bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting left atrial appendage thrombus in patients with persistent atrial fibrillation or flutter and no oral anticoagulation using machine-learning models
Authors: Pieszko K , Makowski B , Bansal M , Hiczkiewicz J , Lojewska K , Musielak B , Uzieblo-Zyczkowska B , Krzesinski P , Kowalik E , Kwiecinski J , Gawalko M , Budnik M , Slomka P , Kaplon-Cieslicka A 
Published: May 2024

Abstract

Background
Atrial fibrillation and flutter (AF/AFL) increase the risk of thromboembolic events by promoting the formation of a left atrial appendage thrombus (LAT). We previously developed artificial intelligence (AI) models to predict LAT based on data from the multicentre, prospective LATTEE registry (Left Atrial Thrombus on Transoesophageal Echocardiography, n= 2489) establishing the utility of AI for identifying the presence of LAT. While our model is now available as an online calculator to date there is no data regarding the utility of our AI in guiding cardioversion in haemodynamically stable patients with persistent arrhythmia and no prior oral anticoagulation (OAC).

Purpose
To assess the performance of AI decision support to perform TOE or readmit the patient after at least 3 weeks of OAC.

Methods
In this study, we applied the LAT-AI model (based on 39 features) and the LAT-AI reduced model (based on 8 features) to patients with no or insufficient prior OAC, who underwent TOE before direct current cardioversion or catheter ablation (n=311). We excluded patients with paroxysmal arrhythmia, resulting in a final cohort of 150 patients originating from four sites. We investigated the sensitivity and specificity of the respective models to predict LAT based on the score thresholds established in previous studies (0.37 for the LAT-AI and 0.34 for the LAT-AI reduced).

Results
The median age in the external cohort was 66 (interquartile range 56-73), 59% were male, and 7.3% had AFL. LAT was found in 17 patients (11%). The LAT-AI model achieved 100% sensitivity (confidence interval [CI]: 40-100) and 12% specificity (95% CI: 7-18). The LAT-AI reduced model achieved 100% sensitivity (95% CI: 87-100) and 14% specificity (95% CI: 8-21). By applying the score threshold which has been derived in our prior studies for the the LAT-AI reduced model, the TOE-first approach would be chosen in 18% and no LAT would be found in this group, while the remaining 82% would be recommended for 3 weeks of OAC before TOE. Such approach could be used to identify patients at low risk of LAT to undergo TOE despite the lack of prior OAC, while the remaining patients at higher risk of LAT could potentially avoid repeated TOE thanks to the 3-week course of OAC before the first TOE.

Conclusion
AI scores allow high sensitivity for prediction of the presence of LAT in patients with AF/AFL irrespective of OAC treatment and have the potential to optimise the management of patients with indications for elective cardioversion and no prior or ineffective OAC.Simulated AI-supported decisionScreenshot of the online app
Development and validation of a machine learning-based prediction model for sudden cardiac death in the general population: insights from the community cardiovascular cohort
Authors: Chen Y Y , Lin Y L , Lee C L , Chien K L , Hsieh Y C , Lip G Y H , Chen S A 
Published: May 2024

Abstract

Background/Introduction
Accurately predicting and managing the risk of sudden cardiac death (SCD) in the general population is a formidable challenge.

Purpose
This study aimed to develop and validate a machine learning (ML)-based prediction model for SCD using data from the Community Cardiovascular Cohort (CCCC) in Taiwan.

Methods
A community-based cohort study was used for model construction . Four ML algorithms, including extreme gradient boosting (XGBoost), random forests (RF), logistic regression, and deep neural network (DNN), underwent meticulous evaluation. Performance assessment encompassed receiver operating characteristic (ROC) curves, area under the curves (AUC), and accuracy metrics. Significant risk factors were identified through feature importance analysis.

Results
We employed a random partitioning strategy, allocating 1744 participants (55%) to the training dataset, 952 participants (30%) to the test dataset, and 476 participants (15%) to the validation dataset. In the data training stage, the XGBoost algorithm demonstrated outstanding prediction performance for SCD (AUC: 1.000); In the validation stage, the XGBoost algorithm demonstrated good prediction performance for SCD prediction (AUC: 0.791, 95%CI: 0.617-0.964; Accuracy: 0.971). Using XGBoost-generated predicted probabilities (P(XGB)), we identified individuals with P(XGB) ≥ 0.5 (Group 1) who displayed significantly higher SCD risk (HR 32.0; 95% CI: 9.29-109.9) compared to those with P(XGB) &lt; 0.5 (Group 0).

Conclusions
Our study demonstrates the effectiveness of ML algorithms, particularly XGBoost, in predicting event of SCD in the general population. The identification of these pivotal risk factors holds profound implications, empowering the identification of high-risk individuals and facilitating the implementation of precisely tailored preventive strategies.Figure 1:KM sruvival curveFigure 2:Feature importance analysis
Same-day discharge strategy in a heart rhythm management clinic - what about patients' reported experience?
Authors: Zeriouh S , Sousonis V , Albenque J P , Jacob S , Mene R , Cardin C , Voglimacci-Stepganopoli Q , Combes N , Combes S , Deharo J C , Boveda S 
Published: May 2024

Abstract

Background and aims
Same-day discharge (SDD) has been adopted for many interventional cardiology procedures, however data on patients’ experience are scarce. The aim of this study was to investigate patient-reported experience of a SDD strategy following electrophysiology procedures (EP) in a Heart Rhythm Management Department.

Methods
Consecutive patients undergoing EP procedures in our centre, who fulfilled pre-defined eligibility criteria for SDD, were asked to complete the study questionnaire, right before hospital discharge. Procedures suitable for SDD ranged from non-invasive (electric cardioversion, tilt test) to invasive ones (EP studies, device replacement, rhythm recorders implantation, ablation of supraventricular tachycardias including atrial fibrillation). The questionnaire aimed to assess patients’ experience before and during the procedure, their satisfaction with the quality of the provided information and their comprehension of the given instructions regarding the post-discharge period and their medication.

Results
The study questionnaire was completed by 501 patients. The majority of participants described SDD as a good or a quite good experience (n=440, 87,8%), while 94,6% of them (n=474) would not hesitate to undergo a second SDD procedure, if necessary. A direct interview with a healthcare team member was viewed as the preferred method of obtaining information on the procedure. At discharge, 1 out of 10 patients were still unsure of the instructions given by the healthcare team, including their anticoagulation treatment. Patient reported satisfaction rates did not differ between invasive and non-invasive procedures. However, after an invasive procedure, patients seemed to significantly have a better understanding of post-discharge instructions.

Conclusion
Patients reported a high level of satisfaction with SDD EP procedures. However, significant efforts need to be made in order to ensure their understanding of post-discharge instructions.Figure : Patients' reported experience
PKP2 gene therapy reduces ventricular arrhythmias, reverses ventricular remodeling, improves heart function, and reduces mortality in a mouse model of arrhythmogenic right ventricular cardiomyopathy
Authors: Yang Z H J , Wu I , Zeng A , Greer-Short A , Aycinena J A , Tefera A E , Shenwai R , Farshidfar F , Van Pell M , Xu E , Reid C , Rodriguez N , Lim B , Chung T W , Dee-Hoskins C 
Published: May 2024

Abstract

Introduction
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Currently, there are no approved treatments that address the underlying genetic cause of this disease, representing a significant unmet need.

Purpose
Mutations in desmosome gene Plakophilin-2 (PKP2) account for approximately 40% of ARVC cases and result in reduced gene expression. Our goal is to examine the feasibility and the efficacy of restoration of PKP2 expression in a cardiac specific knock-out mouse model of Pkp2.

Methods
Adeno-associated virus 9 (AAV9) was used to deliver a wild-type copy of PKP2 gene that is driven by a cardiac-selective promoter and expressed selectively in cardiomyocytes.

Results
We demonstrated that a single-dose AAV9-mediated PKP2 gene therapy effectively prevented disease onset before overt cardiomyopathy and attenuated disease progression after overt cardiomyopathy. Restoration of PKP2 expression led to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, attenuating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. Additional RNA sequencing analyses showed that durable restoration of PKP2 expression led to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology.

Conclusion
These results indicate that a cardiac-selective AAV9-mediated PKP2 gene therapy may be a promising one-time treatment for ARVC patients with PKP2 mutations.
Circadian rhythm in pro-arrhythmic activity of pulmonary vein cardiomyocytes
Authors: Pannell L M K , Carpenter A , Segers F , Koh Y Z , Harmer S C , Piggins H D , Hancox J C , James A F 
Published: May 2024

Abstract

Introduction
Cardiomyocytes in the pulmonary vein (PV) sleeves are a major source of ectopic activity driving atrial fibrillation (AF) and episodes of AF in patients are more prevalent at night. While it is known that circadian clocks within the heart regionally control 24-hour variation in pacemaking and ventricular repolarisation, the mechanisms underlying the nighttime preponderance in AF are unknown.

Purpose
This study addresses the hypothesis that circadian rhythms exist in the pro-arrhythmic activity of PV cardiomyocytes.

Methods
Male Wistar rats maintained in a 24-hour cycle of 12-hr light/dark (lights-on at Zeitgeber time, ZT=0; lights-off, ZT12) were subject to terminal general anaesthesia (140 mg/kg Na pentobarbital i.p.) at ZT=0, 6, 12 or 18 hr and the hearts removed. RNA was extracted from left atrial (LA) appendage (LAA) and proximal PV at the LA/PV junction (3 rats per ZT) and RNA sequencing conducted. Reads were mapped to the rat genome, counts normalised and models in which ZT was or was not included as a factor compared (Likelihood Ratio Test, adjusted-P&lt;0.01). Whole-cell current clamp recordings were made from cardiomyocytes isolated from the proximal PV (n=308) and the LAA (n=264) (N=74 rats). The effects of noradrenaline (NA, 1 µM) and acetylcholine (ACh, 1 µM) were examined. Data were plotted against the ZT of the time of recording and fitted to a sine wave to establish circadian rhythmicity (P&lt;0.05, extra-sum-of-squares F-test). The effect of ≥24 hr constant dark in the period immediately before experiment was examined. Data are reported as mean ± standard error.

Results
The expression of 1368 genes varied significantly with ZT, including circadian clock components (e.g. Bmal1, Per1). PV cells were larger than LAA cells (73±1.6 pF vs 53±1.3 pF, P&lt;0.0001) and had more depolarised resting membrane potential (-69±0.2 mV vs -72±0.1 mV, P&lt;0.0001). Both cell types showed circadian variation in action potential duration at 90% repolarisation (APD90) and frequency of pro-arrhythmic activity. Pro-arrhythmic activity was greatest in PV cells and the frequency was greater during the rest phase (ZT0-12) in both cell types. In contrast, the circadian rhythm in APD90 differed between cell type, with the longest APD­­90 recorded during the active phase in PV cells (ZT12-24) but during the rest phase in LAA cells. Pro-arrhythmic activity was increased by NA and decreased by ACh in both cell types with maximal effect during the rest phase.

Conclusion
Circadian variation in APD90 and proarrhythmic-activity has been demonstrated in isolated proximal PV and LAA cardiomyocytes, with differences in rhythm between the two cell types. RNA sequencing suggests the presence of peripheral clocks in LAA and PV cardiomyocytes. Understanding these mechanisms is important in development of future therapeutic options for AF.
Oxidative stress and mitochondrial function among various types of atrial fibrillation
Authors: Nantsupawat T , Apaijai N , Prommintikul A , Prasertwitayakij N , Chattipakorn S , Chattipakorn N , Wongcharoen W 
Published: May 2024

Abstract

Introduction
Mitochondrial dysfunction has been shown to be associated with atrial fibrillation (AF) in previous studies.

Purpose
We aimed to determine mitochondrial function in various AF types and AF burden to further delineate whether mitochondrial function has graded or quantal response relationship with AF.

Methods
This is a cross-sectional study in patients with atrial high-rate episode (AHRE) or AF who have dual-chamber cardiovascular implantable electronic device (CIED). Patients were categorized into clinical AF and subclinical AF. AF burden was measured as AHRE via CIED interrogations. Oxidative stress and mitochondrial function were determined in peripheral blood mononuclear cells (PBMCs).

Results
There was a total of 54 CIED patients. Mean age was 69.9+12.8 years. There were 9 (16.7%) patients with diabetes mellitus and 36 (66.7%) patients with history of clinical AF. After adjusting with multiple linear regression for age, left ventricular ejection fraction, glomerular filtration rate, history of AF, and diabetes mellitus, we found that clinical AF, as compared to subclinical AF, was independently associated with lower non-mitochondrial respiration (20.8, 6.5-35.6 vs. 48.0, 14.0-60.9 pMol/min, p=0.021) (median, IQR); lower basal respiration (72.1, 47.4-94.4 vs.97.2, 52.1-152.6 pMol/min, p=0.020); and lower ATP production (57.3, 24.7-73.2 vs. 78.6, 45.7-112.0 pMol/min, p=0.014) (Table 1). However, AF burden was not associated with alterations in oxidative stress and mitochondrial function.

Conclusions
Mitochondrial function from PBMC was significantly lower in patients with clinical AF compared to those with subclinical AF. However, there was no association between AF burden and the change in mitochondrial function. The study revealed a quantal response relationship between PBMC’s mitochondrial function and AF.
Unraveling the links between genetics and electrophysiological phenotype of sustained monomorphic ventricular tachycardias in left and biventricular arrhythmogenic cardiomyopathy
Authors: Cabrera Borrego E , Bermudez-Jimenez F J , Gasparetti A , Macias-Ruiz R , Jimenez-Jaimez J 
Published: May 2024

Abstract

Background and objective
Arrhythmogenic cardiomyopathy (ACM) is an inherited disease with a high arrhythmogenic potential. Despite previous research efforts, a comprehensive electrophysiological characterization of sustained monomorphic ventricular tachycardias (SMVT) by genotype has not yet been achieved.

Purpose
Establishing a correlation between the electrophysiological SMVT substrate and the causative genotype of left and biventricular ACM.

Methods
Observational and retrospective multicenter study of a serie of 71 patients from 18 European and American centers with left/biventricular ACM, carriers of pathogenic genetic variants, in whom an electrophysiological study (EPS) was performed for SMVT ablation. Localization of SMVT-circuit in the EPS was performed by activation mapping, pacemapping and substrate characterization by voltage and decremental-conduction functional analysis.

Results
The cohort had a median age of 49,65 IQR 19,06 years, with the majority being male (54, 76.1%). Significant differences, according to genotype, were found in the anatomical localization of SMVT critical isthmus (p 0.001), figure 1. Patients with mutations in desmoplakin showed biventricular involvement and SMVTs with positive QRS in V1. Substrate could be located in endocardium and epicardium of left ventricle (LV) inferolateral segments. Patients with filamin-C variants had exclusive LV impairment, although the morphology and origin of SMVTs were identical to those observed in desmoplakin. In the case of mutations in lamin-A, the substrate was found mainly in LV septal endocardium. Patients with variants in plakoglobin-2, desmoglein-2 and TMEM43 showed biventricular involvement with negative QRS in V1 SMVTs and right ventricular origin (in the free wall in the case of plakoglobin-2 and in the outflow tract in the case of desmoglein-2 and TMEM43). During clinical follow-up, 26,03 IQR 54,47 months, approximately one third of patients (19, 26,8%) experienced recurrence of clinical SMVT, with significant differences between genotypes (log-rank 0,001), figure 2.

Conclusions
The analysis of these data provides discriminatory SMVT localization patterns between the different genotypes and evaluates the effectiveness of EPS as a therapeutic tool in this group of patients.
Clinical features and prognosis according to genotype variation in hypertrophic cardiomyopathy
Authors: Kim S H , Jeong J H , Kim H J , Choi J I , Choi Y , Kim S H , Park S Y , Oh Y S 
Published: May 2024

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition with many identified disease-causing genetic variants. However, little is known about the clinical course based on the genotype. This study investigates the relationship between the genotype and clinical outcome in patients with HCM.

Method
A total of 127 patients diagnosed with HCM and underwent genetic testing using a next-generation sequencing panel included ≥30 cardiomyopathy-related genes at two tertiary hospitals. The genotype-positive group (N=51) with pathogenic/likely-pathogenic variants and the genotype-negative group (N=76) were compared in terms of imaging phenotypes and clinical outcomes. The primary outcome was a composite of sudden cardiac death (SCD) and ventricular arrhythmia.

Result
Among the genotype-positive group, MYBPC3 (37%), MYH7 (29%) and TNNI3 (16%) variants were predominantly identified. The genotype-positive group was diagnosed at a younger age (51.1 ± 14.0 vs 59.7 ± 11.7, p&lt;0.001), showed a higher maximal ventricular wall thickness (17.2 ± 5.1 vs 14.2 ± 4.0, p&lt;0.001), and a higher prevalence of late gadolinium enhancement on cardiac magnetic resonance imaging (86.5% vs 54.4%, p=0.003) compared to the genotype-negative group. The genotype-positive group had a higher incidence of the primary outcome (39.2% vs 9.2%, p&lt;0.001).

Conclusion
The patients with pathogenic/likely pathogenic variants exhibited morphological characteristics associated with a high risk of SCD, and experienced worse clinical outcomes.
Demographics, clinical features and genetics of inherited arrhythmias in Oman
Authors: Alazri K , Alabri I , Al Shehhi M , Alhinai M , Alamri T , Alsheala N , Alshabibi A 
Published: May 2024

Abstract

Background
Inherited arrhythmia syndromes (IAS) are a group of rare disorders that result from genetic mutations in several genes encoding ion channels causing disruption in its structure and function and predispose affected individuals to various symptoms including sudden cardiac death (SCD). They include congenital long QT syndrome, Brugada syndrome (BrS), progressive cardiac conduction disease, short QT syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). There have been few reports of long QT syndrome from the Arabian Gulf region but this is the first comprehensive review of multiple inherited arrhythmia syndromes in the region.

Objectives
Our objective are to describe the demographics of children and adults with inherited arrhythmia syndromes, report the presenting clinical features, genetic mutations and management strategies. Also, to report some unique and rare genetic findings in our population.

Methods
This is a descriptive retrospective study that included children and adults with inherited arrhythmia syndromes diagnosed and treated at a national heart center over 16 years, between 2006 to 2022. Data collected included patient demographics, geographical distribution, clinical features, genetic reports and management strategies.

Result
One hundred and six patients were included in the analysis. Sixty-six (62.3%) were males, and 68 (64.2%) were adults and 38 (35.8%) were children. Three inherited arrhythmia syndromes were found in our population that included Long QT, Brugada and catecholaminergic polymorphic ventricular tachycardia (CPVT), which accounted for 58 (54.7%), 39 (36.8%) and 9 (8.5%), respectively. Seventy-six (71.7%) of the patients were reported to be from consanguineous families. Most children, 31 (91.4%) had long QT, whereas most adults, 39(54.9%) had Brugada. The clinical features varied based on the type of arrhythmia. There were 28(26.4%) asymptomatic individuals who were diagnosed incidentally. Syncope was the most common presenting symptom in patients with Long QT, 24(41.4%) and Brugada syndrome, 20(51.3%). Palpitations, 4(44.4%) and bradycardia, 4(44.4%) were the predominant presenting features in patients with CPVT. The treatment modalities included beta blockers and antiarrhythmics, implantable cardioversion defibrillators(ICDs), pacemakers, and left sympathetic ganglionectomy(LSGs). We identified 36 individuals with pathogenic or likely pathogenic variants and 12 VOUS(variants of uncertain significance) in different genes of IAS.

Conclusion
This is the first comprehensive study on the inherited arrhythmia syndromes in Oman and the Arabian Peninsula. We provided insights about demographics, clinical, genetic profile and the treatment strategies of the most common IAS in the region. Tis study hat will help in early detection of the different types of arrhythmias and early intervention to prevent sudden cardiac death in patients and their relatives.