Surface ECG Research Articles

Abstract 4113336: Characteristics and Outcomes of Ventricular Tachycardia Ablation in Patients with the HeartMate 3 Left Ventricular Assist Devices: Results From a Large Single-Center Registry

HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device (LVAD). In patients with HM3 and recurrent ventricular tachycardia (VT), data on the outcomes of catheter ablation (CA) are insufficient. We report our institutional experience with CA of VT in patients with the HM3.Consecutive patients with HM3 and recurrent drug-refractory VT undergoing CA were included. Ablation sites were identified using activation/entrainment mapping (stable VTs) and/or late/fractionated potential ablation and pace-mapping (unstable VTs). Between 2016-2023 a total of 431 patients (age 58±13, INTERMACS 3±0.98, 44% ischemic cardiomyopathy) received an HM3 LVAD at our institution. Of these, 15 (3.4%) underwent CA for recurrent VT despite therapy with 1.3±0.8 antiarrhythmic drugs a median of 700 days from the LVAD surgery (2 patients <1 month from the surgery). The LV access was transseptal in 12 (80%) cases, retrograde aortic in 2 (13%) and both in 1 (7%). A total of 23 distinct VTs were targeted. Of these, 21 (91%) were mapped with activation/entrainment mapping, always utilizing an intracardiac RV reference due to excessive surface ECG noise, and 2 (9%) were hemodynamically unstable with reduced LVAD flows and targeted with substrate-based ablation. A total of 3 (13%) VTs were targeted adjacent to the HM3 inflow cannula, and 20 (87%) from substrate remote from the HM3 cannula. At post-procedural programmed ventricular stimulation, non-inducibility of all targeted VTs was achieved in 13 (87%) patients, 1 patient had residual inducible clinical VT, and in 1 patient no post-procedural programmed stimulation was performed. Periprocedural complications occurred in 1 (7%) case (small pericardial effusion not requiring intervention). At 12 months follow-up following the index procedure, no death occurred and one patient received heart transplantation. Of the remaining 14 patients, 6 (42%) remained free from VT (2 with VT ablation <1 month post-LVAD and 12 with VT ablation >=1 month post-LVAD). In this large single-center HM3 registry, a minority of patients underwent CA for recurrent drug-refractory VT (3.4% over a 7-year period). CA of VT in HM3 recipients is feasible and appears safe also when performed soon after LVAD surgery. Myocardial scar from the underlying cardiomyopathic process rather than the apical cannula is the dominant substrate responsible for VT in these patients.

Associations between biomarkers and P-wave indices in patients with heart failure

Abstract Background Atrial structural abnormalities linked to the risk of atrial fibrillation (AF), as indicated by P-wave indices on surface ECG, are associated with the fibrotic transformation of the atrial myocardium. To what extent incident AF can be predicted by ECG characteristics in patients with advanced atrial structural remodeling, such as patients with heart failure (HF), is less well studied. Purpose To evaluate the association between P-wave indices and biomarkers implicated in cardiac fibrosis, and incident AF in patients with HF. Methods Patients with new-onset or worsening of HF were prospectively recruited in a observational study (n=501) and followed-up for 5 years. Blood samples were collected for analysis using proximity extension assay that included a subset of biomarkers that were associated with fibrosis development (TIMP-2, MMP-2, MMP-3, MMP-9, ST-2, GDF-15, Gal-3). All ECGs ever recorded in the hospital catchment area were exported in digital format and processed using Glasgow algorithm for calculation of the P-wave indices (P-wave duration [PWD], P-wave terminal force in V1 [PTFV1] and P-wave axis [Paxis]) and rhythm identification. AF diagnosis was ascertained by manual ECG review. Only patients who did not have AF reported or ECG documented at enrolment were included in the analysis. Of those subjects, 121 patients also had biomarkers of fibrosis analyzed. Cox-regression analyses were used to assess biomarkers’ and p-wave indices’ associations with incident AF. Results After exclusion of patients with prevalent AF (n=317), 184 patients comprised the study group (mean age of 71 years, 33.2% women, 121 patients with biomarker data available). During follow-up, incident AF was observed in 39 patients. At enrolment, PWD>120 ms was observed in 38.7%, abnormal PTFV1>40 mm*ms in 24.5% and Paxis<0° in 5.4%. Among the seven biomarkers assessed, five demonstrated significant associations with incident AF in adjusted analyses: TIMP4 (HR 1.78; 95%CI 1.03-3.05; p=0.037); MMP2 (HR 1.97; 95%CI 1.03-3.80; p=0.042), MMP3 (HR 1.39; 95%CI 1.03-1.88; p=0.031); ST2 (HR 1.91; 95%CI 1.29-2.83; p=0.001) and GDF-15 (HR 2.56; 95%CI 1.50-4.35; p=0.001) (Figure 1). However, none of the tested P-wave variables (P-wave duration, P-wave terminal force, and P-wave axis) were associated to incident AF. Conclusions In this prospective long-term follow-up study of patients admitted for acute HF, biomarkers with proven associations to fibrosis were strongly associated with incident AF. P-wave indices used for prediction of AF in epidemiological cohorts appear to have limited value in patients with HF who have high prevalence of ECG atrial abnormalities at baseline.

Artificial intelligence-enhanced electrocardiography derived body mass index as a predictor of future cardiometabolic disease

Abstract Background Obesity, a key risk factor for cardiometabolic diseases, is poorly evaluated by body mass index (BMI), which doesn't account for visceral fat and fat distribution. Given that obesity-related cardiac changes can manifest in surface ECG changes, we hypothesised that an AI-ECG model could predict BMI, and the discrepancy between AI-predicted and actual BMI (delta-BMI) could indicate cardiometabolic health. We also sought to understand the biological mechanisms contributing to the AI-ECG-derived delta-BMI. Methods The AI-ECG model was developed using a data split of 60/10/30% in a USA secondary care dataset of 512,950 ECGs and externally validated in the UK Biobank (N = 42,386), employing a residual neural network architecture. Model performance was evaluated using Mean Absolute Error (MAE), Pearson correlation coefficient (r), and coefficient of determination (R2). The study aimed at identifying incident cardiometabolic diseases, using Cox regression analyses adjusted for BMI, age, and sex. To assess the underlying biological associations of delta-BMI, phenome-wide, genome-wide, metabolome-wide, and proteome-wide association studies were performed. Results In the test set, the model achieved an MAE of 3.95 (3.93–3.97), r of 0.65 (0.65-0.66), and R2 of 0.43 (0.42-0.43). In the UKB, the model achieved an MAE of 2.94 (2.91–2.96), r of 0.62 (0.62–0.63) and R2 of 0.39 (0.38-0.40). The top tertile of delta-BMI showed an increased risk of future cardiometabolic disease (test set: HR 1.15, p<0.001; UKB: HR 1.58, p<0.001) and diabetes mellitus (test set: HR 1.25, p<0.001; UKB: HR 2.28, p<0.001) after adjusting for covariates including measured BMI. Phenotypic profiling highlighted associations between delta-BMI and cardiometabolic diseases, anthropometric measures of truncal obesity, and pericardial fat mass. Metabolic and proteomic profiling associates delta-BMI positively with valine, lipids in small HDL, syntaxin-3, and carnosine dipeptidase 1, and inversely with glutamine, glycine, colipase, and adiponectin. A genome-wide association study revealed associations with regulators of cardiovascular/metabolic traits. These results highlight delta-BMI's potential as a non-invasive, ECG-based biomarker for cardiometabolic risk stratification. Conclusion Our study demonstrates the effectiveness of an AI-enhanced ECG model in accurately predicting BMI, validated across diverse populations. The introduction of delta-BMI as a predictor of cardiometabolic disease offers valuable additional prognostic insights beyond traditional BMI assessments. Our exploration of biological pathways, spanning phenotypic, genotypic, metabolomic, and proteomic associations, contributes to a comprehensive understanding of the association between delta-BMI and cardiometabolic disease. The clinical implications could extend to enhanced screening strategies, personalised risk assessment, and motivation for lifestyle interventions.

Predicting Spontaneous Termination of Atrial Fibrillation Based on Analysis of Standard Electrocardiograms: ASystematic Review.

Forward prediction of atrial fibrillation (AF) termination is a challenging technical problem of increasing significance due to rising AF presentations to emergency departments worldwide. The ability to non-invasively predict which AF episodes will terminate has important implications in terms of clinical decision-making surrounding treatment and admission, with subsequent impacts on hospital capacity and the economic cost of AF hospitalizations. MEDLINE, EMCare, CINAHL, CENTRAL, and SCOPUS were searched on 29 July 2023 for articles where an attempt to predict AF termination was made using standard surface ECG recordings. The final review included 35 articles. Signal processing techniques fit into three broad categories including machine learning (n = 14), entropy analysis (n = 12), and time-frequency/frequency analysis (n = 9). Retrospectively processed ECG data was used in all studies with no prospective validation studies. Most studies (n = 33) utilized the same ECG database, which included recordings that either terminated within 1 min or continued for over 1 h. There was no significant difference in accuracy between groups (H(2) = 0.058, p-value = 0.971). Only one study assessed recordings earlier than several minutes preceding termination, achieving 92% accuracy using the central 10 s of paroxysmal episodes lasting up to 174. No studies attempted to forward predict AF termination in real-time, representing an opportunity for novel prospective validation studies. Multiple signal processing techniques have proven accurate in predicting AF termination utilizing ECG recordings sourced from a database retrospectively.

Lesion size index-guided radiofrequency catheter ablation using an impedance-based three-dimensional mapping system to treat sustained atrial tachycardia in a horse.

Sustained atrial tachycardia at an atrial rate of 191/min on the surface ECG was detected in a 6-year-old Warmblood mare. The vectorcardiogram obtained from a 12-lead ECG suggested a caudo-dorsal right atrial origin of the arrhythmia. Impedance-based three-dimensional electro-anatomical mapping, using the EnSite™ Precision Cardiac Mapping System revealed a clockwise macro-reentry around a line of conduction block in the caudomedial right atrium. Ten radiofrequency applications were applied to isolate the caudal vena cava myocardial sleeves at a power of 35 W and mean contact force of 14 ± 3 g until a lesion size index of 6 was reached. Sinus rhythm was restored at the first energy application. Successful isolation was confirmed by demonstrating entrance and exit block. Holter monitoring 5 days post-ablation revealed no abnormalities. To date, 9 months after treatment, no recurrence has been observed. The use of lesion size index-guided ablation and isolation of the arrhythmogenic substrate in the caudal vena cava may minimise the risk of recurrence.

The G4 resolvase Dhx36 modulates cardiomyocyte differentiation and ventricular conduction system development.

Extensive genetic studies have elucidated cardiomyocyte differentiation and associated gene networks using single-cell RNA-seq, yet the intricate transcriptional mechanisms governing cardiac conduction system (CCS) development and working cardiomyocyte differentiation remain largely unexplored. Here we show that mice deleted for Dhx36 (encoding the Dhx36 helicase) in the embryonic or neonatal heart develop overt dilated cardiomyopathy, surface ECG alterations related to cardiac impulse propagation, and (in the embryonic heart) a lack of a ventricular conduction system (VCS). Heart snRNA-seq and snATAC-seq reveal the role of Dhx36 in CCS development and in the differentiation of working cardiomyocytes. Dhx36 deficiency directly influences cardiomyocyte gene networks by disrupting the resolution of promoter G-quadruplexes in key cardiac genes, impacting cardiomyocyte differentiation and CCS morphogenesis, and ultimately leading to dilated cardiomyopathy and atrioventricular block. These findings further identify crucial genes and pathways that regulate the development and function of the VCS/Purkinje fiber (PF) network.

HCN2-based biological pacing in a modified rat AV-block model

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Eurostars - Heartpace 114245 Background Electronic pacemakers have several important shortcomings which are difficult to overcome due to their hardware-based design. Gene therapy-based biological pacemakers may provide a different platform which can overcome these limitations. Such biological pacemaker strategies center around overexpression of the pacemaker ion channel HCN2, either alone or with other transgenes to potentiate pacemaker performance, such as the skeletal muscle sodium channel SkM1. In order to develop clinically applicable pacemaker gene therapies further engineering is needed, which would benefit from a reliable small animal model. At present it is unknown if the rat AV block model can be used to evaluate ion channel-based biological pacing. Aim In the present study, we aim to validate a modified rat AV-block model for the evaluation of HCN2 and SKM1-based biological pacing. Methods AV-block was generated in female rats by epicardially applied needle ablation of the AV-nodal region, as previously described (N.K. ). Complete AV-block was confirmed 7 days post-ablation by loss of P-wave and QRS-complex association on the body surface ECG. Seven days post-ablation, 3 groups of animals were injected into the left ventricular apex with Ad5-TNNT2-HCN2, Ad5-TNNT2-SkM1 or saline (control). 14 days post-ablation, ECG analysis was performed during anesthesia under baseline and after i.v. administration of isoprenaline. Upon completion of functional testing, tissue samples were harvested followed by gene expression analysis using qPCR. Results Injection of Ad5-TNNT2-HCN2, Ad5-TNNT2-SkM1 or saline did not result in ectopic activation patterns in baseline conditions 7 days after injection. Administration of isoprenaline results in reversal of the QRS complexes 90% of total measurement time in Ad5-TNNT2-HCN2 injected animals. Saline and Ad5-TNNT2-SkM1 showed no change in activation pattern upon isoprenaline administration. Gene expression analysis revealed expression of HCN2 in the injection site following Ad5-TNNT2-HCN2 injection, with minimal spread to non-target regions. However, this analysis also showed Ad5-TNNT2-SkM1 did not express well in this context. Conclusion Our modified rat AV-block model, when administered with isoprenaline, recapitulated expected biological pacemaker activity of HCN2 gene delivery. However, lack of effective expression of SkM1 renders direct comparison of these relevant transgenes difficult. Nevertheless, we expect this rat AV-block model can provide a valuable tool for the evaluation of novel ion channel-based biological pacemaker strategies.

Effectiveness of dynamic atrioventricular optimization during patient exercise in cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy (CRT) is considered the standard treatment for patients with heart failure and prolonged QRS duration. Recent studies suggest that atrioventricular delay (AVD) optimization can play a key role in QRS narrowing, thus improving CRT outcomes. For this purpose, device-based algorithms have been developed. In particular, the SyncAV algorithm continuously monitors the patient’s intrinsic AVD and dynamically adjusts the pacing AVD to allow fusion of the left ventricle pacing with intrinsic right ventricle depolarization. SyncAV optimization is usually performed in a single patient condition, i.e. at rest, and in a single operating scenario of the device, i.e. during atrial sensing. Purpose This study aims to compare QRS narrowing after AVD optimization using SyncAV in CRT-treated patients at rest, during moderate exertion, and during an increase in the atrial pacing rate. Methods This is a prospective, non-randomized, non-blinded, multicenter study. The study population consisted of patients in sinus rhythm, PR interval < 350 ms, and rest ventricular rate < 100 bpm. Within one month from the implant, patients were assessed for AVD optimization with SyncAV, selecting the offset (i.e. 10 to 40% AVD) that resulted in the shortest QRS duration (QRSd). Subsequently, patients performed moderate physical activity using a bicycle ergo-meter while a surface ECG was collected. QRSd was assessed once patients achieved a heart rate over 20 bpm to baseline heart rate, up to 100 bpm. Finally, QRSd narrowing was evaluated during a programmed increase in atrial pacing (i.e. >20 bpm of baseline atrial rate). Results Nine patients were treated with CRT and enrolled (age 67,3 ± 13,2 years; 66% male; LV ejection fraction 33,7±2,9 %; intrinsic QRSd 155,6 ± 12,7 ms) with intact atrioventricular conduction (PR interval 170,6±25,8 ms). The median SyncAV offset that provided the best QRSd reduction was 20 % (10 - 35%). Intrinsic QRSd was reduced to 132,7 ± 10,0 ms (-14,2±9,4%) with standard biventricular pacing and to 122,0 ± 11,2 ms (-21,2±8,5%) with SyncAV optimization. During exercise the mean heart rate was 88,1 bpm, the QRSd was reduced to 132,7 ± 10,0 ms (-14,2±9,4%) with standard biventricular pacing and to 124,9 ± 14,9 ms (-19,3±10,8 %) with SyncAV optimization. The mean heart rate during atrial pacing was 90 bpm with paced QRSd of 126,0 ±13,9 ms (-18,9±7,3% from baseline) with SyncAV optimization and paced PR interval of 198,2±22,7ms. Conclusion We evaluated the effectiveness of SyncAV for AVD optimization in out-of-clinic. This study demonstrates the possibility of narrowing the QRSd using SyncAV at several activity levels. Nevertheless, a deeper evaluation is needed to confirm our findings, investigating the SyncAV role in a larger population of patients.

Slow pathway ablation in pediatric patients: long-term outcomes in a high-volume center according to baseline electrophysiologic characteristics

Abstract Background Slow pathway ablation (SPA) in pediatric patients with documented paroxysmal supraventricular tachycardia (PSVT) has been proven safe and effective. Arrhythmia induction is often difficult in the pediatric population. Accordingly, empirical SPA is frequently adopted in this population. Real-world data about long-term outcomes of slow pathway ablation (SPA) in relation to tachycardia inducibility and electrophysiologic characteristics in pediatric patients with PSVT in a high-volume center are lacking. Purpose To compare long-term clinical outcomes of SPA in pediatric patients with and without intraprocedural documentation of DAVP and AV nodal reentrant tachycardia induction. Methods In this retrospective sigle-center study, all SPA procedures performed on pediatric patients (under 18 years) at our Institution since 2016 were considered. All patients had documented PSVT with short RP interval, no evidet ventricular pre-excitatio on surface ECG and normal echocardiography. Baseline EPS was performed to exclude the presence of concealed accessory pathway and isoproterenol infusion was used to exclude focal atrial tachycardias. According to intraprocedural EP characteristics, three group of patients were identified: Group 1 with AVNRT induction; Group 2 with dual atrioventricular nodal physiology (DAVP) and no tachycardia induction; Group 3 without DAVP. According to previous documentation of a short RP PSVT and after discussion with patients’ families, SPA was performed in all patients. The endpoint of the ablation was to eliminate slow pathway conduction and AV node re-entrant beat. Follow up visits were scheduled three and twelve months after ablation for all patients. Results 1734 patients underwent SPA since 2016 at our Institution. 1092 patients (73.4%) showed AVNRT induction during EPS (Group 1). 433 patients (14.2%) showed DAVP without tachycardia induction (Group 2). 209 patients (12.4%) didn’t show DAVP at EPS (Group 3). Age and gender were similar among the three groups. SPA was performed with acute procedural success in all patients. After 36-month median follow-up, freedom from palpitations was 98.5% in Group 1, 97.1% in Group 2 and 92.3% in Group 3. A survival analysis showed the best outcomes in group 1 and no significant difference in recurrence rate among the groups 2 and 3 (Figure 1). No permanent heart blocks, neither other major complication was observed. Conclusions When performed by experienced operators and in high-volume centers, SPA is a safe and effective procedure in pediatric patients with documented short RP PSVT. Success rate is highest with AVNRT induction and good without AVNRT induction, regardless of AV node dual conduction at baseline EPS. Such high success rate depends on careful exclusion of others arrhythmia mechanisms (i.e., focal atrial tachycardias, AV re-entrant tachycardias) that, although infrequent in children, are the main determinants of arrhythmia recurrences.

Cardiac tumors with life threatening arrhythmia, an eight year single centre experience

Abstract Background Cardiac tumors are rare cardiac disorders which occur either as primary or secondary tumors. They have a wide variety of clinical presentations from accidental discovery till sudden cardiac death. Manifestations are mainly due to mass effect, local invasion, embolization, or constitutional symptoms. (1) Cardiac tumor related arrhythmias are more often incessant, especially in younger children, and the mechanism can be reentry or triggered automaticity. (2) Arrhythmia management depends on its clinical impact as well as tumor size, site, and nature. Surgical resection is preferred in life threating arrhythmias however, the decision should be tailored. Purpose To describe our institution’s tailored approach in treatment of cardiac tumors presenting with life threatening ventricular arrhythmias (VAs), including surgical resection, coiling of feeding vessels or even ICD implantation with long term rhythm monitoring. Methods We reviewed patients with primary cardiac tumors presenting to our center from 2015 to 2023 with emphasis on those with life threatening VAs. Patient records were examined for clinical presentation, ECGs, imaging modalities, histopathological analysis of the resected tumors and interrogation data for those with cardiac implantable electronic devices (CIEDS). Results Over 8 years, 64 patients were diagnosed to have primary cardiac tumors. Of those, 3.8% (6 patients) presented with life threatening monomorphic VT, half of them were pediatrics. Tissue characterization by CMR and histopathological analysis for the resected tumors revealed: 4 fibromas, one lipoma and one hemangioma. Surface ECGs during VT showed exit at, or close to, the site of the tumor (Table). Total surgical resection was performed in four cases (3 fibromas and one lipoma), one of them (the youngest, 6 months old) died during the postoperative period due to refractory heart failure. Partial resection was done in one patient with fibroma as the tumor involved the majority of RV free wall while the patient with hemangioma underwent coiling of the feeding vessels twice with marked decrease in the tumor size however he had one further episode of VT, so ICD was implanted. Over a mean follow up period of 3 years, four patients had no recurrence of tachycardia as confirmed with implantable loop recorders (ILRs) while the patient with ICD had infrequent episodes. Conclusion Total surgical resection, albeit risky, is highly effective in eliminating life threatening VAs caused by cardiac tumors. Other modalities like partial resection or coiling of the feeding vessels could be effective in high-risk patients. Devascularization, in our hemangioma case was not totally protective. Finally, ILRs were highly beneficial in confirming long-term freedom of arrhythmia after resection.Table: VT exit, tumor site and typeECG, CMR, angiogram& surgical view

Repolarization gradient induces local depolarization abnormalities in Brugada Syndrome

Abstract Background Transmural voltage gradient in right ventricular outflow tract (RVOT) induces diagnostic ECG-phenotype in Brugada syndrome(BrS). Moreover, RVOT depolarization abnormalities have been described as contributors to BrS phenotype and arrhythmogenesis. Purpose To investigate the effect of ajmaline administration on J-elevation of RVOT unipolar signals in BrS patients. Moreover, we wanted to assess whether ajmaline-induced unipolar J-point elevation variations induced local depolarization abnormalities. Methods 21 BrS patients with spontaneous type-1 ECG pattern were enrolled. Due to the absence of BrS ECG pattern at the study, patients underwent RV endocardial mapping with the CARTO3 system, before (PRE) and after (POST) ajmaline administration. The PRE and POST data were exported from CARTO and converted into Matlab format using OpenEP. J-elevation for each point was calculated as the amplitude of the unipolar signal at J wave with respect to baseline. Activation time (AT) of each point was defined as the difference between local depolarization (minimum dV/dt of the unipolar signal) and surface ECG depolarization (time of the minimum signal on V2). With an automatic algorithm, corresponding PRE and POST points were selected. The difference between POST and PRE of each parameter was calculated to obtain the differential values delta-J and delta-AT. Differential values were then interpolated on the mesh of each subject to obtain 3D maps. The deltaJ map was divided into four intervals based on quartiles. We then selected a ROI 'IN' on a region with the greatest deltaJ variation, and a second ROI 'OUT' on the zone of lowest variation. The same ROIs were applied to the deltaAT map. The mean value of the respective differential parameters was extracted in each ROI. Results Greatest delta-J values were found in the RVOT/anterior wall. delta-J in the ROI 'IN' was greater than in the ROI 'OUT' (1.68 [1.11-2.28] vs 0.56 [0.38-0.93] mV, p<0.001). delta-AT in the ROI ‘IN’ was greater than in the ROI ‘OUT’ (27.96 [20.39-44.89] vs 7.62 [4.24-16.69] ms, p<0.001). A good correlation was found between delta-J and delta-AT, considering the data for the two ROIs together (Spearman R coefficient=0.71, p<0.001). Conclusions Our study shows that the repolarization gradient, evaluated by localized delta-J increase in RVOT, justifies BrS ECG phenotype and local depolarization abnormalities. A strong correlation was present in these RVOT areas between J-elevation variation and slow conducting zones.

First experience of focal pulsed field ablation for premature ventricular contractions

Abstract Introduction Pulsed field ablation (PFA) has emerged as a novel strategy to achieve ablation of cardiac tissue. Clinical evidence suggests a remarkable lesion durability and safety profile for AF ablation. Nonetheless, a growing interest exists in broadening its field of application for catheter ablation of ventricular arrhythmias (VA). The CENTAURI system arises as a promising PFA system for targeting VA as it allows pulsed electric field (PEF) delivery via standard, commercially available focal ablation catheters and concomitant coupling with their mapping systems. Purpose To assess, for the first time, the feasibility of focal PFA via the CENTAURI system for premature ventricular complex (PVC) ablation. Methods We conducted a prospective analysis of patients with either high burden (>10%) or symptomatic idiopathic PVC undergoing focal PFA using CENTAURI system at our institution. Procedures were performed between December 2022 and August 2023. Acute and long-term success were defined as no PVC recurrence during a 24h in-hospital monitoring period, and ≥80% burden reduction with absence of symptoms after at least 30 days post-ablation, respectively. PVC monitoring was performed by implantable loop recorder (ILR) or surface ECG Holter monitoring. Results Fourteen patients (age range: 16-87 years; 10 females) were included. Procedures were performed via the CENTAURI system in combination with CARTO 3 system and EnSite X EP system in 4 (28.6%) and 10 cases (71.4%) respectively. Targeted ablation sites were the right ventricular outflow tract (6 cases), right moderator band (2 cases), left postero-medial papillary muscle -PM- (2 cases), and right posterior PM, tricuspid annulus, left posterior fascicle and aortomitral continuity (AMC) in one case. On average, 6.5 applications were delivered to the site of origin with a mean contact force of 11g. Procedural duration and fluoroscopy time were 102 and 8.9 minutes. Two minor complications were observed: one transitory ST depression (solved after i.v. nitrate administration) after repeated applications to AMC, and a femoral pseudoaneurysm. The remaining 12 procedures were uneventful. Although most of the procedures were performed under general anesthesia due to concerns about potential significant muscular contraction, 3 cases (21.4%) were successfully managed with light sedation, without significant muscular contraction nor map shift. Incomplete abolishment of PVC during first 24 h was observed in 2 patients (14.3%). After a median follow-up of 113 days (IQR: 83-188), recurrences were detected in one patient (7.14%). Conclusion Herein we report the feasibility and efficacy of PVC ablation using a focal PEF delivery system (CENTAURI). Furthermore, we describe the possibility of performing PVC ablation with this technology under light sedation, which might be important for minimizing anesthesia impact on PVC burden.Table of characteristicsPVC morphologies

Preliminary implantation experience in Europe with a novel insertable cardiac monitor

Abstract Background The LUX-Dx is a new insertable cardiac monitor (ICM) available in the European market since October 2022. Purpose To describe the initial experience of LUX-Dx implantation in Europe and report feedbacks from operators and patients. Methods The system includes an incision tool and a single-piece insertion tool that is pre-loaded with the small (1.2 cm3) ICM. The implantation procedure is straightforward and comprises the incision, the creation of the device pocket, the insertion of the ICM, the verification of sensing and the incision closure. Following implantation, patients are provided with a mobile device preloaded with the App which connects to their ICM and transmits data daily, or as needed, to the management system. We analyzed data and feedbacks collected at 20 European centers at the time of implantation and before patient discharge. Results A total of 175 implantation procedures were performed in 20 European centers. The most frequent indications for ICM implantation were syncope (n = 119, 68%) and cryptogenic stroke (n=15, 9%). Most procedures (157, 90%) were performed in electrophysiology laboratories by expert operators. The procedure was performed under local anesthesia in 169 (97%) patients, and systemic or local antibiotics were used before the procedure in 96 (55%) cases. A surface ECG mapping was performed before 65 (37%) insertions. All ICMs were implanted in the left parasternal region, with an orientation of 45° in 159 (91%) patients. Device repositioning was required after verification of sensing in 6 (3%) patients. The ICM was successfully implanted in all patients and no procedural complications were reported; the median time from skin incision to suture was 4 min (25th-75th percentiles 2-7). The mean R-wave amplitude was 0.38±0.34 mV at implantation and 0.42±0.38 mV before patient discharge (on average after 1 day). The P-wave visibility, i.e., the ratio between the number of clearly identifiable P-waves and the number of heart cycles during 10 sec ECG with a regular 1:1 conduction, was 92±21% at implantation and 93±18% before discharge. Survey questions on the overall operator experience with the implantation procedure are reported in Figure 1 and those on the patient experience are reported in Figure 2. Conclusions Implantation of the LUX-Dx seems fast and uncomplicated; operator and patient feedbacks are positive. Post-implantation sensing values, i.e. R-wave sensing and P-wave visibility, are good.Figure 1Figure 2

"UNUSUAL" ATRIAL FLUTTER: A CASE REPORT

Abstract A 64–years old male patient was admitted in the Emergency Department with signs of heart failure in a setting of dilated hypokinetic cardiomyopathy with severe depression of left ventricular ejection fraction and no severe coronary artery disease. In the previous medical history: systemic arterial hypertension, obesity, dysthyroidism due to amiodarone, history of atrial fibrillation treated by transcatheter ablation in the left atrium with pulmonary veins isolation (PVI) and the creation of an anterior line in 2010. The ECG documented an atrial flutter rhythm 2:1 probably typical (Fig. 1). An indication was therefore made for hospitalization in Cardiology. After the restoration of a good hemodynamic state, given the persistence of the atrial tachyarrhythmia, an indication for transcatheter ablation was formulated. The electrophysiological study highlighted an activation sequence suggestive of typical common flutter (cranial–caudal right atrial activation; proximal–distal left atrial activation). We then proceeded to ablate the cavo–tricuspid isthmus without interrupting the arrhythmia. Therefore, left and right atrial electroanatomical mapping was performed which confirmed the right isthmic block and documented the left origin of the flutter, showing conduction gaps in the ostia of the pulmonary veins and in the previous anterior ablation line between the mitral annulus and the right superior pulmonary vein (RSPV) (Fig 2,3). Ablation of these gaps effectively stopped the arrhythmia. At the end of the procedure, after stimulation via atrial bursts of up to 200 msec there was no induction of arrhythmias. One month after the procedure, there was an improvement in the contractile function of the left ventricle. Discussion: This clinical case offers us an example of how the analysis of the surface ECG alone is not sufficient to adequately describe the complexity of the arrhythmic substrate characterizing an arrhythmia such as atrial flutter or atrial fibrillation. The electrophysiological study through electroanatomical reconstruction of endocavitary activation proves indispensable for the correct identification and consequent treatment of these complex arrhythmias, with clear clinical benefits for the patient.

REPOLARIZATION GRADIENT CAUSES LOCAL DEPOLARIZATION ABNORMALITIES IN BRUGADA SYNDROME

Abstract Background Transmural voltage gradient in RVOT induces ECG–phenotype in Brugada syndrome(BrS). Moreover,RVOT depolarization abnormalities have been described as contributors to BrS phenotype and arrhythmogenesis. Purpose To investigate the effect of ajmaline administration on J–elevation of RVOT unipolar signals in BrS patients. Moreover,we wanted to assess whether ajmaline–induced unipolar J–point elevation variations induced local depolarization abnormalities. Methods 21 BrS patients with spontaneous type–1 ECG pattern were enrolled. Due to the absence of BrS ECG pattern at the study, patients underwent RV endocardial mapping with the CARTO3 system, before (PRE) and after (POST) ajmaline administration. The data were exported from CARTO and converted into Matlab format using OpenEP. J–elevation for each point was calculated as the amplitude of the unipolar signal at J wave with respect to baseline. Activation time (AT) of each point was defined as the difference between local depolarization (minimum dV/dt of the unipolar signal) and surface ECG depolarization(time of the minimum signal on V2). With an automatic algorithm, corresponding PRE and POST points were selected. The difference between POST and PRE of each parameter was calculated to obtain the differential values delta–J and delta–AT. Differential values were then interpolated on the mesh of each subject to obtain 3D maps. The deltaJ map was divided into four intervals based on quartiles. We then selected a ROI ‘IN‘ on a region with the greatest deltaJ variation, and a second ROI ‘OUT‘ on the zone of lowest variation. The same ROIs were applied to the deltaAT map. The mean value of the respective differential parameters was extracted in each ROI. Results Greatest delta–J values were found in the RVOT/anterior wall. delta–J in the ROI ‘IN‘ was greater than in the ROI ‘OUT‘ (1.68 [1.11–2.28] vs 0.56 [0.38–0.93] mV, p<0.001). delta–AT in the ROI ‘IN’ was greater than in the ROI ‘OUT’ (27.96 [20.39–44.89] vs 7.62 [4.24–16.69] ms, p<0.001). A good correlation was found between delta–J and delta–AT, considering the data for the two ROIs together (Spearman R coefficient=0.71, p<0.001). Conclusions: Our study shows that the repolarization gradient, evaluated by localized delta–J increase in RVOT, justifies BrS ECG phenotype and local depolarization abnormalities. A strong correlation was present in these RVOT areas between J–elevation variation and slow conducting zones.

Activation pattern of the coronary sinus facilitates the differentiation for ventricular outflow tract arrhythmias.

The accuracy of surface ECG algorithms for predicting the origin of outflow tract ventricular arrhythmias (OT-VAs) might be questioned. Intracardiac electrograms recorded at anatomic landmarks could provide new predictive insights. We aim to evaluate the efficacy of a novel criterion utilizing the activation pattern of the coronary sinus (CS) in localizing OT-VAs, including VAs originating from the right ventricular outflow tract (RVOT), endocardial left ventricular outflow tract (Endo-LVOT), and epicardial left ventricular outflow tract (Epi-LVOT). We measured the ventricular activation time of the mitral annulus (MA) from the onset of the earliest QRS complex of VAs to the initial deflection over the isoelectric line at local signals, namely the QRS-MA interval. The activation at 3 and 12 o'clock of the MA was recorded as the QRS-MA3 and QRS-MA12 intervals, respectively. Their predictive values were compared to previous ECG algorithms. A total of 68 patients with OT-VAs were enrolled (51 for development and 17 for validation). From early to late, the ventricular activation sequences at MA12 were as follows: Epi-LVOT, Endo-LVOT, and RVOT. In LBBB morphology OT-VAs, the QRS-MA12 interval was significantly earlier for LVOT origins than RVOT origins. In the combined cohort of development and validation cohort, a cut-off value of ≤10 ms predicted the LVOT origin with a sensitivity of 100% and specificity of 78%. The QRS-MA12 interval ≤ -24 ms additionally predicted epicardial LVOT sites of origin. The QRS-MA interval could accurately differentiate the OT-VAs localization.

Long QT interval revealing severe hypcalcemic dilated cardiomypathy : A case report

Hypcalcemia is a rare cause of dilated cardiomyopathy, but should be suspected in the presence of an obvious long QT interval on the surface ECG; we report a case of 46 years-old-woman, with surgical history of thyroidectomy 6 years ago, admited in our cardiology departement for mangement of congestive heart failure secondary to dilated cardiomyopathy, her surface ECG showed sinus rhythm with long QT interval, his blood tests showed severe hypocalcemia and low serum concentration of parathyroid hormone (PTH), cardiac magnetic resonance imaging was in favor of non ischemic dilated cardiomyopathy. Concomitant with conventionel heart failure treatement, our patient had received parenteral calcium supplementation, vitamin D, levothyrox; after four weeks, heart failure symptomes were relieved, the intervalle QT has shortened, but persistant severe left ventricular systolic dysfuction. Hypoparathyroidism is frequent after thyroidectomy, and could be responsible of severe hypocalcemia which in turn may induce irreversible dilated cardiomyopathy.

Effect of curcumin on inflammatory and oxidative stress markers in Lipopolysaccharide induced animal models of pre-eclampsia

Introduction: A substantial percentage of fetal, maternal, and neonatal morbidity and mortality is traced to Pre-eclampsia, a life threatening disease. Typical symptoms of the disease include de novo hypertension, proteinuria, renal failure, neurological problems, elevated liver enzymes, and uteroplacental dysfunction. It is estimated that almost 8-10% of all pregnancies are affected by preeclampsia in India. Pre-eclampsia incidentally also involves immune system changes on similar lines as a typical pregnancy. Immune cells like CD4+ T-helper 1 (TH1) cells, cytotoxic NK cells, and autoreactive B cells secrete substances that cause an increase in innate immune activation and inflammation in the maternal circulation and uteroplacental unit, instead of immune changes that promote tolerance and inhibit reactivity to the fetus and placenta. Placental and systemic oxidative stress are the key factors in the emergence of preeclampsia. A number of physiological changes, mineral shortages, and increased oxygen use during pregnancy can all be considered potential causes of oxidative stress. There is yet no effective and secure pharmaceutical treatment for preeclampsia. Pregnancy related safety concerns and the complex aetiology are two significant barriers to the development of pre-eclampsia medications. Medicinal plants and derived products have long been recognized as valuable assets in the treatment of a variety of diseases. Curcumin is a naturally occurring substance with significant in vitro therapeutic promise. The objective of this study was to develop LPS (lipopolysaccharide) induced animal model of Pre-eclampsia and to estimate and compare the hemodynamic parameters, inflammatory markers, oxidative stress markers and proteinuria in pregnant control, LPS-induced Pre-eclampsia, and curcumin-treated Pre-eclampsia in experimental rats. Material and methods: Pre-eclampsia was induced by single dose of 0.5μg/kg LPS. Wistar rats were divided into 8 groups of 8 animals. Female wistar rats were placed with male rats overnight and examined the next morning for the presence of sperm in vaginal smears. The day on which sperm was detected was designated as gestational day 0. After confirmation of pregnancy, each rat was weighed and randomized into groups. Pregnant Wistar rats were given 0.5 μg /kg of body weight LPS intraperitoneally on gestational day 5 for developing Pre-eclampsia models. Protein estimation in urine was done after 24 hours. On 19th or 20th gestation day animals were anesthetized and blood pressure was measured through a non-invasive tail-cuff method using the AD instrument and also through invasive method by inserting a arterial catheter in either of the carotid arteries towards the heart. ECG recording was done through surface ECG recording. Blood was collected by cardiac puncture, centrifuged, and stored at -80ºC on 19th or 20th gestation day. Inflammatory markers were estimated through ELISA reader. Oxidative stress markers were estimated. Pregnancy outcome was assessed through placental weight, number of pup’s delivered and pup’s weight. Statistical analysis was done using one way analysis of variance (ANOVA) followed by post hoc Tukey‘s test for intergroup comparisons. Results: In LPS induced model of pre-eclampsia, single-dose treatment with LPS (0.5ug/kg) induced marked pre-eclampsia in rats. Treatment with curcumin significantly decreased the level of proteinuria, hemodynamic parameters, inflammatory markers and oxidative stress markers in pregnant LPS+ curcumin-treated group when compared with the pregnant LPS group. Treatment with curcumin significantly increases pup’s weight and number of pups. Conclusion: On the basis of this experimental study, it is proposed that curcumin appears to be a potential therapeutic agent as measured by effect on hemodynamic changes, proteinuria, inflammatory markers, oxidative stress markers and pregnancy outcomes in LPS-induced pre- eclampsia. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Leukocyte Ig-like receptor B4 (Lilrb4a) alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation

BackgroundHeart failure is usually accompanied by activation of the sympathetic nerve, and excessive activation of the sympathetic nerve promotes cardiac remodeling and cardiac dysfunction. In the isoproterenol (ISO)–induced animal model, it is often accompanied by myocardial hypertrophy, fibrosis, and inflammation. Leukocyte immunoglobulin-like receptor B4a (Lilrb4a), an immunosuppressive regulatory receptor, plays a vital role in cardiovascular disease. However, the effect of Lilrb4a on ventricular arrhythmia in an ISO-induced mouse model remains unclear. ObjectiveThe purpose of this study was to explore the role and molecular mechanism of Lilrb4a in ISO-induced arrhythmogenic remodeling. MethodsLilrb4a knockout mice and Lilrb4a overexpression mice were infused with ISO (15 mg/kg per 24 hours, 4 weeks). Echocardiography and histology evaluations of myocardial hypertrophy and cardiac structural remodeling were conducted. Surface electrocardiography and electrophysiologic examination were used to evaluate cardiac electrical remodeling and susceptibility to ventricular arrhythmias. Quantitative reverse transcriptase–polymerase chain reaction analysis and Western blotting were used to detect the expression levels of ion channel proteins and signal pathway proteins. ResultsThe results discovered that ISO induced cardiac hypertrophy, fibrosis, and inflammation and led to electrical remodeling and the occurrence of ventricular arrhythmias. Lilrb4a alleviated cardiac structural and electrical remodeling and protected against the occurrence of ventricular arrhythmias in ISO-induced mice by gain-of-function or loss-of-function approaches. The mechanism is that Lilrb4a inhibited NF-κB signaling and MAPK signaling activation mediated by transforming growth factor kinase 1. ConclusionLilrb4a alleviates cardiac dysfunction and ISO-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation through the regulation of NF-κB signaling and MAPK signaling activation.

Muscle Fatigue Analysis and Stress Detection from Surface EMG and ECG Data Obtained Using Deep Learning for Upper-Limb Trauma Rehabilitation

Background: The repetitive nature of physical rehabilitation may result in excess muscular fatigue, which can adversely impact an individual's motor function, leading to discomfort or even physical injury. Moreover, individuals who have experienced trauma tend to encounter difficulties concentrating, which can significantly impede their physical capabilities. Regrettably, existing therapeutic approaches do not appear to consider the potential mental exhaustion of patients. This study aimed to create a bidirectional long short-term memory (Bi-LSTM) model for assessing muscle fatigue stage and mental stress conditions during physical rehabilitation of trauma-injured patients. Methods: Data corresponding to 188 EMG signals and 223 ECG signals were collected from the Jimma University physiotherapy clinic and prepared for signal processing. Since the 4th-order Butterworth filter performs better than the other filters, it was chosen to denoise the data. The data were then split at a ratio of 60:20:20 to train, validate, and test the data. Finally, the developed Bi-LSTM model was deployed. Results: The Bi-LSTM model achieved an accuracy of 95% for multiclass muscle fatigue classification, and 97% accuracy was achieved for the binary classification of mental stress. The GUI provides a setting appropriate for routine model usage. Conclusion: The results indicate that monitoring the muscle condition and mental status of traumatized patients can be performed in a clinical setting for effective physical rehabilitation.