RESUMEN
BACKGROUND: Sudden cardiac arrest (SCA) ranks among the most common causes of death worldwide. Because SCA is most often lethal, yet mostly occurs in individuals without previously known cardiac disease, the identification of patients at risk for SCA could save many lives. In unselected SCA victims from the community, common genetic variants (which are not disease-causing per se, but may increase susceptibility to ventricular fibrillation) are found to be associated with increased SCA risk. However, whether rare genetic variants contribute to SCA risk in the community is largely unexplored. METHODS AND RESULTS: We here investigated the involvement of rare genetic variants in SCA risk at the population level by studying the prevalence of 6 founder genetic variants present in the Dutch population (PLN-p.Arg14del, MYBPC3-p.Trp792fsX17, MYBPC3-p.Arg943X, MYBPC3-p.Pro955fsX95, PKP2-p.Arg79X, and the Chr7q36 idiopathic ventricular fibrillation risk haplotype) in a cohort of 1440 unselected Dutch SCA victims included in the Amsterdam Resuscitation Study (ARREST). The six studied founder mutations were found to be more prevalent (1.1%) in the ARREST SCA cohort compared with an ethnically and geographically matched set of controls (0.4%, n=1379; P<0.05) or a set of Dutch individuals drawn from the Genome of the Netherlands (GoNL) study (0%, n=500; P<0.02). CONCLUSIONS: This finding provides proof-of-concept for the notion that rare genetic variants contribute to some extent to SCA risk in the community.
Asunto(s)
Muerte Súbita Cardíaca/etiología , Variación Genética , Características de la Residencia , Estudios de Casos y Controles , Muerte Súbita Cardíaca/epidemiología , Femenino , Efecto Fundador , Geografía , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Países Bajos/epidemiología , PrevalenciaRESUMEN
AIMS: The reported proportion of ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OHCA) has declined worldwide. VF decline may be caused by less VF at collapse and/or faster dissolution of VF into asystole. We aimed to determine the causes of VF decline by comparing VF proportions in relation to delay from emergency medical services (EMS) call to initial ECG (call-to-ECG delay), and VF dissolution rates between two study periods. METHODS: Data from the AmsteRdam REsuscitation STudies (ARREST), an ongoing OHCA registry in the Netherlands, were used. We studied cardiac OHCA in the study periods 1995-1997 (n=917) and 2006-2012 (n=5695). Cases with available ECG and information on call-to-ECG delay were included. We tested whether initial VF proportion and VF dissolution rates differed between both study periods using logistic regression. RESULTS: Despite a 15% VF decline between the periods, VF proportion around EMS call remained high in 2006-2012 (64%). The odds ratio (OR) for VF proportion in 2006-2012 vs. 1995-1997 was 0.52 (95%-CI 0.45-0.60, P<0.001), with similar rates of VF dissolution in both periods (P=0.83). VF decline was higher for unwitnessed collapse (OR 0.41, 95%-CI 0.28-0.58) and collapse at home (OR 0.50, 95%-CI 0.42-0.59), but not for categories of bystander CPR, age or sex. CONCLUSION: VF proportion early after collapse remains high. VF decline is explained by the occurrence of less initial VF, rather than faster dissolving VF. An increase in unwitnessed OHCA and collapse at home contributes to the observed VF decline.
Asunto(s)
Reanimación Cardiopulmonar/métodos , Paro Cardíaco Extrahospitalario/etiología , Sistema de Registros , Fibrilación Ventricular/epidemiología , Anciano , Servicios Médicos de Urgencia , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Oportunidad Relativa , Paro Cardíaco Extrahospitalario/epidemiología , Paro Cardíaco Extrahospitalario/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Fibrilación Ventricular/complicacionesRESUMEN
AIMS: Out-of-hospital cardiac arrest (OHCA) remains a major cause of death. We aimed to determine whether type-2 diabetes mellitus (T2DM) is associated with reduced pre-hospital and in-hospital survival rates after OHCA. METHODS AND RESULTS: An observational community-based cohort study was performed among 1549 OHCA patients with ECG-documented ventricular tachycardia/ventricular fibrillation (VT/VF). We compared pre-hospital and in-hospital survival rates between T2DM patients and non-diabetic patients. Analyses among T2DM patients were stratified according to current T2DM treatment, used as proxy for T2DM severity. Proportions of neurologically intact survival were analysed. Pre-hospital survival rates were lower in T2DM patients (n = 275) than in non-diabetic patients (n = 1274); 48.7 vs. 55.8% (univariate P = 0.032). Type-2 diabetes mellitus was associated with lower pre-hospital survival [OR 0.75 (0.58-0.98); after evaluation of the risk factors, we found no relevant confounding]. Patients treated with insulin only had lower pre-hospital survival rates than patients treated with oral glucose-lowering drugs only (37.3 vs. 53.3%, univariate P = 0.034), partially explained by location of OHCA and EMS response time [ORadj 0.62 (0.33-1.17)]. In-hospital survival rates were also lower in T2DM patients (n = 134) than in non-diabetic patients (n = 711); 40.3 vs. 57.7%, univariate P < 0.001. In those patients whose cause of OHCA was retrieved (n = 771), T2DM was significantly associated with lower in-hospital survival [ORadj 0.57 (0.37-0.87)]. Neurologically intact status at discharge was similarly high among T2DM and non-diabetic patients (94.4 vs. 94.6%, P = 0.954). CONCLUSION: T2DM is associated with lower pre-hospital and in-hospital survival rates after OHCA. Neurologically intact status at hospital discharge is high both among T2DM and non-diabetic patients.
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Diabetes Mellitus Tipo 2/mortalidad , Servicios Médicos de Urgencia , Mortalidad Hospitalaria , Paro Cardíaco Extrahospitalario/mortalidad , Taquicardia Ventricular/mortalidad , Fibrilación Ventricular/mortalidad , Anciano , Anciano de 80 o más Años , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Electrocardiografía , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Sistema Nervioso/fisiopatología , Paro Cardíaco Extrahospitalario/diagnóstico , Paro Cardíaco Extrahospitalario/fisiopatología , Paro Cardíaco Extrahospitalario/terapia , Alta del Paciente , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/terapia , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/fisiopatología , Fibrilación Ventricular/terapiaRESUMEN
BACKGROUND: In recent years, a wider use of automated external defibrillators (AEDs) to treat out-of-hospital cardiac arrest was advocated in The Netherlands. We aimed to establish whether survival with favorable neurologic outcome after out-of-hospital cardiac arrest has significantly increased, and, if so, whether this is attributable to AED use. METHODS AND RESULTS: We performed a population-based cohort study, including patients with out-of-hospital cardiac arrest from cardiac causes between 2006 and 2012, excluding emergency medical service-witnessed arrests. We determined survival status at each stage (to emergency department, to admission, and to discharge) and examined temporal trends using logistic regression analysis with year of resuscitation as an independent variable. By adding each covariable subsequently to the regression model, we investigated their impact on the odds ratio of year of resuscitation. Analyses were performed according to initial rhythm (shockable versus nonshockable) and AED use. Rates of survival with favorable neurologic outcome after out-of-hospital cardiac arrest increased significantly (N=6133, 16.2% to 19.7%; P for trend=0.021), although solely in patients presenting with a shockable initial rhythm (N=2823; 29.1% to 41.4%; P for trend<0.001). In this group, survival increased at each stage but was strongest in the prehospital phase (odds ratio, 1.11 [95% CI, 1.06-1.16]). Rates of AED use almost tripled during the study period (21.4% to 59.3%; P for trend <0.001), thereby decreasing time from emergency call to defibrillation-device connection (median, 9.9 to 8.0 minutes; P<0.001). AED use statistically explained increased survival with favorable neurologic outcome by decreasing the odds ratio of year of resuscitation to a nonsignificant 1.04. CONCLUSIONS: Increased AED use is associated with increased survival in patients with a shockable initial rhythm. We recommend continuous efforts to introduce or extend AED programs.
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Desfibriladores/estadística & datos numéricos , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Vigilancia de la Población , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Desfibriladores/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Paro Cardíaco Extrahospitalario/diagnóstico , Vigilancia de la Población/métodos , Estudios Prospectivos , Tasa de Supervivencia/tendenciasRESUMEN
BACKGROUND: Atrial fibrillation (AF) is associated with sudden cardiac death. We aimed to study whether AF is associated with ventricular fibrillation (VF), the most common cause of sudden cardiac death and whether this association is independent of confounders, ie, concomitant disease, use of antiarrhythmic or QT-prolonging drugs, and acute myocardial infarction. METHODS AND RESULTS: We performed a community-based case-control study. Cases were patients with out-of-hospital cardiac arrest because of ECG-documented VF. Controls were age-/sex-matched non-VF subjects from the community. VF risk in AF patients was studied by means of (conditional) logistic regression, adjusting for all available confounders. We studied 1397 VF cases and 3474 controls. AF occurred in 215 cases (15.4%) and 90 controls (2.6%). AF was associated with a 3-fold increased risk of VF (adjusted odds ratio, 3.1 [2.1-4.5]). VF risk in AF cases was increased to the same extent across all age/sex groups and in AF cases who had no comorbidity (adjusted odds ratio 3.0 [1.6-5.5]) or used no confounding drugs (antiarrhythmics, 2.4 [1.4-4.3]; QT-prolonging drugs, 3.1 [1.8-5.4]). VF risk was similarly increased in AF cases with acute myocardial infarction-related VF (adjusted odds ratio 2.6 [1.4-4.8]), and those with non-acute myocardial infarction-related VF (adjusted odds ratio 4.3 [1.9-10.1]). CONCLUSIONS: AF is independently associated with a 3-fold increased risk of VF. Comorbidity, use of antiarrhythmic or QT-prolonging drugs, or acute myocardial infarction does not fully account for this increased risk.
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Fibrilación Atrial/epidemiología , Fibrilación Ventricular/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/mortalidad , Estudios de Casos y Controles , Comorbilidad , Factores de Confusión Epidemiológicos , Muerte Súbita Cardíaca/epidemiología , Electrocardiografía , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio/epidemiología , Países Bajos/epidemiología , Oportunidad Relativa , Medición de Riesgo , Factores de Riesgo , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/mortalidadRESUMEN
INTRODUCTION: Since the recognition of inherited sodium (Na(+)) channel disease, the cardiac Na(+) channel has been extensively studied. Both loss-of-function and gain-of-function mutations of the cardiac Na(+) channel are associated with cardiac arrhythmia and sudden cardiac death. Pathophysiological mechanisms that may induce arrhythmia are unravelled and include alterations in biophysical properties due to the mutation in SCN5A, drug use and circumstantial factors. Insights into the mechanisms of inherited Na(+) channel disease may result in tailored therapy. However, due to the complexity of cardiac electrical activity and pathophysiological mechanisms, pharmacotherapy in cardiac Na(+) channel disease remains challenging. AREAS COVERED: This review discusses various mechanisms involved in inherited Na(+) channel disorders, focussing on Brugada syndrome (Brs) and long QT syndrome type 3 (LQTS3). It aims to provide an overview of developments in pharmacotherapy, discussing both treatment and which drugs to avoid to prevent arrhythmia. EXPERT OPINION: Altered biophysical properties of cardiac Na(+) channels are the basis of arrhythmias in patients with inherited Na(+) channel diseases such as BrS and LQTS3. The effects of such biophysical derangements are strongly modulated by concomitant factors. Tailored drug therapy is required to prevent arrhythmia and is best achieved by educating patients affected by Na(+) channel disorders.
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Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Miocardio/metabolismo , Canales de Sodio/fisiología , Potenciales de Acción , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/prevención & control , Síndrome de Brugada/tratamiento farmacológico , Síndrome de Brugada/metabolismo , Síndrome de Brugada/prevención & control , Trastorno del Sistema de Conducción Cardíaco , Humanos , Síndrome de QT Prolongado/tratamiento farmacológico , Síndrome de QT Prolongado/metabolismo , Síndrome de QT Prolongado/prevención & control , Mutación , Canales de Sodio/genéticaRESUMEN
AIMS: To evaluate changes in QT duration during low-dose haloperidol use, and determine associations between clinical variables and potentially dangerous QT prolongation. METHODS: In a retrospective cohort study in a tertiary university teaching hospital in The Netherlands, all 1788 patients receiving haloperidol between 2005 and 2007 were studied; ninety-seven were suitable for final analysis. Rate-corrected QT duration (QTc) was measured before, during and after haloperidol use. Clinical variables before haloperidol use and at the time of each ECG recording were retrieved from hospital charts. Mixed model analysis was used to estimate changes in QT duration. Risk factors for potentially dangerous QT prolongation were estimated by logistic regression analysis. RESULTS: Patients with normal before-haloperidol QTc duration (male ≤430 ms, female ≤450 ms) had a significant increase in QTc duration of 23 ms during haloperidol use; twenty-three percent of patients rose to abnormal levels (male ≥450 ms, female ≥470 ms). In contrast, a significant decrease occurred in patients with borderline (male 430-450 ms, female 450-470 ms) or abnormal before-haloperidol QTc duration (15 ms and 46 ms, respectively); twenty-three percent of patients in the borderline group, and only 9% of patients in the abnormal group obtained abnormal levels. Potentially dangerous QTc prolongation was independently associated with surgery before haloperidol use (OR(adj) 34.9, pâ=â0.009) and before-haloperidol QTc duration (OR(adj) 0.94, pâ=â0.004). CONCLUSION: QTc duration during haloperidol use changes differentially, increasing in patients with normal before-haloperidol QTc duration, but decreasing in patients with prolonged before-haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery before haloperidol use predict potentially dangerous QTc prolongation.