First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial.

BACKGROUND: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with nonischemic cardiomyopathy, an increasingly prevalent population that is referred for advanced therapies globally. METHODS: We conducted an international, multicenter, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for ICD implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomly assigned (1:1) to ablation plus an ICD versus conventional medical therapy plus an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite end point of VT recurrence, cardiovascular hospitalization, or death. RESULTS: Randomly assigned patients had a mean age of 55 years (interquartile range, 46-64) and left ventricular ejection fraction of 40% (interquartile range, 30%-49%); 81% were male. The underlying heart disease was ischemic cardiomyopathy in 35%, nonischemic cardiomyopathy in 30%, and arrhythmogenic cardiomyopathy in 35%. Ablation was performed a median of 2 days before ICD implantation (interquartile range, 5 days before to 14 days after). At 31 months, the primary outcome occurred in 49.3% of the ablation group and 65.5% in the control group (hazard ratio, 0.58 [95% CI, 0.35-0.96]; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (hazard ratio, 0.51 [95%CI, 0.29-0.90]; P=0.02). A statistically significant reduction in both ICD shocks (10.0% versus 24.6%; P=0.03) and antitachycardia pacing (16.2% versus 32.8%; P=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0% versus. 33.7%; hazard ratio, 0.82 [95% CI, 0.43-1.56]; P=0.55) or mortality (8.9% versus 8.8%; hazard ratio, 1.40 [95% CI, 0.38-5.22]; P=0.62]) were observed. Ablation-related complications occurred in 8.3% of patients. CONCLUSIONS: Among patients with cardiomyopathy of varied causes, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02848781.

Association between big endothelin-1 and CHADS2/CHA2DS2-VASc scores in non-valvular atrial fibrillation.

BACKGROUND: Endothelial function, as measured by big endothelin-1 (ET-1), has been demonstrated to be useful in predicting adverse long-term events in patients with cardiovascular disease. Nevertheless, there are little data about the association between big ET-1 and thromboembolism risk in atrial fibrillation (AF). We aimed to investigate the relationship between big ET-1 and CHADS2/CHA2DS2-VASc scores used for evaluating thromboembolic risk in patients with non-valvular AF. METHODS: The study population consisted of 238 consecutive AF patients (67.6% with paroxysmal AF and 32.4% with persistent AF). The patients were divided into two groups (high- or low-intermediate risk group) based on CHADS2 and CHA2DS2-VASc scores (score ≥ 2 or < 2, respectively). Clinical, laboratory, and echocardiographic parameters were evaluated, and the CHADS2/CHA2DS2-VASc scores were compared between groups. The association between big ET-1 levels and CHADS2/CHA2DS2-VASc score was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of CHADS2/CHA2DS2-VASc scores. RESULTS: The high CHADS2/CHA2DS2-VASc score group had older age, higher big ET-1 levels, and enlarged left atrial diameter than the low CHADS2/CHA2DS2-VASc score group (P < 0.05). Multiple logistic regression analysis revealed that big ET-1 level was an independent determinant of high CHADS2/CHA2DS2-VASc scores [odds ratio (OR) = 2.545 and OR = 3.816; both P < 0.05]. CONCLUSIONS: Our study indicates that in non-valvular AF, big ET-1 was significantly correlated with CHADS2/CHA2DS2-VASc scores and an independent predictor of high CHADS2/CHA2DS2-VASc scores. Big ET-1 may serve as a useful marker for risk stratification in this setting.

Single Nucleotide Polymorphism rs10919543 in FCGR2A/FCGR3A Region Confers Susceptibility to Takayasu Arteritis in Chinese Population.

BACKGROUND: Takayasu arteritis (TA) is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. METHODS: Four single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA locus (rs12524487), associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. RESULTS: Among the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 2.402 - 17.763, P < 0.001) for TA. Among TA patients, the level of eosinophil granulocytes (Eos) in the peripheral blood was observed to be higher in the GG group of rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] ×109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] ×109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed. CONCLUSIONS: Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.