bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term follow-up of cardiac resynchronization therapy patients with non-ischemic dilated cardiomyopathy assessed by radionuclide angiography
Authors: Valzania C , Bonfiglioli R , Fallani F , Frisoni J , Biffi M , Boriani G , Galie' N 
Published: November 2020

Abstract

Background
While the beneficial effects of cardiac resynchronization therapy (CRT) have been widely investigated soon after CRT implantation, relatively few data are available on long-term clinical outcomes of CRT recipients.

Aim
To investigate long-term outcomes of CRT patients with non-ischemic dilated cardiomyopathy stratified as responders and non-responders according to radionuclide angiography.

Methods
Consecutive heart failure patients with non-ischemic dilated cardiomyopathy undergoing CRT implantation at our University Hospital between 2007 and 2013 were enrolled. All patients were assessed with equilibrium Tc99 radionuclide angiography at baseline and after 3 months of CRT. Left ventricular (LV) ejection fraction was computed on the basis of relative end-diastolic and end-systolic counts, and intraventricular dyssynchrony was derived by Fourier phase analysis. Response to CRT was defined by an absolute increase in LV ejection fraction (LVEF) ≥5% at 3-month follow-up. Clinical outcome was assessed after 10 years through hospital records review.

Results
Forty-seven patients (83% men, 63±11 years) were included in the study. At 3 months, 25 (53%) patients were identified as CRT responders according to LVEF increase (from 26±8 to 38±12%, p&lt;0.001). In these patients, LV dyssynchrony decreased from 59±30° to 29±18° (p&lt;0.001). Twenty-two (47%) patients were defined as non-responders. No significant changes in LVEF and LV dyssynchrony (50±30° vs. 38±19°, p=0.07) were observed in non-responders. At long-term follow-up (11±2 years), all-cause and cardiac mortality rates were 24% and 12% in responders vs. 32% and 27% in non-responders, respectively (p=ns). Heart transplantation was performed in 3 patients. One (4%) patient among CRT responders compared with 6 (27%) patients among non-responders died of worsening heart failure (p=0.03).

Conclusions
Although late overall mortality of non-ischemic CRT recipients was not significantly different between mid-term responders and non-responders, CRT responders were at lower risk of worsening heart failure death.

Funding Acknowledgement
Type of funding source: None
Molecular mechanism of a new cardiac syndrome associated with a regulatory element deletion of chromosome 4q25
Authors: Baudic M , Murata H , Le Scouarnec S , Foucal A , Lindenbaum P , Ishikawa T , Si-Tayeb K , Gaborit N , Makita N , Makiyama T , Shimizu W , Vieyres C , Probst V , Schott J.J , Barc J 
Published: November 2020

Abstract

Introduction
We identified a large family of 53 members of whom 22 present a new cardiac syndrome characterized by electrical disorders and developmental defects following an autosomal dominant model. Among the affected family members 6 are implanted with a pacemaker, 2 experienced syncope and one a sudden death at 43yo. Linkage analysis points, with high confidence, to the chromosome 4q25 region. This region is associated with the Ankyrin syndrome (mutation in ANK2) sharing partly the electrical defects observed in the affected family members. No mutation was found in the coding region of the 4q25 region as well as in the coding and non-coding part of the ANK2.

Objective
Our aims are first to identity the responsible mutation present in this family and understand the molecular mechanisms leading to this new syndrome.

Method
Whole genome sequencing (WGS) has been employed to identify genetic variants responsible for this syndrome. ChIP-seq and ATAC-seq were used for functional annotation and genome editing (CRISPR-Cas9) to generate iPS cellular models.

Results
By WGS we uncovered a deleted region of 15kb in a gene desert area on 4q25, segregating in all affected relatives. Five other families (3 French and 2 Japanese) presenting the same phenotype show overlapping deletions. We generated human cardiac epigenetic data and identified among the 15kb deleted region a unique active enhancer region within the presence of a transcript factor CTCF binding site. Isogenic cell lines where the 15kb and the CTCF binding have been deleted are under investigation.

Conclusion
We identified a new cardiac syndrome and for the first time a mutation located within a gene desert area leading to severe and complex cardiac disorders. We demonstrated the presence of a likely gene regulatory element. Experiments are ongoing to characterize the molecular mechanisms and consequence of the deletion on gene expression.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Pays de la loire - Etoiles montantes
MOG1 restores the expression and function of SCN5A-p.R104W through sec23a-mediated forward trafficking
Authors: Luo L , Wang Y , Du Y , Dong C , Ma A , Wang T 
Published: November 2020

Abstract

Background
Brugada syndrome (BrS) is an inherited disease which causes fatal arrhythmias and sudden cardiac death. Mutations in SCN5A gene, which encoding cardiac sodium channel (NaV1.5), are the most common genotype of BrS patients. Some SCN5A-related variants were reported to retain NaV1.5 in endoplasmic reticulum (ER) due to trafficking deficiency. MOG1 was previously reported to interact with NaV1.5 and increased sodium current (INa) through enhancing the trafficking. However, its molecular mechanisms are still unclear. Coat protein complex II (COPII) is responsible for the ER to Golgi transport. Sec23 forms the inner coat of COPII and participates in cargo proteins selection.

Purpose
To demonstrate that MOG1 rescues SCN5A-related variants by enhancing the forward trafficking through Sec23a-NaV1.5 interaction.

Methods
Site directed mutagenesis, immunofluorescence staining, biotinylation assay, Western blot analysis and whole-cell patch clamp recording were used. CRISPR/Cas9 was used to knock out Sec23a expression in HEK293 cells.

Results
We found that SCN5A-p.R104W was characterized as reduced NaV1.5 level and lack of INa. The variant SCN5A-p.R104W was mainly distributed in ER. MOG1 could rescue the total and surface expression of SCN5A-p.R104W but could not restore INa (Figure 1a). Considering that most patients are heterozygous, co-transfection of SCN5A-WT and SCN5A-p.R104W were obtained. We found MOG1 could increase both NaV1.5 level and INa of heterozygous expressed SCN5A-p.R104W. We further revealed an interaction between NaV1.5 and Sec23a by co-immunoprecipitation (Co-IP) assay. The interaction between NaV1.5 and Sec23a was increased by MOG1, which indicates that Sec23a participates in MOG1-mediated increase in NaV1.5 level (Figure 1b). Knockout of Sec23a reduced cell surface, but not total, NaV1.5 level (Figure 1c and 1d). Next, the Sec23a knockout HEK293 cells were co-transfected with SCN5A-p.R104W and pcDNA3 or MOG1. MOG1 could not increase SCN5A-p.R104W protein level in Sec23a knockout cells.

Conclusion
Our data demonstrated a novel mechanism that MOG1 restores the expression and function of SCN5A-p.R104W by enhancing its forward trafficking through Sec23a-NaV1.5 interaction.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Natural Science Foundation of China
Trend in the prevalence of atrial fibrillation 7 years after the Great East Japan Earthquake
Authors: Tamaki K , Koshiyama M , Ohsawa M 
Published: November 2020

Abstract

Background
The age-adjusted prevalence rate of atrial fibrillation (AF) had kept increasing until 2-year after the Great East Japan Earthquake (reported in ESC2017). Whether the elevated prevalence was tentative or not has not been sufficiently elucidated yet.

Methods
Community dwellers aged 40 to 74 years living in Iwate Prefecture who underwent annual health checkups (2010 (n=17490), 2011 (n=174236), 2012 (n=183612), 2013 (n=188429), 2014 (n=188424), 2015 (n=193610), 2016 (n=194882), 2017 (n=195428) account for approximately 30% of total population) were enrolled. Participants were divided into two age categories (40–64, 65–74 years). Direct age-adjusted prevalence rate of AF in each year was estimated using the 2010 population as the reference.

Result
Data are shown in the figure.

Conclusion
Prevalence rates of AF increased only in elderly people for up to 3 years after the disaster. This indicated that accelerated development of AF in elderly people due to stressful life after the disaster would not end within a short term and lasted at least 3 years after the disaster.
Figure 1

Funding Acknowledgement
Type of funding source: None
Pause-triggered episode classification algorithms and high-priority review queue concept for cardiac monitoring devices
Authors: Rajagopal G , Landman S.R 
Published: November 2020

Abstract

Background
Cardiac monitoring technologies often utilize monitoring centers or services in which technicians adjudicate arrhythmia episodes. Arrhythmias with a high prevalence of false detections (such as pauses) can slow down the review process while also delaying review of time-sensitive true episodes.

Objective
To develop algorithms that can stratify device-detected pause episodes into low- and high-priority queues to facilitate monitoring center review.

Methods
The high priority queue algorithm identifies episodes which are likely to be true pause episodes. The algorithm consists of four conditions, which identify features that were found to be predictive of true pauses, including the number of beats in the episode, the noise status of the last pre-pause beat, and the relative flatness of the ECG signal. Using a similar set of features, a set of criteria was determined that would identify pause-triggered episodes that were highly unlikely to be true pauses. 11,567 pause episodes were used for development with 19,520 separate episodes used for validation. All episodes were adjudicated by a cardiac monitoring center. The validation dataset consisted of 18,280 (93.6%) false pauses and 1240 (6.4%) true pauses.

Results
The high-priority queue algorithm identified true pause episodes with a sensitivity of 82.3% and specificity of 96.8% in the validation dataset (see table). The low-priority queue algorithm flagged 78.4% of all pause episodes as low-priority in the validation dataset, with only 4 true pause episodes (&lt;0.1%) flagged as low priority.

Conclusion
The high-priority queue algorithm for device detected pause episodes could potentially identify ∼82% of all true pause notifiable episodes, expediting their review process. The low-priority queue successfully identifies a large percentage (∼80%) of false pause-triggered episodes, which would help to improve monitoring center efficiency as false pause-triggered episodes are a large driver of artifact / normal sinus rhythm episodes.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Medtronic
Hardware challenges with an anticoagulation strategy guided by detection of atrial fibrillation by an implantable loop recorder
Authors: Mittal S , Brenner D , Oliveros S , Bhatt A , Preminger M , Sichrovsky T , Musat D 
Published: November 2020

Abstract

Background
A “pill-in-the-pocket” anticoagulation strategy, guided by ECG data from an implantable loop recorder (ILR), has been advocated as a clinical strategy. However, a fundamental requirement is the ability to reliably obtain daily ECG data from patients.

Objective
To determine the reliability of daily ECG data transfer from ILRs.

Methods
We evaluated patients implanted with an ILR in whom we sought to withhold oral anticoagulation (OAC) unless atrial fibrillation (AF) was detected. The ILR transmits data nightly to a bedside monitor. Once received, the data are sent to a central server. Over the course of a month, we tracked for each patient whether ECG data were received by the server.

Results
The study included 170 AF patients with an ILR where we planned to withhold OAC unless AF was documented. Daily ECG data were automatically transmitted and retrievable in only 36 (21%) patients. Two (1%) pts had not a single day of connectivity, 6 (4%) pts were connected &lt;7 days, and 16 (9%) pts were connected &lt;14 days. Wireless connectivity was lost for &gt;48 hours in 89 (52%) patients (Figure). Most patients experienced multiple reasons for data transmission failure within the month.

Conclusions
To determine whether an ILR guided OAC strategy is feasible, reliable daily transmission of ECG data is a fundamental prerequisite. Current technology facilitated daily ECG data transfer in only 1/5 of patients. In the remaining, there was either extended loss of connectivity or no connectivity at all. A “pill-in-the-pocket” anticoagulation approach is currently difficult given existing hardware limitations.

Funding Acknowledgement
Type of funding source: None
Impact of smoking cessation after the new diagnosis of atrial fibrillation on the risk of stroke: a nationwide cohort study
Authors: Lee S.R , Choi E.K , Jung J.H , Han K.D , Oh S , Lip G 
Published: November 2020

Abstract

Background
There are limited data about the impact of modifying behavior such as smoking cessation after atrial fibrillation (AF) diagnosis on the clinical outcome.

Purpose
To evaluate the association between smoking cessation after newly diagnosed AF and the risk of stroke.

Methods
Among subjects with new-onset AF between 2010 and 2016, those who received a national health checkup exam within 2 years before and after the AF diagnosis were included. Subjects were categorized into 4 groups according to the status of smoking before and after AF diagnosis: (i) never smoker; (ii) new smoker after AF diagnosis; (iii) quit-smoker after AF diagnosis; and (iv) persistent smoker. The primary outcome was incident stroke during follow-up.

Results
A total of 97,869 patients were included (mean age 61±12, men 62%, and mean CHA2DS2-VASc 2.3±1.5). During a median of 3 years of follow-up, stroke occurred in 3,121 patients (1.0 per 100 person-years). Never smoker, new smoker, quit-smoker, and persistent smoker was 79%, 2%, 7%, and 12% of the total study population, respectively. After multivariable adjustment, new smoker and persistent smoker were associated with an increased risk of stroke compared to never smoker (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.48–2.28 for new smoker; HR 1.66, 95% CI 1.48–1.86 for persistent smoker) (Figure). Quit-smoker who stopped smoking after AF diagnosis also showed a higher risk of stroke than never smoker (HR 1.19, 95% CI 1.03–1.38). The quit-smoker group showed a lower compared to those who continued smoking after AF diagnosis (HR 0.720, 95% CI 0.608–0.851).

Conclusion
Smoking cessation after AF diagnosis showed a lower risk of stroke compared to patients smoking persistently. Lifestyle change as smoking cessation after diagnosis of AF could modify the risk of stroke in patients with new-onset AF.
Hazard ratio of smoking status for AF

Funding Acknowledgement
Type of funding source: None
Late gadolinium enhancement location and transcatheter ablation efficacy in a large cohort of patients affected by myocarditis with arrhythmic manifestation
Authors: Persampieri S , Bergonti M , Gasperetti A , Narducci M.L , Perna F , Catto V , Carbucicchio C , Di Biase L , Basso C , Andreini D , Natale A , Dello Russo A , Pelargonio G , Tondo C , Casella M 
Published: November 2020

Abstract

Introduction
Myocarditis is a complex inflammatory disease, usually secondary to viral infections or immune system dysregulation, with extremely heterogeneous clinical manifestations. Among them, potentially life-threatening ventricular arrhythmias (VA) may present at any stage of the disease as an expression of myocardial electrical instability.

Purpose
Our aim was to evaluate the efficacy of radiofrequency catheter ablation (RFCA) of VA in our large cohort of myocarditis, trying to understand the predictors of RFCA success.

Methods and results
144 patients (61 men; age 43 [29–54] years) with history of myocarditis with arrhythmic presentation (118 biopsy-proven, 82%) composed our population. At presentation, 26% of patients suffered of ventricular tachycardia (VT) while in 17% cardiac arrest occurred: overall 49 patients (35%) were implanted with an ICD. The median left ventricular ejection fraction (LVEF) was 58% (48–61%). An intensive non-invasive and invasive work-up was performed: 104 patients underwent cardiac magnetic resonance (CMR) that showed late gadolinium enhancement (LGE) in 67 of them (63%). In 37 patients LGE was found in the anteroseptal portion of the left ventricle: this pattern showed association with major arrhythmic relapse (VT and ventricular fibrillation) during follow up (Fig. 1; OR 4.0, CI 95% 1.14–14.1, p=0.03). 95 patients underwent endocardial RFCA, using contact electroanatomic mapping. Interestingly, in patients with anteroseptal LGE RCFA didn't affect significantly the arrhythmic relapse (OR 5, CI 95% 0.9–33, p=0.06). Otherwise RFCA prevent arrhythmic relapse in patients that showed LGE in ventricular portion other than the anteroseptal one (OR 0.027, IC 95% 0.002–0.40, p&lt;0.01). During a median follow-up of 735 days (418–2168) 6 deaths occurred: logistic regression on all-cause death showed LVEF and VT at presentation as the only independent predictors for mortality (p=0.01).

Conclusions
In myocarditis patients with VA, LGE pattern predicts arrhythmic relapse during follow-up. RFCA success rate is strictly linked to scar location, being significantly higher in patients with non-anteroseptal LGE.
Figure 1

Funding Acknowledgement
Type of funding source: None
Outcome after practical isthmus ablation of scar-related atrial tachycardia guided by high-density mapping
Authors: Jungen C , Akbulak R , Kahle A , Eickholt C , Schaeffer B , Dinshaw L , Schleberger R , Nies M , Gunawardene M , Muenkler P , Klatt N , Hartmann J , Jularic M , Willems S , Meyer C 
Published: November 2020

Abstract

Background
High-density mapping (HDM) has been found to precisely identify the practical isthmus of scar-related atrial tachycardia (AT) circuits. Since practical isthmuses have been found to be shorter than the usual anatomical isthmuses targeted ablation has been proposed. However, outcome data are sparse. Here we describe HDM-guided catheter ablation by targeting the practical isthmus in patients with scar-related ATs.

Methods and results
In 250 consecutive patients with scar-related ATs HDM-guided catheter ablation with the support of a 64-electrode mini-basket catheter has been performed. Most patients underwent a prior catheter ablation (98%) while 13% had a prior cardiac valve surgery and 6% an underlying congenital heart disease. A total of 355 ATs occurred in the index procedure, of which 64% had a macro-, 26% a micro-reentry and 10% a focal mechanism. The ATs had a mean cycle length of 304±4.3 ms and in 237 patients (95%) an acute termination into sinus rhythm was achieved. They were mainly located in the left atrium (72%) but also in the right atrium (25%), bi-atrially (5%) or in the CS (3%) (see figure). Targeting the practical isthmus revealed arrhythmia freedom in 53% of patients after a single procedure during a mid-term follow-up (median 489 days, range 95–1407 days). Freedom from any arrhythmia could be achieved in 74% of patients after multiple procedures and in 93% of patients after multiple procedures and optimal clinical therapy, including pharmaceutical or electrical cardioversion.

Conclusions
HDM-guided catheter ablation of the practical isthmus in patients with scar-related ATs leads to a high acute success rate. Nevertheless, multiple procedures are necessary in a relevant number of patients resulting in a low recurrence rate.

Funding Acknowledgement
Type of funding source: None
Predictors of silent cerebral infarction associated with catheter ablation for atrial fibrillation
Authors: Furukawa Y , Watanabe T , Yamada T , Morita T , Tamaki S , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Kawahira M , Fukunami M 
Published: November 2020

Abstract

Introduction
Cather ablation (CA) has been identified as an effective and safe treatment option for patients with atrial fibrillation (AF). One of the serious complications associated AF is cerebral infarction (CI). Recent studies reported that CA was associated with lower incidence of ischemic stroke in patients with AF. However, CA for AF itself has a potential risk of CI. Several previous studies showed that the incidence of silent CI (SCI) assessed by magnetic resonance imaging (MRI) of the brain occurred 5 to 18% during CA for AF. Recently, CA for AF made a remarkable progress in technology. However, there are few information available that the impact of 3-dimensional electroanatomical mapping system on the incidence of SCI. This study aimed to clarify the prevalence and predictors of SCI during CA for AF.

Methods
We enrolled 893 consecutive patients (male 534, age 71±10 years), who underwent CA for AF and MRI of brain 1 day after the procedure. We collected patients data such as physical examinations, blood sampling, echo cardiography, and CA data. A brain MRI was performed the next day following the procedure to identify any CIs. One-hundred and forty-six of patients used the Rhythmia® mapping system catheter, and the other mapping system such as CARTO or EnSite system used in the remaining 747 patients.

Results
The MRI depicted acute micro-CIs in 144 (16%) patients, but neither symptoms nor abnormal neurological findings were present in these patients. Patients with SCI had significantly higher prevalence of persistent AF (60 vs 43%, p=0.0002), CHADS2 Score (2 (1–3) vs 1 (1–2), p=0.0001), higher prevalence of previous stroke (19 vs 12%, p=0.02), larger left atrial (LA) diameter (43.2±6.4 vs 41.7±6.5mm, p=0.01), lower left ventricular ejection fraction (LVEF) (59.0±13.2 vs 64.2±11.3%, p≤0.0001), higher B-type natriuretic peptide level (221±236 vs 163±225 pg/dl, p≤0.0001), more Rhythmia® mapping system use (30 vs 8%, p&lt;0.0001), and longer procedure time (129±46 vs 108±39 min, p≤0.0001) than those without SCI, while there were no significant differences in age, LA appendage flow velocity, kind of anti-coagulant agent between the two groups. Multivariate regression analysis identified Rhythmia® use [odds ratio (OR) 4.26, (95% CI 2.32–7.84), p=0.0001], LVEF (OR 1.02, p=0.0059), CHADS2 score (OR 1.27, p=0.009), and procedure time (OR 1.005, p=0.04) as independent risk factors of acute SCI during CA for AF.

Conclusion
Acute SCI occurred about 16% after CA for AF. Rhythmia® mapping system use exhibited a higher incidence of acute SCI after catheter ablation for AF than the other mapping system use. Rhythmia® mapping system use, LVEF, CHADS2 score, and procedure time are associated with SCI relating CA for AF.

Funding Acknowledgement
Type of funding source: None