bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpectedly high prevalence of structural genomic variations in the Long QT Syndrome: evidence for broader clinical uptake
Authors: Mazzanti A , Memmi M , Gambelli P , Guarracino A , Colombi B , Nastoli J , Trancuccio A , Kukavica D , Marino M , Bloise R , Napolitano C , Priori S G 
Published: November 2023

Abstract

Background
Long QT syndrome (LQTS) is an inherited channelopathy predisposing young and otherwise healthy individuals to ventricular arrhythmias causing syncope or sudden cardiac death. Point mutations in the KCNQ1, KCNH2, and SCN5A genes are the most common causes of LQTS, and up to 75% of patients can be genotyped by standard DNA sequencing. However, standard genetic testing fails to detect structural genomic rearrangements - including large deletions or duplications of DNA segments - known as copy number variants (CNVs). While previous studies suggested that CNVs account for less than 5% of genotype-negative cases(1-2), no recent data have been reported.

Purpose
The study aimed to determine the prevalence and spectrum of CNVs in LQTS susceptibility genes in unrelated patients who tested negative for point mutations in a panel of 16 genes associated with LQTS.

Methods
Next-generation sequencing (NGS) was used to screen CNVs in unrelated, clinically diagnosed LQTS patients without point mutations in 16 genes associated with LQTS. Loss of heterozygosity in LQTS-associated genes was used to assess the presence of CNVs using standard commercial software. The multiplex ligation-dependent probe amplification (MLPA) assay was used to confirm the CNVs identified by NGS.

Results
The cohort included 48 patients (63% women; mean age 31±19 years, range 3 years to 68 years) with definitive clinical diagnosis of LQTS (mean QTc 490±33 ms) according to the 2022 ESC guidelines(3). Overall, 7/48 patients (15%, 95% CI 6-28%) had CNVs. Six of the seven CNVs involved KCNQ1 in the heterozygous state, including three large deletions (exons 3-6, exons 12-15, and exon 16) and three duplications (exon 2, exons 3-6, and exons 3-15), whereas the remaining patient had a complete KCNH2 deletion. MLPA confirmed all CNVs identified by NGS. Of note, no CNVs were identified in LQTS-related genes whose pathogenicity has been questioned.

Conclusions
Our study highlights the unexpectedly high prevalence of structural genomic rearrangements in the KCNQ1 and KCNH2 genes in LQTS patients. Routine screening for copy number variants in LQTS patients is critical for accurate diagnosis, risk stratification, and personalized treatment strategies.Figure 1
Using the 3D architecture of scar to predict life-threatening ventricular arrhythmias, still a long way to go
Authors: Amador R , Bello A R , Freitas P , Guerreiro S , Abecasis J , Coutinho Santos A , Saraiva C , Santos P G , Costa F M , Carvalho M S , Carmo P , Cavaco D , Morgado F , Adragao P 
Published: November 2023

Abstract

Background
Late gadolinium enhancement (LGE) has been proposed as an independent predictor of ventricular arrhythmias.

Purpose
The purpose of this study was to assess if myocardial scar characterization could enhance the risk stratification for life-threatening arrhythmias and sudden cardiac death (SCD).

Methods
We included patients with an indication for ICD or CRT-D implantation who underwent cardiac magnetic resonance for clinical proposes since February/2018 and in whom a 3D-LGE dataset was obtained. Patients with channelopathies (n=2) or inappropriate imaging quality (imaging artifacts; n=7) were excluded. Scar characterization using ADAS software was performed in 3D-LGE datasets in all but 16 patients, where 2D datasets were used. The primary endpoint was the composite of appropriate ICD therapy (classified as ATP or shock), sustained ventricular tachycardia or SCD.

Results
A total of 116 patients were analysed (mean age 66 ± 14 years; 81% male; mean LVEF 34 ± 14%; 74 patients with ischemic and 42 with non-ischemic cardiomyopathy; 40 patients received a device in the setting of secondary prevention). During a median follow-up of 2.3 years (IQR 1.3 – 3.3 years) there were 23 events (18 appropriate ICD therapies [9 shocks and 9 ATP], 3 episodes of VT under the threshold for ICD therapy and 2 SCD). No statistically significant differences were found between patients with or without events in terms of scar mass, border zone (BZ) mass, BZ channels (BZC), BZC mass, number of channels detected, and scar heterogeneity (BZ mass / scar mass ratio) - all p values &gt; 0.2 – Figure. Restricting the analysis to only primary prevention cases yielded similar results. Overall, 26 patients did not show any channel. Four of these (all with non-ischemic LGE) experienced an arrhythmic event, yielding a negative predictive value of 83% (95% CI 64-93%) for the absence of channels.

Conclusion
In this cohort with still relatively limited follow-up duration, no single parameter reflecting scar tissue characterization was able to predict appropriate device therapies or sudden cardiac death.
Rates of sudden cardiac death in the young down by 50%: insights from a 20-year nationwide study in Denmark
Authors: Hansen C J , Svane J , Warming P E , Lynge T H , Garcia R , Banner J , Winkel B G , Tfelt-Hansen J 
Published: November 2023

Abstract

Background/Introduction
Sudden cardiac death in the young (SCDY) constitutes an important public health problem and many years lost to society. Several initiatives have been implemented to reduce the rate of SCDY, e.g. improved resuscitation. Declining rates of overall and cardiovascular disease mortality have been well-documented; however, reliable information on the contemporary incidence of SCD is sparse.

Purpose
This study aimed to evaluate the temporal trends in SCDY aged 1—49 in Denmark over 20 years.

Method
All consecutive SCDY in Denmark from 2000-2019 were identified by a multi-source approach, where all deaths were screened using death certificates, autopsy reports, and nationwide registry data. Deaths in individuals aged 1-35 were assessed throughout the entire study period, whereas deaths aged 36-49 were assessed from 2007-2019. Patient characteristics and causes of death were compared throughout the study period. Annual incidence rates (IR) per 100.000 person-years (p-y) were calculated using Poisson regression and corrected for age and sex by direct standardization. Temporal changes in SCD incidences were computed as annual percentage changes (APC).

Results
During the study period, we identified 3.206 SCD aged 1—49 years; the mean age was 42 years [IQR 33-46], and 73% were male. Over the 20-year period, patient demographics and major causes of death remained similar. The rate of witnessed SCD declined significantly from 51% to 29% (p &lt;0.001).
For SCD aged 1—35, the standardized IR decreased from 2.98/100.000 p-y (95%CI 2.34;3.75) to 1.79/100.000 p-y (95%CI 1.30;2.40), equivalent to a 42% reduction and an APC of -3.6% (95%CI -2.7;-4.5). Among SCD aged 36-49, the IR declined from 24.57/100.000 p-y (95%CI 21.70;27.71) to 10.84/100.000 p-y (95%CI 8.94;13.03), equivalent to a 56% reduction and an APC of -5.9% (95%CI -3.9;-7.9); the intergroup difference was significant (p = 0.4).

Conclusion
The incidence rates of SCDY declined by almost 50% during the study period for all SCDY, but the decline was significantly higher among older individuals (36-49 years). Improved resuscitation of cardiac arrests has been a critical contributor to decreasing SCD mortality, as demonstrated by the significant decline in witnessed SCDY.Incidence rates of SCD in the young
Global Constructive Work is associated with ventricular arrythmias after cardiac resynchronization therapy
Authors: Saffi H , Winsloew U , Sakthivel T , Hoejgaard E V , Linde J , Philbert B , Vinther M , Joens C , Bundgaard H , Risum N 
Published: November 2023

Abstract

Aim
Non-invasive left ventricular (LV) pressure-strain loops provide a novel method for quantifying myocardial work by incorporating LV pressure in measurements of myocardial deformation. Early studies suggest that myocardial work parameters such as Global Constructive Work (GCW) could be useful and reliable in arrhythmia prediction particularly in patients undergoing cardiac resynchronization therapy.
The aim of this study was to evaluate whether the magnitude of GCW was associated with occurrence of ventricular arrhythmias in patients after cardiac resynchronization therapy.

Method and results
Patients on guideline-recommended treatment with a cardiac resynchronization therapy defibrillator (CRT-D) were evaluated by 2D speckle-tracking echocardiography including measurements of GCW at least six months after implantation. The primary outcome was a composite of appropriate defibrillator therapy and sustained ventricular arrhythmia under the monitor zone. A total of 162 patients (mean age 66 years (±10), 122 males (75%)), were included. 16 (10%) patients experienced the primary outcome during a median follow-up of 18 months (IQR: 12-25) after the index echocardiography. Patients with below-median GCW (&lt;1,473 mmHg%) had a hazard ratio for the outcome of 8.14 [95% CI: 1.83-36.08], P=0.006 compared to patients above the median in a univariate model and remained an independent predictor after multivariate adjustment for eGFR and QRS duration (hazard ratio 4.75 [95% CI: 1.01 – 22.28], P&lt;0.05.

Conclusion
In patients treated with CRT-D, GCW below median level was associated with a 5-fold increase in risk of ventricular arrhythmias.
Efficacy and safety of percutaneous left stellate ganglion block in patients with refractory electrical storm: our five years experience
Authors: Compagnoni S , Baldi E , Gentile F , Currao A , Sanzo A , Rordorf R , Savastano S 
Published: November 2023

Abstract

Background
Neuromodulation by percutaneous stellate ganglion block (PSGB) with local anaesthetic has proven its antiarrhythmic effect suitable for an emergency setting.

Purpose
To assess the efficacy and safety of PSGB performed with an anterior anatomical approach in patients with refractory electrical storm.

Methods
Patients with electrical storm were enrolled from November 2017 to December 2022. Left PSGB (PLSGB) was performed after failure of at least one intravenous antiarrhythmic drug. Its repetition or a continuous infusion of the local anaesthetic were considered in selected cases. Clinical data, characteristics of the block and complications were collected. The efficacy was evaluated by comparing the number of arrhythmias treated with ATP or DC-shocks by external or internal defibrillator in the hour before the block with that in the hour after the block. Per-patient efficacy was assessed by comparing the number of ATP/shocks in the 12 hours before the first procedure with that in the 12 hours after the last one.

Results
37 patients were enrolled: 76% male, mean age 65 years; 11 with dilated cardiomyopathy, 18 with chronic ischemic heart disease, 11 with ST-elevation myocardial infarction, 3 with non-ST-elevation myocardial infarction, 1 with arrhythmogenic right ventricular cardiomyopathy and 1 with drug intoxication. A total of 62 PLSGBs were performed: 19 for ventricular tachycardia (VT), 26 for ventricular fibrillation (VF) and 17 for both VT and VF episodes; 15 on intubated patients, 4 in extracorporeal circulation, 14 in refractory cardiac arrest, 7 in cardiogenic/septic shock, 28 on patients on single antiplatelet therapy, 11 on dual antiplatelet therapy, 33 on anticoagulant therapy. PLSGBs were performed during intravenous infusion of antiarrhythmics (amiodarone in 30, lidocaine in 37 procedures). The local anaesthetic used was lidocaine in 27/62 PLSGB, bupivacaine in 6/62 and both in 29/62. The per-procedure analysis showed a significant reduction of the number of ATP/shocks in the hour after PLSGB compared with the hour before [0 (0-0) vs 5 (1-8) p&lt;0.001]. Similarly, in the per-patient analysis, the number of ATP/shocks significantly decreased in the 12 hours after the PLSGB compared with that in the 12 hours before [0 (0-1.3) vs 7 (4.8-12.5) p&lt;0.001]. No complications occurred.

Conclusions
This case series reports our five years experience in performing PLSGB for antiarrhythmic purpose and it confirms its efficacy and safety in the treatment of refractory electrical storm. In particular, the anatomical approach requires few tools and can be easily performed at the bedside.
Artemisinin combined with low dose quinidine suppresses ventricular tachyarrhythmia in a model of Brugada syndrome
Authors: Jeong H , Yoon N 
Published: November 2023

Abstract

Background
The mechanism of Brugada syndrome (BrS) is unclear. One of the mechanisms has been suggested that uneven dispersion of Ito channel between epicardium and endocardium induced ventricular arrhythmia. Artemisinin, which originates from a Chinese herb and is used widely as an antimalarial drug, is reported to inhibit the Ito channel in a canine experimental model previously.

Objective
We aimed to investigate the effect of artemisinin, alone and in combination with low dose quinidine, on the suppression of ventricular tachyarrhythmia in BrS in a canine experimental model.

Methods
We recorded transmural pseudo-ECG and epicardial/endocardial action potentials (APs) from coronary-perfused canine right ventricular wedge preparation. We used acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and Ito agonist NS5806 (6 – 10 μM) to mimic the BrS model. We induced ventricular arrhythmia and then perfused low dose quinidine (1 – 2 μM) alone and additionally perfused artemisinin (100 – 150 μM) to suppress the arrhythmia. We evaluated ventricular arrhythmia inducibility and measured AP duration, J wave area, notch index, and T wave dispersion.

Results
The provocation agents induced prominent J wave in all sample models. In 6 sample models out of 8 for artemisinin alone group, ventricular arrhythmia was induced. Artemisinin suppressed ventricular arrhythmia and recovered the AP dome in all preparations. J wave area and epicardial notch index were also decreased after artemisinin perfusion. The low dose quinidine (1 – 2 μM) did not completely suppressed the ventricular arrhythmia in 6 out of 6 sample models. However, additional artemisinin (100 – 200 μM) infusion suppressed the ventricular arrhythmia in all sample models and restored the AP dome. J wave area and epicardial notch index were also decreased.

Conclusions
Our findings suggest that artemisinin can alleviate ventricular arrhythmia in the BrS wedge preparation model. Combining artemisinin with low dose quinidine may further suppress ventricular arrhythmia by inhibiting potassium channels, including Ito channel. Artemisinin might reduce the therapeutic dose of quinidine by additional inhibition of potassium channels.
Single beta-blocker or combined amiodarone therapy in ICD and CRT-D patients - Insights from the German DEVICE-registry
Authors: Wiedmann F , Ince H , Stellbrink C H , Kleemann T H , Eckardt L , Brachmann J , Gonska B D , Kaab S , Perings C H , Jung W , Lugenbiel P , Hochadel M , Senges J , Frey N , Schmidt C 
Published: November 2023

Abstract

Background
Because of its antiarrhythmic potency and due to the lack of alternatives, amiodarone is often used for antiarrhythmic therapy in patients with ICD or CRT-D systems. To date, robust data on the safety and clinical benefit of amiodarone therapy in these patients are missing.

Objective
This study was designed to assess the periprocedural and post-procedural outcome of combined therapy with beta-blockers plus amiodarone compared to treatment with single beta-blockers in this "real life" cohort of ICD recipients of the German DEVICE registry.

Methods
4,499 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE Registry were enrolled 03/2007-02/2014. Patients' characteristics, procedural data, periprocedural complications, and post-procedural clinical outcome, were analyzed.

Results
12.7 % (572 patients) received amiodarone in addition to beta-blocker therapy. These patients were slightly older and more frequently male than the 3,927 patients with sole betablocker therapy. The two cohorts of patients had no relevant differences in terms of underlying cardiomyopathy. Stroke, and chronic kidney disease were more often present in the patient group receiving amiodarone. Early implantation-associated complications were similar between the groups. One-year overall mortality was, however, significantly higher in the beta-blocker plus amiodarone cohort (adjusted HR 2.09; p&lt;0.001). This was particularly pronounced in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. Interestingly, amongst the surviving patients, amiodarone was not associated with a significantly reduced risk of ICD discharges, syncopal events. Further, the occurrence of VT storm or incessant VTs and the number of patients scheduled for intracardiac ablation did not differ among both groups while the rate of rehospitalization was lower in the cohort with sole beta-blockers.

Conclusions
Taken together, these retrospective "real-word" data suggest an increased all-cause mortality under amiodarone therapy, particularly in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. In surviving patients, rates of arrhythmic events were comparable.Abstract Figure
Lipomatous metaplasia is the best CT predictor for conducting channel localization in scar-related ventricular tachycardia ablation
Authors: Zucchelli G , Parollo M , Mazzocchetti L , Segreti L , Barletta V , De Lucia R , Grifoni G , Sbragi S , Canu A , Viani S , Paperini L , Soldati E , Di Cori A 
Published: November 2023

Abstract

Introduction
Recent evidence has shown that intramyocardial lipomatous metaplasia (LM) can be directly identified with cardiac computer tomography (CT) and plays a significant role in ventricular arrhythmogenesis and facilitation in structural heart disease.

Purpose
We sought to explore the diagnostic performance of three different CT features (LM, CT channels, wall thinning) identified at ADAS3D post-processing as electroanatomical substrate predictors and their potential role in planning and aiding ventricular tachycardia (VT) scar dechanneling procedures.

Methods
All patients undergoing VT ablation at our institution were enrolled. CT images were post-processed with ADAS3D software to assess LM and left ventricle wall thickness. Images were then retrospectively imported into CARTO3 software and concordance between CT and electroanatomical features (conducting channels, channel entrances, bipolar scar, voltage channels, ablation VISITAGs) was assessed at a cardiac segment level.

Results
From July 2016 to December 2022 131 patients underwent VT ablation at our institution. 88 patients did not undergo preprocedural CT examination, 15 patients had a low-quality CT scan and, at ADAS3D analysis 9 patients did not have significant LM. 19 patients (14 ischemic and 5 non-ischemic, 323 cardiac segments) were then included for analysis. 90 segments (27,86%) showed LM, 93 segments (28,79%) showed thickness &lt; 5 mm and 12 segments (3,72%) held CT channels. In terms of conducting channel prediction, in ischemic patients, LM showed 70% sensitivity, 89% specificity, 73% PPV and 88% NPV when compared to CT channels (10% sensitivity, 98% specificity, 70% PPV, 72% NPV) or wall thinning (61% sensitivity, 82% specificity, 58% PPV and 84% NPV). In non-ischemic patients LM showed with 69% sensitivity, 81% specificity, 39% PPV and 94% NPV when compared to CT channels (15% sensitivity, 100% specificity, 100% PPV, 87% NPV) or wall thinning (46% sensitivity, 82% specificity, 32% PPV and 89% NPV). Overall, at multivariate analysis only LM (OR 12,46 95% C.I. 6,59-23,58) and wall thinning (OR 4,73 95% C.I. 2,45-9,14) were independent predictors for conducting channel.

Conclusion
Lipomatous metaplasia is the best CT predictor for conducting channel presence both in ischemic and non-ischemic patients with scar related ventricular tachycardia and a potentially useful tool for procedure planning and guidance.CT predictors for EAM substrate findingsMultivariate forest plots
A valuable electrophysiological insight to distinguish right from left outflow tract ventricular arrhythmia -local activation time in the anterior intraventricular vein and distal great cardiac vein-
Authors: Doi J , Hachiya H 
Published: November 2023

Abstract

Background
Although several ECG criteria have been helpful to differentiate right from left outflow tract ventricular arrhythmias (OTVAs), discriminating OTVA origins especially with left bundle branch block (LBBB) is still considered challenging.

Objective
The aim of this study was to investigate the local activation time (LAT) in the anterior intraventricular vein (AIV) and distal great cardiac vein (d-GCV), and to identify an electrophysiological method of distinguishing right from left OTVAs.

Methods
We measured the LAT relative to the QRS onset of OTVAs in the AIV and d-GCV using a microelectrode with a lumen catheter in patients undergoing successful OT-VA ablation between January 2017 and July 2022 in our institution. The ECG parameters such as the V2 transition-ratio and V2S/V3R index to distinguish right-OT-VAs from left-OT-VAs with LBBB were also investigated.

Results
Local potentials at the AIV and/or d-GCV OTVA sites in 76 consecutive patients (mean age: 56.5±16.2 year-old, right-OTVAs:40, left-OTVAs:36) were analyzed. The LAT of the AIV/d-GCV was significantly shorter for right-OTVAs than left-OTVAs (d-GCV -26.7±26.8 vs. -2.7±21.4 msec, p&lt;0.001, AIV -9.9±23.2 vs. 16.9±18.2 msec, p&lt;0.001), and associated with the identification of right-OTVAs and left-OTVAs (AUC: d-GCV: 0.76 [95%CI 0.65-0.86], AIV: 0.81 [0.70-0.92]). Defining a LAT &lt;0ms in the AIV (sensitivity: 0.74, specificity: 0.75), &lt;-24ms in the d-GCV (sensitivity: 0.83, specificity: 0.60) as cutoff values respectively, the overall odds ratio (OR) increased more for right-OTVAs than left-OTVAs (OR; AIV: 6.7 [1.9-23.4], p=0.002, d-GCV: 7.5 [2.5-22.1], p&lt;0.001). In the multivariate analysis, a LAT&lt;-24ms in the d-GCV was revealed as an independent predictor certifying right-OTVA origins (OR 14.4 (2.1-95.1), p=0.006), which was superior to the V2 transition-ratio and V2S/V3R index.

Conclusion
The AIV/d-GCV activation time could outperform other previous ECG criteria to discriminate right-sided from left-OTVA ventricular arrhythmias with LBBB.