bluuebunny/crossref_metadata_2025 huggingface dataset:
Low voltage mapping in atrio-ventricular nodal reentry tachycardia ablation: safety and efficacy in a single center experience
Authors: Martignani C , Spadotto A , Bartoli L , Angeletti A , Diemberger I , Massaro G , Ziacchi M , Bertelli M , Lazzeri M , Carecci A , Biffi M
Published: November 2023

Background

Atrio-ventricular nodal reentry tachycardia (AVNRT) is one of the most common supraventricular arrhythmias. Transcatheter ablation is the first-choice strategy for its treatment. Despite various ablation techniques, using different signal analyses and different energy sources, the reported incidence rate of AVNRT recurrences and high-grade or complete atrioventricular block are about 5% and 1% respectively. Voltage mapping for slow pathway localization is a novel technique for the treatment of AVNRT, that may increase procedural safety and effectiveness, particularly in pediatric patients.

Purpose

To evaluate the safety and efficacy of ablation of slow conduction pathway identified via three-dimensional voltage mapping of Koch’s triangle.

Methods

108 consecutive patients (45% male, mean age 58.6±15.4 years) scheduled for AVNRT ablation in our center underwent three-dimensional voltage mapping of the right atrial septum and Koch’s triangle. Voltage map was aimed at detecting an area of low voltage (voltage bridge) below the His bundle (adjusting the high-voltage slider to 1,5 mV), corresponding to the slow conduction pathway. Focusing on this target, we evaluated the number of radiofrequency (RF) pulses and RF time application for effective ablation of the slow conduction pathway defined by accelerated junctional rhythm (AJR) induction during RF delivery and absence of post-ablative AVNRT inducibility. After RF ablation, all patients underwent clinical evaluation every 3 months to identify AVNRT recurrences.

Results

Voltage mapping was performed in all patients. The mean duration of mapping was 5.7±3.8 minutes. In all patients, a low voltage bridge could be identified. Using this target, RF was delivered until AJR was elicited (mean number of RF pulses at 30W, 50°C = 1.5±1.1; mean time to AJR: 25±12 s). After successful ablation of the slow conduction pathway, AVNRT was no more inducible. No atrioventricular conduction defect (atrioventricular block of any grade) occurred after RF ablation in any patient (AH pre vs. AH post: 148.5±22.8 ms vs. 153.6±17.8 ms, p=n.s.; HV pre vs. HV post: 20.5±18.7 ms vs. 21.8±17.3 ms, p=n.s.; Wenkebach point pre vs. Wenkebach point post: 320.4±45.3 ms vs. 326.2±38.7 ms, p=n.s.). All patients were discharged without antiarrhythmic drug therapy. Overall, during a 2-year follow up, 4 patients had a recurrence of AVNRT (incidence rate of recurrences: 0.025/year).

Conclusions

Voltage mapping can easily identify the low voltage bridge area of Koch’s triangle as a target for slow pathway ablation. RF ablation of the slow pathway identified in this way is safe and effective. Success in slow pathway ablation can be achieved with a low number of very precise RF pulses. This approach can prevent the risk of ablation-related atrioventricular conduction defects and reduce the risk of AVNRT recurrences.
Increased levels of circulating endostatin are linked to orthostatic hypotension
Authors: Ricci F , Larsson A , Hamrefors V , Ruge T , Olshansky B , Sutton R , Fedorowski A , Johansson M
Published: November 2023

Background

Orthostatic hypotension (OH) occurs when blood pressure regulation fails. The underlying molecular mechanism of OH remain largely unexplored. Endostatin is a biologically active molecule cleaved by matrix metalloproteinases, elastases and cathepsins from collagen XVIII in the extracellular matrix and inhibits angiogenesis. Circulating levels of endostatin have been proposed to be involved in blood pressure (BP) regulation, by inducing nitric oxide release. To date, the relationship between endostatin and OH have not been examined.

Purpose

We aimed to investigate circulating levels of endostatin in patients with verified OH by tilt test at a tertiary syncope unit compared with healthy age- and sex-matched controls from the same geographical region.

Methods

We performed an age- and sex-matched case-control study in 150 patients with OH verified by positive head-up tilt-testing and other cardiovascular autonomic tests at a tertiary syncope unit, and 150 healthy controls with negative active standing tests and no history of syncope, orthostatic intolerance, and endocrine disease. High-sensitivity chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin in a blinded fashion. Receiver operating characteristic curves were constructed to analyze the discriminative ability of endostatin in OH compared with healthy controls. Multivariate logistic regression was used to assess the association between endostatin, OH and hemodynamic variables adjusting for age and sex.

Results

Study characteristics are displayed in the Table. Patients with OH had significantly higher absolute levels of circulating endostatin compared with healthy controls (59,024 ± 2513 vs. 44,090 ± 1978 pg/mL, p<0.001). Multivariate-adjusted logistic regression analysis controlling for age, sex, minimum systolic and minimum diastolic BP during tilt, identified endostatin as an independent determinant for OH (beta-coefficient 0.80, p=0.025). The obtained area under the curve was 0.70, P<0.001, Figure).

Conclusions

Our findings indicate that patients with orthostatic hypotension have increased circulating levels of endostatin, independent of age, sex, and hemodynamic variables. Our results highlight the relevance of investigating the molecular pathways related to orthostatic hypotension. Further studies are warranted to assess the prognostic and therapeutic role of endostatin assessment in individuals with orthostatic hypotension.Tablestudy characteristicsFigureROC Curve
Diagnostic approach at specialized syncope units in the netherlands: a cross-sectional, nationwide survey
Authors: Van Zanten S , De Jong J S Y , Scheffer M G , Kaal E C A , De Groot J R , De Lange F J
Published: November 2023

Introduction

The European Society of Cardiology Guidelines recommend a structural approach for the initial evaluation of syncope patients, yet implementation of such approach appears cumbersome. There are several specialized Syncope Units in the Netherlands. Here we investigated the diagnostic strategy of specialized Syncope Units and adherence areas for syncope patients.

Purpose

We aimed to identify the current network of Syncope Units in the Netherlands and to assess to which extent the units fulfil requirements as indicated by the European Heart Rhythm Association consensus and the current guidelines.

Methods

All units Neurology, Internal Medicine, and Cardiology in hospitals in the Netherlands were contacted. Units with specialized Syncope care were included and requested to fill out a questionnaire of 25 questions regarding which medical specialties are involved during evaluation, which diagnostic tests are available and being performed and which adherence regions were associated. We specifically investigated whether the Syncope Units adhered to the consensus statements 1 and 3 as described by the European Heart Rhythm Association position paper as gold standard for best practices.

Results

Specialized care for syncope was reported in 20/72 hospitals. Most (17/20) reported that multiple specialties are involved during the initial evaluation. 19/20 had either Neurology, Cardiology, or both responsible for the Syncope Unit. 18/20 perform guideline-based orthostatic blood pressure measurement. A non-invasive-beat-to-beat blood pressure monitor was present in 11/20 units. 16/20 perform tilt table testing and do > 48 per year, 3/16 this was during the initial evaluation and 15/20 perform carotid sinus massage. The adherence areas cover 64.2% of the Netherlands. Both European Heart Rhythm Association consensus statements 1 and 3 for best practice were met in 4/20 of the Syncope Units, 4/20 only met consensus statement 1 and 14/20 only met consensus statement 3.

Conclusion

We identified 20 Syncope Units in the Netherlands. The diagnostic approach varies in the medical specialties involved, protocols for cardiovascular testing, and timing of diagnostic tests. Most units did not completely perform the Guideline suggested initial evaluation. Four out of 20 Syncope Units met the European Heart Rhythm Association consensus statements for best clinical practice.Overview Syncope Units NetherlandsAdherence of the Syncope Unit
Quantitative autonomic testing after recovery from acute COVID-19 infection: comparison with findings in controls and individuals with neurogenic autonomic dysfunction
Authors: Mascarenhas L , Kohno R , Mcdonald D , Colburn S , Benditt D
Published: November 2023

Background/Introduction

Cardiovascular autonomic dysfunction (CvAD) is believed to contribute to the persistence of troublesome symptoms following apparent recovery from an acute COVID-19 infection. Common complaints in this setting include cognitive impairment (‘brain fog’), fatigue, and both postural and exertional intolerance with a sensation of excessive rapid heart beating. However, while the occurrence of CvAD post-acute COVID-19 has been widely recognized, its quantitative assessment remains largely unexplored.

Purpose

The purpose of this study was to determine whether quantitative cardiovascular autonomic testing in post-acute COVID-19 patients differ from findings in Controls and are more similar to individuals with Neurogenic CvAD, such as those with Pure Autonomic Failure.

Methods

Quantitative autonomic testing was prospectively undertaken in two patient groups: post-acute COVID-19 and Neurogenic CvAD patients, and in control subjects. Acute COVID-19 was documented by the nasopharyngeal PCR method and all affected patients had recovered at least 1 week prior to their autonomic study. Neurogenic CvAD patients were studied as part of their diagnostic evaluation, and none had a COVID-19 infection prior to their study. Measurements included i) heart rate (HR) and blood pressure (BP) responses during active standing (AS), ii) time to BP nadir and time to BP recovery during AS, iii) Valsalva ratio (VR), and iv) respiratory sinus arrhythmia (RSA). The unpaired student t-test and Mann Whitney U test were used to analyze normally and non-normally distributed data, respectively, between post-acute COVID patients and the Control and Neurogenic CvAD patients. All variables were continuous and presented as means with corresponding standard deviations (SD) when normally distributed or interquartile ranges (IQR) when non-normally distributed. A p-value of <0.05 was considered statistically significant.

Results

Post-acute COVID-19 patients (N=55, 83.6% female) and Controls (N=82, 86.6% female) were of similar age (39 [IQR 27.3, 49.2] vs. 33 [IQR 21.4, 40.0] years, respectively, p=0.034). Neurogenic CvAD patients (N=27, 51.9% female) were older (68 [IQR 62.9, 74.3], p<0.00001). The main findings (Table 1, mean [SD]) indicate that post-acute COVID-19 patients exhibited HR and BP responses during AS similar to the Control group; on the other hand, average VR, maximum systolic BP drop during AS, and maximum HR increase during AS in COVID-19 patients trended towards findings in Neurogenic CvAD patients.

Conclusion

Recovered post-acute COVID-19 patients referred for autonomic dysfunction evaluation due to persisting symptoms exhibit autonomic testing findings similar to control subjects but trending towards observations in neurogenic CvAD.
A leadless ventricular pacemaker providing atrioventricular synchronous pacing in the real-world setting: results from the Micra AV post-approval registry
Authors: Garweg C , Chinitz J , Marijon E , Haeberlin A , Winter S , Iacopino S , Curnis A , Breitenstein A , Hussin A , Mela T , El-Chami M F , Roberts P R , Piccini J P , Stromberg K , Clementy N
Published: November 2023

Introduction

Advances in leadless pacemaker technology have enabled accelerometer based atrioventricular synchronous (AVS) pacing by sensing atrial mechanical contraction. However, longer-term performance of these devices in real-world clinical practice has not been assessed.

Objectives

To report the performance of the Micra AV transcatheter pacemaker from the worldwide Micra AV post-approval registry (PAR) through 1-year post-implant.

Methods

The Micra AV PAR is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of the Micra AV system in the real-world setting. Patients enrolled in the Micra AV PAR will be followed for 3 years. For the present interim analysis, baseline characteristics, total AV synchrony index (sum of %AM-VP, %AM-VS, and AV conduction mode switch percentage), major complications, and system revisions through 12-months of implant were summarized and compared to a historical cohort of 2,667 transvenous dual chamber (TV-DC) pacing patients.

Results

The device was successfully implanted in 797 of 801 patients (99.4%) at 98 centers in 19 countries between February 2020 and April 2022. Mean age was 74.1±15.1 years, 42.2% were female, and 31.3% were precluded from transvenous device therapy. Micra AV patients were on average older (74.1 vs. 71.1 yrs, P<0.0001) and had a significantly higher incidence of renal disease (22.3% vs. 9.8%, P<0.0001) compared with TV-DC patients. Mean follow-up was 7.7±6.4 months. Through 12-months, the major complication rate was 4.2% in Micra AV patients compared to 8.8% TV-DC patients (HR: 0.48, P<0.001, Figure). At 12-months, the system revision rate was 1.9% in Micra AV patients compared to 5.5% for TV-DC patients (HR: 0.28, P<0.001). The reduction in system revisions was largely driven by the absence of lead dislodgements requiring revision. Of the 397 patients with device interrogation files available for analysis, 315 (79.4%) were programmed to VDD mode at last follow-up and had a median AV synchrony index of 86.4% (IQR: 68.8% - 97.4%).

Conclusions

The Micra AV leadless pacemaker was implanted with a high rate of success in patients with a high co-morbidity burden, with a significantly lower rate of complications and system revisions through 12-months compared to dual-chamber transvenous pacemakers despite patients being older and having a higher incidence of renal disease. Longer-term performance will continue to be assessed in this ongoing trial.Major Complications Through 12-months
New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase 4 inhibitors: A Chinese population-based cohort study
Authors: Gao X , Zhang N , Gao T , Tse G , Lip G Y H , Liu T , Zhou J
Published: November 2023

Background and Aims

Type 2 diabetes mellitus (T2DM) is an independent risk factor for syncope. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) shows strong cardiovascular benefits, but a therapeutic benefit on syncope has not been previously investigated. This study aims to investigate the incidence of new-onset syncope in T2DM patients treated with SGLT2i v.s. dipeptidyl peptidase-4 inhibitors (DPP4i) in a Chinese population.

Methods

This was a retrospective cohort study of T2DM patients treated with SGLT2i or DPP4i between January 1st, 2016, and December 31st, 2020, in Hong Kong. The study outcomes were new-onset syncope, cardiovascular mortality and all-cause mortality.

Results

A total of 55370 patients (50.48% male; median age: 62.78 years) were included with a median follow-up of 5.56 years. In the matched cohort (SGLT2i: n=18751; DPP4i: n=18751), SGLT2i use was significantly associated with lower risks of syncope (HR: 0.49, 95%CI: [0.41, 0.57], P < 0.0001), cardiovascular mortality (HR: 0.35, 95%CI: [0.26, 0.46], P < 0.001) and all-cause mortality (HR: 0.30, 95%CI: [0.26, 0.34], P < 0.0001). Of the SGLT2i types, empagliflozin (HR: 0.79, 95%CI: [0.59, 1.05], P = 0.0999), dapagliflozin (HR: 0.70, 95%CI: [0.58, 0.85], P = 0.0004), canagliflozin (HR: 0.48, 95%CI: [0.36, 0.63], P < 0.0001) and ertugliflozin (HR: 0.45, 95%CI: [0.30, 0.68], P = 0.0001) were all associated with significantly lower risks of syncope.

Conclusions

SGLT2i is associated with lower risk of new-onset syncope, cardiovascular death and all-cause death compared to DPP4i. Of the different SGLT2i, dapagliflozin, canagliflozin and ertuglifolzin were significantly associated with lower risks of new-onset syncope.
Conventional cardiovascular risk factors in young individuals with three-vessel coronary artery disease experiencing sudden cardiac death
Authors: Vahatalo J H , Holmstrom L , Pakanen L , Kaikkonen K , Perkiomaki J , Huikuri H V , Junttila M J
Published: November 2023

Background

Coronary artery disease (CAD) is a major cause of sudden cardiac death (SCD) in young victims under 50 years of age. Despite the young age, highly advanced CAD is a common finding at autopsies.

Purpose

We aimed to determine the prevalence of conventional cardiovascular risk factors in ischemic SCD victims under the age of 50 years with a three-vessel CAD detected at autopsy.

Methods

The study population was derived from the Fingesture study, consisting of consecutive victims of SCD in Northern Finland between years 1998-2017 (n=5,869). All victims underwent medico-legal autopsy with histological examinations, and toxicology investigations was performed if necessary. Pre-mortem clinical history was obtained from available medical records and medication, questionnaires to closest family members and police reports about the conditions of the death.

Results

In the Fingesture study, a total of 266 SCDs caused by CAD were observed in victims under 50 years of age. Three-vessel disease was detected in 118 victims (44%). The victims with three-vessel disease had more commonly a history of diabetes (26% vs. 14%, p=0.017) compared with victims with fewer major coronary arteries affected. No statistically significant difference was detected in the prevalence of known dyslipidemia (16% vs. 9%, p=0.134), hypertension (29% vs. 19%, p=0.103), male gender (88% vs. 91%, p=0.552), family history of SCD (33% vs. 36%, p=0.841), smoking (81% vs. 72%, p=0.371), or mean age (45 years vs. 44 years, p=0.120).

Conclusions

The history of diabetes was the only conventional risk factor associated with three-vessel disease in young individuals who experienced SCD determined to be caused by CAD. Along with previous studies, these results highlight the role of diabetes in the development of CAD and adverse outcomes in young people.
Burden and impact of comorbid depression on in-hospital outcomes of Hypertrophic Cardiomyopathy patients in the USA: a nationwide analysis, 2020
Authors: Bhanushali A D I T I , Sampath S , Ahmed H , Mohammed A D I L S , Ganampet N , Muslehuddin Z A I N A B , Bandaru R , Allamneni R A K E S H , Behera A , Kumar S , Adompreh-Fia K O K O U , Desai R U P A K
Published: November 2023

Background

Depression has emerged as a critical risk factor for development and progression of various cardiovascular diseases; however, the association between depression and Hypertrophic Cardiomyopathy (HCM) outcomes is less clear. We aimed to determine the impact of comorbid depression on patients hospitalized with HCM.

Methods

The National Inpatient Sample (2020) was assessed to identify patients hospitalized with HCM using relevant ICD-10 codes. Propensity score matching of 1:1 was performed and the cohort was divided into two - those with comorbid depression (HCM-D+) and those without (HCM-D-). Baseline characteristics and comorbidities were compared between the two cohorts. Impact of comorbid depression on hospitalized HCM patients was evaluated using a multivariate regression analysis adjusting for confounders.

Results

We identified a cohort of 15530 in-hospital HCM patients with a median age of 67 years (66.9% females, 33.1% males, 74.6% whites, 19.1% blacks, 4.3% hispanics, 1.7% Asians). Amongst 15530, 85.5% admissions were non-elective. The HCM-D+ cohort had significantly higher rates of comorbidities such as hypertension (76.4% vs 71.4%), hyperlipidemia (62.5% vs 52.4%), obesity (27.9% vs 24.9%), smoking (28.1% vs 25.7%), dementia (8.2% vs 4.4%) and cancer (7.5% vs 5.8%) (p<0.001). When in-hospital outcomes were compared, HCM-D+ cohort paradoxically appeared to have 44% lower risk of all-cause mortality (OR-0.56; 95%CI: 0.37- 0.84), 22% lower risk of composite end points (all-cause mortality, heart failure, atrial fibrillation, cardiac arrest including ventricular fibrillation, acute ischemic stroke) (OR-0.78; 95%CI:0.66-0.91), 21% lower risk of atrial fibrillation alone (OR-0.79; 95%CI:0.67-0.92) (p<0.001).

Conclusion

Despite having higher rates of comorbidities, comorbid depression in HCM patients appeared to improve in-hospital outcomes. Further studies are needed to uncover the paradoxical protection provided by underlying depression.
Association between scar quantification and documented history of ventricular tachycardia in patients with hypertrophic cardiomyopathy
Authors: Mann C , Gharib D , Widmann K , Tosun R , Dachs T M , Kronberger C , Hengstenberg C , Zelniker T A , Dalos D
Published: November 2023

Background

Hypertrophic cardiomyopathy (HCM) is a major risk factor for sudden cardiac death, and it is crucial to accurately identify patients who may benefit from implantable cardioverter defibrillator (ICD) implantation. Therefore, accurate risk stratification remains an unmet clinical need for patients with obstructive (HOCM) and non-obstructive (HNCM) hypertrophic cardiomyopathy.

Methods and Aim

Consecutive HCM patients were enrolled at a tertiary academic center and underwent cardiac magnetic resonance imaging. We aimed to explore risk factors for a documented history of ventricular tachycardia (VT).

Results

In total 246 HCM (160 HNCM, 86 HOCM) patients were included in the present analysis. Patients with HOCM and HNCM had similar rates of documented VTs (20.0% vs. 23.2%, p=0.61). However, the HCM-risk-score was significantly lower in HNCM patients (4.56% vs. 3.36%, p=0.003).

There was no significant difference in age (53 vs. 57 years, p=0.65), sex (female sex 30% vs. 42%, p=0.14), or echocardiographic parameters, including the maximum outflow tract gradient (59 vs. 67 mmHg, p=0.71), the maximum wall thickness (21 vs. 20 mm, p=0.088), and the left atrial diameter (57 vs. 56 mm, p=0.59), in patients with versus without a history of documented VT.

Furthermore, NT-proBNP (1040 vs. 1199 pg/mL, p=0.74) and high sensitivity troponin-T levels (22 vs. 19 ng/L, p=0.38) did not differ between groups.

Patients with a history of VT were significantly more likely to have late gadolinium enhancement (LGE, 80% vs 50%, p=0.007) and had a higher percentage of LGE in relation to the left ventricular mass (9.2% vs 3.7%, p=0.001). These findings were consistent in patients with HOCM and HNCM (3.32% vs. 5.72% p=0.085).

In an adjusted logistic regression model, the percentage of LGE was independently associated with the presence of VT (Odds ratio 1.27 [95%CI 1.08-1.50]).

Conclusion

These findings suggest that LGE may be a useful imaging marker for risk assessment in patients with HOCM and HNCM.
Prevalence and prognostic value of epilepsy and Brugada syndrome
Authors: Villatore A , Rossetto E , Sala S , Della Bella P , Di Resta C , Peretto G
Published: November 2023

Background

The correlation between Brugada syndrome (BrS) and epilepsy has been previously reported. Sudden death (SD) is a manifestation of BrS due to malignant ventricular arrhythmias (VA), but may occur also in patients with epilepsy. Whether seizure is an uncommon event in BrS, or certain genetic variants are responsible for both seizure and arrhythmia in a subset of patients with BrS, is still to be clarified.

Purpose

To evaluate the comorbidity with epilepsy in a large cohort of patients with BrS at a referral center.

Methods

We retrospectively screened a large cohort of patients with BrS (n=238) in regular follow-up at a third-level center for arrhythmia management. Patients who previously received a diagnosis of epilepsy were enrolled. Patients with epilepsy (BrS/E+) were compared with a control group of consecutive patients without epilepsy (BrS/E-) matched for sex and age. The study endpoints were: 1) prevalence of epilepsy; 2) comparison between BrS/E+ and BrS/E- phenotypes, and assessment of VA incidence by 8-year follow-up.

Results

Of 238 BrS patients, 13 (5%) had a pre-existing diagnosis of epilepsy. Tonic-clonic seizures were present in 9/13, absence seizures in 3/13, and both in 1/13. Among BrS/E+ patients (median age 52 years, IQR 37-67, 80% males) 69% had spontaneous type 1 ECG pattern (9/13), and 46% presented with syncope (6/13), of which 50% arrhythmia-related (3/6). Electrophysiological study was performed in 8 BrS/E+ patients, and tested positive for sustained ventricular tachycardia/fibrillation in 50%. ICD was implanted in 61% (8/13), all in primary prevention. As compared with the matched control group (n=13), there were no differences in terms of ECG pattern, syncope, and ICD implantation rate (p>0.050). However, BrS/E+ had a positive trend for familiarity for SD (5/13 vs. 1/13, p=0.063), and more frequently experienced VA during follow-up (4/13 vs. 0/13, p=0.030).

Conclusion

Our retrospective analysis revealed a prevalence of 5% of epilepsy among a large cohort of BrS patients. Epilepsy was associated with a higher frequency of VA events during follow-up.
Interpretable machine learning model using Extreme Gradient Boosting with Nonnegative Matrix Factorization improves the accuracy of arrhythmic risk prediction in Brugada Syndrome
Authors: Tse G , Zhou J , Li S , Lee S , Li K H C , Leung K S K , Wong W T , Mililis P , Asvestas D , Bazoukis G , Letsas K P , Liu T , Zhang Q
Published: November 2023

Background

Both depolarization and repolarization abnormalities contribute to ventricular arrhythmogenesis in Brugada syndrome (BrS). In this study, we tested the hypothesis that incorporating latent features extracted by various nonnegative matrix factorization (NML) techniques into an interpretable machine learning (IML) prediction model can outperform IML models without latent variables and logistic regression model.

Methods

This study was based on a published anonymised dataset of BrS patients from the Hong Kong, China. XGBoost was selected as the IML model, with and without incorporating latent features using 11 different NMF techniques: Bayesian nonnegative matrix factorization (BNMF), Iterated Conditional Modes nonnegative matrix factorization (ICM), Fisher Nonnegative Matrix Factorization for learning Local features (LFNMF), Alternating Nonnegative Least Squares Matrix Factorization Using Projected Gradient (bound constrained optimization) method for each subproblem (LSNMF), Non-smooth Nonnegative Matrix Factorization (NSNMF), Probabilistic Nonnegative Matrix Factorization (PMF), Probabilistic Sparse Matrix Factorization (PSMF), Sparse Nonnegative Matrix Factorization (SNMF) based on alternating nonnegativity constrained least squares, Sparse Network-Regularized Multiple Nonnegative Matrix Factorization (SNMNMF), Penalized Matrix Factorization for Constrained Clustering (PMFCC) and Separable Nonnegative Matrix Factorization (SepNMF).

Results

A total of 548 patients were included (7.3% females, age at diagnosis: 51.0 [38.0-61.0] years old. Of these, 66 suffered from spontaneous ventricular tachyarrhythmias over 84±55 months follow-up. The baseline model using multivariable logistic regression achieved an area under the curve (AUC) of 0.78 [0.72-0.85], which was improved to 0.88 [0.83-0.93] for the IML model without NMF. The AUC was further increased by incorporating additional latent variables extracted using NSNMF (0.95 [0.92-0.98]) and PMFCC (0.94 [0.88-1.00]).

Conclusion

Incorporation of latent variables by different NMF techniques into an IML prediction model significantly improved the accuracy of risk prediction in BrS.
Roles of atrial arrhythmias in triggering torsade de pointes in patients with acquired long QT syndrome
Authors: Tochibora R , Takasugi N , Endo S , Yoshida A , Watanabe T , Kawaguchi T , Takasugi M , Yamada Y , Kanamori H , Okura H
Published: November 2023

Background

Little is known about a role of atrial arrhythmias (AAs) in triggering Torsade de Pointes (TdP) in patients with long QT syndrome (LQTS).

Purpose

To determine the prevalence of AAs-induced TdP in acute acquired LQTS patients and to classify the AAs’ roles in the development of TdP.

Methods

Initiation patterns of 81 episodes of TdP obtained from 34 consecutive acquired LQTS patients (14 men; median age, 69 years; median QTc, 645.5 ms) with documented TdP were analysed. The patients were divided into 2 groups based on the presence or absence of AAs involvement in triggering TdP: AAs-induced and non-AAs-induced groups.

Results

AAs-induced group comprised 52.9% (18/34) of the patients studied. TdP was preceded by AAs-induced short-long sequences (SLSs) in 41.2% (14/34) of the patients and directly induced by R-on-T AAs (AAs coincidentally encounter a vulnerable repolarizing region during the T wave) in 23.5% (8/34). AAs-induced group experienced TdP after initiating therapy more frequently than non-AAs-induced group (2.5 vs. 1, p=0.008). AAs triggered 48 (59.3%) of the 81 TdP episodes. AAs-induced SLS comprised 67.8% (40 /59) of the SLS-induced TdP episodes. R-on-T AAs accounted for 23.5% (19/81) of the TdP episodes.

Conclusions

Our observations suggest that AAs are associated with the onset mechanism of TdP in more than half of acute acquired LQTS patients and even increase TdP frequency. Thus, AAs are not benign but rather can be lethal in acute acquired LQTS patients.Representative casesAnalysis of Torsade de Pointes episodes
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

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

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 > 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

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 <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

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 (<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<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

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<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<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

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

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<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