Ventricular Activation Research Articles

Hybrid Neural State-Space Modeling for Supervised and Unsupervised Electrocardiographic Imaging.

State-space modeling (SSM) provides a general framework for many image reconstruction tasks. Error in a priori physiological knowledge of the imaging physics, can bring incorrectness to solutions. Modern deep-learning approaches show great promise but lack interpretability and rely on large amounts of labeled data. In this paper, we present a novel hybrid SSM framework for electrocardiographic imaging (ECGI) to leverage the advantage of state-space formulations in data-driven learning. We first leverage the physics-based forward operator to supervise the learning. We then introduce neural modeling of the transition function and the associated Bayesian filtering strategy. We applied the hybrid SSM framework to reconstruct electrical activity on the heart surface from body-surface potentials. In unsupervised settings of both in-silico and in-vivo data without cardiac electrical activity as the ground truth to supervise the learning, we demonstrated improved ECGI performances of the hybrid SSM framework trained from a small number of ECG observations in comparison to the fixed SSM. We further demonstrated that, when in-silico simulation data becomes available, mixed supervised and unsupervised training of the hybrid SSM achieved a further 40.6% and 45.6% improvements, respectively, in comparison to traditional ECGI baselines and supervised data-driven ECGI baselines for localizing the origin of ventricular activations in real data.

Antiarrhythmic Mechanisms of Epidural Blockade After Myocardial Infarction.

Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular tachyarrhythmias and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear, and its use after myocardial infarction is limited by concerns for potential right ventricular dysfunction. Myocardial infarction was created in Yorkshire pigs (N=22) by left anterior descending coronary artery occlusion. Approximately, six weeks after myocardial infarction, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. Right and left ventricular hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity and intrinsic cardiac neural activity, and ventricular effective refractory periods and slope of restitution (Smax) were assessed before and after TEA. Ventricular tachyarrhythmia inducibility was assessed by programmed electrical stimulation. TEA reduced inducibility of ventricular tachyarrhythmias by 70%. TEA did not affect right ventricular-systolic pressure or contractility, although left ventricular-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular effective refractory periods prolonged significantly at critical sites of arrhythmogenesis, and Smax was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both baroreflex sensitivity and intrinsic cardiac neural activity. TEA does not compromise right ventricular function in infarcted hearts. Its antiarrhythmic mechanisms are mediated by increases in ventricular effective refractory period and ARIs, decreases in Smax, and reductions in border zone electrophysiological heterogeneities. TEA improves parasympathetic function, which may independently underlie some of its observed antiarrhythmic mechanisms. This study provides novel insights into the antiarrhythmic mechanisms of TEA while highlighting its applicability to the clinical setting.

Optimizing electrical efficacy of leadless cardiac resynchronization therapy and leadless left ventricular septal pacing: Insights on left and right ventricular activation from electrocardiographic imaging

BackgroundLeadless cardiac resynchronization therapy (CRT) using the WiSE-CRT system is an emerging heart failure treatment. An implanted electrode delivers lateral or septal endocardial left ventricular pacing (LVP) upon detection of a right ventricular pacing (RVP) stimulus from a co-implanted device, thus generating biventricular pacing (BiVP). Electrical efficacy data regarding this therapy, particularly leadless LV septal pacing (LVSP) for potential conduction system capture, is limited. ObjectiveTo evaluate the acute performance of leadless CRT using electrocardiographic imaging (ECGi), and assess the optimal pacing modality (OPM) of LVSP based on RV and LV activation. MethodsTen WiSE-CRT recipients underwent an ECGi study testing: RVP; BiVP; LVP only; and LVP with an optimised atrioventricular delay (LV-OPT). BiV, LV and RV activation times (BIVAT-90, LVAT-95, RVAT-90), plus LV and BiV dyssynchrony index (LVDI, BIVDI) were calculated from reconstructed epicardial electrograms. The individual OPM yielding the greatest improvement from baseline was determined. ResultsBiVP generated a 23.7% improvement in BiVAT-90 (p=0.002). An improvement of 43.3% was observed at OPM (p=0.0001), primarily through reductions in RVAT-90. At OPM, BiVAT-90 improved in patients with lateral (43.3%, p=0.0001, n=5) and septal LV implants (42.4%, p=0.009, n=5). The OPM varied by individual. LVP or LV(OPT) were mostly superior in patients with LVSP, and for those in SR and LBBB (n=4). ConclusionLeadless CRT significantly improves acute ECGi-derived activation and dyssynchrony metrics. Using an individualised OPM improves efficacy in selected patients. Effective LVSP is feasible, with fusion pacing at LV(OPT) mitigating the potential deleterious effects on RV activation.

Variant patterns of electrical activation and recovery in normal human hearts revealed by noninvasive electrocardiographic imaging.

Although electrical activity of the normal human heart is well characterized by the electrocardiogram, detailed insights into within-subject and between-subject variations of ventricular activation and recovery by noninvasive electroanatomic mapping are lacking. We characterized human epicardial activation and recovery within and between normal subjects using non-invasive electrocardiographic imaging (ECGI) as a basis to better understand pathology. Epicardial activation and recovery were assessed by ECGI in 22 normal subjects, 4 subjects with bundle branch block (BBB) and 4 with long-QT syndrome (LQTS). We compared characteristics between the ventricles [left ventricle (LV) and right ventricle (RV)], sexes, and age groups (<50/≥50years). Pearson's correlation coefficient (CC) was used for within-subject and between-subject comparisons. Age of normal subjects averaged 49 ± 14 years, 6/22 were male, and no structural/electrical heart disease was present. The average activation time was longer in LV than in RV, but not different by sex or age. Electrical recovery was similar for the ventricles, but started earlier and was on average shorter in males. Median CCs of between-subject comparisons of the ECG signals, activation, and recovery patterns were 0.61, 0.32, and 0.19, respectively. Within-subject beat-to-beat comparisons yielded higher CCs (0.98, 0.89, and 0.82, respectively). Activation and/or recovery patterns of patients with BBB or LQTS contrasted significantly with those found in the normal population. Activation and recovery patterns vary profoundly between normal subjects, but are stable individually beat to beat, with a male preponderance to shorter recovery. Individual characterization by ECGI at baseline serves as reference to better understand the emergence, progression, and treatment of electrical heart disease.

Electrocardiographic Criteria for Diagnosis of Acute Myocardial Infarction in Patients with Left Bundle Branch Block

In patients with normal heart and normal conduction system, the initial depolarized segment in ventricle is interventricular septum which begins with septal fascicle of the left bundle branch from left side and direction to right side followed by a simultaneous depolarization of the remaining ventricular free walls from endocardium to pericardium via the right and left bundle branches. But among patients with left bundle branch block (LBBB), the initial septal activation is changing direction and become from right to left then the left ventricular activation is delayed, ST segment and T wave abnormalities occur, and septal Q waves indicative of an MI are absent in this condition. About 0.5 percent of patients with acute myocardial infarction had left bundle-branch block. Because this changes the patients with left bundle branch block (LBBB) and acute myocardial infarction (MI) is challenge to the clinician. The diagnosis of MI with electrocardiogram (ECG) is so difficult in the setting of LBBB because of the characteristic ECG changes caused by altered interventricular septal and left ventricle free wall depolarization. Here we review the ECG diagnostic criteria included all criteria until now and short summary of patient with acute MI and LBBB condition.

The association between paced left ventricular activation time and cardiac reverse remodeling in heart failure patients with left bundle branch block.

The association between paced LVAT and cardiac structure and function at baseline, as well as whether longer LVAT is associated with worse cardiac reverse remodeling in patients with heart failure (HF) and left bundle branch block (LBBB) has not been well investigated. The purpose of this study is to investigate the association between paced LVAT and baseline echocardiographic parameters and cardiac reverse remodeling at follow-up. Patients with HF and LBBB receiving successful left bundle branch pacing (LBBP) from June 2018 to April 2023 were enrolled and grouped based on paced LVAT. NT-proBNP and echocardiographic parameters were recorded during routine follow-up. The relationships between paced LVAT and echocardiographic parameters at baseline and follow-up were analyzed. Eighty-three patients were enrolled (48 males, aged 65 ± 9.8, mean LVEF 32.1 ± 7.5%, mean LVEDD 63.0 ± 8.5 mm, median NT-proBNP 1057[513-3158] pg/mL). The paced QRSd was significantly decreased (177 ± 17.9 vs. 134 ± 18.5, p < .001) and median paced LVAT was 80[72-88] ms. After a median follow-up of 12[9-29] months, LVEF increased to 52.1 ± 11.2%, LVEDD decreased to 52.6 ± 8.8 mm, and NT-proBNP decreased to 215[73-532]pg/mL. Patients were grouped based on paced LVAT: LVAT < 80 ms (n = 39); 80 ≤ LVAT < 90 ms (n = 24); LVAT ≥ 90 ms (n = 20). Patients with longer LVAT had larger LVEDD and lower LVEF (LVEDDbaseline: p < .001; LVEFbaseline: p = .001). The difference in LVEF6M was statistically significant among groups (p < .001) and patients with longer LVAT had lower LVEF6M, while the difference in LVEF1Y was not seen (p = .090). There was no significant correlation between ΔLVEF6M-baseline, ΔLVEF1Y-6M and LVAT respectively (ΔLVEF6M-baseline: p = .261, r = -.126; ΔLVEF1Y-6M: p = .085, r = .218). Long paced LVAT was associated with worse echocardiographic parameters at baseline, but did not affect the cardiac reverse remodeling in patients with HF and LBBB. Those with longer LVAT required longer time to recover.

Outcomes with physiologic His bundle pacing in patients with narrow QRS complex

BackgroundIn patients with narrow QRS complex, both ventricular and biventricular pacing is associated with increased cardiac morbidity and mortality. This risk is not decreased by ventricular pacing avoidance algorithms, which cause nonphysiologic atrioventricular (AV) delays. ObjectiveThis study aimed to report outcomes in patients with narrow QRS complex when the paced complex is in normal range and physiologic AV delays are programmed. MethodsIn 196 patients with QRS duration of 92 ± 10 ms, permanent pacing was done at the site of the His bundle electrogram. The pacemakers were then programmed to maintain physiologic AV delays and to increase heart rates in response to exercise. Patients received usual care and were observed for 3 years. ResultsThe paced complex exhibited a delta wave, and the ventricular activation time, QRS axis, and lead I voltage remained in normal range. Physiologic programming resulted in His bundle pacing burden of 92%. In patients with decreased ejection fraction, there was significant improvement in left ventricular function, left ventricular dilation, and mitral regurgitation (P < .003). In patients with normal ejection fraction, left ventricular function remained normal without new valvular abnormalities. The 3-year all-cause mortality was 10%, and there was no increase in heart failure admissions. ConclusionIn patients with narrow QRS complex, when paced QRS morphology is maintained in normal range and AV dyssynchrony is avoided, His bundle pacing is associated with low all-cause mortality and improvement in abnormal echocardiographic parameters. The paced QRS morphology and physiologic AV delays may be important factors to evaluate in future trials of conduction system pacing.

Clinical and Electrophysiological Outcomes of Left Bundle Area Pacing Compared to Biventricular Pacing: An Updated Meta-analysis.

Left bundle branch area pacing (LBBAP) is a novel pacing strategy that uses the conduction system distal to the left bundle branch block level for direct activation of the left bundle and right ventricular myocardium. Our meta-analysis compared the structural, electrophysiological, clinical, and procedural outcomes of LBBAP and biventricular pacing (BVP). The meta-analysis included two randomized controlled trials and showed significant reductions in the left ventricular (LV) systolic and diastolic volumes with LBBAP compared to BVP, together with statistically significant reductions in the QRS duration, New York Heart Association (NYHA) functional class, and heart failure (HF) hospitalizations. The fluoroscopic time was also significantly shorter in the LBBAP group. However, no significant change in the LV ejection fraction was noted. Procedural complications were slightly higher in the LBBAP group, albeit not to a statistically significant degree. Our findings suggest that LBBAP may be a superior alternative to standard BVP in improving the structural, electrophysiological, and clinical components of cardiomyopathy, including the NYHA class and HF hospitalizations. LBBAP is a more physiological pacing strategy that results in normal ventricular activation and may be a viable alternative to BVP for cardiac synchronization therapy.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, regulates ventricular electromechanical activities and enhances arrhythmogenesis

BackgroundIbrutinib, a Bruton's tyrosine kinase inhibitor used in cancer therapy, exerts ventricular proarrhythmic effects; however, the underlying mechanisms remain unclear. Excitation-contraction coupling (E-C) disorders are pivotal for the genesis of ventricular arrhythmias (VAs), which arise mainly from the right ventricular outflow tract (RVOT). In this study, we aimed to comprehensively investigate whether ibrutinib regulates the electromechanical activities of the RVOT, leading to enhanced arrhythmogenesis, and explore the underlying mechanisms. MethodsWe utilized conventional microelectrodes to synchronously record electrical and mechanical responses in rabbit RVOT tissue preparations before and after treatment with ibrutinib (10, 50, and 100 nM) and investigated their electromechanical interactions and arrhythmogenesis during programmed electrical stimulation. The fluorometric ratio technique was used to measure intracellular calcium concentration in isolated RVOT myocytes. ResultsIbrutinib (10–100 nM) shortened the action potential duration. Ibrutinib at 100 nM significantly increased pacing-induced ventricular tachycardia (VT) (from 0% to 62.5%, n = 8, p = 0.025). Comparisons between pacing-induced VT and non-VT episodes demonstrated that VT episodes had a greater increase in contractility than that of non-VT episodes (402.1 ± 41.4% vs. 232.4 ± 29.2%, p = 0.003). The pretreatment of ranolazine (10 μM, a late sodium current blocker) prevented the occurrence of ibrutinib-induced VAs. Ibrutinib (100 nM) increased late sodium current, reduced intracellular calcium transients, and enhanced calcium leakage in RVOT myocytes. ConclusionIbrutinib increased the risk of VAs in the RVOT due to dysregulated electromechanical responses, which can be attenuated by ranolazine or apamin.

A porcine large animal model of radiofrequency ablation-induced left bundle branch block

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic Background and Objective ECG features of left bundle branch (LBB) block (LBBB) can be observed in up to 20–30 % of patients that suffer from heart failure with reduced ejection fraction. The resulting mechanical intraventricular asynchrony contributes to the worsening of left ventricular hemodynamics and has a relevant impact on the prognosis of the affected patients. The fact that we still cannot accurately predict which LBBB patients will benefit from cardiac resynchronization therapy (CRT) underscores that our understanding of the pathophysiology of LBBB remains incomplete. Here, a translational animal model of LBBB could be a major contributor to improving our knowledge of the molecular and translational pathomechanisms underlying LBBB. Methods A total of 15 male pigs underwent RF catheter ablation of the LBB, guided by fluoroscopy and intracardiac ECG signals. Before LBBB induction and after a follow-up period of one week or three weeks, a thorough clinical characterization was performed including 12-lead ECG, echocardiography, and electroanatomical mapping. To further test the feasibility of cardiac resynchronization in our model, 3 pigs were implanted with a CRT pacemaker on day seven after LBB ablation. Results Upon LBB ablation, 12-lead ECGs displayed typical characteristics of LBBB like a QRS broadening, a QRS slurring in left lateral leads, and a change of the QRS axis. The QRS width was prolonged from 64.2±4.2 ms to 93,4±7.4 ms and the R wave peak time in V6 was extended from 19.3±3.9 ms to 42.7±4.2 ms. Cardiac electromechanical asynchrony was further confirmed by echocardiography, where the appearance of a septal flash, the prolongation of the septal to posterior wall movement delay and extended left ventricular as well as interventricular electromechanical delays were documented. Electroanatomical mapping demonstrated a shift of the left ventricular breakthrough site. After LBBB-induction, left ventricular activation times, defined as the average of the maximum 10 % of activation times minus the average of the minimum 10 % of activation times were significantly prolonged from 36.3±7.1 ms to 60.8±10.2 ms while right ventricular activation times remained unchanged. Finally, RF-induced LBBB persisted over an observation period of three weeks. The pigs that underwent CRT showed a reduction in QRS duration from 99.1±8.2 ms on day seven after LBBB induction to 75.5±8.2 ms and echocardiography provided additional evidence of successful resynchronization. Conclusions In summary, our porcine large animal model accurately recapitulates the electrical and electromechanical phenotype, observed in LBBB patients. This closed-chest model of LBBB therefore provides an experimental platform to study both, molecular and translational characteristics of cardiac electromechanical asynchrony in a reproducible and clinically relevant setting.

CineECG demonstrates abnormal electrical activity in preclinical plakophilin-2-pathogenic variant carriers with a normal 12-lead ECG

Abstract Background/introduction Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease. The presence of a pathogenic variant (PV) of the plakophilin-2 (PKP2) gene increases the likelihood of developing this disease. Although cardiac screening is routinely performed, early detection of ACM remains challenging. CineECG as a tool for analysis of the 12-lead electrocardiogram (ECG) can provide a 3D-reconstruction of the average pathway of electrical activation. With the emergence of this technique, a new insight in ventricular activation patterns can be obtained. CineECG might therefore be of aid in identifying early signs of disease in preclinical PKP2-PV carriers with a normal 12-lead ECG. Purpose This study aimed to analyze the ECG’s of preclinical PKP2-PV carriers with CineECG to determine the ventricular electrical activation patterns and to compare these patterns to the normal CineECG trajectory. Methods The 12-lead ECG’s of 19 preclinical PKP2-PV carriers were selected and evaluated by three experts on depolarization abnormalities. CineECG analysis was conducted in all preclinical PKP2-PV carriers to ascertain the average location and direction of the ventricular electrical activation. The resulting CineECG trajectory was then compared to the normal CineECG, which was previously determined from normal ECG’s from the PTB-XL database. The CineECG was considered abnormal if more than 15% of the CineECG trajectory was outside the normal distribution. Results Expert analysis of the ECG’s revealed no depolarization abnormalities (e.g. abnormal electrical heart axis, pathological Q-waves or low voltage, and ECG Task Force Criteria were absent). The CineECG trajectory was abnormal in most cases (11 out of 19 PKP2-PV carriers), while the other eight carriers exhibited normal CineECG trajectories. Figure 1 shows three examples of A) a normal case, B) a PKP2-PV carrier with a normal CineECG and C) a PKP2-PV carrier with an abnormal CineECG. In example C, the activation pattern is abnormal as the latest activation is aimed towards inferior and far to the left basal area of the heart. Conclusions CineECG analysis of the normal 12-lead ECG’s of preclinical PKP2-PV carriers resulted in the finding of abnormal electrical activation patterns in the majority of carriers. CineECG could therefore be a sensitive tool to unveil subtle and early abnormalities in the depolarization that would otherwise not be easily detected.Figure 1

Impact of left bundle branch area pacing on right cardiac chambers dimensions and function. a medium term single center echocardiographic study

Abstract Introduction Left bundle branch area pacing (LBBAP) has become, in the last years, the preferred method for physiological pacing due to a wider target area, optimal pacing and sensing thresholds, and stable parameters over time. LBBAP ensures rapid and synchronous left ventricular (LV) activation through the left-sided conduction system. On the other hand, there is little data on right ventricular (RV) activation in LBBAP. The purpose of this study was to evaluate the impact of LBBAP on the right heart anatomy and function over a mid-term follow-up period. Material and methods All consecutive patients with successful LBBAP for bradyarrhythmic indications between February 2021 and July 2022 at our institution were eligible for this study. Left bundle branch capture was defined as a paced QRS complex of right bundle branch block morphology, and proof of transition from non-selective to selective capture with differential pacing maneuvers. To avoid confounders, patients with LV ejection fraction below 40% and with severe valvular disease were excluded. In the end, 57 patients were prospectively evaluated. Patient and procedural characteristics were recorded at baseline and follow-up. Also, right atrial (RA) volume, RV basal diameter, tricuspid annulus peak systolic elevation (TAPSE), RV S` wave (RVS`W), and tricuspid regurgitation (TR) were evaluated before the procedure and at the end of the follow-up period. Results The mean age of the patients was 68.9± 10 years, and 70% were males. 29.8% had a baseline right bundle branch block, and 22.8% had a left bundle branch block morphology. The baseline LV ejection fraction was 54.3 ± 9.9 %. The paced QRS duration was similar to the baseline values (128.5 ± 16.3 vs. 134.4 ± 30.4 msec, p=0.119). The pacing and sensing thresholds were 0.7 ± 0.3 V at 0.4 ms pulse duration and 9.7 ± 4.2 mV, respectively. The mean LV activation time (measured as the R wave peak time in V6) was 80.9 ± 12 msec, and the mean RV activation time (measured as the difference between QRS duration and LV activation time) was 51.9 ± 24.2 msec. The patients were followed over a mean period of 591.2 ± 150.3 days. There were no complications over the follow-up period that led to pacing interruption. The follow-up pacing (0.6 ± 0.2 V, p=0.003) and sensing (11.7 ± 6 mV, p= 0.023) thresholds showed significant improvement compared to the procedural values. The right heart echocardiographic evaluation showed non-statistically significant changes between the follow-up and the baseline values for RA volumes (57.9 ± 33.7 vs. 51.5 ± 28.4 ml, p=0.122), RV basal diameter (32.8 ± 5.4 vs. 31.8 ± 6.4 mm, p=0.31), RVS`W (12.8 ± 3.2 vs. 12.85 ± 2.7 cm/sec, p=0.933), and TR (1.8±0.8 vs. 2±1, p=0.07). On the other hand, there was a significant improvement in the TAPSE (22.2±4.3 vs. 20.7±3.6 mm, p=0.021). Conclusions LBBAP was associated with preserved dimensions and function of the right cardiac chambers over a medium-term follow-up period.

Real-time assessment of LV synchrony in AV block population undergoing LBB pacing using ECG Imaging

Abstract Background Left bundle branch pacing (LBBP) may prevent right ventricular (RV) pacing-induced dyssynchrony (DYS). Nowadays, real-time assessment of DYS correction is indirectly measured with QRS narrowing. Non-invasive ECG imaging (ECGI) technique may provide an evaluation of electrical resynchronization based on quantitative assessment of ventricular local activation time (LAT) maps. Purpose To assess whether real-time ECGI could evaluate LV synchrony achieved through LBBP, in a consecutive AV block (AVB) population. Methods A cohort of 12 patients with AVB were included. ECGI was performed during the implant procedure. ECGI signals were computed using an artificial intelligence derived cardiac geometry model. Ventricular LAT maps were obtained when pacing from septal RV and with LBBP (lead placed according to guidelines ECG criteria) for each of the patients. The following parameters were obtained from ECGI LAT maps to assess intra and interventricular DYS pacing at the RV septal and LBB locations: total activation time (TAT), left ventricular activation time (LVAT), left ventricular dyssynchrony index (LVDI), ventricular electrical uncoupling (VEU = mean LVAT – mean RV activation time) and histogram overlap between LV and RV activation times distribution. RESULTS: Nine of the 12 patients were men (75%), with a median age of 79[Q1 75-Q3 82]. QRS duration during RV septal pacing was 150 ms [138-172]. Median LVEF was 47% [26-59]. In Figure 1, it can be observed that dyssynchrony variables are corrected across all patients when reaching LBBP. Figure 2 shows activation maps during RV septal pacing and during LBBP, along with the QRS duration, and the RV and LV histogram of activation times. Conclusion ECGI is useful for assessing the LV synchrony correction during LBBP in an AV block population.Dyssynchrony variablesActivation maps with QRS and histograms

From ECG to broadband ECG, focused on the ventricular activation

Abstract Background An ultra-high-frequency ECG (UHF-ECG) technique, recently introduced, provides ventricular activation patterns and identifies electrical dyssynchrony. UHF-ECG interpretation assumes that the ECG amplitude decreases rapidly at higher frequencies with increasing distance from the source. Based on this property, nearby sources can be distinguished. Unfortunately, this assumption has never been experimentally proven. Purpose The study aims to show whether there is a decrease in ECG amplitude with distance from the source and whether this decrease is frequency-dependent. Methods UHF-ECG resting recordings were acquired in 106 subjects. We used a standard electrode setup for a 12-lead ECG. In addition, we recorded UHF-ECG from six extended precordial electrodes. With the help of magnetic resonance images, we measured the distance of all precordial leads to the ventricular geometrical center. For each lead, we determined the amplitude of frequency components by computing the area of the averaged amplitude envelopes in the region of the QRS complex. We analyzed five frequency bands: LF (0.2-20 Hz), MF (20-80 Hz), HF (80-300 Hz), UHF1 (300-500 Hz), and UHF2 (800-1000 Hz). Results The left panel in the figure shows the relative amplitude decrease in five frequency bands with relative distance from the depolarization source. The decay coefficient in the LF band is only 0.56 [0.84, 0.29] median [percentile 25,75] and gradually grows up to 1.23 [1.40, 0.98] in the UHF2 band, p&amp;lt;0.005. It indicates that the amplitude of the ECG signal from distant areas of the ventricles in the LF band drops approximately 50 percent of the original value, and the amplitude in the UHF2 band drops to only 20 percent of the original value. The right panel demonstrates an amplitude decrease with distance and frequency in the background of heart geometry. The circle's area corresponds to the relative signal intensity recorded in a particular body surface electrode V1, V4, and V6 from RV, LV, and septal ventricular segments. The circle marked in red has a size of 1 and is at the smallest distance from the electrode. The right panel includes the LF band (regular ECG) and the UHF2 band of 800-1000 Hz. Conclusion The results show significant differences in ECG signal decay between frequency bands and the ability to localize nearby sources using UHF-ECG. Verifying the principle of frequency dependence of ECG properties opens possibilities for a more accurate description of activation patterns. Combining multiple frequency bands (broadband ECG) has the potential to distinguish the activation of near and distant sources.Different decrease in ECG amplitude

CineECG analysis of body surface potential mapping performed in preclinical and clinical plakophilin-2-variant carriers

Abstract Background/introduction Pathogenic variation of the plakophilin-2 (PKP2) gene is associated with arrhythmogenic cardiomyopathy (ACM). Disease manifestation in PKP2-pathogenic variant (PV) carriers differs greatly. Early detection of disease is crucial and could be of benefit in the risk stratification of this population. 67-lead body surface potential mapping (BSPM) could offer more insight into subtle electrical abnormalities. CineECG is a novel tool which can provide an estimation of the average pathway of ventricular activation based on the BSPM-signals, and could be of added value in the detection of electrical abnormalities. Purpose This study aimed to analyze 67-lead BSPM data with CineECG to ascertain the electrical activation pathway in PKP2-PV carriers and to compare these to the normal CineECG. Methods Ten PKP2-PV carriers underwent 67-lead BSPM. Six carriers were without definite ACM diagnosis (preclinical); no Task Force Criteria (TFC) were met apart from the identification of the pathogenic PKP2-variant. The other four carriers were all diagnosed with definite ACM (symptomatic). The average location and direction of ventricular activation was determined with CineECG, resulting in a CineECG trajectory throughout the ventricles. These results were compared to the normal CineECG trajectory, which was established in a previous study with normal ECG’s from the PTB-XL database. A CineECG trajectory that deviated more than 15% from the normal trajectory was considered abnormal. Additionally, to further determine the added diagnostic value of BSPM and CineECG beyond the standard 12-lead ECG, the 12-lead ECG’s were evaluated for abnormalities by three different ECG-experts. Results Expert evaluation of the 12-lead ECG showed that all preclinical PKP2-PV carriers had a normal ECG (no TFC and no other abnormalities such as abnormal electrical heart axis, pathological Q-waves or low voltage). In the symptomatic carriers, all ECG’s showed either presence of TFC or conduction abnormalities. Of the ten PKP2-PV carriers, eight exhibited an abnormal CineECG trajectory. In the preclinical group, four out of six carriers had an abnormal activation trajectory, while all symptomatic carriers had an abnormal CineECG trajectory. Conclusions Through CineECG analysis of 67-lead BSPM, abnormal ventricular activation was identified in the majority of PKP2-PV carriers. Notably, abnormal activation was observed in four out of six preclinical PKP2-PV carriers while the standard 12-lead ECG showed no abnormalities. Future research in a larger group, which also includes follow-up data, is warranted to determine whether these results are an indication of early signs of disease.Figure 1

Impact of myocardial phenotype on atrioventricular delay optimization at rest and during exercise: insights from a virtual patient study

Abstract Background The usefulness of atrioventricular delay (AVD) optimization in cardiac resynchronization therapy (CRT) for heart failure (HF) patients with left bundle branch block (LBBB) and reduced left ventricular ejection fraction (LVEF) is still debated. Yet, studies have not explored the role of non-electrical myocardial disease substrates in determining optimal AVD settings among patients. Purpose We first hypothesized that acute response to AVD optimization might be modulated by various myocardial disease substrates. Furthermore, we hypothesized that cardiac function is more sensitive to changes in AV coupling during exercise and that this sensitivity is also modulated by underlying myocardial disease substrates. Methods We used the CircAdapt model of the human heart and circulation to simulate different types of LV remodeling that can be found in CRT candidates. First, an LBBB-like pattern of mechanical activation was imposed by delaying LV free wall (LVFW) and interventricular septal (IVS) activation relative to right ventricular free wall activation. Then, two types of LV remodeling were simulated by LV dilation with preserved or impaired myocardial contractility, resulting in LVEF &amp;lt;35%. To investigate the effect of diastolic dysfunction, we increased passive myocardial stiffness of the IVS and LVFW on both substrates with LV remodeling until a mean left atrial pressure (mLAP) of 14 mmHg was reached. CRT was simulated by resynchronizing IVS and LVFW. AVD optimization was conducted by gradually reducing the paced AVD from 220 ms to 40 ms in steps of 20 ms. In each simulation, the optimal paced AVD at rest (cardiac output (CO) and heart rate (HR) of 4.2 L/min and 80 bpm, respectively) was assessed using stroke volume (SV) and mLAP which is used as a measure of LV filling pressure. To investigate the relative effect of these myocardial phenotypes during AVD optimization under exercise, CO and HR were increased step-wise. Results The gain in SV by AVD optimization was larger in the simulations with healthy myocardium than in those with hypo-contractile and stiff myocardium (Figure 1: top-row). However, mLAP was comparably decreased by AVD optimization in healthy and diseased myocardium (Figure 1: bottom row). During exercise, the optimum AVD shifted to shorter values (Figure 2: top-row), and mLAP was much more sensitive to AVD, particularly in the presence of hypo-contractile and stiff myocardium (Figure 2: bottom row). Conclusion Virtual patient simulations show that both myocardial hypocontractility and stiffness dampen the effect of AVD optimization on SV. Furthermore, simulations suggest that patients benefit more from AVD optimization during exercise than during resting conditions. These mechanistic insights may help to gain more benefit from AVD optimization for patients undergoing CRT.AVD optimization at restAVD optimization during exercise

ECG imaging as a real time tool to guide left bundle branch pacing implant in patients with left bundle branch block and resynchronization therapy indication

Abstract Background Left bundle branch pacing (LBBP) has emerged as a promising alternative technique for cardiac resynchronization therapy (CRT). ECG imaging (ECGI) may provide an accurate assessment of electrical resynchronization using real-time maps during LBBP implant. Purpose To evaluate the usefulness of ECGI to guide LBBP implant, by analyzing the ventricular activation times and the degree of resynchronization at each screwing step during the lead implant. Methods Four patients with CRT indication and left bundle branch block (LBBB) referred for LBBP were prospectively enrolled. ECGI was performed during the implant procedure. Cardiac signals were recorded using ECGI and projected into an artificial intelligence-derived geometric model. Thus, generating imageless and non-invasive activation maps at defined stages during lead screwing: basal rhythm (LBBB), right ventricular (RV) septum, mid-septal, deep-septal, and finally pacing from the left bundle branch (according with guidelines ECG criteria). The following parameters were measured: a) total activation time (TAT); b) left ventricular activation time (LVAT); c) left ventricular dyssynchrony index (LVDI) (as a quantifier of intraventricular dyssynchrony); d) ventricular electrical uncoupling (VEU); and e) histogram overlap between LV and RV distribution (the last 2 markers of interventricular dyssynchrony). Results The study cohort comprised men with a median age of 68 [Q1 59- Q3 79], with a median basal LBBB QRS duration of 175 ms [160-188] and a median LVEF of 32% [28-39]. A shortening of the activation times and a decrease in intra and interventricular dyssynchrony was achieved when the final lead position was reached. See the results in Figure 2. Conclusion Real-time and imageless ECGI system may offer a novel approach for guiding LBBP and it is useful to ensure left ventricular resynchronization.ECGI to guide LBBP implantActivation and dyssynchrony measurements

Precordial activation sequences from low frequency analysis in left bundle branch block patients: left bundle branch area pacing vs right ventricular pacing

Abstract Introduction Left bundle branch area pacing (LBBAP) provides a more synchronous and physiological ventricular activation than conventional right ventricular pacing (RVP) in LBBB patients. QRS duration (QRSd) is the standard measurement for assessing depolarization synchrony, but it only provides information about the activation time and not about the activation sequence. Purpose Our aim is to assess the activation sequence by precordial activation delay (pAD) using a low-frequency (LF) ECG method comparing baseline and paced ECG in LBBAP and RVP patients. Methods Twelve-lead ECGs recordings were acquired from 29 patients with LBBB (16 LBBAP and 13 RVP) after 24 hours of sequential LBBAP or RVP. LF-ECG was employed for QRS-complex analysis. The activation time for each lead was computed and an activation sequence constructed by linking them. pAD was calculated as the time between the first and the last lead activation. pAD provides information about both, the delay in ventricular depolarization as indicated by its magnitude, and the depolarization direction (as it can take a positive or negative value indicating a left or right ventricle delay, respectively). Results At baseline, both groups (LBBAP and RVP) showed the latest activation at V5-V6, supported by positive median pAD values with no statistically significant differences between both groups (50 (21, 65) vs. 54 (17, 67) ms, p=0.93). LBBAP reduced V6 delay and pAD values compared to the baseline QRS (basal: 50 (21, 65) vs. paced: 2 (-18, 25) ms, p&amp;lt;0.001) while RVP did not exhibit any difference (basal: 54 (17, 67) vs. paced: 36 (19, 53) ms, p=0.33). LBBAP provided lower pAD values when compared to RVP (2 (-18, 25) vs. 36 (19, 53) ms, p&amp;lt;0.01). Conclusions pAD measured using a LF-ECG analysis is a feasible method to evaluate depolarization synchrony and provides complementary information to QRSd. In contrast to RVP, LBBAP generates a physiological ventricular activation sequence in patients with LBBB.Baseline patients characteristicsVentricular activation sequences and pAD

Effectiveness of left bundle branch area pacing to restore narrow QRS in patients with right bundle branch block

Abstract Background/Introduction Left bundle branch area pacing (LBBaP) is an innovative technique used to capture conduction tissue and maintain ventricular synchrony during pacing. There are few data about the efficacy of LBBaP in right bundle branch block (RBBB). Purpose To compare the response to LBBaP, evaluated by the change in QRS duration (QRSd) after pacing, in patients with RBBB, left bundle branch block (LBBB) or without conduction disorder. Methods A total of 162 patients with pacemaker indication underwent LBBaP with stylet driven lead with dedicated sheaths, between November 2020 and April 2023. ECG characteristics were evaluated. Data are presented in mean ± standard deviation (SD) or n (%). Paired sample t-test was used to compare QRSd before and after pacing. Results Indications for pacing were atrioventricular block (AVB) 48,4 %, sinus node dysfunction (SND) 37,7 %, AVB and SND 10,7 % and cardiac resynchronization therapy 3,1 %. LBBaP was successfully performed in 98 % (159/162) of patients (78 ± 10 years, 62 % male). Overall, baseline QRSd was 113,2 ± 26,7 ms and paced QRSd was 112,3 ± 14,8 ms (p = 0,662), with left ventricular activation time (LVAT) of 69 ± 14 ms (table 1). Baseline ECG showed 18 LBBB, 29 RBBB and 11 undetermined conduction disorder. In every kind of conduction disorder, paced QRSd was reduced to &amp;lt; 120 ms (table 2). Notably, paced QRSd was &amp;lt; 120 ms, regardless of baseline QRSd. In patients with most important pre-existing conduction disorder (QRS ≥ 145 ms), an impressive reduction in QRSd was observed (Delta = -40,8 ms , table 1). Conclusion LBBaP with stylet driven lead is an effective approach to obtain short paced QRS regardless of baseline QRSd and of the nature of the initial conduction disorder. This opens new perspectives for cardiac resynchronization in patients with RBBB.

Significance of Coherent Mapping in unveiling slow conduction zones of ventricular tachycardia substrate in ischemic cardiomyopathy

Abstract Introduction Ventricular tachycardia (VT) presents a formidable challenge, particularly in cases with extensive myocardial scar tissue, complicating critical ablation site identification. Prolonged interventions not only extend procedural durations but also heighten the risk of complications. This study aimed to assess the efficacy of coherent mapping techniques in precisely locating regions of slow conduction within scar tissue and explored potential correlations with electrophysiological markers in scar-related VT. Methods Seventeen patients (mean age: 61.6 ± 9.2 years, mean EF: 28 ± 9%) with ischemic cardiomyopathy (ICM) and frequent implantable cardioverter-defibrillator (ICD) shocks underwent high-density (&amp;gt;2000 points) left ventricular (LV) substrate mapping (15 endo, 2 epicardial) during sinus or right ventricular (RV) pacing and ablation. Coherent mapping tool was utilized for the identification of slow conduction, demonstrated by vector thickening. Bipolar low voltage areas (LVAs) below 0.5 mV were defined as dense scar, and bipolar voltage between 0.5 and 1.5 mV was defined as the border zone (Figure, panel A). Late potentials (LPs) and local abnormal ventricular activities (LAVA) were manually identified and tagged. Isochronal late activation mapping (ILAM) was also performed to elucidate the functional properties of the substrate (Figure, Panel B). Results LPs and LAVA were identified in all cases, with a mean number of LPs being 10.0 ± 7.1. Of these, 14/17 cases had LPs located in dense scar, while 4/17 cases had LPs in the border zone. The mean area of LAVA was 9.9 ± 7.7 mm², located in dense scar in 6/17 cases and in the border zone in 15/17 cases. Average deceleration zones (DZ, &amp;gt;3 isochrones in 1 cm radius) identified by ILAM was 2 ± 1. Coherent mapping consistently identified slow conduction zones adjacent to LVA in all cases, with these coherent map-based slow conduction zones (CM-SCZ) located in dense scar in 3/17 cases and in the border zone in 14/17 cases. The distance of CM-SCZ to LPs was 12.6 ± 13.9 mm (in 4 cases, LPs were recorded on the spot), and the distance to LAVAs was 18.8 ± 13.7 mm (in 2 cases, LAVAs were recorded on the spot). CM-SCZ was colocalized with DZ in 14/17 of the patients. Ablation lesions covered CM-SCZ in 10/17 cases. Over a mean follow-up duration of 11 ± 6.5 months, 4 patients experienced VT recurrence, with 3 having no ablation lesions covering CM-SCZ, and 2 patients died due to pump failure. Conclusion This study underscores the significance of coherent mapping in refining the understanding of VT substrate in ICM. Identifying and ablating CM-SCZ during substrate-based mapping may provide a potential additional benefit for VT ablation. Nevertheless, larger studies are needed to clarify the prognostic significance and validate the clinical benefits of this approach.Figure 1