bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of variant detection rate in genes between two cohorts of Czech living patients versus victims of sudden cardiac death with clinical / post mortem diagnosis of non-ischemic cardiomyopathy
Authors: Borisincova E , Votypka P , Rucklova K , Pilin A , Kulvajtova M , Pohlova Kucerova S , Tavacova T , Kubanek M , Petrkova J , Dobias M , Tomasek P , Macek Jr M , Janousek J , Krebsova A , Kautzner J 
Published: November 2020

Abstract

Introduction
Hereditary cardiomyopathy is associated with an increased risk of ventricular arrhythmia and sudden cardiac death (SCD). Genetic stratification substantiates risk assessment and enables the primary prevention of SCD in relatives at risk. We have analyzed the genetic aetiology of SCD in a representative Czech cohort with post mortem diagnosis of various forms of cardiomyopathy and compared it to living cases with these cardiac disorders.

Patients and methods
Between 2018 and 2019, altogether 47 victims of SCD with post mortem diagnosis of hypertrophic- (HCM; 18/47), arrhythmogenic- (ACM; 19/47) and dilated cardiomyopathy (DCM; 10/47) were identified. Concurrently, genetic testing was performed in 114 living patients (HCM 54/114, ACM 22/114, DCM 38/114). Genetic counselling and cardiologic examination had been carried out in first-degree relatives in all patients/SCD victims. Massively parallel sequencing (MiSeq platform; Illumina.com) was utilized for a custom-made panel comprising 100 candidate genes (Sophia Genetics, Switzerland). The presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses.

Results
The causative detection rate (according to ACMG.net classes 4 or 5) in SCD victims with DCM was 60% (6/10) and in living patients with DCM 47.4% (18/38). Variants in TTN, RBM20, DES and FLNC (mainly truncating variants) prevailed in both groups. The detection rate in ACM was 5% (1/19 in SCN5A gene) in SCD victims and 31.8% (7/22) in living patients. Interestingly, the most prevalent mutated gene PKP2 in living patients was not detected in SCD victims. The detection rate in SCD victims with post mortem diagnosis of HCM was 16% (3/18) and in living patients 35% (19/54). The most prevalent gene was MYBPC3 in both groups, while PRKAG2 was detected in one SCD victim and in one living case who survived cardiac arrest.

Conclusion
Post-mortem genetic analysis in DCM yields a high detection rate and allows potentially effective primary prevention of SCD in relatives at risk. In contrast, the molecular autopsy of HCM and ACM renders a much lower yield which is below the mutation detection rate in living phenotype positive individuals. The results help to improve the genetic counselling in affected families in Czech Republic.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic
Altered auto-phosphorylation of novel TNNI3K variants associated with AV-nodal re-entry tachycardia and conduction disease
Authors: Pham C , Munoz-Martin N , Podliesna S , Milano A , Beekman L , Vermeer A , Frantzen C , Jansen S , Van De Laar I , Nieuwhof K , Christiaans I , Bezzina C.R , Lodder E.M 
Published: November 2020

Abstract

Background
In the past decade, we and others have reported three families with rare genetic variants in TNNI3K, encoding the cardiac-specific troponin-I interacting kinase (TNNI3K), co-segregating with a mixed, but highly penetrant, cardiac phenotype that features predominant atrial/junctional tachycardia occurring in combination with cardiac conduction disease and dilated cardiomyopathy. We demonstrated that while the p.Thr539Ala and p.Gly526Asp TNNI3K variants had decreased auto-phosphorylation activity the p.Glu768Lys variant, present in 3 independent families, leads to increased auto-phosphorylation levels, in line with the finding that increased levels of Tnni3k expression are associated with slower atrial-ventricular conduction in mice.

Objective
Identifying new genetic variants in the TNNI3K gene associated with cardiac disease and assessing their impact on TNNI3K auto-phosphorylation levels.

Methods
Through next generation sequencing of a panel of genes associated with cardiac disease we assessed TNNI3K in patients with cardiac arrhythmias and cardiomyopathies. All variants identified were assessed in vitro for effects on auto-phosphorylation. Briefly, wild-type and mutant TNNI3K constructs were transfected into HEK293 cells, protein was extracted after 48 hours and analyzed with anti-flag and anti-phospho-tyrosine antibodies on Western blot.

Results
We identified 7 novel and rare variants in TNNI3K in 11 additional probands, with predominantly cardiac conduction disease, with or without dilated cardiomyopathy, and atrial-ventricular-re-entry-tachycardia (AVNRT). Of these, multiple variants were found to have aberrant auto-phosphorylation including almost absent auto-phosphorylation capacity for one (TNNI3K-p.Val510Leu). All three-independent wild type TNNI3K transfected HEK293 cell lysates showed similar phosphorylated TNNI3K levels and the kinase-dead negative control demonstrated no phosphorylation activity.

Conclusion
We here present 7 novel genetic variants in TNNI3K in patients with a remarkable overlap in cardiac phenotype consisting mainly of AVNRT and cardiac conduction disease. We further show that some of these variants alter the auto-phosphorylation of TNNI3K. These results indicate a more prevalent role of variants in TNNI3K in human cardiac disease and a possible in vitro functional assay to assess the pathogenicity of such variants.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Dutch Research Council (NWO Talent Scheme VIDI-91718361)
Short and long-term outcomes of medical management of patients with a first episode of arrhythmic storm
Authors: Gonzalez De La Portilla-Concha C.M , Acosta Martinez J , Dominguez Cano J.L , Caballero Valderrama M.R , Abril Molina A , Campos Pareja A , Frutos Lopez M , Garcia Riesco L , Arana Rueda A , Pedrote Martinez A 
Published: November 2020

Abstract

Introduction
There is few data about long-term outcomes of conservative management (without catheter ablation) of patients with a first episode of arrhythmic storm (AS) in the current context. This study analyzes the short and long-term outcomes of implantable cardioverter defibrillator (ICD) patients with a first episode of AS receiving non-interventional management.

Methods
Consecutive patients admitted with a first episode of AS between January 2008 and June 2019 receiving medical management without catheter ablation were included. AS was defined as 3 or more appropriate ICD therapies occurring during a 24 h span. Medical management included: correction of triggers, sedation/mechanical ventilation, antiarrhythmic drugs, ICD reprogramming and neuraxial modulation. Baseline clinical characteristics and follow-up data were recorded. All patients were followed every 6 months at the ICD office. The primary end-point was all-cause mortality.

Results
60 patients (81% male, 62.8±16.2 years, 43% ischaemic, LVEF 35.4±14%) with a first episode of AS treated conservatively were included. Thirty-day survival was 96.5% and 1-year survival was 82%. During a median (interquartilic range) follow-up of 31 (6–69) months, 31 (51.7%) patients died (51.6% due to cardiovascular aetiology) and 35 (58.3%) patients were readmitted (48.5% due to recurrent arrhythmic events and 45.7% due to heart failure). Age [HR 1.05 (95% confidence interval: 1.01–1.08)] and end-diastolic diameter [HR 1.05 (95% confidence interval: 1–2)] were the strongest independent predictors of all-cause mortality.

Conclusion
Despite the severity of this entity, medical management (without catheter ablation) of a first episode of AS is reasonable given its good 30-day and 1-year survival. However, a high rate of AS recurrence and readmissions are observed during long-term follow-up. Efforts are needed in order to identify those patients with a first episode of AS that could benefit from an early catheter ablation strategy.

Funding Acknowledgement
Type of funding source: None
Diabetes mellitus is associated with higher risk of third degree atrioventricular block – a Danish nationwide registry study
Authors: Haxha S , Pedersen-Bjergaard U , Philbert B.T , Lindhardt T.B , Hoejberg S , Schjerning A.M , Ruwald M.H , Gislason G.H , Torp-Pedersen C , Bang C.N 
Published: November 2020

Abstract

Background
Diabetes mellitus (DM) is a risk factor for cardiovascular disease and sudden cardiac death. Increasing evidence shows that DM may be associated with electric disturbances including arrhythmias and atrioventricular block (AVB). However, the association of DM and AVB has never been confirmed in large studies.

Purpose
The present study aims to determine the association of DM and third-degree AVB.

Method
A nationwide nested case-control study of patients &gt;40 years with third-degree AVB between 1995 and end of 2017, matched 1:2 on age and gender with controls from the Danish background population. DM was defined if patients were prescribed oral antidiabetics or insulin, or if they were diagnosed with an ICD10 code of DM type I or II. Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. Conditional logistic regression was used to estimate hazard ratio (HR) and 95% confidence intervals (95% CI) of third degree AVB.

Results
Out of a total population of 8,964,086, we located a total of 32,722 cases with third degree AVB, that were matched 1:2 with 65,422 controls, with a mean age of 75.3 years and 59.1% males. The case group had more DM 18,5% vs 13,3%, acute myocardial infarction 27,0% vs 16.0%, stroke 18.5% vs 16.2%, heart failure 20.0% vs 8.5% and chronic kidney disease 4.7% vs 2.5% compared to the control group. In multivariable analysis adjusted for comorbidities DM remained significantly associated with third degree AVB [HR 1.30 (95% CI: 1.25–1.35)] (Figure)

Conclusion
In this nationwide population study, DM was associated with a higher risk of third degree AVB compared to matched controls without DM. This suggests a low threshold for use of ECG evaluation in case of dizziness or syncope in DM patients, and further, that ECG should be a part of routine controls of DM patients.
Risk of third degree AV block

Funding Acknowledgement
Type of funding source: None
Risk factors for silent and symptomatic atrial fibrillation in an elderly population screening programme:a report from the noninvasive monitoring for early detection of atrial fibrillation (NOMED-AF)
Authors: Mitrega K , Sredniawa B , Stokwiszewski J , Sokal A , Boidol J , Wierucki L , Bleszynska E , Bandosz P , Rutkowski M , Zdrojewski T , Kazmierczak J , Opolski G , Grodzicki T , Lip G.Y.H , Kalarus Z 
Published: November 2020

Abstract

Background
It is important to determine the risk factors that predispose elderly subjects from the general population for symptomatic atrial fibrillation and atrial flutter (AF/AFl), but population-based data for silent AF (SAF) are limited.

Aim
To study risk factors for symptomatic AF and SAF in a general population screen for subjects age ≥65 where continuous monitoring was performed up to 30 days with a vest-based monitor.

Methods
The NOMED-AF study was a cross-sectional study based on a representative population sample (n=3014; mean age 77.5±7.9 years; F=1479). In 680 subjects AF/AFl (including 279 with SAF) was diagnosed. Independent risk factors for AF/AFl and SAF were determine on weighted data using multiple logistic regression.

Results
The independent risk factors for AF/AFl and SAF are summarised in the Table. There are nine independent risk factors for AF/AFl and eight for SAF. Revascularization and obesity were independently associated with patients with (symptomatic) AF/AFl, and CKD was associated with SAF. Other risk factors are common for AF/AFl and SAF.

Conclusions
AF/AFl and SAF have slightly different associated clinical risk factors in this representative population sample aged ≥65 years. This may facilitated targeted screening programmes for high risk subgroups, particularly for SAF.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): The research has received funding from the National Centre for Research and Development under grant agreement (STRATEGMED2/269343/18/NCBR/2016)
Association of QRS duration changes during ergonovine provocation test with arrhythmic complications
Authors: Im S.I 
Published: November 2020

Abstract

Background
Ergonovine is ergoline-derivatives that act at serotonin-receptors (5-HT2receptor). Influence of serotonin and 5-HT2 receptor agonist on cardiomyocytes has been known.

Purpose
However, there was limited data about the association between QRS duration changes during ergonovine provocation test (EPT) and arrhythmic complications.

Methods
A total of 182 patients who underwent coronary angiography (CAG) with EPT were consecutively enrolled (mean age; 53.9±10.4 years, 59.3% male) at our hospital from 2018 to 2019. ECGs recorded closest to the time of CAG were carefully reviewed and measured PR interval, QRS duration, QT and QTc intervals.

Results
41 (22.5%) patients had arrhythmic events including atrial, and ventricular tachycarrhythmia during follow-up. The patients with QRS prolongations had higher incidences of arrhythmic events compared with those without QRS changes (P=0.025). In univariate analysis, diabetes mellitus (P=0.05), coronary artery spasm (P=0.031) and QRS prolongations (P=0.036) were significantly associated with arrhythmic events. In multivariate analysis, QRS prolongations [OR 2.496 (1.077–5.784), P=0.033] was independent risk factors for arrhythmic events at the long-term follow-up. ROC curve analysis were performed to define cut-off point for arrhythmic events (QRS prolongation during EPT&gt;10.6 msec [sensitivity = 0.972; specificity = 0.943]; AUC=0.632; P=0.015)

Conclusion
The patients with QRS duration prolongations during Ergonovine provocation test were associated with higher incidence of arrhythmic events, suggesting more intensive medical therapy with close clinical follow-up will be required.

Funding Acknowledgement
Type of funding source: None
Advanced interatrial block is associated with worst prognosis in patients with previous coronary acute syndrome
Authors: Garcia Talavera C.S , Acena Navarro A , Esteban-Chapel J.A , Camblor Blasco A , Franco Pelaez J.A , Pello Lazaro A.M , Lopez Castillo M , Martin Mariscal M , Hernandez Gonzalez I , Venegas Rodriguez A.M , Canovas Rodriguez E , Kallmeyer Mayor A , Tunon Fernandez J 
Published: November 2020

Abstract

Background
The interatrial block (IAB) has been directly related to the appearance of several atrial tachyarrhythmias. The objective of this study is to establish whether the duration of p wave could predict the appearance of atrial fibrillation (AF), death or stroke in patients with a previous acute coronary syndrome (ACS).

Methods
We have reviewed all ECG of patients with an ACS admitted to our hospital from July 2006 to June 2014 looking for advanced IAB defined as (P-wave duration was ≥120 ms and presented biphasic morphology), excluding those patients with previous AF and who received anticoagulant therapy. These patients were part of the population of the BACS & BAMI (Biomarkers in Acute Coronary Syndrome & Biomarkers in Acute Myocardial Infarction) studies. For all patients we have determined their cardiovascular risk factors. The primary outcome was a combined endpoint that included death, stroke and development of AF. Cox regression was used for the analysis.

Results
A total of 423 patients were included, the mean age was 67.8 years (± 14), and 72.3% were male. Only 12 patients (2.8%) presented advanced IAB. After a median follow-up of 54.7 months, there were 51 events (21 deaths (41.2%) were observed, 17 patients (33.3%) had experienced stroke, and 13 patients (25.5%) had developed AF). Patients with development of primary endpoint were older with higher rates of cardiovascular risk factors, advance IAB and diuretic treatment at discharge.
After a multivariate Cox regression analysis, advanced IAB [HR=2.65 (1.03–6.86); p=0.044], age [HR=1.06 (1.03–1.09) per year; p&lt;0.001] and diuretic treatment at discharge of ACS [HR=1.87 (1.03–3.39); p=0.039] were independent predictors of worse prognosis.

Conclusion
Advanced IAB in ECG at admission with ACS could be a predictor of stroke, development of AF or death in follow up.

Funding Acknowledgement
Type of funding source: None
Electrocardiographic parameters among beta-thalassemia major patients
Authors: Patsourakos D , Aggeli C , Gatzoulis K , Delicou S , Dimitroglou Y , Androulakis A , Tousoulis D 
Published: November 2020

Abstract

Background/Introduction
The majority of beta thalassemia major (β-TM) patients suffer from cardiac disorders, while a significant proportion of them die suddenly. Twelve-lead and signal-averaged electrocardiography are simple, inexpensive, readily available tools for identifying an unfavorable arrhythmiological substrate by detecting the presence of arrhythmias, conduction abnormalities and late potentials (LPs) in these patients.

Methods
47 β-TM patients and 30 healthy controls were submitted to twelve-lead and signal-averaged electrocardiography. Basal rhythm, heart rate, PR interval duration, QRS complex duration and morphology, QTc interval duration and prevalence of LPs were recorded.

Results
β-TM patients demonstrated a more prolonged PR segment (167.74 msec vs. 147.07 msec) (p=0.043), a higher prevalence of PR prolongation (21.05% vs. 0%) (p=0.013) and a higher prevalence of LPs (18/47, 38.3% vs. 2/30, 6.7%) (p=0.002) compared with controls. In particular, every single SAECG parameter significantly differed among patients compared with controls. Among patients, left ventricular ejection fraction was marginally lower and QTc more prolonged among LPs positive subgroup compared with LPs negative subgroup. The prevalence of atrial fibrillation among b-TM patients was estimated at 10.64%.

Conclusions
β-TM patients have a higher prevalence of a prolonged PR segment, atrial fibrillation and LPs. Twelve-lead and SAECG performance was feasible in all subjects and constitutes a readily available tool for assessing myocardial electrophysiological alterations in this patient group, that could have significant impact on survival and quality of life with timely application of appropriate treatment.

Funding Acknowledgement
Type of funding source: None
Identifying at-risk subjects for sustained atrial high-rate episodes using the C2HEST score: the West Birmingham AF project
Authors: Li Y.G , Pastori D , Miyazawa K , Shahid F , Lip G.Y.H 
Published: November 2020

Abstract

Background
Sustained atrial high-rate episodes (SAHREs) (lasting &gt;24h) was associated with unfavorable pragnosis.

Objectives
To evaluate the performance of the C2HEST score in assessing individuals' risk of SAHRE.

Methods
The West Birminghan Atrial Fibrillation (AF) Project included 500 consecutive non-AF patients with implantable cardiac electronic device. The role of the C2HEST score for SAHRE risk stratification was evaluated.

Results
SAHRE was detected in 8.8% of patients (2.09%/year, 95% CI 1.47–2.71) over a mean 4.4 years of follow-up. SAHRE was associated with increased all-cause mortality (P&lt;0.001). The risk of SAHRE increased by C2HEST score (39% higher risk per point increase). The C2HEST score had moderate predictive capability (c-index 0.706 [0.615–0.798], log-rank P=0.003) for SAHRE, which was better than other clinical scores (CHA2DS2-VASc, CHADS2, HATCH).

Conclusions
The C2HEST score was predictive of SAHRE, which may help to identify at-risk subjects who may need intensive device review.
Central Illustration

Funding Acknowledgement
Type of funding source: None
Frequent premature atrial complexes and risk of concurrent atrial fibrillation
Authors: Johnson L.S.B , Napiorkowski N , Dziubinski M , Conen D , Healey J.S , Engstrom G 
Published: November 2020

Abstract

Background
Premature atrial complexes (PACs) predict incident atrial fibrillation (AF) in long-term follow-up studies. It is unclear whether frequent PACs on ambulatory ECG recordings indicate a higher likelihood of concurrent, undiagnosed AF. Furthermore, the reproducibility of a 24 h PAC count is unclear.

Objectives
To determine if frequent PACs on 24 h ambulatory ECG monitoring predicts concurrent AF during subsequent, prolonged ECG monitoring and to assess the diagnostic reliability of PAC counts on a 24 hour ECG recording.

Methods
AF was defined as ≥30 seconds of irregular rhythm without P waves, which was detected by a proprietary algorithm and manually verified. The proportion of AF occurrence during the remainder of the monitoring period was calculated for pre-specified levels of PACs during the first 24 h, and a function describing the association was fitted. The diagnostic reproducibility of a 24 h PAC count was assessed by calculating the likelihood of a PAC count ≥1000/day during the entire monitoring duration for prespecified PAC count levels during the first 24h.

Results
The study population comprised 20,973 patients (41% men, mean age 69.5 years) who had recorded an ambulatory ECG with a monitoring duration of 4–30 days in the United States during the year 2017 (median monitoring duration 16 days). AF was detected in 2,029 (9.7%) of patients and the median time to first occurrence of AF was 5 days. PAC frequency during the first 24 h was associated with AF during the monitoring period beyond the first 24 h, increasing steadily from 4.2% among those with 0–5 PACs, to a plateau around 17% among those with 250–1000 PACs per day and above. (Fig. 1A). The reproducibility of low PAC counts was good. Only 5.5% of patients with 0–5 PACs during the first 24 h of monitoring (31.8% of the population), had ≥1000 PACs on an alternate monitoring day. In contrast, among subjects with 100 PACs the probability of a day with ≥1000 PACs was close to 50% (Fig. 1B).

Conclusion
In patients undergoing ambulatory ECG monitoring, frequent PACs during the first 24 h indicate a higher likelihood of AF occurrence during subsequent days of monitoring. Less than 5 PACs during the first 24 h indicate a low probability of AF or frequent PACs on a subsequent day of ECG monitoring.
Figure 1

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): The Swedish Heart and Lung Foundation; The Swedish Heart and Lung Association