Atrial fibrillation (AF) affects over 33 million individuals worldwide1 and has a complex heritability.2 We conducted the largest meta-analysis of genome-wide association studies for AF to date, consisting of over half a million individuals including 65,446 with AF. In total, we identified 97 loci significantly associated with AF including 67 of which were novel in a combined-ancestry analysis, and 3 in a European specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait loci (eQTL) analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Renal insufficiency dramatically increases the risk of infection complicating pacemaker or ICD surgery. This association should be part of the risk-benefit consideration prior to device implantation. Additional study of more extensive perioperative antibiotic therapy in this subset of patients is warranted.

Background: Atrial fibrillation (AF) has been associated with myocardial oxidative stress, and antioxidant agents have demonstrated antiarrhythmic benefit in humans. We compared serum markers of oxidation and associated inflammation in individuals with or without AF. Methods: Serum markers of oxidative stress and inflammation were compared in a cross-sectional, case-control design study of 40 male individuals, with or without persistent or permanent AF, who were matched for age, sex, diabetes, and smoking status, known confounding variables for the measurement of oxidative stress. We used derivatives of reactive oxidative metabolites (DROMs) and ratios of oxidized to reduced glutathione (E h GSH) and cysteine (E h CySH) to quantify oxidative stress. We also measured inflammatory markers, including high-sensitivity C-reactive protein, interleukins 1␤ and 6, and tumor necrosis factor ␣. Results: Univariate, conditional logistical regression analysis showed that oxidative stress but not inflammatory markers were statistically associated with AF (P <0.05). The increase in the odds ratios for AF for E h GSH, E h CySH, and DROMs were 6.1 (95% CI, 1.3-28.3; P ‫؍‬ 0.02), 13.6 (95% CI, 2.5-74.1; P ‫؍‬ 0.01), and 15.9 (95% CI, 1.7-153.9; P ‫؍‬ 0.02), respectively. There was a stronger correlation between E h GSH and E h CySH (r ‫؍‬ 0.66) than between E h GSH and DROMs (r ‫؍‬ 0.41). In multivariate analysis corrected for statins and other AF