bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing functional-molecular parasympathetic dysfunction in PVC-induced cardiomyopathy via dual stressor PVC and exercise
Authors: Shoureshi P , Ahmad Z , Wang L , Myadam R , Rose B , Das A , Uzelac I , Kaszala K , Ellenbogen K A , Huizar J F , Tan A 
Published: May 2024

Abstract

Background
Exercise intolerance is a common presentation of premature ventricular contractions-induced cardiomyopathy (PVC-CM). In a canine PVC-CM model, previous studies have shown cardiac autonomic nervous system remodeling, resulting in persistent sympathetic excess. Nevertheless, the molecular mechanisms and functional implications of this neural remodeling, as well as parasympathetic alterations, remain unclear.

Purpose
We aim to evaluate the functional-molecular mechanisms of parasympathetic remodeling and its potential contribution to exercise intolerance in an animal model of PVC-CM.

Methods
We studied 15 canines (8 experimental vs 7 sham controls) chronically instrumented with pacemakers and telemetry devices to deliver 12-weeks of bigeminal PVCs (200ms coupling) to induce PVC-CM and to record sympathetic (SNA), vagal nerve activity (VNA) and heart rate (HR) over this period. Exercise challenge was conducted in sinus rhythm (SR) and in the presence of bigeminal PVCs ("dual stressor") at baseline and after development of PVC-CM. Sympatho-vagal neural and HR responses were assessed during and after exercise at baseline and after PVC-CM development, with and without PVCs, thus comparing baseline SR, baseline with PVCs, CM SR and CM with PVCs. Western Blot was performed on intrinsic and extrinsic cardiac neural tissues to evaluate molecular mechanisms of neural remodeling.

Results
Compared to baseline, SNA was significantly higher in PVC-CM in all phases of exercise (rest, exercise, recovery, p=0.03). In contrast, VNA was significantly lower in PVC-CM than baseline during exercise recovery (P=0.014). After exercise, HR recovery (HRR) was impaired (p=0.001), VNA lower (p=0.014) and SNA (p=0.03) higher in PVC-CM compared with baseline. Tyrosine hydroxylase (TH) immunoreactivity in the left ventricle (LV, p=0.001) and stellate ganglia (SG, p=0.03) and trans-cardiac plasma NE levels (p=0.03) were higher in PVC-CM compared with sham. Choline Acetyltransferase (CHAT) was not significantly different in either vagus (p=0.33) or LV (p=0.8) between PVC-CM vs sham. Cardiac (LV) Nerve Growth Factor (NGF), Growth Associated Protein (GAP-43) and beta 1-adrenoreceptor levels were lower (p=0.042, p=0.003, p=0.002 respectively) whereas beta 2-adreno- and muscarinic M2-cholinergic receptors were higher (p=0.02, p&lt;0.01 respectively) in PVC-CM compared with sham.

Conclusion
Neural remodeling in PVC-CM results in an imbalanced sympathetic excess and sympathetic-parasympathetic dysfunction characterized by a loss of sympathetic functional reserve during exercise and impaired parasympathetic activity and HRR after exercise. Adaptive downregulation of NGF might explain this imbalance and dysfunction. These data open the intriguing possibility of neural-targeted therapies to reverse remodeling and restore autonomic function disrupted by chronic PVCs.GraphsMolecular
Linking ablation curves with transmural lesions using a thoracoscopic bipolar biparietal irrigated radiofrequent clamp
Authors: Aerts L , Norup Hertel J , Hermans B J M , Lans R , Saljic A , Maessen J G , Jespersen T , Linz D , Maesen B 
Published: May 2024

Abstract

Background
The cornerstone of atrial fibrillation (AF) ablation is the achievement of long-lasting transmural lesions. However, it is currently unknown when transmurality is reached during ablation using the thoracoscopic bipolar biparietal irrigated radiofrequent (RF) clamp.

Purpose
To study the relation between transmural lesions and their corresponding ablation curves using a thoracoscopic bipolar biparietal irrigated RF clamp in pigs.

Methods
In 4 ventilated pigs, endo-epicardial beating-heart ablation was conducted via sternotomy. In the first 3 pigs, 1 up to 4 ablations were performed at multiple sites on right and left ventricular tissue. Objective indicators of transmurality in the ablation curves were retrospectively identified by visual inspection. After the ablation procedure, the pigs were sacrificed and subsequent macroscopic evaluation was performed. The ablated tissue was excised and immersed in 2,3,5-triphenyltetrazolium chloride-staining at 36 °C. After 90 minutes the lesions were sectioned longitudinally and photographed. The ablated nonviable muscle appears white, and the viable muscle appears red (see Figure 1). In the 4th pig, ablations (up to 5) were applied to the ventricles at multiple sites until one or more of the potential identified indicators were observed in the ablation curve. Subsequent histology was performed as described in the first three pigs.

Results
Three indicators of transmurality were identified in the ablation curves: type I, a sharp impedance rise (blue peak); type II, three power drops with more than one energy level decline in one curve and type III, a first power drop before 11 seconds with subsequent hovering of power levels between 15 and 25 Wattage (Figure 1). In the first 3 pigs, a total of 20 ablations were performed, with 50% (n = 10) of the ablations considered transmural. In 80% of the transmural lesions one of the three types was observed. Among the transmural lesions, 50%, 10%, and 20% corresponds to type I, II, and III indicators of transmurality, respectively, with 20% remaining inconclusive. In the lesions classified not transmural (n = 10, 50%), no type I, II, or III indicators of transmurality was observed. In the fourth pig, all lesions (n=7) were considered transmural based on macroscopic evaluation, comprising 86% of type I and 14% of type III indicators of transmurality.

Conclusion
Three promising ablation curve types of transmurality have been identified that are associated with transmural lesions using the bipolar biparietal irrigated RF clamp. Transmurality of the lesion was confirmed by macroscopic histological evaluation. In the next step, these ablation curve types will be tested and validated in the clinical setting.Figure 1
Proteomic and phosphoproteomic remodeling in a rabbit model of electrical storm
Authors: Tsuji Y , Yamauchi R , Shimojo M , Yamagisawa S , Inden Y , Murohara T 
Published: May 2024

Abstract

Background
Electrical storm (ES), characterized by repetitive ventricular tachycardia/fibrillation (VT/VF) over a short time-interval, is a major problem with substantial mortality in patients with implantable cardioverter-defibrillators (ICDs) and structural heart diseases, but therapeutic strategy in the survivors has not been established, likely due to incomplete understanding of the pathophysiology.

Objective
To explore molecular mechanisms of ICD-shocked VT/VF-related death in experimental ES.

Methods
The model was created by inducing chronic complete atrioventricular-block in ICD-implanted rabbits, causing cardiac hypertrophy, QT-prolongation, and VT/VF-episodes. Relative protein/phosphoprotein abundances in hearts from 5 rabbits with ES (defined as ≥3 VF-episodes/24-hr period) experiencing 81±28 VF-episodes and 5 controls (CTL) were assessed by iTRAQ LC-MS/MS and key regulatory pathways were examined by Ingenuity-Pathway-Analysis.

Results
Proteomic analysis identified 1938 proteins, 302 of which were differentially expressed between ES and CTL (P&lt;0.05). ES was profoundly associated with mitochondrial dysfunction and oxidative phosphorylation inactivation along with decreased measurement and predicted inhibition of electron transport chain-proteins. Reductions in mitochondrial matrix-enzymes inferred downregulation of fatty acid β-oxidation and TCA-cycle. Transcriptional factors including nuclear respiratory factor 1 and peroxisome proliferative activated receptor, gamma, coactivator 1 alpha involved in mitochondrial biogenesis were predicted downregulated and TP53 linked to mitochondrial depolarization upregulated. Phosphoproteome detected 641 phosphorylated proteins, 168 of which have changes in phosphorylation state in ES versus CTL (P&lt;0.05). Aberrant phosphorylation-patterns occurred in Z-disc proteins of sarcomeres and Ca2+-handling proteins. Protein-kinase A and G, calcium, Ca2+/calmodulin protein-kinase, AMP-activated protein-kinase, and extracellular signal-regulated kinases/mitogen-activated protein-kinase signalings were activated, all coupling to nuclear integrators and mitochondrial transcription, which showed prediction opposite to proteomic data.

Conclusions
ES may cause mitochondrial damage, which can explain mechanical dysfunction and associated mortality. Direct effects of ICD-shocked VT/VF merit further investigations.
Wearable self-powered ballistic signal detectors with ferroelectric composites arrays for cardiovascular and diabetic complication
Authors: Lee K H , Kim Y R , Yoon N S , Park H W 
Published: May 2024

Abstract

Background
Flexible and wearable electronic devices with lightweight are needed to monitor and guide treatment in patients with cardiovascular disease and diabetic complication. We aimed to develop self-powered wearable bio-signal sensing arrays for cardiovascular and diabetic complication diagnosis and continuous monitoring.

Methods
Ferroelectric composites were designed to have piezoelectric property and high flexibility. Detection of arterial pulse as ballistogram (BCG) was simultaneously compared with electrocardiogram (ECG) in 20 controls. Heart rate and components of ECG was compared with those of BCG. Then, 9 ferroelectric BCG sensors as a square type array with self-power generation were fabricated to attachable thin film. Pressure distribution with BCG sensor array attached to socks were compared between 20 controls and 20 patients with diabetic neuropathy or vasculopathy during standing and ambulation for gait pressure distribution. Pressure distribution pattern was compared to neuropathy and vasculopathy parameters.

Results
Heart rate between BCG and ECG was significantly correlated (interclass correlation coefficient, ICC 0.99, 95% CI 0.98-0.99, p&lt;0.001). QRS and T wave in ECG were correlated to second and third wave in BCG. Radial artery augmentation index by blood pressure monitoring was significantly correlated to BCG pressure (ICC 0.76, 95% CI 0.38-0.90, p=0.002). Analysis of foot pressure distribution demonstrated the highest pressure point at the anterolateral plantar area below a little tow. However, pressure gradient between anterolateral and anteromedial plantar area in diabetic patients was greater than that in controls (42.3±10.2 mV vs. 31.2±8.5 mV, p=0.024). Pressure gradient in diabetic patients was correlated to ankle-brachial index (ICC 0.62, 95% CI 0.32-0.90, p=0.036), but not to neuropathy parameters.

Conclusion
Wearable BCG sensor could accurately detect heart rate, blood pressure index and significantly correlated to ABI. Pressure distribution pattern and gradient analysis in diabetic patients by wearable BCG sensor arrays might predict diabetic complications. Gait remedial training guided by wearable BCG sensor arrays might aid to prevent diabetic complications.
Source-sink mismatch and conduction block: simulation study
Authors: Oh S , Ahn H J , Choi E K , Shim E B 
Published: May 2024

Abstract

Background
Source-sink mismatch is one of the key concepts in arrhythmia mechanism such as relationship between pulmonary veins and the left atrium in atrial fibrillation. We sought to find the condition for conduction block in various geometries.

Methods
To simulate cardiac atrial tissue, the finite element method was used to discretize the governing equation in a 2D mesh. We evaluated under the following conditions: 6 sizes of source width (0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 mm), 64 types of angle (θ) at the junction (30-330 degrees), 3 conditions of conduction velocity (CV) (x0.5, x0.75, and x1 of normal CV of atrial myocardium).

Results
Conduction block was not observed with source width &gt; 0.5 mm in any settings. In reduced CV condition, conduction block was not observed in θ &lt; 300 degrees when source width &gt; 0.3 mm. The higher CV, conduction block was observed in the narrower θ. In cases of CV of x1.0 and x0.75, conduction block was observed in θ &lt; 180 degrees when source width &lt; 0.3 mm. The smaller source width, conduction block was observed in the narrower θ. The wider θ, the easier conduction block occurred.

Conclusion
Conditions for conduction block due to source-sink mismatch are as follows: smaller source width, higher CV, and wider θ. Source with width &gt; 0.5 mm may not be associated with source-sink mismatch in the atrial tissue. CV slowing by antiarrhythmic drugs can be effective in the aspect of source-sink mismatch.
Clinical risk factors associated with cardiac events in children with BrS-SCN5A
Authors: Cruzalegui J , Martinez Barrios E , Greco A , Diez-Escute N , Cerralbo P , Cesar Diaz S , Zschaeck I , Chipa Ccasani F , Brugada J , Campuzano O , Sarquella Brugada G 
Published: May 2024

Abstract

Introduction
between 20-30% of patients with Brugada syndrome (BrS) are carriers of deleterious genetic variants in the SCN5A gene. However, the risk factors for cardiac events in these patients remain under consideration, especially in the paediatric population, with many risk factors being still undetermined.

Objectives
to investigate and evaluate individual clinical risk factors associated with cardiac events in children with BrS-SCN5A.

Methods
a Spanish retrospective single-centre paediatric cohort study was conducted including 41 BrS patients under 21 years of age carrying rare variants in the SCN5A gene. Demographic, clinical, genetic, and therapeutic variables were collected. Descriptive and univariate analyses were performed to identify independent risk factors for cardiac events. Outcomes were defined as cardiac syncope, ventricular tachycardia/fibrillation (VT/VF), sudden cardiac death (SCD), and appropriate shock in ICD.

Results
Nearly 20% of BrS-SCN5A patients presented with cardiac events. Five patients showing cardiogenic syncope, 4-SCD, 3-VT and 2 appropriate shocks in the ICD. The presence of bradycardia and bradyarrhythmia in baseline EKG (P&lt;0.05), AV block type 1 (P&lt;0.02), type 1 Brugada pattern in fever EKG (P&lt;0.02), atrial fibrillation(P&lt;0.05), arrhythmias in febrile episodes (P&lt;0.05), progressive cardiac conduction defect (PCCD; P&lt;0.001), sick sinus syndrome (SSS; P=0.001) and overlap phenotype (P&lt;0.001) were predictor of cardiac events in this cohort.

Conclusions
We have identified several statistically significant independent risk factors associated with cardiac events and worse phenotype severity in BrS-SCN5A children from a single-centre Spanish cohort. These results may help to improve prognosis assessment, establish accurate risk stratification, and prevent SCD in children with BrS-SCN5A. Future studies in large cohorts of different ethnicities are crucial to strengthen our risk factors in paediatric cohorts at high risk of malignant arrhythmias.
Intra-operative ultra high-frequency ECG in relation to left ventricular reverse remodelling after cardiac resynchronization therapy
Authors: Zegard A , Walton J , Begum R , Stegemann B , Hall P , Brown P , Patel P , Leyva F 
Published: May 2024

Abstract

Aims
Ultra-high-frequency electrocardiography (UHF-ECG) has evolved as a potential tool for the assessment of ventricular dyssynchrony. We sought to determine whether changes in ventricular dyssynchrony at the time of cardiac resynchronization therapy (CRT) device implantation, measured using UHF-ECG, relate to post-implantation left ventricular reverse remodelling (LVRR).

Methods and Results
Patients undergoing CRT (n = 46; aged 70.3 ± 11.2 years; 37/46 male) underwent intra-operative UHF-ECG assessment of ventricular dyssynchrony before and after CRT. Multiple frequency bands (n=16) within the 150 to 1000Hz range were used to create ventricular depolarization maps (Figure). Ventricular dyssynchrony (e-DYS) was assessed using the maximum time difference in ms between the QRS complex centres of mass of leads V1 to V6. Left ventricular reverse remodelling was defined in terms of a reduction in left ventricular end-systolic volume (LVESV) at 3 months post-implantation. During implantation, CRT led to a 103% reduction in e-DYS from 36.6 ms during AAI pacing to 1.4 ms during CRT (P&lt;0.001). CRT also led to a reduction in QRS duration (from 156.3 ms during AAI pacing to 119.9 ms during CRT [P&lt;0.001]) and QRS area (from 100.5 ms*mV (or µVs) during AAI pacing to 65.6 ms during CRT [P&lt;0.001]). In regression analyses, intra-operative Δ e-DYS (ms) was associated with ΔLVESV at 3 months (Figure). In contrast, no associations were observed between intra-operative ΔQRS duration or ΔQRS area and ΔLVESV.

Conclusion
Intra-operative Δ e-DYS derived from UHF-ECG, relates to LVRR after CRT. In contrast, no such relationship emerged for ΔQRS or ΔQRS area.
Electrocardiographic imaging to guide ablation of ventricular arrhythmias shows a higher benefit in patients with low intraprocedural burden
Authors: Parreira L , Carmo P , Nunes S , Mesquita D , Quintal J , Chambel D , Marques L , Machado P , Ferreira A , Seixo F , Adragao P 
Published: May 2024

Abstract

Background and aims
Electrocardiographic imaging (ECGI) provides a non-invasive activation map of focal ventricular arrhythmias that has shown good accuracy regardless of the type of cardiac source used. Pre-procedure diagnosis in cases that are expected to be difficult and management of infrequent or poorly tolerated or multiple arrhythmias are some situations that may benefit the most from having an ECGI performed before the procedure. This study aimed to assess the benefit of the ECGI in patients with low intraprocedural burden.

Methods
We performed 81 ECGI procedures in 64 consecutive patients referred for ablation of ventricular arrhythmias (VAs). Ablations were performed with remote magnetic navigation or manually. The localization of the VAs based on the ECGI and invasive electroanatomic mapping was performed using a segmental model of the ventricles. A perfect match (PM) was defined as a predicted location within the same anatomic segment, whereas a near match (NM) was defined as a predicted location within the same segment or a contiguous one. The agreement between the ECGI and the invasive map was evaluated. The benefit of the ECGI in the subgroup of patients with intraprocedural infrequent VAs, defined as less than 1 VA complex /min, was assessed in terms of the success of the procedure.

Results
The ECGI was performed with the AMYCARD 01 only, in 26 patients, with the VIVO only, in 21 patients, and with both systems in 17 patients. Fifty-one patients underwent ablation. 65 ECGI procedures were performed before ablation in those 51 patients, 37 with Amycard with a rate of PM of 79% and NM of 97%, and 28 ECGI procedures with VIVO with 82% of PM and 93% of NM, not significantly different, respectively, p=0.764 and 0.573. The overall success rate was 80%. The low intraprocedural burden group included 28 patients (2 examples shown in the figure). The success rate was 86%, higher than the overall success rate, and much higher than the previously reported in the literature for this group of patients.

Conclusions
The ECGI was useful in predicting the location of the VA in general but was especially helpful in cases that are usually challenging, like patients with intraprocedural infrequent VAs.
Evolution of the ECG in idiopathic ventricular fibrillation survivors: results from a single-centre UK registry
Authors: Scrocco C , Lee D , Ensam B , Bastiaenen R , Specterman M , Behr E R 
Published: May 2024

Abstract

Background
Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion in subjects with an unexplained cardiac arrest and no evidence of overt structural or electrical cardiac abnormalities (1). It can be associated with an early repolarisation pattern (ERP)(2). Data on the evolution of the ECG in this population are lacking.

Purpose
To compare the baseline ECG characteristic of idiopathic VF survivors and age and gender matched controls, and investigate if the presence of an ERP at ECG is a predictor of risk.

Methods
Forty-nine subjects with idiopathic VF evaluated in our tertiary centre from 1997 to 2022, and followed-up for at least 3 months were included in this study. The first representative ECG available after cardiac arrest was evaluated and compared with that of an age and gender matched control with no symptoms, family history of sudden cardiac death and normal cardiac tests; moreover, comparison was made with a follow-up ECG off antiarrhythmic medications (quinidine, amiodarone and verapamil). Medical notes were reviewed to investigate the presence of events at f-up (SCD/appropriate ICD shock).

Results
The mean age at presentation was 33±7 years; 63% of patients were males, and 16% had previous syncope. Twelve cases (24%) and 6 controls (12%) showed ERP on the resting ECG (P=NS). Only resting heart rate (HR) and QRS duration differed between the two groups (Table 1). Follow-up ECGs in 46 idiopathic VF survivors indicated that resting HR, QRS axis and QTc values were significantly different compared to the baseline ECG. In addition, 4 subjects with ERP at baseline did not exhibit it on the most recent ECG, and 6 subjects without ERP at baseline showed it on the most recent ECG. Over a median follow-up of 3.3 years (IQR 6), 13 subjects experienced appropriate ICD shocks. Kaplan-Meyer survival estimates showed no differences in events between subjects showing ERP or not (log rank p=0.092).

Conclusions
Subjects with idiopathic VF show baseline ECGs similar to those of age and gender matched healthy controls from the general population. ECG parameters tend to change only slightly over long-term follow up. The ERP in idiopathic VF survivors is dynamic and thus its relationship with events may be underestimated.Table 1 Table 2