bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune status comparison in patients with atrial fibrillation or flutter on the base of arterial hypertension
Authors: Ilchyshyna O Y A , Sychov O S , Talaieva T V , Tretiak I V , Stasyshena O V 
Published: October 2022

Abstract

Aims
Atrial fibrillation (AF) and atrial flutter (AFl) take the second place between supraventricular arrhythmias and lead to severe complications such as stroke and heart failure. Mostly these arrhythmias occur on the background of arterial hypertension (AH). The inflammatory theory of arrhythmogenesis in AF and AFl has attracted researcher's attention in recent years. The aim of our work is to compare the immune status of patients with paroxysmal and persistent forms of AF and AFl in patients with AH.

Material and methods
The study involved 103 patients with hypertension and arrhythmias, who were divided into three main groups according to the form of AF/AFl: group 1 (n=35) – with paroxysmal form of AF, group 2 (n=38) - with persistent form of AF, group 3 (n=30) – with persistent form of AFl. For comparison, 2 control groups were formed: 4 (n=23) – patients with hypertension, but without a history of arrhythmias and 5 (n=21) – almost healthy people. The immune status of these patients was assessed by determining the level of monocytes (Mc), lymphocytes subpopulations and T-regulatory cells (T-reg) in the peripheral blood using flow cytometry.

Results
It was noted that the number of classical CD14++CD16- and intermediate CD14++CD16+ Mc was significantly higher in patients with persistent AF and AFl comparing with patients without arrhythmias and healthy people (p&lt;0.005). This fraction of Mc is able to produce proinflammatory cytokines and activate the local renin-angiotensin system, thus triggering the processes of fibrosis in the myocardium. Amount of non-classical CD14+CD16++ Mc was significantly lower in the second group both quantitatively and in percentage (p&lt;0.005). The count of T cells with natural killer (TNK) activity was higher in all groups comparing to normal value, so statistical significance was observed only in comparison with the fifth group. The highest quantity of T-reg cells was found in healthy people comparing to other groups and a strong mathematical significance was obtained in all cases (p&lt;0.005), both comparing the values in percentage and in μl.

Conclusions
Patients with AF and AFl on the hypertension background comparing to hypertensive patients without arrhythmias or healthy people have an increased activity of proinflammatory subpopulation of monocytes, higher amount of T-cells with natural killer activity and reduced T-regulatory cells, whose main function is to control the immune response.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): NSC “M.D. Strazhesko Institute of Cardiology” NAMS of Ukraine
Spectrum of rare and common genetic variants in arrhythmogenic cardiomyopathy
Authors: Lippi M , Chiesa M , Ascione C , Pedrazzini M , Mushtaq S , Rovina D , Riggio D , Di Blasio A , Biondi M L , Pompilio G , Colombo G I , Novelli V , Casella M , Sommariva E 
Published: October 2022

Abstract

Background
Arrhythmogenic cardiomyopathy (ACM) is a rare inherited cardiac disorder, whose genetic cause is elusive in about 50% of cases. ACM pathogenic mutations mainly involve desmosomal genes (PKP2, JUP, DSP, DSG2, DSC2). ACM presents a variable disease course, spanning from mild electrocardiographic alterations and/or contractile dysfunctions, to malignant ventricular arrhythmias and heart failure.

Purpose
In an attempt to broaden etiological diagnosis for ACM patients, this work was aimed at finding potential rare high-impact variants in genes not previously associated with ACM. Secondarily, we meant to assess the impact of genetic polymorphisms on the disease clinical severity.

Methods
We clinically characterized 82 consecutive ACM probands and performed next-generation sequencing, exploring a panel of 174 genes associated with inherited cardiovascular diseases. We evaluated the pathogenicity of rare variants, according to the American College of Medical Genetics / Association for Molecular Pathology guidelines, to select candidates with potential ACM causative role. Further, a genotype-phenotype correlation analysis between common polymorphisms and clinical variables was performed to find genetic factors associated with specific ACM phenotypes. Finally, we carried out event-free survival analyses, linking specific variants to arrhythmias in 8,6±0,7 years follow-up, to estimate their possible impact on arrhythmic risk.

Results
We identified 141 rare genetic variants, of which 23 were classified of high impact, including variants in genes never associated with ACM (e.g. ABCC9, APOB, MIB1). These genes deserve future studies as they could participate in ACM pathogenesis. In addition, we found 69 genotype-phenotype significant associations (p≤0.005) between common variants and clinical parameters. Variants associated to arrhythmic phenotypes were found with genes linked to arrhythmias (e.g. KCNQ1, HCN4) and other cardiomyopathies (e.g. MYBPC3, MYL2). Associations involving substrate impairments were found with genes linked to muscle dysfunctions (e.g. LAMA2, SGCD). Arrhythmia-associated polymorphisms, included in survival analyses, were found to be associated with an increased occurrence of arrhythmic events during patients' follow-up.

Conclusion
The identification of rare high impact variants in novel genes potentially associated with ACM and the observation of genotype-phenotype correlations constitute the starting point to address the current lack of knowledge of the genetic landscape of ACM.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministero Italiano della Salute - Ricerca corrente
Functional analysis of novel SCN5A mutations related to Brugada syndrome
Authors: Namgoong H , Kim S J , Choi S W 
Published: October 2022

Abstract

Brugada syndrome (BrS) is an arrhythmogenic disorder that has been linked to mutations in SCN5A, the gene encoding for the pore-forming α-subunit of the cardiac Na+ channel. Recently, novel SCN5A missense mutations (A385T and R504T) were identified in a BrS patient. Since the mutations are in the loop connecting transmembrane segments 5 and 6 in domain 1 (S5-S6 in DI) and segments 6 and 1 between domain 1 and 2 (DI-DII linker), it can lead to dysfunctional property of the Na+ channel. Here we aimed to characterize the electrophysiological properties of A385T and R504T. The wild-type (WT) and mutant SCN5A were transiently transfected in HEK293 cells, and the Na+ channel was analyzed using the whole-cell patch-clamp technique. WT, A385T, R504T, and double mutant (A385T/R504T) showed no significant differences in the current density and the voltage-dependent activation. Unexpectedly, a rightward shift of the voltage-dependent inactivation was identified in the three groups of mutation. Besides, the recovery from inactivation of double mutant was faster than that of WT. These results suggest that, contrary to the expected mechanism of BrS, the mutations cause a gain-of-function of NaV1.5. However, the current densities of R504T and double mutant transfected with β-subunit SCN1B were significantly suppressed but A385T was not different from WT. The voltage dependent activation and inactivation of all mutants were not significantly different from WT. The recovery from inactivation of all mutants were slower than that of WT. These results suggest that R504T mutation of α-subunit SCN5A interacting with β-subunit SCN1B is responsible to pathophysiological function of novel BrS.

Funding Acknowledgement
Type of funding sources: None.
Genetic variation rs6795970 of the SCN10A gene is associated with PR interval in young population of Republic of Moldova
Authors: Butovscaia C , Buza A , Galea-Abdusa D , Curocichin G 
Published: October 2022

Abstract

Background/Objectives
The electrocardiographic PR interval reflects atrial and atrioventricular nodal conduction time. Prolongation of the PR interval increase risk of atrial fibrillation (AF) and heart block. Genome-wide association studies (GWAS) have identified association of a nonsynonymous single nucleotide polymorphism (SNP), rs6795970, in the SCN10A gene with PR interval in individuals of European and Asian ancestry. The aim of the study was to determine distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova.

Methods
1380 young participants from Republic of Moldova aged between 19–25 years, were genotyped for rs6795970 in the SCN10A gene, using TaqMan SNP Genotyping Assay.

Results
The genotype G/G, A/G, A/A distributions of rs6795970 among participants were 37%, 48%, 15%, respectively (χ2=0.086, p=0.770). The allele frequencies for G and A, in young participants were 61% and 39%, respectively. We observed association between rs6795970_A and a prolongation of the PR interval (p=0.003).

Conclusions
In our study, we determined that distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova was consistent with 1000 Genomes data in the European population. Therefore, our data demonstrate that the A allele is associated with prolongation of the PR interval and at least 15% of all participants (the A/A genotype), may have an increased risk of conduction abnormalities.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National project “Study of molecular genetic polymorphism of metabolic risk factors in young population of the Republic of Moldova National project “Identification and validation of genetic and epigenetic biomarkers in chronic non-communicable diseases with major impact on public health”
Clinical role of genetic testing for overlapping between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy
Authors: Jeong J , Choi J I , Kim Y G , Choi Y Y , Min K J , Roh S Y , Shim J M , Kim J S , Kim Y H 
Published: October 2022

Abstract

Background/Introduction
Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) are inherited arrhythmias that may predispose to sudden cardiac arrest. Although its pathogenetic mechanisms differ, overlapping features between BrS and ARVC have been demonstrated previously. However, it remains to be determined whether genetic testing for ARVC-related gene is needed in patients with BrS.

Purpose
This study is aimed to analyze genetic profiles of BrS patients using next generation sequencing (NGS) based multigene panel including ARVC related genes.

Methods
Patients who were confirmed as BrS or clinically suspected as BrS with type 2 or 3 Brugada pattern electrocardiography were studied. Genetic testing using NGS panels (Illumina Inc., San Diego, CA, USA) included 30 genetic variants associated with inherited arrhythmia and genetic cardiomyopathy.

Results
Among the total 119 patients from BrS registry, 63 patients were confirmed as BrS and 56 patients were clinically suspected as BrS without fulfilling diagnostic criteria. One-hundred-fourteen patients (95.8%) were male, and mean age of onset was 43.6 year-old. Genetic variants were identified in 25 of 42 patients who received genetic testing. Six out of 25 patients (24.0%) showed ARVC-related genotypes (2 PKP2, 1 DSG2, 1 TMEM43, 1 JUP, and 1 DSP) (Figure 1 and Table 1). None of the patients showed structural or electrocardiographic features that fulfill diagnostic criteria of ARVC. It is notable that ARVC-related genotypes were mostly frequently accounted for BrS patients, following SCN5A and SCN10A.

Conclusion
In the clinic setting, ARVC-related genetic variants were identified in significant proportion of BrS patients, supporting that genetic testing of ARVC-overlapping is needed. This study suggests that follow-up including imaging study should be considered in BrS patients with ARVC-related genotypes to monitor disease progression as ARVC.

Funding Acknowledgement
Type of funding sources: None.
Atrial fibrillation in patients with Graves disease: incidence, risk factors and outcomes
Authors: Naser J , Pislaru S V , Stan M N , Lin G 
Published: October 2022

Abstract

Background
Graves' disease (GD) is associated with atrial fibrillation (AF) with a prevalence ranging between 16% and 60%, but its risk factors are not well-defined. We aimed to describe the incidence, risk factors and outcomes of GD-related AF.

Methods
Patients diagnosed with GD between 2009 and 2019 were included retrospectively. We defined GD-related AF as AF diagnosed within 30 days before or any time after diagnosis of GD. Late onset AF was defined as GD-related AF diagnosed more than 90 days after GD diagnosis. Observed AF events were compared to the expected events in the general population utilizing published data of age and sex-specific rates of AF.

Results
Of 1371 patients with GD, AF occurred in 139 (10.1%) patients. Late onset AF occurred in 32 (23%), of which 50% had attained euthyroidism. The observed incidence of AF was higher in GD than that expected in the general population (p&lt;0.001), Figure 1. When comparing the incidence of only late AF to that in the general population, late AF still happened more frequently in GD although not achieving statistical significance (p=0.06), Figure 1. Independent risk factors were age [HR 1.05 (1.03–1.06) per year], overt hyperthyroidism [HR 2.71 (1.35–5.44)], and male gender [HR 2.42 (1.57–3.71)] for early AF and age [HR 1.06 (1.02–1.09) per year], BMI [1.07 (1.01–1.12) per unit], COPD [3.33 (1.08–10.27)), heart failure [HR 4.19 (1.39–17.42)], and treatment with thionamide [vs. radioiodine ablation HR 2.94 (1.38–6.27)] for late AF. AF was associated with higher rates of mortality [HR 16.32 (4.66–56.58)], acute coronary syndrome/stable angina events [HR 3.89 (1.23–12.31)], and cardiac hospitalizations [HR 15.39 (8.17–29.00)] when adjusted to age, sex, and previous AF.

Conclusion
AF occurred in 10.1% of GD patients. Late onset AF is an important entity comprising a quarter of GD-related AF cases and requires surveillance even after restoring euthyroidism. Risk factors for AF in GD are similar to those in general population, although overt hyperthyroidism conferred the highest risk, especially for early AF. Treatment with thionamide was associated with late AF.

Funding Acknowledgement
Type of funding sources: None.
Factors associated with the presence of thrombus in the left atrial appendage and usefulness of the D-Dimer to rule out its presence
Authors: Irigaray Sierra P , Gayan Ordas J , Pueo Crespo E M , Fernandez-Rodriguez D , Pastor Pueyo P , Blanco Ponce E , Matute-Blanco L , Pueyo Balsells N , Barriuso Barrado I , Ramirez Martinez T , Papiol Morales E , Worner Diz F 
Published: October 2022

Abstract

Introduction
A transesophageal echocardiography (TEE) is recommended for non-anticoagulated patients with atrial fibrillation (AF) and &gt;48 hours of evolution requiring electrical cardioversion (ECV) to rule out the presence of thrombus in the left atrial appendage (LAA). It has been proposed that the D-Dimer (DD) value is useful to rule out its presence with high sensitivity and negative predictive value (NPV).

Purpose
To evaluate the prevalence of thrombus in LAA in patients with AF, factors associated with its presence and diagnostic accuracy of different DD cut-off points to rule it out.

Methods
A retrospective observational study in which patients with AF who underwent a TEE prior to ECV were included consecutively.

Results
We included 104 patients (85.6% admitted) between June 2020 and February 2022. In 10 patients (9.6%) thrombus was evidenced in LAA. The mean age was 68.7±11 years and 59.6% were male. Most of the patients had hypertension (64.4%) and 19.2% diabetes. Only 3.8% had had previous stroke. Concerning the echocardiographic findings, the mean left atrial (LA) volume was 56.9±17ml/m2, LA diameter was 49.2±6.4mm and left ventricular ejection fraction (LVEF) was 47.5±17%. Only 12.5% had a CHADS2VASC2 scale ≤2. 69.2% of patients were not under antithrombotic therapy and only 27% had taken anticoagulant agents before (NOAC or antivitamin K). Neither the CHADS2VASC2 score nor the clinical or echocardiographic factors evaluated were significantly associated with the presence of thrombus (Figure 1). 68 patients had DD available (≤48 hours prior to TEE) and of them 8 (11.7%) had thrombus in the LAA. 12 patients (17%) had DD ≤150ng/mL, 42 (61.7%) DD≤500ng/mL and 48 (80%) DD≤10xAge. Figure 2 shows the ROC curve of the DD: AUC 0.72 (CI 0.55–0.9). NPV to rule out thrombus in LAA was 100% for DD≤150 ng/mL (Sensibility (Se) 100%, Specificity (Sp) 20%), 92% for DD≤500 ng/mL (Se 62.5%, Sp 65%), and 90% for DD≤10xAge (Se 37.5%, Sp 80%).

Conclusion
The prevalence of thrombus in LAA in TEE prior to ECV was similar to the previously described. The sample size was insufficient to identify any clinical or echocardiographic factor associated with thrombus. The NPV of a DD≤150ng/mL value was 100%. However, higher cut-off points (500 ng/mL or 10xAge) did not allow to rule out their presence.

Funding Acknowledgement
Type of funding sources: None.
Temporal sequence of atrial fibrillation and chronic obstructive pulmonary disease diagnosis is associated with mortality risk
Authors: Garcia R , Warming P E , Hansen C J , Torp-Pedersen C , Linz D , Tfelt-Hansen J 
Published: October 2022

Abstract

Background
Chronic obstructive pulmonary disease (COPD) is concomitantly present in 13% of atrial fibrillation (AF) patients and negatively impacts prognosis in AF patients (1). Nevertheless, the temporal sequence and time between diagnosis of each disease may vary between individuals (2).

Purpose
To describe whether the temporal sequence of diagnosis of AF and COPD is associated with mortality in patients with both AF and COPD diagnosed.

Methods
This nationwide study assessed all patients between 18 to 85 years diagnosed with both COPD and AF between 1999 and 2018 in Denmark. Follow up started at the time of the second diagnosis. Three groups were defined according to the temporal sequence of diagnosis: COPD diagnosed at least 1 year before AF (COPD-First), AF diagnosed at least 1 year before COPD (AF-First) and COPD and AF diagnosed within a one-year time frame (AF∼COPD).

Results
Among 62,806 patients analyzed (75.0 [69.0–79.7] years; 56.5% males; mean follow-up 2.2 years) 27,809 (44.3%) were in the COPD-First group, 19,556 (31.1%) in the AF-First group and 15,441 (24.5%) in the AF∼COPD group. While age was similar across groups, the sex distribution differed, with the lowest proportion of males (53.1%) in the COPD-First group and the highest (61.2%) proportion of males in the AF-First group. Moreover, cardiovascular risk factors and diseases were more frequent in the AF-First group and the lowest in the COPD-First group.
After 5 years of follow up, 31,494 (58.6%) died. Males died more frequently than females (59.4% vs. 57.4%). Mortality was higher in the COPD-First group (61.8% for COPD-First, 55.1% for AF-First and 57.2% for AF∼COPD, Figure 1) and the causes of death were different among the 3 groups (38.8%, 24.1%, 27.0% for pulmonary cause and 26.1%, 32.8% and 36.6% for cardiac cause in the COPD-First, AF first and AF∼COPD respectively).
In a multivariable Cox-regression model adjusted for age, sex, type 2 diabetes, history of acute myocardial infarction, cancer, chronic kidney disease, stroke, AF∼COPD group (HR 1.14, 95% CI 1.11–1.17; P&lt;0.0001) and COPD-First group (HR 1.26, 95% CI 1.23–1.29; P&lt;0.0001) had a higher risk of death as compared to the AF-First group. Using time between diagnoses in a restricted cubic spline and adjusting for potential cofounders a COPD diagnosis preceding an AF diagnosis was associated with a higher risk of death than an AF diagnosis preceding a COPD diagnosis (Figure 2).

Conclusion
In patients with AF and COPD, the temporal sequence of diagnosis impacts prognosis, independently of other comorbidities. A concomitant diagnosis of AF in patients with already previously diagnosed COPD is associated with the worst prognosis.

Funding Acknowledgement
Type of funding sources: None.
Does body mass index affect atrial fibrillation ablation outcomes
Authors: Aleem S , Al-Sadawi M , Aslam F , Ijaz H , Cao K , Jacob R , Santore L , Almasry I , Fan R , Rashba E , Singh A 
Published: October 2022

Abstract

Background
There are conflicting reports in the literature regarding whether body-mass index (BMI) influences the success and procedural complication rates of atrial fibrillation (AF) ablation.

Purpose
To determine if differences in BMI affect AF ablation outcomes

Methods
At a single academic center, AF ablation procedures were reviewed from 2013 to 2021. Primary outcomes were AF recurrence (after a 90 day blanking period), procedure-related complications, emergency department visits or hospital admission (ED/HOSP). Patients had a minimum of 6 months follow-up

Results
We analyzed 1569 AF ablation consecutive procedures (1093 de novo, 476 repeat ablation) using either radiofrequency or cryoablation. The study population was 65% male with a mean age 62 years, with 28% persistent AF. BMI was separated into three cohorts: &lt;25 kg/m2 (N=218), 25–30 kg/m2 (N=547), and &gt;30 kg/m2 (N=804). There were no significant differences in the type of AF, left atrial diameter, or left ventricular ejection fraction in the BMI subgroups. There was a direct relationship between the prevalence of co-morbid conditions and increasing BMI: hypertension (49.1%, 59.9%, 60.2%; p 0.04), diabetes (6.4%, 13.5%, 21.3%; p 0.01), and obstructive sleep apnea (5.5%, 10.8%, 26.7%; p&lt;0.01). There were no significant differences in AF recurrence, procedural complications or ED/HOSP among the BMI cohorts (p&gt;0.05) (Figure 1). No gender related disparities were noted in outcomes (p&gt;0.05).

Conclusion
Higher BMI was not associated with AF recurrence, complications, or ED/HOSP after AF ablation despite a higher prevalence of comorbid medical conditions

Funding Acknowledgement
Type of funding sources: None.
Heart rate during sinus rhythm predicts paroxysmal atrial fibrillation on 30-day mobile cardiac telemetry monitoring
Authors: Persson A , Ecounomou Lundeberg J E L , Dziubinski M D , Slusarczyk M S , Grotek A G , Johnson L J , Engstrom G E 
Published: October 2022

Abstract

Background
Low mean heart rate at ambulatory ECG monitoring and low resting heart rate are both predictors of later incident atrial fibrillation (AF). The aim of this study is to determine whether mean heart rate at ambulatory ECG is a predictor of paroxysmal AF that can be detected with extended ambulatory ECG registration.

Methods
We included all patients who recorded 2–30 full days of ambulatory ECG using a full disclosure mobile cardiac telemetry device in USA 2019–2020, and without AF on the first full day of registration (n=18,220, mean age 64.4 years, 57.2% women). The association between mean heart rate on the first day and the occurrence of paroxysmal AF (≥30 seconds duration) during subsequent up to 30 day ECG recording was analysed using logistic regression models adjusted for age, sex and duration of ECG recording, according to tertiles of mean heart rate (39–66, 67–76 and &gt;77 beats per minute) as well as modelled using restricted cubic splines.

Results
During a median registration duration of 16 days there were 1,290 cases of paroxysmal AF (7.1%). More paroxysmal AF occurred in the lower tertiles of mean heart rate (11.2% in tertile 1, 6.2% in tertile 2, and 4.4% in tertile 3). After adjustment, low mean heart rate was associated with a higher risk of AF (OR 1.69, 95% CI 1.47–1.93 p&lt;0.001 for tertile 1 vs tertile 2, and OR 1.84, 95% CI 1.58–2.15, p&lt;0.001 for tertile 1 vs tertile 3). Cubic spline curves indicated that lowest risks of AF were seen among subjects with a mean heart rate ≈80 beats per minute.

Conclusion
Low mean heart rate at 24hECG predicts detection of paroxysmal AF during extended ≤30 day ambulatory ECG monitoring.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung foundationSwedish Society for Medical Research