BackgroundCatheter ablation (CA) is a highly effective therapy for the treatment of paroxysmal atrial fibrillation (AF) when compared with antiarrhythmic drug therapy (ADT). No randomized studies have compared the two strategies in persistent AF. The present randomized trial aimed to compare the effectiveness of CA vs. ADT in treating persistent AF.Methods and resultsPatients with persistent AF were randomly assigned to CA or ADT (excluding patients with long-standing persistent AF). Primary endpoint at 12-month follow-up was defined as any episode of AF or atrial flutter lasting >24 h that occurred after a 3-month blanking period. Secondary endpoints were any atrial tachyarrhythmia lasting >30 s, hospitalization, and electrical cardioversion. In total, 146 patients were included (aged 55 ± 9 years, 77% male). The ADT group received class Ic (43.8%) or class III drugs (56.3%). In an intention-to-treat analysis, 69 of 98 patients (70.4%) in the CA group and 21 of 48 patients (43.7%) in the ADT group were free of the primary endpoint (P = 0.002), implying an absolute risk difference of 26.6% (95% CI 10.0–43.3) in favour of CA. The proportion of patients free of any recurrence (>30 s) was higher in the CA group than in the ADT group (60.2 vs. 29.2%; P < 0.001) and cardioversion was less frequent (34.7 vs. 50%, respectively; P = 0.018).ConclusionCatheter ablation is superior to medical therapy for the maintenance of sinus rhythm in patients with persistent AF at 12-month follow-up.Clinical Trial Registration InformationNCT00863213 ().

Background-An implantable cardioverter-defibrillator (ICD) is the therapy of choice for primary prevention in patients with ischemia who are at risk for sudden cardiac death (SCD). One third of patients with significant coronary disease have chronic total coronary occlusion (CTO), which is associated with long-term mortality in patients with previous myocardial infarction. However, the impact of CTO on the occurrence of ventricular arrhythmias and long-term mortality in ICD recipients remains unknown. Methods and Results-All consecutive patients with coronary artery disease receiving ICD therapy for the prevention of SCD were included in the study. Among other characteristics, the existence of CTO was assessed. During follow-up, the occurrence of appropriate device delivery because of ventricular arrhythmias as well as mortality were noted. A total of 162 patients (mean age, 62Ϯ9 years; 93% men) with an ICD were included and followed for a median of 26 months (interquartile range, 12-42). At least 1 CTO was present in 71 (44%) patients. Appropriate device therapy was detected in 18% of the patients during the follow-up. The presence of CTO was associated with higher ventricular arrhythmia and mortality rates (log-rank test, Ͻ0.01). Multivariable analysis revealed that CTO was independently associated with appropriate ICD intervention (hazard ratio, 3.5; Pϭ0.003). Conclusions-In patients with ischemic heart disease receiving ICDs for primary prevention of SCD, CTO is an independent predictor for the occurrence of ventricular arrhythmias and has an adverse impact on long-term mortality. (Circ Arrhythm Electrophysiol. 2012;5:147-154.)

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BackgroundBrugada syndrome (BrS) is a rare genetic cardiac arrhythmia that can lead to sudden cardiac death in patients with a structurally normal heart. Genetic variations in SCN5A can be identified in approximately 20-25% of BrS cases. The aim of our work was to determine the spectrum and prevalence of genetic variations in a Spanish cohort diagnosed with BrS.Methodology/Principal FindingsWe directly sequenced fourteen genes reported to be associated with BrS in 55 unrelated patients clinically diagnosed. Our genetic screening allowed the identification of 61 genetic variants. Of them, 20 potentially pathogenic variations were found in 18 of the 55 patients (32.7% of the patients, 83.3% males). Nineteen of them were located in SCN5A, and had either been previously reported as pathogenic variations or had a potentially pathogenic effect. Regarding the sequencing of the minority genes, we discovered a potentially pathogenic variation in SCN2B that was described to alter sodium current, and one nonsense variant of unknown significance in RANGRF. In addition, we also identified 40 single nucleotide variations which were either synonymous variants (four of them had not been reported yet) or common genetic variants. We next performed MLPA analysis of SCN5A for the 37 patients without an identified genetic variation, and no major rearrangements were detected. Additionally, we show that being at the 30-50 years range or exhibiting symptoms are factors for an increased potentially pathogenic variation discovery yield.ConclusionsIn summary, the present study is the first comprehensive genetic evaluation of 14 BrS-susceptibility genes and MLPA of SCN5A in a Spanish BrS cohort. The mean pathogenic variation discovery yield is higher than that described for other European BrS cohorts (32.7% vs 20-25%, respectively), and is even higher for patients in the 30-50 years age range.

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Brugada syndrome (BrS) is a life-threatening, inherited arrhythmogenic syndrome associated with autosomal dominant mutations in SCN5A, the gene encoding the cardiac Na+ channel alpha subunit (Nav1.5). The aim of this work was to characterize the functional alterations caused by a novel SCN5A mutation, I890T, and thus establish whether this mutation is associated with BrS. The mutation was identified by direct sequencing of SCN5A from the proband’s DNA. Wild-type (WT) or I890T Nav1.5 channels were heterologously expressed in human embryonic kidney cells. Sodium currents were studied using standard whole cell patch-clamp protocols and immunodetection experiments were performed using an antibody against human Nav1.5 channel. A marked decrease in current density was observed in cells expressing the I890T channel (from −52.0±6.5 pA/pF, n = 15 to −35.9±3.4 pA/pF, n = 22, at −20 mV, WT and I890T, respectively). Moreover, a positive shift of the activation curve was identified (V 1/2 = −32.0±0.3 mV, n = 18, and −27.3±0.3 mV, n = 22, WT and I890T, respectively). No changes between WT and I890T currents were observed in steady-state inactivation, time course of inactivation, slow inactivation or recovery from inactivation parameters. Cell surface protein biotinylation analyses confirmed that Nav1.5 channel membrane expression levels were similar in WT and I890T cells. In summary, our data reveal that the I890T mutation, located within the pore of Nav1.5, causes an evident loss-of-function of the channel. Thus, the BrS phenotype observed in the proband is most likely due to this mutation.

Wavelet discrimination criteria in single-chamber ICDs as the sole discriminator can significantly reduce inappropriate therapy for SVT, not only in the range of VTs in the slowest analysed range (340-500 ms for this study) but also for faster VTs. No significant clinical consequences were found when the algorithm was used, but final data should prompt the use of the algorithm in combination with a high rate time-out feature.