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Because of its antiarrhythmic potency and due to the lack of alternatives, amiodarone is often used for antiarrhythmic therapy in patients with ICD or CRT-D systems. To date, robust data on the safety and clinical benefit of amiodarone therapy in these patients are missing OBJECTIVE: This study was designed to assess the periprocedural and post-procedural outcome of combined therapy with beta-blockers plus amiodarone compared to treatment with single beta-blockers in this "real life" cohort of ICD recipients of the German DEVICE registry.4,499 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE Registry were enrolled 03/2007-02/2014.Amiodarone had no significant effect on the success of defibrillation testing. Early implantation-associated complications were similar between the groups. One-year overall mortality was, however, significantly higher in the beta-blocker plus amiodarone cohort (adjusted HR 2.09; p0.001). Interestingly, amongst the surviving patients, amiodarone was not associated with a significantly reduced risk of ICD discharges, syncopal events. Further, the occurrence of VT storm or incessant VTs and the number of patients scheduled for intracardiac ablation did not differ among both groups while the rate of rehospitalization was lower in the cohort with sole beta-blockers.While amiodarone has no adverse effect on the success of defibrillation testing, our data suggest an increased all-cause mortality under amiodarone therapy, especially in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. In surviving patients, rates of arrhythmic events were comparable.

BACKGROUND: Little is known about genome-wide changes in the atrial transcriptome as a cause or consequence of atrial fibrillation (AF), and the effect of its common and clinically relevant comorbidity, heart failure (HF).OBJECTIVE: To explore candidate disease processes for atrial fibrillation, we investigated gene expression changes in atrial tissue samples from patients with and without AF, stratified by HF.METHODS: RNA sequencing was performed in right and left atrial appendage tissue in 195 patients undergoing open-heart surgery from centers participating in the CATCH-ME consortium (no history of AF (n=91), paroxysmal AF (n=53) and persistent/permanent AF (n=51)). Analyses were stratified into patients with and without HF (n=75/120), and adjusted for age, sex, atrial side, and a combination of clinical characteristics.RESULTS: We identified 35 genes associated with persistent AF compared to patients without a history of AF, both in the presence or absence of HF (false discovery rateCONCLUSIONS: Analysis of atrial gene expression profiles identified numerous novel genes associated with persistent AF, in presence or absence of HF. Interestingly, no consistent transcriptional changes were associated with paroxysmal AF, suggesting that AF-induced changes in gene expression predominate other changes.

Background The approval of an entirely subcutaneous implantable-cardioverter defibrillator (ICD) system (S-ICD) has raised attention about this promising technology. It was developed to overcome lead failure and infection problems of conventional transvenous ICD systems. Nevertheless, lead migration of the initial design and inappropriate shock rates have raised concerns regarding its reliability and safety. Objective The purpose of this study was to report the largest multicenter series to date of patients with the new device in comparison with a matched conventional transvenous ICD collective with focus on perioperative complications, conversion of induced ventricular fibrillation (VF), and short-term follow-up. Methods/Results Sixty-nine patients (50 male and 19 female; mean age 45.7±15.7 years) received an S-ICD in three German centers and were randomly assigned to 69 sex- and age-matched conventional ICD patients. The indication was primary prevention in 41 patients (59.4%) without difference between groups (34 control patients; P = .268). The predominant underlying heart disease was ischemic cardiomyopathy in 11 (15.9%), dilated cardiomyopathy in 25 (36.2%), and hypertrophic cardiomyopathy in 10 (14.5%) in the S-ICD group. Mean implantation time was 70.8±27.9 minutes ( P = .398). Conversion rates of induced VF were 89.5% for 65 J (15-J safety margin) and 95.5% including reversed shock polarity (15-J safety margin) in the study group. Termination of induced VF was successful in 90.8% (10-J safety margin, device dependent) of the control patients ( P = .815). Procedural complications were similar between the 2 groups. Mean follow-up was 217±138 days. During follow-up, 3 patients with S-ICD were appropriately treated for ventricular arrhythmias. Three inappropriate episodes (5.2%) occurred in 3 S-ICD patients due to T-wave oversensing, whereas atrial fibrillation with rapid conduction was the predominant reason for inappropriate therapy in conventional devices ( P = .745). Conclusion The novel S-ICD system can be implanted safely with similar perioperative adverse events compared with standard transvenous devices. Our case-control study demonstrates a 10.4% failure of conversion of induced VF with the S-ICD set to standard polarity and 15-J safety margin and comparable inappropriate shock rates during short-term follow-up.

Genome-wide association studies have been increasingly used to study the genetics of complex human diseases. Within the field of cardiac electrophysiology, this technique has been applied to conditions such as atrial fibrillation, and several electrocardiographic parameters including the QT interval. While these studies have identified multiple genomic regions associated with each trait, questions remain, including the best way to explore the pathophysiology of each association and the potential for clinical utility. This review will summarize recent genome-wide association study results within cardiac electrophysiology and discuss their broader implications in basic science and clinical medicine.

Atrial fibrillation (AF) is the most common sustained arrhythmia and has a substantial heritable component. Numerous associations between single nucleotide polymorphisms (SNPs) and AF have been described, but few have been replicated.We sought to systematically replicate SNPs that are reported to be associated with AF in two large study samples of European descent.We searched PubMed for studies reporting associations between SNPs and AF published before July 1, 2007. SNPs were genotyped in two independent case-control samples from Germany and the United States. Associations between SNPs and AF were assessed using logistic regression models adjusting for age, sex, and hypertension. A meta-analysis of the results from the two studies was performed.We identified 21 SNPs and the angiotensin-converting enzyme insertion/deletion polymorphism that were reported to be associated with AF in the literature. Nine of these genetic variants were not represented on common genome-wide SNP arrays. We successfully genotyped 21 of these 22 variants in 2,145 cases with AF from the German Competence Network for Atrial Fibrillation and 4,073 controls from the KORA S4 study and 16 variants in 790 cases and 1,330 controls from the Massachusetts General Hospital. None of the SNPs replicated in independent populations with AF.Our results suggest that previously reported associations to AF were likely false positives and highlight the need for systematic replication of genetic associations in large, independent cohorts to accurately detect variants associated with disease.

Background The Brugada syndrome (BrS) is considered a rare mendelian disorder with autosomal dominant transmission. BrS is associated with an increased risk of sudden cardiac death and specific ECG features consisting of ST-segment elevation in the right precordial leads. Loss-of-function mutations in SCN5A , encoding the pore-forming subunit of the cardiac sodium channel (Na v 1.5), are identified in ~20% of patients. However, studies in families harboring mutations in SCN5A have demonstrated low disease penetrance and, in some instances, absence of the familial SCN5A mutation in some affected members. These observations suggest a more complex inheritance model. Methods To identify common genetic factors modulating disease risk, we conducted a genome-wide association study on 312 individuals with BrS and 1115 ancestry-matched controls. Results Two genomic loci displayed significant association. Replication testing on 2 independent case/control sets from Europe (598/855) and Japan (208/1016) confirmed both associations and revealed a third locus. The cumulative effect of the 3 loci on disease susceptibility was large, with an odds ratio of 21.5 in the presence of more than 4 risk alleles vs less than 2. Two of 3 loci had previously been shown to influence ECG conduction parameters in the general population. The third locus encompasses a transcription factor that has not previously been implicated in cardiac electrical function and arrhythmia. Functional studies in mice heterozygous knockout for this transcription factor identified differences in expression of Na v 1.5 in addition to differences in conduction of the cardiac electrical impulse in the right ventricular outflow tract. Conclusions Our findings (1) indicate that common genetic variation may have a strong impact on predisposition to BrS and (2) identify a new gene involved in the pathogenesis of the disease.