Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications

Objective Epilepsy is associated with increased risk for sudden cardiac death (SCD). We aimed to establish, in a community based study, whether this association is mediated by epilepsy per se, use of antiepileptic medications (AEMs), or both. Methods We studied SCD cases and age/sex matched controls in a case-control study in a large scale general practitioners' research database (n=478 661 patients). SCD risk for symptomatic epilepsy (seizure <2 years before SCD), stable epilepsy (no seizure <2 years before SCD), and use of AEMs (any indication) was determined. Results We identified 926 SCD cases and 9832 controls. Fourteen cases had epilepsy. Epilepsy was associated with an increased SCD risk (cases 1.5%, controls 0.5%; adjusted OR 2.8, 95% CI 1.4 to 5.3). SCD risk was increased for symptomatic epilepsy (cases 0.9%, controls 0.1%; adjusted OR 5.8, 95% CI 2.1 to 15.6), but not with stable epilepsy (cases 0.6%, controls 0.4%; adjusted OR 1.6, 95% CI 0.7 to 4.1). AEM use was found in 23 cases and was associated with an increased SCD risk (cases 2.5%, controls 0.8%; adjusted OR overall 2.6, 95% CI 1.5 to 4.3) among symptomatic epilepsy cases (cases 0.9%, controls 0.1%; adjusted OR 6.4, 95% CI 2.4 to 17.4) and non-epilepsy cases (cases 1.0%, controls 0.4%; adjusted OR 2.3, 95% CI 1.01 to 5.2). Increased SCD risk was associated with sodium channel blocking AEMs (cases 1.6%, controls 0.4%; adjusted OR 2.8, 95% CI 1.1 to 7.2), but not with non-sodium channel blocking AEMs. Carbamazepine and gabapentin were associated with increased SCD risk (carbamazepine: cases 1.1%, controls 0.3%; adjusted OR 3.2, 95% CI 1.1 to 9.2; gabapentin: cases 0.3%, controls 0.1%; adjusted OR 5.7, 95% CI 1.2 to 27.9). Conclusions Epilepsy and AEM use are both associated with increased SCD risk in the general population. Poor seizure control contributes to increased SCD risk in epilepsy, while sodium channel blockade contributes to SCD susceptibility in AEM users

An inherited sudden cardiac arrest syndrome may be based on primary myocardial and autonomic nervous system abnormalities

Background: A recently discovered sudden cardiac arrest (SCA) syndrome is linked to a risk haplotype that harbors the dipeptidyl-peptidase 6 (DPP6) gene as a plausible culprit. Objective: Because DPP6 impacts both cardiomyocyte and neuronal function, we hypothesized that ventricular fibrillation (VF) in risk haplotype carriers arises from functional changes in both the heart and autonomic nervous system. Methods: We studied 6 risk haplotype carriers with previous VF (symptomatic), 8 carriers without VF (asymptomatic), and 7 noncarriers (controls). We analyzed supine and standing heart rate variability, baroreflex sensitivity, pre-VF heart rate changes, and myocardial 123I-meta-iodobenzylguanide (123I-mIBG) scintigraphy. Results: Carriers had longer interbeat intervals than controls (1.03 ± 0.11 seconds vs 0.81 ± 0.07 seconds; P <.001), lower low-frequency (LF) and higher high-frequency (HF) activity, and lower LF/HF ratio (0.68 ± 0.50 vs 2.11 ± 1.10; P = .013) in the supine position. Upon standing up, carriers had significantly larger decrease in interbeat interval and increase in LF than controls (standing-to-supine ratio: 0.78 ± 0.07 vs 0.90 ± 0.07; P = .002; and 1.94 ± 1.03 vs 1.17 ± 0.34; P = .022, respectively), and nonsignificantly larger decrease in HF (0.62 ± 0.36 vs 0.97 ± 0.42; P = .065) and increase in LF/HF ratio (5.55 ± 6.79 vs 1.62 ± 1.24; P = .054). Sixteen of 17 VF episodes occurred at rest. Heart rate immediately before VF was 110 ± 25 bpm. Symptomatic carriers had less heterogeneous 123I-mIBG distribution in the left ventricle than asymptomatic carriers (single-photon emission computed tomography score ≥3 in 7 asymptomatic and 1 symptomatic carrier; P = .008). Conclusion: It can be speculated that these data are consistent with more labile autonomic tone in carriers, suggesting that the primary abnormalities may reside in both the heart and the autonomic nervous system

Women have lower chances than men to be resuscitated and survive out-of-hospital cardiac arrest

AIMS: Previous studies on sex differences in out-of-hospital cardiac arrest (OHCA) had limited scope and yielded conflicting results. We aimed to provide a comprehensive overall view on sex differences in care utilization, and outcome of OHCA. METHODS AND RESULTS: We performed a population-based cohort-study, analysing all emergency medical service (EMS) treated resuscitation attempts in one province of the Netherlands (2006-2012). We calculated odds ratios (ORs) for the association of sex and chance of a resuscitation attempt by EMS, shockable initial rhythm (SIR), and in-hospital treatment using logistic regression analysis. Additionally, we provided an overview of sex differences in overall survival and survival at successive stages of care, in the entire study population and in patients with SIR. We identified 5717 EMS-treated OHCAs (28.0% female). Women with OHCA were less likely than men to receive a resuscitation attempt by a bystander (67.9% vs. 72.7%; P < 0.001), even when OHCA was witnessed (69.2% vs. 73.9%; P < 0.001). Women who were resuscitated had lower odds than men for overall survival to hospital discharge [OR 0.57; 95% confidence interval (CI) 0.48-0.67; 12.5% vs. 20.1%; P < 0.001], survival from OHCA to hospital admission (OR 0.88; 95% CI 0.78-0.99; 33.6% vs. 36.6%; P = 0.033), and survival from hospital admission to discharge (OR 0.49, 95% CI 0.40-0.60; 33.1% vs. 51.7%). This was explained by a lower rate of SIR in women (33.7% vs. 52.7%; P < 0.001). After adjustment for resuscitation parameters, female sex remained independently associated with lower SIR rate. CONCLUSION: In case of OHCA, women are less often resuscitated by bystanders than men. When resuscitation is attempted, women have lower survival rates at each successive stage of care. These sex gaps are likely explained by lower rate of SIR in women, which can only partly be explained by resuscitation characteristics

A Complex Double Deletion in LMNA Underlies Progressive Cardiac Conduction Disease, Atrial Arrhythmias, and Sudden Death

Background-Cardiac conduction disease is a clinically and genetically heterogeneous disorder characterized by defects in electrical impulse generation and conduction and is associated with sudden cardiac death. Methods and Results-We studied a 4-generation family with autosomal dominant progressive cardiac conduction disease, including atrioventricular conduction block and sinus bradycardia, atrial arrhythmias, and sudden death. Genome-wide linkage analysis mapped the disease locus to chromosome 1p22-q21. Multiplex ligation-dependent probe amplification analysis of the LMNA gene, which encodes the nuclear-envelope protein lamin A/C, revealed a novel gene rearrangement involving a 24-bp inversion flanked by a 3.8-kb deletion upstream and a 7.8-kb deletion downstream. The presence of short inverted sequence homologies at the breakpoint junctions suggested a mutational event involving serial replication slippage in trans during DNA replication. Conclusions-We identified for the first time a complex LMNA gene rearrangement involving a double deletion in a 4-generation Dutch family with progressive conduction system disease. Our findings underscore the fact that if conventional polymerase chain reaction-based direct sequencing approaches for LMNA analysis are negative in suggestive pedigrees, mutation detection techniques capable of detecting gross genomic lesions involving deletions and insertions should be considered. (Circ Cardiovasc Genet. 2011;4:280-287.

High haemoglobin A1c level is a possible risk factor for ventricular fibrillation in sudden cardiac arrest among non-diabetic individuals in the general population

Aims: This study aimed to establish whether higher levels of glycated haemoglobin (HbA1c) are associated with increased sudden cardiac arrest (SCA) risk in non-diabetic individuals. Methods and results: Case-control study in non-diabetic individuals (HbA1c six-fold increased VF risk [adjusted odds ratio (ORadj) 6.74 (5.00-9.09)] and that 0.1% increase in HbA1c level was associated with 1.4-fold increase in VF risk, independent of concomitant cardiovascular risk factors. Increased VF risk at higher HbA1c is associated with acute myocardial infarction (MI) as cause of VF [OR 1.14 (1.04-1.24)], but the association between HbA1c and VF was similar in non-MI patients [OR 1.32 (1.21-1.44)] and MI patients [OR 1.47 (1.37-1.58)]. Conclusion: Among non-diabetic individuals, risk of VF increased with rising HbA1c levels, independent of concomitant cardiovascular disease. Future studies should establish whether HbA1c level may be used as biomarker to recognize individuals at risk for VF

Implantable cardioverter-defibrillators have reduced the incidence of resuscitation for out-of-hospital cardiac arrest caused by lethal arrhythmias

Background-Over the last decades, a gradual decrease in ventricular fibrillation (VF) as initial recorded rhythm during resuscitation for out-of-hospital cardiac arrest (OHCA) has been noted. We sought to establish the contribution of implantable cardioverter-defibrillator (ICD) therapy to this decline. Methods and Results-Using a prospective database of all OHCA resuscitation in the province North Holland in the Netherlands (Amsterdam Resuscitation Studies [ARREST]), we collected data on all patients in whom resuscitation for OHCA was attempted in 2005-2008. VF OHCA incidence (per 100 000 inhabitants per year) was compared with VF OHCA incidence data during 1995-1997, collected in a similar way. We also collected ICD interrogations of all ICD patients from North Holland and identified all appropriate ICD shocks in 2005-2008; we calculated the number of prevented VF OHCA episodes, considering that only part of the appropriate shocks would result in avoided resuscitation. VF OHCA incidence decreased from 21.1/100 000 in 1995-1997 to 17.4/100 000 in 2005-2008 (P<0.001). Non-VF OHCA increased from 12.2/100 000 to 19.4/100 000 (P<0.001). VF as presenting rhythm declined from 63% to 47%. In 2005-2008, 1972 ICD patients received 977 shocks. Of these shocks, 339 were caused by a life-threatening arrhythmia. We estimate that these 339 shocks have prevented 81 (minimum, 39; maximum, 152) cases of VF OHCA, corresponding with 33% (minimum, 16%; maximum, 63%) of the observed decline in VF OHCA incidence. Conclusions-The incidence of VF OHCA decreased over the last 10 years in North Holland. ICD therapy explained a decrease of 1.2/100 000 inhabitants per year, corresponding with 33% of the observed decline in VF OHCA

Implantable Cardioverter-Defibrillators Have Reduced the Incidence of Resuscitation for Out-of-Hospital Cardiac Arrest Caused by Lethal Arrhythmias

Background-Over the last decades, a gradual decrease in ventricular fibrillation (VF) as initial recorded rhythm during resuscitation for out-of-hospital cardiac arrest (OHCA) has been noted. We sought to establish the contribution of implantable cardioverter-defibrillator (ICD) therapy to this decline. Methods and Results-Using a prospective database of all OHCA resuscitation in the province North Holland in the Netherlands (Amsterdam Resuscitation Studies [ARREST]), we collected data on all patients in whom resuscitation for OHCA was attempted in 2005-2008. VF OHCA incidence (per 100 000 inhabitants per year) was compared with VF OHCA incidence data during 1995-1997, collected in a similar way. We also collected ICD interrogations of all ICD patients from North Holland and identified all appropriate ICD shocks in 2005-2008; we calculated the number of prevented VF OHCA episodes, considering that only part of the appropriate shocks would result in avoided resuscitation. VF OHCA incidence decreased from 21.1/100 000 in 1995-1997 to 17.4/100 000 in 2005-2008 (P <0.001). Non-VF OHCA increased from 12.2/100 000 to 19.4/100 000 (P <0.001). VF as presenting rhythm declined from 63% to 47%. In 2005-2008, 1972 ICD patients received 977 shocks. Of these shocks, 339 were caused by a life-threatening arrhythmia. We estimate that these 339 shocks have prevented 81 (minimum, 39; maximum, 152) cases of VF OHCA, corresponding with 33% (minimum, 16%; maximum, 63%) of the observed decline in VF OHCA incidence. Conclusions-The incidence of VF OHCA decreased over the last 10 years in North Holland. ICD therapy explained a decrease of 1.2/100 000 inhabitants per year, corresponding with 33% of the observed decline in VF OHC