No abstract

Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9,826 cases among 150,272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77,690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications.

IntroductionAtrial high-rate episodes (AHREs) are associated with an increased risk of developing atrial fibrillation and thromboembolism. The characteristics of ‘real world’ patients developing AHREs are poorly known.MethodsWe included 496 consecutive patients with cardiac implantable electronic devices (CIEDs). Primary endpoint was occurrence of AHREs, defined as > 175 bpm and lasting > 5 min, in a median follow-up of 16.5 (IQR 3.9–38.6) months (1082.4 patient-years). We also tested the predictive value of clinical risk scores for AHREs.ResultsMean age was 68.8 ± 14.0 years, and 35.5% were women; AHREs were recorded in 173 patients [34.7%, 16.0%/year, 95% confidence interval (CI) 13.7–18.6]. Multivariable Cox regression analysis showed that age [hazard ratio (HR) 1.020, 95% CI 1.004–1.035, p = 0.011], prior AF (HR 3.521, 95% CI 2.831–5.206, p < 0.001), white cell count (HR 1.039, 95% CI 1.007–1.072, p = 0.016) and high C reactive protein (CRP; HR 1.039, 95% CI 1.021–2.056, p = 0.038) were independently associated with AHREs. ROC curve analysis showed that the APPLE score (C statistic 0.53, 95% CI 0.48–0.59; p = 0.296) ALARMEc score (C statistic 0.51, 95% CI 0.44–0.57; p = 0.810) were non-significantly associated with AHRE. Similar results were obtained for CHADS2 and CHA2DS2VASc scoreConclusionAHREs are common in CIEDs patients, with age, prior AF, inflammatory markers (high CRP, white cell count) being factors associated with AHREs onset. Clinical risk scores showed limited value for AHREs prediction in this cohort.Electronic supplementary materialThe online version of this article (10.1007/s00392-018-1244-0) contains supplementary material, which is available to authorized users.

Biomarkers of inflammation are significantly associated with LA/LAA thrombus outcomes in AF patients prospectively treated with rivaroxaban.

Female sex, secondary prevention, and experience of ICD shock therapy are important risk factors affecting shock anxiety in Japanese patients. Attention should be paid to the after-effects of ICD shock in these patients, regardless of the shock type, with particular attention to women and patients who require secondary prevention.