bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel mutation in transmembrane protein 168 causes fatal ventricular arrhythmogenesis in Brugada syndrome
Authors: Ogita H , Zankov D.P , Shimizu A 
Published: November 2020

Abstract

Brugada syndrome (BrS) is diagnosed by a typical electrocardiography (ECG) with ST-segment elevation in precordial leads and tends to induce sudden cardiac death (SCD) due to ventricular tachycardia/fibrillation. About 20% of SCDs in non-structural cardiac diseases are considered to be caused by BrS. In patients with BrS, loss of function mutations in the Na+ channel is often observed, but the causative gene mutation is not detected for about 70% of BrS patients. Here, we investigated a family with clinically diagnosed BrS, in which no known gene mutations related to BrS had not been found, by whole exome sequencing. Novel heterozygous variant (c. 1616G&gt;A, p. R539Q) in transmembrane protein 168 (TMEM168) was identified only in symptomatic family members. Similar to endogenous TMEM168, both wild-type and mutant TMEM168 localized at the nuclear membrane. Na+ current density in whole-cell patch-clamp recordings was significantly reduced in HL-1 cardiomyocytes transfected with TMEM168 R539Q mutant, compared with those with wild-type TMEM168. Next, heterozygous Tmem168 1616G&gt;A knock-in mice were generated by the CRISPR/Cas9 genome editing technology. Although the knock-in mice had no abnormalities in ECG at the physiological state, the treatment with ajmaline caused various arrhythmias including ventricular tachycardia/fibrillation in the knock-in mice, but not in wild-type mice. Na+ current density and the parameters of action potentials were remarkably impaired in the cardiomyocytes of the knock-in mice. Optical mapping analysis in the whole heart showed the reduced left ventricular conduction velocity in the knock-in mice. The expression of Nav1.5, an α-subunit of the cardiac Na+ channel, was significantly decreased in the mutant TMEM168-transfected HL-1 cells and the knock-in hearts. We found that the decrease was caused by the enhanced ubiquitination of Nav1.5, which was mediated by increased binding of Nedd4–2 E3 ubiquitin ligase to Nav1.5 in the knock-in hearts. Co-immunoprecipitation experiments demonstrated that overactivity of Nedd4–2 is a result of Tmem168 mutant-mediated sequestration of a chaperon protein αB-crystallin, a Nav1.5-binding molecule that interferes with the interaction of Nedd4–2 with Nav1.5. These findings reveal the molecular mechanism of TMEM168 R539Q mutation-induced fatal ventricular arrhythmias in BrS.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): JSPS Grants-in-aid for Scientific Research
The Atrial fibrillation Better Care (ABC) pathway is associated to a lower incidence of cardiac complications in patients with atrial fibrillation: a report from the ATHERO-AF study
Authors: Pastori D , Pignatelli P , Violi F , Lip G.Y.H 
Published: November 2020

Abstract

Background
The integrated management of atrial fibrillation (AF) patients according to the Atrial fibrillation Better Care (ABC, A, Avoid stroke with anticoagulation; B, better symptom management; C, Cardiovascular and comorbidity risk management) pathway has associated with a reduced incidence of thromboembolic events and mortality. However, whether this approach also results in a lower rate of cardiac complications is unknown.

Purpose
To investigate the rate of major adverse cardiovascular events (MACE) in AF patients according to compliance with the ABC pathway.

Methods
This prospective single-center cohort study included 1157 patients with nonvalvular AF from the ATHERO-AF study. The A, B, and C groups were defined as follows: “A” by a Time in Therapeutic Range ≥70% in vitamin K antagonists-treated patients or appropriate dose for patients on direct oral anticoagulants; “B” by a European Heart Rhythm Association (EHRA) symptom scale I-II (vs. III-IV), and “C” as optimized cardiovascular comorbidity management (i.e. use of ACE inhibitors in heart failure patients, blood pressure &lt;140/90, use of statins and beta blockers in patients with prior ischemic heart disease). The primary end point was a composite of MACE including fatal/non-fatal myocardial infarction, coronary revascularization and cardiovascular death (progressive heart failure, sudden cardiac death and procedure-related death).

Results
Overall, 458 (39.6%) patients were optimally managed according to the ABC (ABC-compliant group), while the remaining 729 patients presented at least one uncontrolled component (ABC non-compliant group). During a mean follow up of 35 months, (2688 patient-years), 64 MACE were recorded 2.38%/year. Kaplan Meier curve analysis showed a significant higher rate of MACE in ABC non-compliant group compared to the ABC-compliant (54 and 10 MACE in each group, respectively, log-rank test p=0.006, figure). The risk of MACE increased by the number of uncontrolled ABC components: Hazard ratio HR) for 1 component 1.697, 95% Confidence Interval 95% CI 0.814–3.537, p=0.158; HR for 2 components 4.157, 95% CI 1.994–8.665, p&lt;0.001); HR for 3 components 5.100, 95% CI 1.596–16.295, p=0.006.
ABC non-compliant group remained associated with an increased risk of MACE using Cox proportional hazard regression analysis (HR 2.175, 95% CI 1.098–4.309, p=0.026) after adjustment for CHA2DS2VASc score, antiplatelet drugs and digoxin use.

Conclusion
The majority of AF patients is not currently optimally managed. An integrated care ABC approach is associated with a reduced risk of MACE in the AF population.
Figure 1. Kaplan-Meier curves

Funding Acknowledgement
Type of funding source: None
High rate of stroke and low rate of atrial fibrillation in low socioeconomic strata and blacks: the atrial fibrillation paradox
Authors: Kostis J.B , Zinonos S , Cabrera J , Kostis W.J 
Published: November 2020

Abstract

Background and introduction
Persons living in areas of low socioeconomic status (SES) usually have higher rates of adverse cardiovascular events (CVE) including stroke. Also, atrial fibrillation (AF) is associated with higher rate of CVEs. One would expect that both the rate of stroke and the occurrence of AF would be higher in areas of low SES.

Purpose and methods
Using MIDAS, a validated statewide data base of all hospitalizations for cardiovascular disease in NJ with follow up of more than 25 years, we examined the rate of hospitalization for AF by SES in patients with history of myocardial infarction for the years 1995 to 2015 (n=258,339). Zip codes in New Jersey were aggregated into 4 categories representing quarters of the distribution of SES areas.

Results
At one-year follow-up, patients in the lowest SES (lowest 25th percentile) and Blacks were more likely to suffer a stroke (p&lt;0.0001). During one-year follow-up, patients in the lowest 25th percentile (Figure) were significantly less likely (p&lt;0.0001) to be readmitted with a diagnosis of AF. Blacks had lower rate of admission with a diagnosis AF compared to Whites (p&lt;0.0001) (Figure). Cox proportional hazards regression adjusting for demographics and co-morbidities confirmed the validity of these differences. In this analysis patients in the lowest SES quartile and Blacks were less likely to be admitted with AF than those in the highest quartile (HR 0.95, 95% CI 0.92–0.99). Also, Blacks were less likely to be admitted with AF than Whites (HR 0.76, 95% CI 0.71–0.82). This phenomenon (AF paradox) of lower incidence of AF in low SES and in Blacks has been attributed to under-ascertainment of AF in these groups, that may lead to underuse of anticoagulation and result in the occurrence of stroke.

Conclusion
Atrial fibrillation is underdiagnosed in patients at low socioeconomic strata and in Blacks and may lead to underuse of anticoagulation and the occurrence of stroke. Special efforts are warranted in detecting AF in these groups.

Funding Acknowledgement
Type of funding source: None
Prognostic implication of electrocardiographic left ventricular strain in patients undergoing Transcatheter Aortic Valve Implantation
Authors: Drakopoulou M , Soulaidopoulos S , Stathogiannis K , Oikonomou G , Toskas P , Kouroutzoglou A , Papanikolaou A , Synetos A , Latsios G , Sideris S , Tousoulis D , Toutouzas K 
Published: November 2020

Abstract

Background
Electrocardiographic (ECG) strain has been linked to excess cardiovascular morbidity and mortality in asymptomatic patients with aortic stenosis.

Purpose
We aim to determine the differential impact of baseline ECG-strain on long-term mortality after transcatheter aortic valve implantation (TAVI).

Methods
Patients with severe and symptomatic aortic stenosis (effective orifice area [EOA]≤1cm2), who were scheduled for TAVI with a self-expanding valve between May 2015 and May 2018 were consecutively enrolled. Left ventricular strain was defined as the presence of ≥1mm convex ST-segment depression with asymmetrical T-wave inversion in leads V5 to V6 on baseline ECG. Patients were excluded, if they had bundle branch block or a permanent pacemaker at baseline. Baseline parameters were compared, and multivariate Cox proportional hazard regression models were generated to assess outcome difference. The primary clinical endpoint was cumulative mortality defined according to the criteria proposed by the Valve Academic Research Consortium-2.

Results
Of the 171 patients screened, 56 patients were excluded due to left bundle branch block or paced rhythm. In the 115 included patients (mean age: 81.4±7), 36 patients (31.3%) had strain pattern on pre-TAVI ECG. There were no differences in baseline characteristics between the two groups. During a median follow-up of 2.32 years (IQR 1.62 to 3), 11 patients (9.6%) reached the primary clinical endpoint. Patients in the strain group had higher incidence of all-cause mortality compared to patients without left ventricular strain (25% vs 2.5%, χ2=14.4, p&lt;0.001). Kaplan-Meier survival analysis showed a significantly decreased cumulative probability of survival at 3 years in patients with LV-strain compared with patients without LV-strain (log-rank p=0.002, Figure 1). In the multivariate analysis, left ventricular strain [Exp(B): 8.952, 95% Confidence Interval (CI): 1.215–65.938, B=2.192, p=0.031] and QRS duration [Exp(B): 1.058, 95% CI: 1.022–1.095, B=0.056, p&lt;0.001] were found to be independent predictors of all-cause mortality after TAVI.

Conclusion
Baseline ECG left ventricular strain was an independent predictor of long-term mortality post TAVI. Systematic strain measurements might aid in risk-stratifying patients scheduled for TAVI.
Figure 1

Funding Acknowledgement
Type of funding source: None
Anxiety-depressive disorders and quality of life in patients with atrial fibrillation
Authors: Demenko T , Chumakova G.A 
Published: November 2020

Abstract

Background
Mental disorders in patients with cardiovascular disease have a significant impact on the course, the prognosis of the underlying disease and quality of life (QOL).

Objective
We aimed to examine the prevalence of anxiety and depressive disorders and their impact on the quality of life in patients with atrial fibrillation (AF).

Materials and methods
In 52 with permanent AF and 50 with paroxysmal AF patients, we administered the depression scale Tsung, the scale of situational anxiety (SA) and personal anxiety (PA) Spielberger-Hanin; QOL was assessed the SF-36 quality of life assessment scale. Correlation analysis using Spearman's rank correlation coefficient.

Results
The prevalence symptoms mild depression situational or neurotic genesis was 21.1% (12 patients) in Group 1 and 12.0% (6 patients) in Group 2 (p&gt;0.05). Subdepressive state was two percents of patients in Group 1 and Group 2.
The incidence SA was 59.6% (31 patients) in Group 1 and 52.0% (26 patients) in Group 2. The incidence PA was 74.0% (37 patients) in Group 2 and 67.3% (35 patients) in Group 1.
The average score the physical component of health (PCH) was 29,8±4,3 in Group 1, the mental component of health (MCH) – 49.5±7.4 points; p&lt;0.05. In Group 2: PCH – 44.8±6.6 points, MCH – 26.6±7.5 points; p&lt;0.05.
Correlation analysis showed negative strong correlations between SA and MCH (r=−0.64, p=0.0005) and between PA and MCH (r=−0.69, p&lt;0.0001), between SA and PCH (r=−0.71, p=0.0001), between depression and PCH (r=−0.69, p=0.023).
Negative statistically significant correlation between depression and MCH (r=−0.69, p=0.54) and negative medium correlation between depression and PCH (r=−0.64, p=0.23).

Conclusion
These findings suggest that we did not identify patients with symptoms of a true depressive (that can cause pseudodementia and influenced to complete tests). 16.5% patients with AF had mild depression of situational or neurotic genesis. Depression may be a pathogenetic factor of AF or develop because of paroxysms AF – psychological stress.
More than 50% patients in Group 1 and Group 2 had an increased anxiety score. SA is more common in patients with permanent AF, probably because older people difficult to adapt to a new situation. PA is more common in patient with paroxysmal AF, probably because disease is sudden and causes anxiety.
The PCH of QOL is more impairment in patients with permanent AF, because complications (for example heart failure) impairment physical activity. However, PCH also reduced in patient with paroxysmal AF, because disease is sudden may occur during physical activity. The MCH of QOL is more impairment in patients with paroxysmal AF, because waiting attack effect on mental health and social functioning. An increased level of anxiety and depression negatively affected the mental and physical health of patients with AF.

Funding Acknowledgement
Type of funding source: None
Predictors of success for Brugada syndrome epicardial ablation
Authors: Grossi S , Bianchi F , Blandino A , Sibona Masi A , Pintor C , Musumeci G 
Published: November 2020

Abstract

Epicardial right ventricular outflow tract (RVOT) ablation has been described for the treatement of Brugada syndrome (BrS) high risk patients.

Purpose
Success evaluation of epicardial ablation for BrS.

Methods
Type 1 ECG was defined as spontaneous if recorded in absence of drugs and/or specific conditions. BrS patients were scheduled for ablation if presented at least one of: spontaneous type 1 ECG, syncope, ventricular arrhythmias (VA).
Programmed electrical stimulation (PES) was performed (2 extrastimuli, 2 sites) in basal conditions and after ajmaline infusion. Epicardial subxifoid access and electroanatomical endo-epicardial maps were obtained during sinus rhythm. Delayed fragmented/low-frequency, low-voltage electrograms (EGM) were targeted: substrate area measured in basal conditions and after ajmaline.

Epicardial ablation
Radiofrequency (RF) was delivered (50 W power control mode) till complete elimination of targeted EGM and BrS-ECG pattern after ajmaline. Eventually PES repeated: if positive a repeated PES scheduled at follow-up (fu).
Success was defined as absence of type 1 ECG either spontaneous or with ajmaline challenge at 3 month. Recurrences were scheduled to redo ablation.

Results
55 patients were submitted to 58 ablation procedures. 38 spontaneous type 1 ECG: 18 symptomatic for syncope/polimorphic VT/VF or appropriate ICD shock; 13 had VA induction at PES. 4 patients with ajmaline-type 1 ECG had VA induction. 36% of the symptomatic patients and 26% of asymptomatic had PES-VA induction. In all patients abnormal EGM area (cm2) was detected in epicardial RVOT (table 1).
Acute success: No patient had ECG type 1 with ajmaline. 5 patients had PES induction of VA. Complications: 1 cardiac tamponade, 16 mild pericarditis.
At FU of 1,1±0,6 yrs no patient had spontaneous ECG type 1 nor arrhythmic events. 50 had negative ajmaline challenge (90% success rate after single procedure), 3 underwent redo: 2 had negative ajmaline challenge at FU, 1 had persistence type 1-ajmaline induction; 2 are scheduled for redo. No patient had VT induction at PES.
Multivariate analysis: Single procedure success was not related either to history (symptoms, VA, type 1 ECG) or to procedural findings (PES results, substrate area).

Conclusion
Epicardial substrate ablation was safe end effective in BrS. No clinical or procedural findings were related to success

Funding Acknowledgement
Type of funding source: None
Analysis on the factors related to the acute success rate of fluoroless catheter ablation in patients with supraventricular tachycardias: a single-center experience
Authors: Jan M , Yazici M , Habjan S , Prolic Kalinsek T , Topalovic M , Zizek D , Stublar J , Rupar K , Lakic N 
Published: November 2020

Abstract

Background
In this retrospective study, we aimed to detect factors related to the acute success rate (ASR) of radiofrequency (RFA) and cryo-ablation (CRA) of SVTs guided by three-dimensional (3D) electroanatomical mapping (EAM) system completely without the use of fluoroscopy (FLR).

Methods and results
We analyzed 324 consecutive patients with SVTs [age was 30.65±20.71 (3.6–83.1) years, 147 patients &lt;19 years old and 50.3% (163/224) patients were female]. There were 112 patients with accessory pathways (APs), 36 patients with atrial tachycardia (ATs), and 176 patients with atrioventricular nodal reentrant tachycardia (AVNRT). All procedures [(RFA (n=257), CRA (n=51), combined RFA and CRA (n=16)] were performed guided by the 3D EAM system completely without the use of FLR. Intracardiac echocardiography (ICE) was used as an imaging tool when transseptal approach was needed for treatment of left-sided arrhythmias. The acute success rate (ASR) was 90.4% (293/224). There were no procedural complications. After the first procedure, patients were divided into the “ablation success” group (group I, n=293) and the “ablation failure” group (group II, n=31). Two groups were similar in terms of age, BMI, gender distribution, and type of ablation procedure. In group II, number of ablation lesions was significantly higher than group I [respectively; 17.93±11.7 vs. 10.5±14.5; p=0.003]. Additionally, total ablation time (TAT) [respectively; 552.6±298.6 vs. 449.7±448.1; p=0.1] and total procedural time (TPT) [respectively; 116.3±54.2 vs. 94.5±82.0; p=0.05] were mildly higher. When compared to Group I, the number of patients with right-sided tachycardias was significantly higher in Group II.[67.74% (21/31 vs. 21.5% (63/293; p&lt;0.001]. ASR was the highest for patients with AVNRT and lowest for patients with ATs [respectively; 95.4% (168/176) vs. 75.0% (27/36); p&lt;0.001]. Binary logistic regression analysis (Nagelkerke R Square=0.201) showed that SVTs originating from the right side were an independent risk factor for procedural failure. Patients with right-sided SVTs faced an approximately 11-fold increased risk of failed ablation (OR=10.69, 95% CI 2.49–45.78, p=0.001). Type of arrhythmia, type of ablation procedure, the sex category, age, and BMI were not independent risk factors for failed ablation. A significant risk factor for recurrence could not be detected.

Conclusions
This study revealed that catheter ablation of SVTs completely without the use of fluoroscopy can be performed with high ASR and without procedural complications. Likewise, ASR of fluoroless ablation was the highest for patients with AVNRT and lowest for patients with AT. Moreover, right-sided SVTs were an independent risk factor for ablation failure.

Funding Acknowledgement
Type of funding source: None
Pre-ablation left atrial function predicts the presence of low voltage zone in patients undergoing paroxysmal atrial fibrillation ablation: OLAF-LVZ predictive score
Authors: Oka T , Yoshimoto I , Koyama Y , Tanaka K , Hirao Y , Tanaka N , Okada M , Kitagaki R , Okamura A , Iwakura K , Fujii K , Inoue K 
Published: November 2020

Abstract

Background
Preoperative left atrial (LA) function is associated with paroxysmal atrial fibrillation (PAF) ablation outcome. The presence of left atrial low voltage zone (LVZ) is also associated with recurrence. We hypothesized that reduced pre-ablation LA function reflects the presence of LVZ.

Purpose
We investigated the association between baseline LA function and the presence of LVZ in patients undergoing initial PAF ablation. Further, we sought to create the new predictive scoring for the presence of LVZ.

Methods
Consecutive 305 patients who underwent LA voltage mapping during initial PAF ablation from January 2017 to October 2019 in our institute were retrospectively analyzed. We performed 256-slice MDCT at baseline. As the representative of LA function, we calculated LA emptying fraction (LAEF), where LAEF = {[(maximum LAV) − (minimum LAV)]/(maximum LAV)} x 100. LVZ was defined as regions where bipolar peak-to-peak voltage was &lt;0.5mV. We performed the univariate and multivariate analysis to assess the association between LAEF and the presence of LVZ. Second, we performed receiver operating characteristic (ROC) analysis for the prediction of LVZ. We combined multivariate predictors and created the predictive scoring for LVZ.

Results
Out of 305 pts, 56 pts (18%) had LVZ in LA. In univariate analysis, low body mass index, higher percentage of female sex, higher age, higher E/e', larger maximum LA volume and lower LAEF (29.3±11.8% vs. 41.2±9.7, P&lt;0.0001) was associated with the presence of LVZ. In multivariate logistic regression analysis, Low LAEF revealed the strongest predictor for LVZ (LAEF; Odds ratio [OR]/10% increase: 0.54, 95% CI: 0.39–0.82, P=0.0016). High age and female sex also remained as the independent predictors (Age; OR/10 y.o. increase: 1.80, 1.23–3.03, P=0.0042, Female; OR: 2.51, 1.15–5.49, P=0.0213). In ROC analysis, LAEF had moderate predictive accuracy for the presence of LVZ. (Area under the ROC curve: 0.77, Best cut-off value: 31%, P&lt;0.0001) (Figure 1). We created OLAF-LVZ predictive score by combining Old age (1 point, ≥65), LAEF (2 points, LAEF ≤31%) and Female sex (1 point). OLAF score had gradient effect on the incidence of LVZ (2%, 11%, 25%, 45%, 71%, OLAF score; 0, 1, 2, 3, 4, respectively, P&lt;0.0001) (Figure 2).

Conclusions
In PAF patients, preoperative LAEF was strongly associated with the presence of LVZ. LVZ might reflect the myocardial injury causing LA dysfunction. OLAF-LVZ predictive score: combination of Old age (≥65), Female sex, and LAEF (≤31%) could be useful to stratify the risk of the presence of LVZ.

Funding Acknowledgement
Type of funding source: None