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.

The clinical and electrophysiological characteristics of nonsustained repetitive monomorphic ventricular tachycardia from the left His-Purkinje system.

BACKGROUND: Repetitive monomorphic ventricular tachycardia (RMVT) arising from the left His-Purkinje system can occasionally be encountered during clinical practice. We describe eight cases as a unique entity in this study to characterize the clinical and electrophysiological features of the patients. METHODS: Eight patients with frequent palpitation (five men with median age of 28 years) were included in the study from January 2003 to July 2018. Twelve-lead ECG (Electrocardiogram), Holter, and echocardiographic tests were performed after medical history interrogations and physical examinations. Antiarrhythmic drug therapy was essential to all patients, and catheter ablation was attempted if the patients could not tolerate or were not responsive to drug therapy. RESULTS: No patients had a history of syncope and a family history of sudden cardiac death. ECGrecording was characterized by frequent ventricular extrasystoles, ventricular couplets, and salvos of nonsustained VT competitive with sinus rhythm. The QRS morphology of ectopic beats was in the right bundle branch block pattern with severe left axis deviation. The width of the QRS complex from ECG was 135 ms (120-140) during ventricular tachycardia. Verapamil had no effect on all VT individuals. Enlargement of the left ventricle was found in two patients. Four out of six cases were successful with catheter ablation treatment. CONCLUSION: RMVT arising from the left His-Purkinje system is a special arrhythmic and nonverapamil-sensitive entity. The electrophysiological mechanism of this treatment appears to be focal firing, which is amendable to catheter ablation in symptomatic and high-burden patients.

Ablation at Right Coronary Cusp as an Alternative and Favorable Approach to Eliminate Premature Ventricular Complexes Originating From the Proximal Left Anterior Fascicle.

BACKGROUND: Premature ventricular complex (PVC) with narrow QRS duration originating from proximal left anterior fascicle (LAF) is challenging for ablation. This study was performed to evaluate the safety and feasibility of ablation from right coronary cusp (RCC) for proximal LAF-PVC and to investigate this PVC's characteristics. METHODS: Mapping at RCC and left ventricle and ECG analysis were performed in 20 patients with LAF-PVC. RESULTS: The earliest activation site (EAS), with Purkinje potential during both PVC and sinus rhythm, was localized at proximal LAF in 8 patients (proximal group) and at nonproximal LAF in 12 patients (nonproximal group). The Purkinje potential preceding PVC-QRS at the EAS in proximal group (32.6±2.5 ms) was significantly earlier than that in nonproximal group (28.3±4.5 ms, P=0.025). Similar difference in the Purkinje potentials preceding sinus rhythm QRS at the EAS was also observed between proximal and nonproximal groups (35.1±4.7 versus 25.2±5.0 ms, P<0.001). In proximal group, the distance between the EAS to left His bundle and to RCC was shorter than that of nonproximal group (12.3±2.8 versus 19.7±5.0 mm, P=0.002, and 3.9±0.8 versus 15.7±7.8 mm, P<0.001, respectively). No difference in the distance from RCC to proximal LAF was identified between the 2 groups. PVCs were successfully eliminated from RCC for all proximal groups but at left ventricular EAS for nonproximal groups. The radiofrequency application times, ablation time, and procedure time of nonproximal group were longer than that of proximal group. Electrocardiographic analysis showed that, when compared with nonproximal group, the PVCs of proximal group had narrower QRS duration; smaller S wave in leads I, V5, and V6; lower R wave in leads I, aVR, aVL, V1, V2, and V4; and smaller q wave in leads III and aVF. The QRS duration difference (PVC-QRS and sinus rhythm QRS) <15 ms predicted the proximal LAF origin with high sensitivity and specificity. CONCLUSIONS: PVCs originating from proximal LAF, with unique electrocardiographic characteristics, could be eliminated safely from RCC.

Novel Strategy for Predicting Conduction Abnormalities During Transcatheter Closure of Perimembranous Ventricular Septal Defect in Adults.

BACKGROUND: In this study we evaluated the feasibility and efficacy of predicting conduction system abnormalities under 3-dimensional (3D) electroanatomic mapping guidance during transcatheter closure of perimembranous ventricular septal defects (pmVSDs) in adults.Methods and Results:The distribution of the His-Purkinje system (HPS) close to the margins of pmVSDs in the left ventricle was identified using 3D electroanatomic mapping and near-field HPS was further confirmed by different pacing protocols. Of the 20 patients in the study, 17 (85%) were successfully treated by transcatheter intervention. The minimum distance between the margins of the pmVSD and near-field HPS, as measured by 3D electroanatomic mapping, ranged from 1.3 to 3.9 mm (mean [± SD] 2.5±0.7 mm). Five patients with a minimum distance <2 mm had a higher risk (3/5; 60%) for adverse arrhythmic events, whereas patients with a distance >2 mm were at a much lower risk (1/15; 6.7%) of procedure-related conduction block (P=0.032). No other adverse events were recorded during the follow-up period (median 30 months). CONCLUSIONS: A minimum distance between the pmVSD and near-field HPS <2 mm was associated with a relatively high risk of closure-related conduction block. 3D electroanatomic mapping may be helpful in guiding decision making for transcatheter closure and reduce the incidence of adverse arrhythmic events.

Compartmentalized Structure of the Moderator Band Provides a Unique Substrate for Macroreentrant Ventricular Tachycardia.

Background Papillary muscles are an important source of ventricular tachycardia (VT). Yet little is known about the role of the right ventricular (RV) endocavity structure, the moderator band (MB). The aim of this study was to determine the characteristics of the MB that may predispose to arrhythmia substrates. Methods Ventricular wedge preparations with intact MBs were studied from humans (n=2) and sheep (n=15; 40-50 kg). RV endocardium was optically mapped, and electrical recordings were measured along the MB and septum. S1S2 pacing of the RV free wall, MB, or combined S1-RV S2-MB sites were assessed. Human (n=2) and sheep (n=4) MB tissue constituents were assessed histologically. Results The MB structure was remarkably organized as 2 excitable, yet uncoupled compartments of myocardium and Purkinje. In humans, action potential duration heterogeneity between MB and RV myocardium was found (324.6±12.0 versus 364.0±8.4 ms; P<0.0001). S1S2-MB pacing induced unidirectional propagation via MB myocardium, permitting sustained macroreentrant VT. In sheep, the incidence of VT for RV, MB, and S1-RV S2-MB pacing was 1.3%, 5.1%, and 10.3%. Severing the MB led to VT termination, confirming a primary arrhythmic role. Inducible preparations had shorter action potential duration in the MB than RV (259.3±45.2 versus 300.7±38.5 ms; P<0.05), whereas noninducible preparations showed no difference (312.0±30.3 versus 310.0±24.6 ms, respectively). Conclusions The MB presents anatomic and electrical compartmentalization between myocardium and Purkinje fibers, providing a substrate for macroreentry. The vulnerability to sustain VT via this mechanism is dependent on MB structure and action potential duration gradients between the RV free wall and MB.

Ventricular arrhythmias involving the His-Purkinje system in the structurally abnormal heart.

His-Purkinje-related ventricular arrhythmias are a subset of ventricular tachycardias that use the specialized cardiac conduction system. These arrhythmias can occur in various different forms of structural heart disease. Here, we review the basic science discoveries and their analogous clinical observations that implicate the His-Purkinje system as a crucial component of the arrhythmia circuit. While mutations serve the molecular basis for arrhythmias in the heritable cardiomyopathies, transcriptional and posttranslational changes constitute the adverse remodeling leading to arrhythmias in acquired structural heart disease. Additional studies on the electrical properties of the His-Purkinje network and its interactions with the surrounding myocardium will improve the clinical diagnosis and treatment of these arrhythmias.

Localized Structural Alterations Underlying a Subset of Unexplained Sudden Cardiac Death.

BACKGROUND: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported. METHODS: We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations. RESULTS: VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm2) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers (P<0.001). In the 9 patients without structural alteration, we observed a high incidence of Purkinje triggers (7/9 versus 4/15, P=0.033). Catheter ablation resulted in arrhythmia-free outcome in 15/18 patients at 17±11 months follow-up. CONCLUSIONS: This study shows that localized structural alterations underlie a significant subset of previously unexplained sudden cardiac death. In the other subset, Purkinje electrical pathology seems as a dominant mechanism.

Electrophysiological Characteristics of Bundle Branch Reentry Ventricular Tachycardia in Patients Without Structural Heart Disease.

BACKGROUND: The distinct electrophysiological features of bundle branch reentry ventricular tachycardia (VT) in patients without structural heart disease have not been systemically characterized. METHODS: Nine patients (mean age, 29.6 years) with normal left ventricular function were enrolled. Bundle branch reentry VT with right and left bundle branch block (BBB) patterns was induced in 1 and 9 patients, respectively. The right bundle was attempted to record by a 6F decapolar or quadripolar catheter. Electroanatomic mapping of the left ventricle was performed in 6 patients. In all left BBB pattern VT, the mean VT cycle length was 329.3±89.1 ms, and the median HV interval during tachycardia was longer than that of baseline (78 [73-100] versus 71 [64.5-88] ms; P=0.11). RESULTS: The H-RB interval during VT was slightly shorter (P=0.14); however, the median RB-V interval was markedly longer than that during sinus rhythm (50 [29.5-83] versus 30 [8-51] ms; P=0.043]. In 6 patients with 3-dimensional mapping of the left ventricle, a slow anterograde or retrograde conduction over left HIS-Purkinje system with normal myocardial voltage was identified. In addition, Purkinje-related VTs (1.0±1.3 types) were also induced in 5 patients. Ablation was applied in distal left BB in patients with baseline left BBB and in one narrow QRS patient with sustained Purkinje-related VT, whereas right BB was targeted in other patients. During a mean follow-up of 31.4 months, frequent premature ventricular contractions occurred in one patient, and new VT developed in the other patient. CONCLUSIONS: Bundle branch reentry VT can occur in young patients with extensive conduction disturbances within HIS-Purkinje system. Ablation targeting at the distal left BB which bifurcates into left posterior and anterior fascicle can preserve the residual atrioventricular conduction, but intensive follow-up is needed.

Clinical, electrocardiographic, and electrophysiological characteristics of left upper septal fascicular ventricular tachycardia.

Aims: We sought to investigate the clinical, electrocardiographic, and electrophysiological characteristics of left upper septal fascicular ventricular tachycardia (LUS-VT). Methods and results: Eleven consecutive patients with LUS-VT were identified among 196 patients with left fascicular ventricular tachycardia (VT). Clinical VTs presented as paroxysmal in 8 patients and incessant in 3 patients. Six patients had previous left posterior fascicular VT ablation history. All VTs had narrow QRS complexes with QRS duration of 101.1 ± 9.2 ms. The frontal QRS axis was normal or right deviation. Precordial morphology was either right bundle branch block type or similar to that of sinus rhythm. A retrograde His with H-V interval of 21.9 ± 7.2 ms was recorded during VT. The earliest Purkinje potential (PP) to QRS interval during VT averaged 35.7 ± 4.5 ms. Clear diastolic potentials (DPs) with high frequency and low amplitude were found in only one patient. Ten patients were managed successfully by 11 ablation sessions, and 1 patient declined ablation. Successful targets at the left upper septum were sites with the earliest PP (9 cases) or with DP (1 case) during VT. After ablation, 2 cases (10%) developed new left anterior hemiblock or incomplete left bundle branch block. No VT recurred during a median follow-up period of 3.2 (range 1.0-12.7) years. Conclusion: LUS-VT presented as narrow QRS complex tachycardia. Some LUS-VTs occurred after ablation targeting left posterior fascicular VT. The VTs can be managed successfully by focal ablation at the left upper septum with a mild risk of fascicular injury.

Human His-Purkinje System: Abnormalities of Conduction, Rhythm Disorders and Case Studies.

This review covers many of the arrhythmias and conduction abnormalities related to His-Purkinje System. These include junctional premature complexes, junctional and fascicular tachycardias, bundle branch reentry (BBR), and the role of apparent conduction in various forms of supraventricular tachycardias (SVT) with or without involvement of accessory pathways (AP).

Non-Reentrant Fascicular Tachycardia: Clinical and Electrophysiological Characteristics of a Distinct Type of Idiopathic Ventricular Tachycardia.

BACKGROUND: The most common form of idiopathic Purkinje-related ventricular tachycardia (VT) is the reentrant type. We describe the clinical and electrophysiological characteristics of focal non-reentrant fascicular tachycardia. METHODS AND RESULTS: Among 530 idiopathic VT patients who were referred for ablation, we identified 15 (2.8%) with non-reentrant fascicular tachycardia (11 men, 45±21 years). Sinus rhythm ECG showed normal conduction intervals with a His-ventricular interval of 41±4 ms. All patients had monomorphic VT (cycle length: 337±88 ms) with a relatively narrow QRS (123±12 ms), and they did not respond to verapamil during the initial presentation. VT exhibited right bundle-branch block/superior axis configuration in 11 patients (73%) and inferior axis in 3 (20%). In 1 patient (7%), VT exhibited left bundle-branch block/superior axis configuration. During ablation, spontaneous VT occurred in 3 patients (20%) and nonentraintable VT or identical premature ventricular complex was induced in 9 (60%). A high-frequency presystolic Purkinje potential was recorded during VT/premature ventricular complex, preceding the QRS by 25±16 ms. VT recurrence was observed in 4 patients (27%), and among them, 3 underwent pacemap-guided ablation during the first session. A second ablation with activation mapping guidance eliminated the VT during the 88±8-month follow-up. CONCLUSIONS: Among idiopathic VT cases referred for ablation, 2.8% were focal non-reentrant fascicular tachycardia, which had distinct clinical characteristics and usually originated from the left posterior fascicle, and less commonly from the left anterior fascicle and right ventricular Purkinje network. Catheter ablation is effective, whereas pacemap-guided approach is less efficacious.

Cardiac Purkinje fibers and arrhythmias; The GK Moe Award Lecture 2015.

Purkinje fibers/cells continue to be a focus of arrhythmologists. Here we review several new ideas that have emerged in the literature and fold them into important new points. These points include the following: some proteins in Purkinje cells are specific to Purkinjes; pacemaker function in Purkinje may be similar to that of the sinus node cell; sink-source concerns about tracts/sheets of Purkinje fibers; role of Ito in arrhythmias; and genetic lesions in Purkinjes and their high impact on cardiac rhythm. Although new ideas about the remodeled Purkinje cell are not the focus of this review, one can easily imagine how Purkinjes and their function may be altered in diseased hearts.

Mapping and ablating ventricular premature contractions that trigger ventricular fibrillation: trigger elimination and substrate modification.

Ventricular fibrillation (VF) is a malignant arrhythmia, usually initiated by a ventricular premature contraction (VPC) during the vulnerable period of cardiac repolarization. Ablation therapy for VF has been described and increasingly reported. Targets for VF triggers are VPC preceded Purkinje potentials or the right ventricular outflow tract (RVOT) in structurally normal hearts, and VPC triggers preceded by Purkinje potentials in ischemic cardiomyopathy. The most important issue before the ablation session is the recording of the 12-lead electrocardiogram (ECG) of the triggering event, which can prove invaluable in regionalizing the origin of the triggering VPC for more detailed mapping. In cases where the VPC is not spontaneous or inducible, ablation may be performed by pacemapping. During the session, mapping should be focused on the earliest activation and determining the earliest potential is the key to a successful ablation. However, a modification of the Purkinje network might be applied when the earliest site cannot be determined or is located close to the His-bundle. Furthermore, the electrical isolation of the pulmonary artery (PA) can suppress RVOT type polymorphic ventricular tachycardia in some patients with rapid triggers from the PA. Suppression of VF can be achieved by not only the elimination of triggering VPCs, but also by substrate modification of possible reentry circuits in the Purkinje network, or between the PA and RVOT. Further studies are needed to evaluate the precise mechanisms of this arrhythmia.

Focal Purkinje ventricular tachycardia ablation in structurally normal heart.

A 21-year-old man presented with recurrent palpitations and giddiness. Clinical examination, echocardiography, and magnetic resonance imaging revealed a structurally normal heart. Electrocardiography showed broad-complex tachycardia with 250 beats per minute, which required cardioversion. An electrophysiological study could not induce tachycardia by programmed electrical stimulation. On isoprenaline infusion, frequent ventricular ectopics, bigeminy, nonsustained ventricular tachycardia, and broad-complex tachycardia similar to clinical tachycardia were readily inducible. This was considered to be ventricular tachycardia due to enhanced automaticity. Using 3-dimensional electroanatomical mapping, successful ablation was undertaken. The patient was asymptomatic on follow-up after 12 and 18 months.