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Background: Recurrence prevention after Atrial Fibrillation (AF) termination by Eelectrical Cardioversion (ECV) remains challenging. Increasing attention is paid to pathophysiological effects of non-Antiarrhythmic Drugs (non-AADs), nevertheless, with heterogeneous results. Objective: We evaluated the potential benefits of different non-AADs as adjunctive therapy to Antiarrhythmic Drugs (AADs) for AF recurrence prevention after sinus rhythm restoration by ECV in high-risk patients. Methods: The study was conducted among high-risk AF patients after successful ECV. Prescription of class IC or class III AAD was required. Data were acquired in a face-to-face baseline interview and 1-, 3-, 6-, 9-, 12-month follow-up interviews. Results: 113 patients were included. Total AF recurrence rate reached 48.7%. Angiotensin-Converting Enzyme Inhibitor (ACEI) or angiotensin receptor blocker (ARB) intake, compared with non-use, demonstrated AF recurrence rate reduction by 8.5% (46.3 vs. 54.8%), with odds ratio (OR) reduced by 28.9% (OR 0.711, 95% confidence interval (CI) 0.310-1.631, p = 0.420). Among mineralocorticoid receptor antagonist (MRA) users, AF recurrence rate was reduced by 25.1% (29.6 vs. 54.7%) and OR by 65.1% (OR 0.349, 95%CI 0.138-0.884, p = 0.023). Present statin therapy reduced AF recurrence rate by 4.2% (46.8 vs. 51.0%) and OR by 15.5% (OR 0.845, 95%CI 0.402-1.774, p = 0.656). Diuretic use showed reduction of AF recurrence rate by 10.2% (41.7 vs. 51.9%) and OR by 33.9% (OR 0.661, 95%CI 0.297-1.469, p = 0.308). Conclusion: Non-AADs demonstrated practical benefits as adjunctive therapy to AADs for AF recurrence prevention after ECV in high-risk patients, with statistically significant results established for concomitant MRA intake.

Atrial fibrillation (AF), the most common type of arrhythmia, has a heritable component. Variants at locus 4q25 are best associated with the risk of AF development in genome-wide association studies. Left atrial volume is an independent predictor of recurrence of AF after successful sinus rhythm restoration. The aim of our study was to investigate potential association between genetic variants at 4q25 locus and the risk of AF and echocardiographic parameters. We included 241 AF patients and 119 control individuals into the study. Left ventricle ejection fraction (LVEF, %) and left atrial volume index (LAVI, ml/m2) were assessed by transthoracic echocardiography during outpatient visits. We selected five 4q25 genetic variants (rs6825911, rs1126483, rs10004516, rs6838973, rs2200733) for the analysis. Variant rs6838973 was found to be associated with reduced risk of AF in additive (CCTT) and dominant (CC vs. CT+TT) models of inheritance. On the other hand, additive (CC2 (IQR = 10.0) and median LVEF was 56.0% (IQR = 13.0). Statistically significant association was observed only between LAVI and variant rs1126483 in the dominant model of inheritance (median LAVI in CC vs. CT+TT – 38 ml/m2 vs. 40 ml/m2, U = 1602.5, p = 0.032). No significant association was found for LVEF and the analysed genotypes.

BackgroundLarge-scale genome-wide association studies have identified hundreds of single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD). However, collectively, these explain HypothesisHere, we hypothesize that mitochondrial (MT) SNVs might present one potential source of this “missing heritability”.MethodsWe analyzed 265 MT-SNVs in ∼500,000 UK Biobank individuals, exploring two different CAD definitions: a more stringent (myocardial infarction and/or revascularization; HARD=20,405), and a more inclusive (also angina and chronic ischemic heart disease; SOFT=34,782).ResultsIn HARD cases, the most significant (PT (control region) and m.12612A>G (ND5), found more frequently in cases (OR=1.05), potentially related to reduced cardiorespiratory fitness in response to exercise, as well as for m.12372G>A (ND5) and m.11467A>G (ND4), present more frequently in controls (OR=0.97), previously associated with lower ROS production rate. In SOFT cases, four MT-SNVs survived multiple testing correction (at FDRG (ND4) and m.15452C>A (CYB) have previously shown significant associations with body height. In line with this, we observed that CAD cases were slightly less physically active and their average body height was ∼2.00 cm lower compared to controls, both traits known to be related to an increased CAD risk. Gene-based tests identified CO2 associated with HARD/SOFT CAD, whereas ND3 and CYB associated with SOFT cases (PConclusionsWe found only spurious associations between MT genome variation and HARD/SOFT CAD and conclude that more MT-SNV data in even larger study cohorts may be needed to conclusively determine the role of MT-DNA in CAD.

The aims of this centre-based survey, promoted and disseminated by the European Heart Rhythm Association (EHRA) was to investigate the current practice for the investigation of Sudden Unexplained Death in the Young (SUDY) amongst European countries. An online questionnaire composed of 21 questions was submitted to the EHRA Research Network, European Cardiac Arrhythmia Genetics (ECGen) Focus Group members, and European Reference Network GUARD-Heart healthcare partners. There were 81 respondents from 24 European countries. The majority (78%) worked in a dedicated clinic focusing on families with inherited cardiac conditions and/or SUDY or had easy access to a nearby one. On average, an autopsy was performed in 43% of SUDY cases. Macroscopic examination of the body and all organs were completed in 71% of cases undergoing autopsy, and expert cardiac examination in 32%. Post-mortem genetic testing was requested on average in 37% of Sudden Arrhythmic Death Syndrome (SADS) cases, but not at all by 20% of survey respondents. Psychological support and bereavement counselling for SADS/SUDY families were available for ≤50% of participants. Whilst electrocardiogram (ECG) and echocardiography were largely employed to investigate SADS relatives, there was an inconsistent approach to the use of provocative testing with exercise ECG, sodium channel blocking drugs, and/or epinephrine and genetic testing. The survey highlighted a significant heterogeneity of service provision and variable adherence to current recommendations for the investigation of SUDY, partly attributable to the availability of dedicated units and specialist tests, genetic evaluation, and post-mortem examination.

Introduction: Large-scale genome-wide association studies have identified >200 single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD), collectively explaining Hypothesis: Mitochondrial (MT) genetic variants presents an underexplored one potential source of the “missing heritability”. Methods: We analyzed 265 MT-SNVs in ∼500,000 UK Biobank individuals, exploring two different CAD definitions: including (SOFT=34,782) vs. excluding (HARD=20,405) angina, using the array, sex, birth year and first five principal components as covariates. Results: In SOFT cases, four MT-SNVs survived multiple testing correction (at FDRT (rs28358278, OR=1.28, MAF=0.02, T114T in MT-ND3), m.15301G>A (rs527236045, OR=1.03, MAF=0.04, L185L in MT-CYB), m.11251A>G (rs869096886, OR=1.03, MAF=0.2, L164L in MT-ND4) and m.15452C>A (rs193302994, OR=1.03, MAF=0.2, L236I in MT-CYB), the latter two previously associated with height in the UK Biobank. In HARD cases, no MT-SNVs survived multiple testing correction, the most significant nominal (P T (rs41528348, OR=1.05, MAF=0.1, in the D-LOOP) and m.12612A>G (rs28359172, OR=1.05, MAF=0.04, V92V in MT-ND5) could potentially increase CAD risk, whereas m.12372G>A (rs2853499, OR=0.97, MAF=0.22, L12L in MT-ND5), m.11467A>G (rs2853493, OR=0.97, MAF=0.22, L236L in MT-ND4) and m.15301G>A (rs193302991, OR=0.97, MAF=0.04, L185L in MT-CYB) may confer protective effects. Previously, several of these variants have been associated with a number of blood cell traits in the UK Biobank, including the mean corpuscular hemoglobin levels (m.295C>T, m.12612A>G, m.12372G>A) and volume (m.295C>T and m.12612A>G). In addition, m.12372G>A was significantly association with five other blood cell traits, including the mean platelet volume and white/red blood cell count, as well as with several renal biomarkers, and m.12612A>G was associated with height. Conclusions: Our results indicated only spurious associations of the MT-SNV with the occurrence of CAD. More data in larger study cohorts may be needed to conclusively determine the role of MT-DNA in CAD.

Background. Minor part of atrial fibrillation (AF) patients develops the disease without any well-known risk factors, which is a particular form of the disease, known as a lone AF. Rare genetic variants were described as causative for lone AF. The aim of this study was to investigate occurrence of rare genetic variants in lone AF patients. Material and Methods. We performed Mendeliome sequencing for 21 lone AF patients. Lone AF was defined as AF in individuals younger than 65 years in the absence of cardiovascular or structural heart disease, endocrinologic or pulmonary disease, chronic kidney disease, obesity and excessive alcohol consumption. Data analysis was performed by current laboratory pipeline. We analyzed 453 cardiomyopathy, arrhythmias and sudden cardiac death related genes. Results. In eight out of 21 (38%) lone AF patients rare likely pathogenic variants were found (Table 1.). Seven rare truncating TTN variants and one LMNA missense variant were observed. Four unrelated patients were positive for the same TTN variant c.13696 C > T; p.(Gln4566Ter). The same variant was previously found in ARVC patient in our laboratory. Segregation analysis and phenotyping of relatives is ongoing. Conclusions. Rare genetic variants are common causes of the lone atrial fibrillation. TTN gene variant c.13696C > T; p.(Gln4566Ter) is a potential founder variant in the Baltic population. Table 1. Genetic variants in lone AF Gender Age of AF onset Genetic variant Family history Male 53 LMNA: p.(Ser326Thr) AF in mother Male 11 TTN: p.(Trp31854Ter) AF in father Male 30 TTN: p.(GLn4566Ter) AF in uncle Female 45 TTN: p.(GLn4566Ter) Negative Male 37 TTN: p.(GLn4566Ter) AF in father Male 25 TTN: p.(GLn4566Ter) AF in father, maternal and paternal grandmother Female 60 TTN: p.(Arg27414Ter) Sudden cardiac death at the age of 50 in grand father Female 52 TTN: p.(Arg1012Ter) AF in mother

Background and Objectives: Recurrence of atrial fibrillation (AF) within six months after sinus rhythm restoration with direct current cardioversion (DCC) is a significant treatment challenge. Currently, the factors influencing outcome are mostly unknown. Studies have found a link between genetics and the risk of AF and efficacy of rhythm control. The aim of this study was to examine the association between eight single-nucleotide variants (SNVs) and the risk of AF development and recurrence after DCC. Materials and Methods: Regarding the occurrence of AF, 259 AF cases and 108 controls were studied. Genotypes for the eight SNVs located in the genes CAV1, MYH7, SOX5, KCNN3, ZFHX3, KCNJ5 and PITX2 were determined using high-resolution melting analysis and confirmed with Sanger sequencing. Six months after DCC, a telephone interview was conducted to determine whether AF had recurred. A polygenic risk score (PRS) was calculated as the unweighted sum of risk alleles. Multivariate regression analyses were performed to assess SNV and PRS association with AF occurrence and recurrence after DCC. Results: The risk allele of rs2200733 (PITX2) was significantly associated with the development of AF (p = 0.012, OR = 2.31, 95% CI = 1.206–4.423). AF recurred in 60% of patients and the allele generally associated with a decreased risk of AF of rs11047543 (SOX5) was associated with a greater risk of AF recurrence (p = 0.014, OR = 0.223, 95% CI = 0.067–0.738). A PRS of greater than 7 was significantly associated (p = 0.008) with a higher likelihood of developing AF after DCC (OR = 4.174, 95% CI = 1.454–11.980). Conclusions: A higher PRS is associated with increased odds of AF recurrence after treatment with DCC. PITX2 (rs2200733) is significantly associated with an increased risk of AF. The protective allele of rs11047543 (SOX5) is associated with a greater risk of AF recurrence. Further studies are needed to predict the success of rhythm control and guide patient selection towards the most efficacious treatment.

A causative role of OBSCN gene in development of cardiomyopathies was recently described. Lone atrial fibrillation (LAF) shares genetic variants with inherited cardiovascular disorders including cardiomyopathies. Currently, there is no data available on the link between OBSCN variants and LAF. The