A case of reversible Mobitz type II atrioventricular block after the use of injectable antipsychotics

Although Mobitz type II atrioventricular block is an arrhythmia based on a permanent organic disorder of the His-Purkinje system, reversible factors should be considered. Here, we report the association between a rare reversible Mobitz type II atrioventricular block and antipsychotic medication in a 75-year-old patient with schizophrenia.

Therapeutic Effect of His-Purkinje System Pacing Proportion on Persistent Atrial Fibrillation Patients With Heart Failure

Background His-Purkinje system pacing(HPSP) combined with atrioventricular node (AVN) ablation is an effective therapy for atrial fibrillation (AF) patients with heart failure (HF).However, AVN ablation is accompanied with some limitations and disadvantages. HPSP combined with β -blocker reduces inherent heart rate and increases pacing ratio, which may be an alternative to HPSP combined with AVN ablation. This study was to assess the therapeutic effect of different His-Purkinje system pacing proportions on AF patients with HF. Methods The study enrolled 30 consecutive persistent AF patients with HF who underwent HPSP. Heart rate was controlled by medical therapy. New York Heart Association (NYHA) classification, serum NT-proBNP concentration, echocardiographic parameters were assessed at each follow-up. Results The best cut-off value of pacing proportion to predict MACE by ROC analysis was 71%. In high pacing proportion group, there were significant improvements of NYHA classification, NT-proBNP concentration, LVEF and LVEDD from the baseline in wide QRS complex patients and HFrEF patients, and there were significant improvements in NYHA classification, NT-proBNP concentration from baseline in narrow QRS complex patients and HFpEF patients, moderate but no significant improvements of LVEF and LVEDD were observed in those patients groups. In low pacing proportion group, there were no significant improvements of NT-proBNP concentration, LVEDD or LVEF regardless of baseline QRS duration or LVEF (P > 0.05). Conclusion High pacing proportion of HPSP has a beneficial effect on the prognosis of persistent AF patients with heart failure.

Diagnosis and Management of Complex Reentrant Arrhythmias Involving the His-Purkinje System

The His-Purkinje system is a network of bundles and fibres comprised of specialised cells that allow for coordinated, synchronous activation of the ventricles. Although the histology and physiology of the His-Purkinje system have been studied for more than a century, its role in ventricular arrhythmias has recently been discovered with the ongoing elucidation of the mechanisms leading to both benign and life-threatening arrhythmias. Studies of Purkinje-cell electrophysiology show multiple mechanisms responsible for ventricular arrhythmias, including enhanced automaticity, triggered activity and reentry. The variation in functional properties of Purkinje cells in different areas of the His-Purkinje system underlie the propensity for reentry within Purkinje fibres in structurally normal and abnormal hearts. Catheter ablation is an effective therapy in nearly all forms of reentrant arrhythmias involving Purkinje tissue. However, identifying those at risk of developing fascicular arrhythmias is not yet possible. Future research is needed to understand the precise molecular and functional changes resulting in these arrhythmias.

Importance of the Activation Sequence of the His or Right Bundle for Diagnosis of Complex Tachycardia Circuits

In this review, we emphasize the unique value of recording the activation sequence of the His bundle or right bundle branch (RB) for diagnoses of various supraventricular and fascicular tachycardias. A close analysis of the His to RB (H-RB) activation sequence can help differentiate various forms of supraventricular tachycardias, namely atrioventricular nodal reentry tachycardia from concealed nodofascicular tachycardia, a common clinical dilemma. Furthermore, bundle branch reentry tachycardia and fascicular tachycardias often are included in the differential diagnosis of supraventricular tachycardia with aberrancy, and the use of this technique can help the operator make the distinction between supraventricular tachycardias and these other forms of ventricular tachycardias using the His-Purkinje system. We show that this technique is enhanced by the use of multipolar catheters placed to span the proximal His to RB position to record the activation sequence between proximal His potential to the distal RB potential. This allows the operator to fully analyze the activation sequence in sinus rhythm as compared to that during tachycardia and may help target ablation of these arrhythmias. We argue that 3 patterns of H-RB activation are commonly identified—the anterograde H-RB pattern, the retrograde H-RB (right bundle to His bundle) pattern, and the chevron H-RB pattern (simultaneous proximal His and proximal RB activation)—and specific arrhythmias tend to be associated with specific H-RB activation sequences. We show that being able to record and categorize this H-RB relationship can be instrumental to the operator, along with standard pacing maneuvers, to make an arrhythmia diagnosis in complex tachycardia circuits. We highlight the importance of H-RB activation patterns in these complex tachycardias by means of case illustrations from our groups as well as from prior reports.

Regional and Temporal Variation of Ventricular and Conduction Tissue Activity During Ventricular Fibrillation in Canines

Background: Rigorous study of ventricular fibrillation (VF) is not feasible in humans. The spatiotemporal characteristics of prolonged VF remain undefined, limiting our understanding of this lethal rhythm. Methods: VF was mapped in 4 canines. The endocardial and epicardial left ventricle (LV) and right ventricle (RV) were sequentially mapped at 0 to 15, 15 to 30, 30 to 45, and 45 to 60 minutes post-induction. Ten consecutive beats were used to determine average cycle length and regularity index of ventricular and His-Purkinje system signals in discrete regions during each time interval. Results: Average VF time was 58±12 minutes. The shortest ventricular cycle length was present in the RV apical region (70±10 msec) at 0 to 15 minutes and at 15 to 30 minutes (89±31 msec) and LV apical region at 45 to 60 minutes (242±163 msec). The His-Purkinje system cycle length was the shortest at the RV outflow tract (75±3 msec) at 0 to 15 minutes, RV inflow and free wall (89±12 msec) at 15 to 30 minutes, LV apical region (83±14 msec) at 30 to 45 minutes, and inferior and inferolateral LV (145±23 msec) at 45 to 60 minutes. Regularity index was the highest in the RV inflow and free wall (78%) at 0 to 15 minutes, RV apical region (86%) at 15 to 30 minutes, LV septum and epicardial anterior RV (80%) at 30 to 45 minutes, and anterior and anterolateral LV (75%) at 45 to 60 minutes. Conclusions: These data suggest significant regional changes in electrical activity throughout VF in canines. A transition of fastest electrical activity from RV to LV apical regions across VF was observed. Further studies are warranted to confirm the above findings.

Automated Framework for the Inclusion of a His–Purkinje System in Cardiac Digital Twins of Ventricular Electrophysiology

Personalized models of cardiac electrophysiology (EP) that match clinical observation with high fidelity, referred to as cardiac digital twins (CDTs), show promise as a tool for tailoring cardiac precision therapies. Building CDTs of cardiac EP relies on the ability of models to replicate the ventricular activation sequence under a broad range of conditions. Of pivotal importance is the His–Purkinje system (HPS) within the ventricles. Workflows for the generation and incorporation of HPS models are needed for use in cardiac digital twinning pipelines that aim to minimize the misfit between model predictions and clinical data such as the 12 lead electrocardiogram (ECG). We thus develop an automated two stage approach for HPS personalization. A fascicular-based model is first introduced that modulates the endocardial Purkinje network. Only emergent features of sites of earliest activation within the ventricular myocardium and a fast-conducting sub-endocardial layer are accounted for. It is then replaced by a topologically realistic Purkinje-based representation of the HPS. Feasibility of the approach is demonstrated. Equivalence between both HPS model representations is investigated by comparing activation patterns and 12 lead ECGs under both sinus rhythm and right-ventricular apical pacing. Predominant ECG morphology is preserved by both HPS models under sinus conditions, but elucidates differences during pacing.

Comparison of efficacy and safety of His-Purkinje system pacing versus cardiac resynchronisation therapy in patients with pacing-induced cardiomyopathy: protocol for a randomised controlled trial

IntroductionRecent studies have shown that the His-Purkinje system pacing (HPSP) can achieve electrocardiomechanical synchronisation, and thus improve cardiac function. For patients with pacing-induced cardiomyopathy (PICM) who should be treated with pacemaker upgrade, the HPSP is a viable alternative to cardiac resynchronisation therapy (CRT). However, no randomised controlled trial has been performed to evaluate the efficacy and safety of HPSP in patients with PICM. The present study compared the efficacy and safety of HPSP with that of traditional CRT in the treatment of patients with PICM.Methods and analysisThis study is a single-centre, randomised controlled non-inferiority trial. This trial was carried out at the cardiac centre of Beijing Anzhen Hospital. A total of 46 patients with PICM who needed pacemaker upgrade treatment between January 2022 and December 2023 will be enrolled in this study. Patients will be randomised into an investigational group (HPSP) and a control group (CRT) at a 1:1 ratio. The primary outcome is the duration of QRS complex (QRS width), and the secondary outcomes are NT-proBNP (N terminal pro B type natriuretic peptide), C reactive protein, the number of antibiotics used, left ventricular ejection fraction, end systolic volume, end diastolic volume, the hospitalisation duration, the incidence of postoperative infection, pacemaker parameters (threshold, sensing and impedance), the 6-minute walking test, and quality of life (36-Item Short Form Survey scale), all-cause mortality, cardiovascular death, heart failure-related rehospitalisation rate, other rehospitalisation rates, major complication rates and procedure costs.Ethics and disseminationThis study has been approved by the Beijing Anzhen Hospital Medical Ethics Committee (No. 2020043X).Trial registration numberChinese Clinical Trial Registry (ChiCTR2000034265).

A case of infra-nodal Wenckebach conduction block with alternating bundle branch block

Background Atrioventricular (AV) node normally has decremental conduction property and a longer refractory period than His-Purkinje system (HPS). This results in AV conduction delay or block at the level of AV node in response to short-coupled atrial premature beats. Prolonged refractoriness in HPS can produce unusual physiological patterns of AV conduction such as conduction delay or infra-nodal block in the distal elements of HPS. Case presentation We present a case in which atrial premature stimulation produces infra-nodal Wenckebach conduction block which initiates long-short cycle sequence within the bundle branches resulted in alternating bundle branch block and atypical pattern of Ashman phenomenon. Conclusions This case highlights the importance of recognizing the unusual physiological AV conduction patterns of HPS. The long-short cycle sequence in the bundle branches of distal HPS and linking phenomenon can result in alternating bundle branch block without the presence of HPS disease.

In-vivo endocardial and epicardial quantitative comparison of multi-wave based non-invasive inverse electrocardiography

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the Dutch Heart Foundation Introduction Non-invasive mapping of ventricular activation using inverse electrocardiography (iECG) in patients with cardiomyopathy during sinus rhythm, may improve risk stratification for sudden cardiac death. However, iECG is complicated by multiple simultaneous endocardial activation waves (multi-wave) mediated by the His-Purkinje system, especially when the QRS complex is narrow. The activation estimation should be based on a realistic physiological model of the His-Purkinje system combining multiple waves initiated at His-Purkinje associated endocardial locations. Equivalent double layer based iECG provides an estimation of both the endocardial and epicardial surface. To improve accuracy, equivalent double layer based iECG was supplemented with electro-anatomical structures associated with the His-Purkinje system to test initial ventricular activation (Figure, Panel C). Multi-wave iECG local activation timing (LAT) maps and invasive LAT maps during sinus rhythm were quantitatively compared. Purpose Quantitative comparison of multi-wave iECG in His-Purkinje mediated cardiac activation using invasive activation maps in patients. Methods Thirteen patients referred for invasive electro-anatomical mapping (EAM) of the endocardial and epicardial surface were included. Prior to EAM, each subject underwent 64 electrode body surface potential mapping, cardiac computed tomography (CT) imaging, and 3D imaging of electrode positions. Anatomical models of the ventricles, lungs and thorax were created using CT images and supplemented with electrode positions (Figure, Panel A-B). Electro-anatomical structures associated with the His-Purkinje system were incorporated in ventricular anatomical models (Figure, Panel C) and multiple simultaneous activation waves were simulated. Invasive endocardial and epicardial LAT maps were quantitatively compared to iECG LAT maps. Invasive EAM LAT maps were quantitatively compared to estimated iECG LAT maps (Figure, Panel D) using inter-map correlation coefficients (CC, Pearson’s) and absolute differences (AD). Results Mean inter-map CC and AD were 0.54 ± 0.19 and 18 ± 7 ms respectively for the epicardial surface (n = 13). Similar to the RV endocardial surface (n = 10, CC = 0.50 ± 0.29, AD = 20 ± 8 ms) and the LV endocardial surface (n = 4, CC = 0.44 ± 0.26, AD = 25 ± 7 ms). Conclusion(s): Quantitative comparison of the multi-wave iECG method showed overall moderate performance. This novel iECG method provides a physiologically more realistic and more robust estimation of sinus rhythm and may serve as a tool for detection of electro-anatomical substrates and risk stratification. Compared to other available non-invasive ECG methods, multi-wave iECG captures His-Purkinje mediated ventricular activation better. This method might also be useful for the accurate detection and localization of structural conduction disorders. Abstract Figure. Multi-Wave inverse electrocardiography

Simulated heterogeneity in purkinje-ventricular electrophysiology following acute myocardial infarction remodelling

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Wellcome Trust Senior Research Fellowship in Basic Biomedical Sciences Background Coronary heart disease is a common substrate for sudden cardiac death. Several clinical and experimental studies on ischemic heart diseases have highlighted the involvement of the His-Purkinje system in the initiation and maintenance of ventricular arrhythmias. Biophysically-detailed mathematical models and computational multiscale simulations can help in gather insights of the cellular and tissue mechanisms underlying the trigger and maintenance of arrhythmias. Purpose The goal of this study is to evaluate the effects of ionic remodelling on human Purkinje and ventricular cells in the acute stage post myocardial infarction. Methods Two recently published computational models were used to represent the electrophysiology of cardiac Purkinje and ventricular cells, including transmural heterogeneity (endo, mid, epi myocytes). Cardiac ionic remodelling was observed at the border zone of the infarcted region, mostly in canine and porcine models. For both ventricular and Purkinje models, remodelling was implemented as a variation of the number of function channels, i.e., of the current conductance for Na+, Ca2+ and K+ currents. Simulations were performed for both models at different pacing frequencies (cycle length from 400 to 1000 ms) to assess a set of action potential (AP) biomarkers and AP rate-dependence at fast pacing. Early afterdepolarisation (EADs) were induced at slow pacing under hERG block. Results Figure 1 reports the results for the ventricular (A) and Purkinje (B) electrophysiology for the healthy (blue) and post-infarction (red) tissues at 1 Hz (left), at different frequencies (middle) and under 85% hERG block at 0.25 Hz (right). At 1 Hz, ionic remodelling reduced the AP depolarisation rate, abolished the AP notch and led to AP prolongation for both models. Purkinje AP showed also elevated resting membrane potentials and increased diastolic depolarisation. The mid-cardiomyocyte and Purkinje models showed a small increase in the APD- rate dependence slope. Ionic remodelling did not affect significantly the EAD dynamics in the ventricular model, apart from further delaying the AP repolarisation. In the Purkinje model, ionic remodelling led to automaticity and changed the EAD dynamics, which disappeared from the paced AP but occurred after the spontaneous AP. Conclusion In this study we investigated the effects of ionic current remodelling in ventricular and Purkinje cells following acute myocardial infarction. Results showed that remodelling at the border zone increased the heterogeneity between Purkinje and ventricular cells. A further step into the investigation of pro-arrhythmic mechanisms induced by myocardial infarction will be to perform multiscale simulations at whole organ level in 3D anatomical models of human ventricles, including the His-Purkinje system. Abstract Figure 1