bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifelong and mature-onset syncope in older adults may have different mechanisms
Authors: Torabi P , Rivasi G , Hamrefors V , Sutton R , Brignole M , Fedorowski A 
Published: October 2021

Abstract

Background
Syncope is a common clinical problem with a sharp rise in the incidence after 70 years. In older patients, syncope is often a diagnostic challenge. It is unclear whether the age at which patients experience syncope for the first time impacts the results of syncope investigation.

Purpose
To study the influence of early-onset vs. mature-onset syncope on clinical characteristics and final head-up tilt (HUT) diagnosis in a large sample of unexplained syncope patients.

Methods
Consecutive patients (n=1928) with unexplained syncope after initial evaluation examined with a standard HUT protocol in a syncope unit were stratified into age groups below and above 60 years. Clinical characteristics and the final HUT diagnosis were analysed in relation to self-reported age at first syncope and age at investigation. The distribution of age at first syncope was bimodal with peaks at 15 and 70 years (Figure 1). In the present analysis, patients aged &gt;60 years (n=836) with early-onset (&lt;30 years) and mature-onset (&gt;60 years) syncope were compared.

Results
Vasovagal syncope (VVS) was more common in early-onset syncope, 39% vs 19% (p&lt;0.001), (Figure 2). Orthostatic hypotension (OH) was more common in mature-onset syncope, 23% vs 7% (p&lt;0.001), as was hypertension, 59% vs 40% (p=0.001). The frequency of carotid sinus syndrome (CSS) was not affected by age at first syncope in patients aged &gt;60 years.Complex syncope etiology (findings suggesting overlap between VVS, OH and/or CSS) was more common among patients with early-onset syncope, 37% vs 26% (p=0.023). No definite HUT-derived diagnosis was more common in mature-onset syncope, 23% vs 13% (p=0.023). Heart failure, 9% vs 2% (p=0.024) and atrial fibrillation, 20% vs 9% (p=0.013) were more common in mature-onset syncope. Prodromes were less common in mature-onset syncope, 26% vs 52% (p&lt;0.001), however there was no significant difference in reported palpitations preceding syncope and dizziness on standing.

Conclusions
Mature-onset syncope was more often associated with absence of prodromes, orthostatic hypotension, inconclusive HUT findings and presence of heart failure and atrial fibrillation suggesting cardiac syncope to be the likely cause. Early-onset syncope was associated with presence of prodromes, vasovagal reflex mechanism and complex syncope diagnosis. Lifelong and mature-onset unexplained syncope may have different pathophysiological mechanisms in older patients and aetiologies other than vasovagal syncope should be carefully considered in patients with first-ever syncope in later life.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish heart and lung foundationCrafoord foundation
Prognostic impact of percentage of ventricular pacing in patients requiring pacemaker implantation after transcatheter aortic valve replacement
Authors: Dias Ferreira Reis J.P , Mendonca T , Castelo A , Rodrigues I , Fiarresga A , Ramos R , Cacela D , Oliveira M , Cruz Ferreira R 
Published: October 2021

Abstract

Background
Despite the continuous developments of transcatheter aortic valve implantation (TAVI), around 15% of the patients (P) who undergo this procedure require permanent pacemaker (PM). Right ventricular pacing (RVP), particularly with a cumulative percentage of ventricular pacing (CVp) above 40%, has been associated with detrimental effects on ventricular function and an increased risk of cardiovascular events in non-TAVI patients.

Aim
To evaluate the long-term prognostic significance of RVP, regarding overall mortality and the combined endpoint of overall mortality/heart failure hospitalization in P requiring a PM after TAVI.

Methods
We retrospectively examined P who underwent TAVI with a self-expanding valve from 2009 to 2020 at our institution. All P had pre-procedural clinical evaluation, cardiac computed tomographic angiography, transthoracic echocardiography and electrocardiography performed. CVp was determined from stored PM data. P with previous PM were excluded. Post-TAVI PM implantation was defined as a device implantation during hospital stay or during the first month after discharge.

Results
474P, 57% male, mean age 81.7±6.5 years with a mean left ventricular ejection fraction of 51.5±14.6% were analysed. Mean follow-up was 18.7 months. Mean STS score and mean Euroscore II were, respectively, 6.89% and 5.76%. Mean gradient was 51.67 mmHg and mean aortic valve area 0.71 cm2. After TAVI, 104P (21.9%) required PM implantation, with a mean CVp of 65.3±43.4%. Post-TAVI PM was not associated with a worse outcome - overall mortality: HR 1.13, 95% CI 0.72 – 1.78, p=0.57; combined mortality/heart failure hospitalization: HR 1.22, 95% CI 0.87 – 1.70, p=0.24. The follow-up Kaplan-Meier curves according to the need for PM post-TAVI were similar: log rank p=0.24. A CVp cut-off of 40% was not associated with any of the study endpoints - overall mortality: HR 1.72, 95% CI 0.38–7.86, p=0.48; combined mortality/heart failure hospitalization: HR 1.32, 95% CI 0.45–3.91, p=0.61. Also, a CVp cut-off of 40% did not provide an accurate risk stratification as survival free of events was similar between these P and those below this cut-off (log rank p=0.11) and in comparison, with P without PM (log rank p=0.65).

Conclusions
In P submitted to TAVI with a self-expanding valve, the need for PM implantation is common, but not associated with increased risk of total mortality or heart failure hospitalization during a 18 months follow-up period. A CVp cut-off of 40% showed poor discriminative ability regarding long-term events in this population.

Funding Acknowledgement
Type of funding sources: None.
Temporary prolongation of corrected QT interval after cardioneuroablation for functional bradyarrhythmias
Authors: Wichterle D , Jansova H , Stiavnicky P , Stojadinovic P , Peichl P , Cihak R , Kautzner J 
Published: October 2021

Abstract

Background
There are controversial reports on QT interval response to ganglionic plexi ablation that are selectively targeted during cardioneuroablation (CNA) or occurs as collateral lesion during left atrial ablation procedures. Both shortening or prolongation of the heart-rate corrected QT interval (QTc) with therapeutic or safety implications were described.

Purpose
In this retrospective study, we investigated longitudinal changes of QTc after CNA.

Methods
The study included 108 patients (age: 39±12 years, 60% males) who underwent biatrial cardioneuroablation (radiofrequency time: 15.5±6.7 min) for symptomatic functional bradyarrhythmias. Surface ECG examinations were performed on the day before the CNA (N=108), 1 hour after the CNA (N=106), on the 1st post-ablation day (N=50), at the 3-month (N=99), and 1-year (N=63) follow-up visits. Automated measurements of QT interval were employed for the analysis. Four formulas (Bazett, Framingham, Fridericia, and Hodges) were used for the correction of QT interval to instant heart rate.

Results
QTc significantly prolonged immediately after the CNA with rapid return to baseline values (Figure and Table). This was particularly valid for QT correction by Framingham formula (and similarly for Fridericia and Hodges formulas). The QTc by Bazett formula, which is known to overestimate QT at higher heart rates, returned to baseline more slowly and incompletely. Several mechanisms may contribute to observed QTc dynamics: (1) direct effect of autonomic denervation with recovery phenomenon; (2) QT hysteresis with an extremely long time constant; or (3) artifact due to suboptimum QT correction to a substantial change of heart rate.

Conclusions
The study suggests that CNA produces acute prolongation of QTc interval with rapid decay and virtual normalization in 3 months. CNA in otherwise healthy subjects is not likely associated with substantial long-term risk of long-QT-associated arrhythmias. In the same way, we cannot confirm earlier observations of clinically significant QTc shortening effect of ganglionated plexi ablation.

Funding Acknowledgement
Type of funding sources: None. Figure 1Table 1
Repolarization heterogeneity within the myocardial infarction border zone correlates with variability of myocyte remodeling
Authors: Vermoortele D , Amoni M , Ingelaere S , Holemans P , Willems R , Sipido K , Claus P 
Published: October 2021

Abstract

Background
Myocardial infarction (MI) results in a regional scar, with a border zone (BZ) of surviving myocytes interspersed with fibrosis providing an anatomical substrate for re-entry. Heterogeneous repolarization within the BZ may add a functional component aggravating re-entrant arrhythmias.

Purpose
We studied BZ heterogeneity and developed novel methodology for high resolution mapping of local in vivo activation-repolarization intervals (ARI) within the BZ and for studying the relation to cellular action potential (AP) profiles of cells isolated from the BZ.

Methods
Anterior-septal myocardial infarction was induced in 5 domestic pigs by 120-minute occlusion of the left anterior descending artery followed by reperfusion (18.9±4.7% of the left ventricle). After 1-month, electro-anatomical mapping was performed. Contact mapping was used to define the BZ (bipolar voltage 0.5–1.5mV). A non-contact recording of a 64-electrode array was translated to 2048 non-contact electrograms distributed over the LV. The non-contact electrograms were processed to determine the ARIs using a custom-made algorithm, validated against monophasic action potential recordings. After 2–4 days recovery, single cardiomyocytes were enzymatically isolated from the anterior-septal BZs and remote regions. Cardiomyocytes were field stimulated at 1Hz at 37°C and cellular AP duration (APD) was optically recorded (fluorescent voltage-sensitive dye Di-8-Annepps).

Results
In vivo, regional ARIs tended to be longer in the BZs than remote. ARI heterogeneity, quantified as the standard deviation of ARIs in a neighborhood of 1cm radius, was increased in the BZ (anterior BZ: 3.4±1.0 ms, P=0.052, septal BZ: 3.6±1.7 ms, P=0.027 vs remote: 2.0±0.5 ms). Cellular APD was measured in large population samples (&gt;100 cells per region in each pig) and was longer in BZ myocytes compared to the remote region. Cellular APD heterogeneity, measured as the standard deviation within cell population samples pooled by region per animal, was increased in the BZ (anterior BZ: 105.9±17.0 ms, P=0.0010; septal BZ: 98.1±20.8 ms, P=0.0127 vs remote: 73.9±8.6 ms). Cell APD correlated to in vivo ARI (R2=0.34, P=0.021) and cellular heterogeneity correlated strongly with in vivo heterogeneity (R2=0.67, P=0.002).

Conclusion
In the BZ of MI, in vivo regional heterogeneity adds a functional substrate for re-entry that may result from heterogeneous cellular remodeling and increased cell-cell APD variability.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): KU Leuven BOF-C1 “Blood pressure induced premature ventricular beats as triggers for ventricular arrhythmia in ischemic cardiomyopathy”
lncRNA CDKN2B-AS1 associated to ventricular fibrillation during acute myocardial infarction
Authors: Pan-Lizcano R , Nunez L , Pinon P , Flores X , Aldama G , Calvino R , Vazquez-Rodriguez J.M , Hermida M 
Published: October 2021

Abstract

Introduction
Sudden death (SD) due to ventricular fibrillation (VF) during acute myocardial infarction (AMI) is one of the leading causes of death in Western societies. However, the pathophysiology of the disease is not well defined. Recently, it has been proposed that non-coding RNA (ncRNA) may play a determinant role in the genesis of different diseases. In fact, alterations in the expression of long non-coding RNAs (lncRNAs) have been associated with different types of arrhythmias and, also, with acute coronary syndrome. However, little is known about the role of lncRNAs in VF in AMI.

Purpose
The aim of this preliminary study is to identify lncRNAs associated to VF in AMI.

Methods
This preliminary study included 24 patients with AMI, 12 with clinically proven VF and 12 without VF. Expression of 10 lncRNAs (CDKN2B-AS1, KCNQ1OT1, MT-LIPCAR, MALAT1, MIAT, NEAT1, SLC16A1-AS1, LNC-TK-2–4, TNFRSF14-AS1, UCA1) and 2 Housekeeping (ACTB and RPLP0) were analyzed using real-time PCR (qPCR). The Fold Change value with a logarithm transformation [log 2 (2–ΔΔCq)] was calculated. The D'Agostino & Pearson and Shapiro-Wilk test and an unpaired t-test were performed in Graphpad-Prism and Qbase programs.

Results
The lncRNA “cyclin-dependent kinase inhibitor 2B antisense noncoding RNA” (CDKN2B-AS1), also named as ANRIL, showed a significantly lower expression in patients that with VF during AMI (2–ΔΔCq (IQ): Control = 1.099 [0.634–1.583] vs FV=0.507 [0.221–1.022], P=0.018). It is important to note that this lncRNA has been previously associated to myocardial infarction and other cardiovascular diseases as atherosclerosis and hypertension.

Conclusions
Our preliminary results suggest that lncRNA CDKN2B-AS1 could be related to the presence of VF during AMI. Most research must be done to clarify the role of lncRNA in the pathophysiology of VF during AMI.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): Sociedad Española de Cardiología
A territory-wide study of arrhythmogenic right ventricular cardiomyopathy patients from Hong Kong
Authors: Lakhani I , Zhou J , Zhang Q , Tse G 
Published: October 2021

Abstract

Background
Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a hereditary disease characterised by fibrofatty infiltration of the right ventricular myocardium that predisposes affected patients to malignant ventricular arrhythmias, dual-chamber cardiac failure and sudden cardiac death (SCD).

Methods
This was a territory-wide retrospective cohort study of patients diagnosed with ARVC/D between 1997 and 2019. The primary outcome was incident ventricular tachycardia/ventricular fibrillation (VT/VF). The secondary outcomes were new-onset heart failure with reduced ejection fraction (HFrEF) and all-cause mortality.

Results
This study consisted of 115 ARVC/D patients (median age: 60 [44.1–70.2] years; 58% male). Of these, 51 and 24 patients developed incident VT/VF and new-onset HFrEF, respectively. Five patients underwent cardiac transplantation, and 14 died during follow-up. Multivariate Cox regression identified prolonged QRS duration as a predictor of VT/VF (P&lt;0.05). Female gender, prolonged QTc duration, the presence of epsilon waves and T-wave inversion (TWI) in any lead except aVR/V1 predicted new-onset HFrEF (P&lt;0.05). Female gender, prolonged QTc duration and the presence of epsilon waves, in addition to the parameters of older age at diagnosis of ARVC/D, prolonged QRS duration and worsening ejection fraction predicted all-cause mortality (p&lt;0.05). Clinical scores were also developed to predict new-onset HFrEF (Table 1a-c) and all-cause mortality (Table 2a-c). This was followed by the application of a non-parametric machine learning survival analysis models for outcome prediction. These machine learning algorithms better capture nonlinear and interactive patterns within survival data compared to traditionally used Cox regression models, which assume the existence of a hazard function between survival data and censored outcomes. The present study introduced weighted random survival forests models for the prediction of incident VT/VF, HFrEF and all-cause mortality. Findings indicate that these machine learning wRSF models performed the best in the prediction of all three aforementioned outcomes compared to other analytical methods.

Conclusion
Clinical and electrocardiographic parameters are important for assessing prognosis in ARVC/D patients. Machine learning algorithms appear to be the most optimal tools for event prediction, and as such should potentially be used to aid risk stratification and decision-making in the clinical setting.

Funding Acknowledgement
Type of funding sources: None.
Evaluation of electrocardiographic predictors of brugada type response during flecainide challenge
Authors: Shen X , Zhang A.A , Sia C.H , Tan B.Y , Lim P.C.Y , Chua K.C.M , Ho K.L , Lim E.T.S , Ching C.K , Chong D.T.T 
Published: October 2021

Abstract

Background/Introduction
Brugada syndrome (BrS) is a hereditary channelopathy with an increased risk of sudden cardiac death. Most BrS patients manifest non type 1 Brugada pattern electrocardiography (ECG). Sodium channel blockade is a well-established diagnostic tool for Brugada syndrome. However, intravenous sodium channel blockade is not readily available in all parts of the world. In addition, severe ventricular arrhythmias during drug challenge have an estimated prevalence of 1%. Determining the predictors of a positive test would improve our understanding and facilitate appropriate use of these tests.

Purpose
We aimed to identify ECG predictors of Brugada type response during flecainide challenge and provide an independent assessment of current published ECG criteria predictive of a positive flecainide challenge.

Methods
We analysed the clinical and electrocardiographic data of 526 consecutive individuals referred from a national pre-participation exercise screening program who underwent flecainide challenge for an ECG suspicious of Brugada pattern. ECG recordings included both conventional and high precordial leads (1 and 2 space up ECGs in V1 and V2 – 1V1, 1V2, 2V1, 2V2). Twelve-lead ECGs were evaluated for the width of the β angle, β score, baseline J wave elevation, width of QRS, absence of isoelectric segment in lead II, ST/ QT ratio, presence of S wave in Leads II, III and V5 as well as the presence of R wave in aVR.

Results
Flecainide challenge was positive in 121 (23%) of the 526 cases. Baseline QRS duration was greater in the conventional lead placement [V1 (102.4±20.0 ms vs 97.6±14.0 ms, p=0.003), V2 (111.1±33.5 ms vs 100.9±13.1 ms, p=0.001)] as well as 1 space up [1V1 (108.9±21.0 ms vs 100.6±18.2 ms, p&lt;0.001), 1V2 (117.4±26.6 ms vs 103.2±18.3, p&lt;0.001)] and 2 space up [2V1 (113.6±23.4 ms vs 102.5±19.3 ms, p&lt;0.001), 2V2 (121.6±26.1 ms vs 106.8±19.1 ms, p&lt;0.001)] in cases with a subsequent positive response. A QRS duration of ≥120ms in V2 yielded a sensitivity of 16.5%, specificity of 93.8%, positive predictive value of 44.4% and negative predictive value of 79% for a positive flecainide challenge. Other predictors of positivity included that of a shorter ST duration in lead II (107.0±19.9 ms vs 118.1±24.4, p&lt;0.001) and a shorter ST/ QT ratio (0.30±0.09 vs 0.32±0.07, p=0.006).

Conclusion
In this population, a wider QRS duration, shortened ST segment in lead II and ST/QT ratio were predictors of a positive response to flecainide challenge when BrS was suspected on a baseline ECG. Prior published ECG parameters such as β angle, β score, baseline J wave elevation, presence of S wave in Leads II, III and V5 as well as the presence of R wave in aVR did not perform as well in predicting for a positive response to flecainide challenge in our population.

Funding Acknowledgement
Type of funding sources: None. Baseline CharacteristicsECG Findings
Novel variant of the glycerol-3-phosphate dehydrogenase-1 Like (GPD1-L) gene in Japanese Brugada syndrome patients
Authors: Usuda K , Hayashi K , Ishikawa T , Aizawa Y , Kato T , Kusayama T , Tsuda T , Usui S , Sakata K , Kawashiri M , Mishima H , Yoshiura K , Makita N , Takamura M 
Published: October 2021

Abstract

Background
The incidence of Brugada syndrome (BrS) varies among racial groups. Several studies reported Glycerol-3-Phosphate Dehydrogenase 1-Like (GPD1-L) gene is associated with BrS. However, most of these studies were reported from Western countries, so the evidence about GPD1-L mutation is limited especially among Asian BrS patients. This study aimed to search for rare variants in GPD1-L among Japanese BrS patients and to investigate the pathogenicity.

Method
We performed whole-exome sequencing for patients with Brugada type 1 ECG pattern from Japanese multicenter BrS cohort consisting of SCN5A-negative BrS probands (n=288) and controls (n=372). We conducted patch-clamp study in human embryonic kidney (HEK) 293 cells cotransfected with the wild-type sodium channel (SCN5A) and wild-type or mutant GPD1-L expression plasmid.

Results
We identified a rare variant in GPD1-L, p.D262N (c.784g&gt;a) in 2 of 288 BrS probands, which was not identified in 372 controls. The minor allele frequency of the variant is 0.0014% in the Genome Aggregation Database. One proband was a 49-year-old man and the other was 34-year-old man who both developed a ventricular fibrillation. ECGs of both probands showed Brugada Type 1 pattern after administration of the pilsicainide. In functional study, coexpression of D262N GPD1-L with SCN5A in HEK293 cells significantly reduced inward sodium currents compared with wild-type GPD1-L. Additionally, inward sodium currents with D262N were similar to those with A280V GPD1-L, which was associated with BrS in previous reports (Figure). Also, several pathogenicity prediction programs, such as SIFT (score: 0.031) and PolyPhen2 (score: 0.937) predicted deleterious effects of GPD1-L D262N.

Conclusion
We identified a rare variant in GPD1-L at the rate of 0.7% in Japanese BrS patients without SCN5A mutations. GPD1-L, p.D262N reduces inward sodium currents and may be a novel susceptible variant for BrS in the Japanese population.

Funding Acknowledgement
Type of funding sources: None. Figure 1. Current–voltage curve