infarction between January 1988 and December 2002. MAIN OUTCOME MEASURES: Differences over time in rates of in-hospital death, ventricular fibrillation and left ventricular failure. RESULTS: The proportion of South Asians increased from 22% in 1988-92 to 37% in 1998-2002. Indices of infarct severity were similar in South Asian and white patients, with declining frequencies of ST elevation infarction (88.2% to 77.5%, p < 0.0001), Q wave development (78.1% to 56.9%, p < 0.0001) and mean (interquartile range) peak serum creatine kinase concentrations (1250 (567-2078) to 1007 (538-1758) IU/l, p < 0.0001) between 1988-92 and 1998-2002. Rates of in-hospital death (13.0% to 9.4%, p < 0.01), ventricular fibrillation (9.2% to 6.0%, p < 0.001) and left ventricular failure (33.2% to 26.5%, p < 0.0001) all declined; these changes did not interact significantly with ethnicity. Odds ratios for the effect of time on risk of death increased from 0.81 (95% CI 0.70 to 0.93) to 1.02 (95% CI 0.87 to 1.21) after adjustment for ethnicity and indices of infarct severity (ST elevation, peak creatine kinase, Q wave development and treatment with a thrombolytic). CONCLUSIONS: In the past 15 years, death from acute myocardial infarction among South Asians has declined at a rate similar to that seen in white patients. This is largely caused by reductions in indices of infarct severity.
Asunto(s)
Pueblo Asiatico/estadística & datos numéricos , Infarto del Miocardio/mortalidad , Población Blanca/estadística & datos numéricos , Estudios Transversales , Femenino , Mortalidad Hospitalaria , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etnología , Pronóstico , Fibrilación Ventricular/etnología , Fibrilación Ventricular/mortalidadRESUMEN
BACKGROUND: Reduced cardiac sodium current slows conduction and renders the heart susceptible to ventricular fibrillation. Loss of function mutations in SCN5A, encoding the cardiac sodium channel, are one cause of the Brugada syndrome, associated with slow conduction and a high incidence of ventricular fibrillation, especially in Asians. In this study, we tested the hypothesis that an SCN5A promoter polymorphism common in Asians modulates variability in cardiac conduction. METHODS AND RESULTS: Resequencing 2.8 kb of SCN5A promoter identified a haplotype variant consisting of 6 polymorphisms in near-complete linkage disequilibrium that occurred at an allele frequency of 22% in Asian subjects and was absent in whites and blacks. Reporter activity of this variant haplotype, designated HapB, in cardiomyocytes was reduced 62% compared with wild-type haplotype (P=0.006). The relationship between SCN5A promoter haplotype and PR and QRS durations, indexes of conduction velocity, was then analyzed in a cohort of 71 Japanese Brugada syndrome subjects without SCN5A mutations and in 102 Japanese control subjects. In both groups, PR and QRS durations were significantly longer in HapB individuals (P< or =0.002) with a gene-dose effect. In addition, up to 28% and 48% of variability in PR and QRS durations, respectively, were attributable to this haplotype. The extent of QRS widening during challenge with sodium channel blockers, known to be arrhythmogenic in Brugada syndrome and other settings, was also genotype dependent (P=0.002). CONCLUSIONS: These data demonstrate that genetically determined variable sodium channel transcription occurs in the human heart and is associated with variable conduction velocity, an important contributor to arrhythmia susceptibility.
Asunto(s)
Pueblo Asiatico/genética , Sistema de Conducción Cardíaco/fisiología , Proteínas Musculares/genética , Canales de Sodio/genética , Fibrilación Ventricular/etnología , Fibrilación Ventricular/genética , Adolescente , Adulto , Anciano , Animales , Células CHO , Niño , Cricetinae , Muerte Súbita Cardíaca/epidemiología , Femenino , Genes Reporteros , Predisposición Genética a la Enfermedad/etnología , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Miocitos Cardíacos/fisiología , Canal de Sodio Activado por Voltaje NAV1.5 , Fenotipo , Polimorfismo Genético , Regiones Promotoras Genéticas/genética , Fibrilación Ventricular/fisiopatologíaRESUMEN
Since 1992, the Brugada syndrome has been increasingly recognized worldwide, although its incidence and distribution remain unclear. In Asia, several cases have been reported in Japan, Thailand, Singapore, and Vietnam. However, little information is available from the Chinese population. Since June 1997, we have identified 10 patients with the diagnosis of the Brugada syndrome from six hospitals in Taiwan. All patients were male with the mean age of 46 +/- 7 years (range 36-61). They all had a normal chemistry profile, coronary angiography and echocardiography. Clinical presentations varied from seizure and syncope to sudden cardiac death. MRI and ultrafast CT of the heart did not show any abnormalities. Sustained ventricular tachycardia/ventricular fibrillation (VF) was induced in 7 of 8 patients who underwent an electrophysiologic study. The pharmacological provocation test was positive in 4 of 5 patients. One of the 4 patients who had a genetic study showed SCN5A gene mutation. An implantable cardioverter defibrillator (ICD) was implanted in 8 patients. During a mean follow-up of 29 +/- 17 months (range 2-54), 3 of 8 patients who had an ICD received appropriate ICD discharges after implantation. These 3 patients who were subsequently treated with antiarrhythmic agents have had no further recurrent ICD discharges. Two patients who refused ICD implantation are alive and well without taking antiarrhythmic agents. Our study showed that the clinical characteristics of our patients are similar to those described in the literature and that ICD is an effective treatment modality for patients with recurrent VF. However, antiarrhythmic agents may be beneficial for suppressing arrhythmia recurrences in selected patients.
Asunto(s)
Taquicardia Ventricular/etnología , Taquicardia Ventricular/fisiopatología , Adulto , Antiarrítmicos/uso terapéutico , Cateterismo Cardíaco , China/etnología , Angiografía Coronaria , Ecocardiografía Doppler , Electrocardiografía Ambulatoria , Ejercicio Físico , Prueba de Esfuerzo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Procainamida/uso terapéutico , Síndrome , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapia , Taiwán , Fibrilación Ventricular/etnología , Fibrilación Ventricular/fisiopatologíaRESUMEN
Since 1992 the Brugada syndrome has gained recognition as a cause of ventricular fibrillation. The syndrome was originally described in patients with the diagnostic triad of (1) right bundle branch block, (2) an electrocardiogram (ECG) with persistent ST-segment elevation in leads V1, V2, and V3, and (3) sudden cardiac death. Two different types of ST-segment elevation, coved and saddleback, have been described. All patients originally described had structurally normal hearts. The definition of the Brugada electrocardiogram (originally right bundle branch block and ST-segment elevation in V1, V2, and V3 in characteristic coved or saddleback configuration) has been evolving since the initial description, and not all patients with the Brugada electrocardiogram have the Brugada syndrome. We designed a trial to determine the prevalence in our population at the Medical Center of Louisiana in New Orleans of the Brugada ECG as it was originally defined. ECGs performed in 1997 were examined for changes consistent with the Brugada electrocardiogram. Those ECGs with changes secondary to another identifiable cause were excluded. The amount and type of ST-segment elevation in leads V1, V2, and V3 were recorded for the remaining ECGs. From a total of 55,446 electrocardiograms performed on 27,328 patients, we were able to identify only 18 ECGs with the changes originally described by Brugada, and none of them meet current criteria. Our study suggests that in our patient population the ECG now considered typical of the Brugada syndrome is rare.
Asunto(s)
Bloqueo de Rama/epidemiología , Fibrilación Ventricular/epidemiología , Adulto , Bloqueo de Rama/etnología , Muerte Súbita Cardíaca/epidemiología , Femenino , Humanos , Louisiana/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Fibrilación Ventricular/etnologíaRESUMEN
Australian doctors need to be aware of this little-known syndrome, which is a cause of sudden cardiac death. It is more common among Southeast Asian people, who make up a considerable proportion of our population. We report two cases which represent very different clinical presentations of this condition.
Asunto(s)
Muerte Súbita Cardíaca/etiología , Adulto , Asia Sudoriental/etnología , Australia/epidemiología , Bloqueo de Rama/etnología , Bloqueo de Rama/genética , Muerte Súbita Cardíaca/etnología , Electrocardiografía , Humanos , Masculino , Persona de Mediana Edad , Síncope/etiología , Síndrome , Taquicardia Ventricular/etnología , Taquicardia Ventricular/genética , Fibrilación Ventricular/etnología , Fibrilación Ventricular/genéticaRESUMEN
OBJECTIVE: To determine the changing risk of ventricular fibrillation, the prognostic implications, and the potential long term prognostic benefit of earlier hospital admission, after acute myocardial infarction. DESIGN: Prospective observational study. SETTING: A district general hospital in east London. PATIENTS: 1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction. MAIN OUTCOME MEASURES: Time of onset of pain and ventricular fibrillation, and long term survival of patients admitted with acute myocardial infarction. RESULTS: The rate of ventricular fibrillation in these hospital inpatients was high in the first hour from onset of pain (118 events/1000 persons/h; 95% confidence interval (CI) 50.7 to 231) and fell rapidly to an almost constant low level by six hours; 27.4% of patients with early ventricular fibrillation died in hospital, compared with 11.6% of those without (p < 0.0001), but mortality in patients who survived to hospital discharge was not altered by early ventricular fibrillation (five year survival: 75.0% (95% CI 60.0% to 84.8%) with ventricular fibrillation v 73.3% (95% CI 69.6% to 76.6%) without ventricular fibrillation). CONCLUSIONS: Patients successfully resuscitated from early ventricular fibrillation have the same prognosis as those without ventricular fibrillation after acute myocardial infarction. Faster access to facilities for resuscitation must be achieved if major improvements in the persistently high case fatality of patients after acute myocardial infarction are to be made.
Asunto(s)
Infarto del Miocardio/complicaciones , Fibrilación Ventricular/complicaciones , Anciano , Urgencias Médicas , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etnología , Infarto del Miocardio/mortalidad , Oportunidad Relativa , Pronóstico , Análisis de Regresión , Riesgo , Tasa de Supervivencia , Fibrilación Ventricular/etnología , Fibrilación Ventricular/mortalidadRESUMEN
Sudden cardiac death has been reported in patients with a unique electrocardiographic (ECG) abnormality showing right bundle branch block and ST segment elevation in the precordial leads. This syndrome was first described by Brugada and Brugada and has not been previously described in a Chinese population. We report here the first three cases in Singapore. The first patient was a 49-year-old man who presented with syncope, associated with generalized convulsions. The second patient was a 25-year-old man who complained of palpitations but no syncope. The third patient was a 77-year-old man who presented with recurrent episodes of syncope and collapsed with ventricular fibrillation. All patients had no past cardiac or drug history of note. The neurological examination and investigations were normal. All three patients showed a unique right bundle branch block pattern with ST segment elevation in leads V1-3. The echocardiogram and 24-h ambulatory ECG monitoring, were normal. Single vessel disease was present in the third patient. Electrophysiological studies performed in all three patients were able to induce ventricular fibrillation. The patient with resuscitated cardiac death underwent an implantable cardioverter defibrillator implantation. The importance of this syndrome is that the recognition of the unique ECG pattern enables early identification and treatment of these patients.
Asunto(s)
Bloqueo de Rama/fisiopatología , Paro Cardíaco/fisiopatología , Síncope/etiología , Síndrome , Adulto , Anciano , Bloqueo de Rama/etnología , Bloqueo de Rama/terapia , China/etnología , Desfibriladores Implantables , Electrocardiografía , Paro Cardíaco/diagnóstico , Paro Cardíaco/etnología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Singapur , Síncope/etnología , Fibrilación Ventricular/complicaciones , Fibrilación Ventricular/etnología , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/terapiaRESUMEN
STUDY OBJECTIVE: To determine whether race, when controlled for income, is an independent predictor of survival to hospital discharge after out-of-hospital cardiac arrest (OHCA). METHODS: Prospective OHCA data were collected over 4 years (1991-1994) from a convenience sample of OHCA patients transported to nine hospitals in three suburban counties. Race was determined from hospital and vital statistics records. The average household income was identified from ZIP codes and used as a marker of socioeconomic status. Demographic data and known predictors of survival were compared between blacks and whites. A logistic regression analysis was used to assess the association between race, income, and survival. RESULTS: Of the 1,690 patients, 223 (13%) were blacks and 1,467 (87%) were whites. Average household income was less for blacks than for whites ($40,225 versus $46,193; P < .001), but both populations were affluent by national standards (national percentile ranks were 73% and 88%, respectively). The populations were no different in percentage of witnessed arrests (57% versus 61%; P = .465). Blacks were younger (mean +/- SD, 62 +/- 16 versus 68 +/- 15 years; P < .001); less frequently received bystander CPR (11% versus 20%; P = .002); less often had ventricular tachycardia or ventricular fibrillation (37% versus 50%; P < .001); and had a shorter advanced life support call-response interval (median, 4 versus 6 minutes; P < .001). The odds ratio for survival (white/black) was .931 (95% confidence interval, .446 to 1.945). CONCLUSION: Race was not found to predict adverse OHCA outcomes in this affluent population.