Subject(s)
Atrial Fibrillation , Electrocardiography , Purkinje Fibers , Humans , Atrial Fibrillation/physiopathology , Purkinje Fibers/physiopathology , Male , Middle Aged , Aged , FemaleABSTRACT
BACKGROUND: Left bundle branch block (LBBB) represents a frequently encountered conduction system disorder. Despite its widespread occurrence, a continual dilemma persists regarding its intricate association with underlying cardiomyopathy and its pivotal role in the initiation of dilated cardiomyopathy. The pathologic alterations linked to LBBB-induced cardiomyopathy (LBBB-CM) have remained elusive. OBJECTIVE: This study sought to investigate the chronologic dynamics of LBBB to left ventricular dysfunction and the pathologic mechanism of LBBB-CM. METHODS: LBBB model was established through main left bundle branch trunk ablation in 14 canines. All LBBB dogs underwent transesophageal echocardiography and electrocardiography before ablation and at 1 month, 3 months, 6 months, and 12 months after LBBB induction. Single-photon emission computed tomography imaging was performed at 12 months. We then harvested the heart from all LBBB dogs and 14 healthy adult dogs as normal controls for anatomic observation, Purkinje fiber staining, histologic staining, and connexin43 protein expression quantitation. RESULTS: LBBB induction caused significant fibrotic changes in the endocardium and mid-myocardium. Purkinje fibers exhibited fatty degeneration, vacuolization, and fibrosis along with downregulated connexin43 protein expression. During a 12-month follow-up, left ventricular dysfunction progressively worsened, peaking at the end of the observation period. The association between myocardial dysfunction, hypoperfusion, and fibrosis was observed in the LBBB-afflicted canines. CONCLUSION: LBBB may lead to profound myocardial injury beyond its conduction impairment effects. The temporal progression of left ventricular dysfunction and the pathologic alterations observed shed light on the complex relationship between LBBB and cardiomyopathy. These findings offer insights into potential mechanisms and clinical implications of LBBB-CM.
Subject(s)
Bundle-Branch Block , Disease Models, Animal , Electrocardiography , Dogs , Animals , Bundle-Branch Block/physiopathology , Bundle-Branch Block/etiology , Heart Conduction System/physiopathology , Tomography, Emission-Computed, Single-Photon/methods , Purkinje Fibers/physiopathology , Myocardium/pathology , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/etiologyABSTRACT
We report the case of a 36-year-old woman who presented to the emergency department complaining of palpitations and asthenia. Investigations showed frequent ventricular ectopy and severe left ventricular ejection fraction impairment. She was diagnosed with a peculiar condition defined multifocal ectopic premature Purkinje-related contractions syndrome, which in some cases can be associated with a dilated cardiomyopathy phenotype. Genetic testing showed a novel mutation in the SCN5A gene (c.673C > G). In the context of acute left ventricular dysfunction in a young patient, we discuss the clinical presentation of this rare condition and its clinical management, as well as its genetic substrate.
Subject(s)
Mutation , NAV1.5 Voltage-Gated Sodium Channel , Humans , Female , Adult , NAV1.5 Voltage-Gated Sodium Channel/genetics , Ventricular Premature Complexes/genetics , Ventricular Premature Complexes/physiopathology , Ventricular Premature Complexes/diagnosis , Electrocardiography , DNA/genetics , Purkinje Fibers/physiopathology , DNA Mutational Analysis , PhenotypeABSTRACT
BACKGROUND: Three-dimensional (3D) mapping of the ventricular conduction system is challenging. OBJECTIVE: The purpose of this study was to use ripple mapping to distinguish conduction system activation to that of adjacent myocardium in order to characterize the conduction system in the postinfarct left ventricle (LV). METHODS: High-density mapping (PentaRay, CARTO) was performed during normal rhythm in patients undergoing ventricular tachycardia ablation. Ripple maps were viewed from the end of the P wave to QRS onset in 1-ms increments. Clusters of >3 ripple bars were interrogated for the presence of Purkinje potentials, which were tagged on the 3D geometry. Repeating this process allowed conduction system delineation. RESULTS: Maps were reviewed in 24 patients (mean 3112 ± 613 points). There were 150.9 ± 24.5 Purkinje potentials per map, at the left posterior fascicle (LPF) in 22 patients (92%) and at the left anterior fascicle (LAF) in 15 patients (63%). The LAF was shorter (41.4 vs 68.8 mm; P = .0005) and activated for a shorter duration (40.6 vs 64.9 ms; P = .002) than the LPF. Fourteen of 24 patients had left bundle branch block (LBBB), with 11 of 14 (78%) having Purkinje potential-associated breakout. There were fewer breakouts from the conduction system during LBBB (1.8 vs 3.4; 1.6 ± 0.6; P = .039) and an inverse correlation between breakout sites and QRS duration (P = .0035). CONCLUSION: We applied ripple mapping to present a detailed electroanatomic characterization of the conduction system in the postinfarct LV. Patients with broader QRS had fewer LV breakout sites from the conduction system. However, there was 3D mapping evidence of LV breakout from an intact conduction system in the majority of patients with LBBB.
Subject(s)
Catheter Ablation , Heart Conduction System , Heart Ventricles , Myocardial Infarction , Tachycardia, Ventricular , Humans , Male , Female , Heart Conduction System/physiopathology , Middle Aged , Heart Ventricles/physiopathology , Heart Ventricles/diagnostic imaging , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Catheter Ablation/methods , Myocardial Infarction/physiopathology , Myocardial Infarction/complications , Electrocardiography , Purkinje Fibers/physiopathology , Aged , Imaging, Three-Dimensional , Body Surface Potential Mapping/methodsABSTRACT
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.
Subject(s)
Electrophysiologic Techniques, Cardiac , Heart Conduction System/physiopathology , Models, Cardiovascular , Precision Medicine , Algorithms , Bundle of His/physiopathology , Electrocardiography , Humans , Magnetic Resonance Imaging , Purkinje Fibers/physiopathologyABSTRACT
BACKGROUND: Purkinje ectopics (PurkEs) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity. OBJECTIVE: The purpose of this study was to examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF. METHODS: Consecutive patients with PurkE-initiated idiopathic VF from 4 arrhythmia referral centers were included. We evaluated demographic characteristics, medical history, clinical circumstances associated with index VF events, and electrophysiological characteristics of PurkEs. An electrophysiology study was performed in most patients to confirm the Purkinje origin. RESULTS: Eighty-three patients were included (mean age 38 ± 14 years; 44 [53%] women), of whom 32 had a history of syncope. Forty-four patients had VF at rest. PurkEs originated from the right ventricle (RV) in 41 patients (49%), from the left ventricle (LV) in 36 (44%), and from both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. The clinical characteristics of patients with RV vs LV PurkE origins were similar, except for sex. RV PurkEs were more frequent in men than in women (76% vs 24%), whereas LV and biventricular PurkEs were more frequent in women (81% vs 19% and 83% vs 17%, respectively) (P < .0001). CONCLUSION: PurkEs triggering idiopathic VF originate dominantly from the RV in men and from the LV or both ventricles in women, adding to other sex-related arrhythmias such as Brugada syndrome or long QT syndrome. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation.
Subject(s)
Electrocardiography , Heart Ventricles/physiopathology , Purkinje Fibers/physiopathology , Risk Assessment/methods , Ventricular Fibrillation/epidemiology , Ventricular Premature Complexes/epidemiology , Adult , Coronary Angiography , Echocardiography , Female , France/epidemiology , Heart Ventricles/diagnostic imaging , Humans , Incidence , Magnetic Resonance Imaging, Cine/methods , Male , Purkinje Fibers/diagnostic imaging , Retrospective Studies , Risk Factors , Sex Distribution , Sex Factors , Ventricular Fibrillation/diagnosis , Ventricular Fibrillation/etiology , Ventricular Premature Complexes/complications , Ventricular Premature Complexes/diagnosisABSTRACT
The cardiac conduction system is a network of heterogeneous cell population that initiates and propagates electric excitations in the myocardium. Purkinje fibers, a network of specialized myocardial cells, comprise the distal end of the conduction system in the ventricles. The developmental origins of Purkinje fibers and their roles during cardiac physiology and arrhythmia have been reported. However, it is not clear if they play a role during ischemic injury and heart regeneration. Here we introduce a novel tamoxifen-inducible Cre allele that specifically labels a broad range of components in the cardiac conduction system while excludes other cardiac cell types and vital organs. Using this new allele, we investigated the cellular and molecular response of Purkinje fibers to myocardial injury. In a neonatal mouse myocardial infarction model, we observed significant increase in Purkinje cell number in regenerating myocardium. RNA-Seq analysis using laser-captured Purkinje fibers showed a unique transcriptomic response to myocardial infarction. Our finds suggest a novel role of cardiac Purkinje fibers in heart injury.
Subject(s)
Heart Conduction System/physiology , Integrases/genetics , Myocardial Infarction/physiopathology , Purkinje Fibers/physiology , Alleles , Animals , Animals, Newborn , Cell Lineage , Heart Conduction System/physiopathology , Heart Ventricles/pathology , Mice , Mice, Transgenic , Myocardial Infarction/pathology , Myocardium/pathology , Myocytes, Cardiac/physiology , Purkinje Fibers/physiopathology , RNA-Seq , Regeneration , Tamoxifen/pharmacology , Transcriptome , Ventricular FunctionABSTRACT
BACKGROUND: The underlying mechanism of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) has been postulated to be reentrant activation in the Purkinje fiber network of the left posterior fascicle or the left anterior fascicle (LAF). However, changing of cardiac axis deviation in sinus rhythm (SR) or during ILVT after radiofrequency catheter ablation (RFCA) has been rarely analyzed. METHODS: Of the 232 patients with sustained ILVT induced and surface electrocardiogram (ECG) in SR recorded before and after RFCA, the changes of ECG morphology in SR and during ILVT were analyzed. RESULTS: The surface ECG in SR changed in 114 (49.1%) patients after RFCA. ILVT could still be induced in 27 (23.7%) patients. In comparison with the original ILVT, three forms of ECG morphology were observed. In eight patients, the ILVT morphology was unchanged. In the 13 patients with ILVT axis deviation conversion after ablation, the successful target was more proximal. In the six patients with ILVT morphology change but without axis deviation conversion after ablation, the successful ablation site was more distal. Among 15 patients with recurrent ILVT during follow-up, seven patients had previous axis deviation changes in SR after RFCA, the changes maintained in four patients and recovered in three patients. CONCLUSIONS: The morphology changes on surface ECG in SR after RFCA would not be a necessary prerequisite or a good endpoint for ILVT ablation. To analyze ILVT morphology changes after ablation would help to further clarify an appropriate approach for catheter ablation of ILVT.
Subject(s)
Catheter Ablation , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/surgery , Adolescent , Adult , Aged , Anti-Arrhythmia Agents/pharmacology , Child , Child, Preschool , Electrocardiography , Female , Humans , Male , Middle Aged , Purkinje Fibers/physiopathology , Tachycardia, Ventricular/drug therapy , Verapamil/pharmacologyABSTRACT
His-Purkinje conduction system pacing (HPCSP) in the form of His bundle pacing (HBP) and left bundle branch pacing (LBBP) allows normal left ventricular activation, thereby preventing the adverse consequences of right ventricular pacing. HBP has been established for several years with centers from China, Europe, and North America reporting their experience. There is international guidance as to how to implant such systems with the differing patterns of His bundle capture clearly described. LBBP is a more recent innovation with potential advantages including improved pacing parameters. HPCSP has been extensively studied in a variety of indications including cardiac resynchronization therapy, atrioventricular node ablation, and bradycardia pacing. This review will focus on the clinical outcomes of HPCSP including mortality and morbidity of heart failure hospitalization and symptoms.
Subject(s)
Bradycardia/therapy , Bundle of His/physiopathology , Bundle-Branch Block/therapy , Cardiac Conduction System Disease/therapy , Cardiac Pacing, Artificial , Bradycardia/physiopathology , Bundle-Branch Block/physiopathology , Cardiac Conduction System Disease/physiopathology , Cardiac Resynchronization Therapy , Heart Conduction System/physiopathology , Humans , Purkinje Fibers/physiopathologyABSTRACT
BACKGROUND: Calmodulin mutations are associated with arrhythmia syndromes in humans. Exome sequencing previously identified a de novo mutation in CALM1 resulting in a p.N98S substitution in a patient with sinus bradycardia and stress-induced bidirectional ventricular ectopy. The objectives of the present study were to determine if mice carrying the N98S mutation knocked into Calm1 replicate the human arrhythmia phenotype and to examine arrhythmia mechanisms. METHODS: Mouse lines heterozygous for the Calm1N98S allele (Calm1N98S/+) were generated using CRISPR/Cas9 technology. Adult mutant mice and their wildtype littermates (Calm1+/+) underwent electrocardiographic monitoring. Ventricular de- and repolarization was assessed in isolated hearts using optical voltage mapping. Action potentials and whole-cell currents and [Ca2+]i, as well, were measured in single ventricular myocytes using the patch-clamp technique and fluorescence microscopy, respectively. The microelectrode technique was used for in situ membrane voltage monitoring of ventricular conduction fibers. RESULTS: Two biologically independent knock-in mouse lines heterozygous for the Calm1N98S allele were generated. Calm1N98S/+ mice of either sex and line exhibited sinus bradycardia, QTc interval prolongation, and catecholaminergic bidirectional ventricular tachycardia. Male mutant mice also showed QRS widening. Pharmacological blockade and activation of ß-adrenergic receptors rescued and exacerbated, respectively, the long-QT phenotype of Calm1N98S/+ mice. Optical and electric assessment of membrane potential in isolated hearts and single left ventricular myocytes, respectively, revealed ß-adrenergically induced delay of repolarization. ß-Adrenergic stimulation increased peak density, slowed inactivation, and left-shifted the activation curve of ICa.L significantly more in Calm1N98S/+ versus Calm1+/+ ventricular myocytes, increasing late ICa.L in the former. Rapidly paced Calm1N98S/+ ventricular myocytes showed increased propensity to delayed afterdepolarization-induced triggered activity, whereas in situ His-Purkinje fibers exhibited increased susceptibility for pause-dependent early afterdepolarizations. Epicardial mapping of Calm1N98S/+ hearts showed that both reentry and focal mechanisms contribute to arrhythmogenesis. CONCLUSIONS: Heterozygosity for the Calm1N98S mutation is causative of an arrhythmia syndrome characterized by sinus bradycardia, QRS widening, adrenergically mediated QTc interval prolongation, and bidirectional ventricular tachycardia. ß-Adrenergically induced ICa.L dysregulation contributes to the long-QT phenotype. Pause-dependent early afterdepolarizations and tachycardia-induced delayed afterdepolarizations originating in the His-Purkinje network and ventricular myocytes, respectively, constitute potential sources of arrhythmia in Calm1N98S/+ hearts.
Subject(s)
Calmodulin , Heart Ventricles/metabolism , Mutation, Missense , Myocytes, Cardiac/metabolism , Purkinje Fibers/metabolism , Sick Sinus Syndrome/congenital , Amino Acid Substitution , Animals , Calmodulin/genetics , Calmodulin/metabolism , Disease Models, Animal , Heart Ventricles/physiopathology , Humans , Male , Mice , Mice, Transgenic , Purkinje Fibers/physiopathology , Sick Sinus Syndrome/genetics , Sick Sinus Syndrome/metabolism , Sick Sinus Syndrome/physiopathologyABSTRACT
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.
Subject(s)
Electrophysiologic Techniques, Cardiac , Purkinje Fibers/physiopathology , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/therapy , Adolescent , Adult , Anti-Arrhythmia Agents/therapeutic use , Catheter Ablation , Child , Echocardiography , Electrocardiography , Female , Humans , Male , Middle AgedABSTRACT
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.
Subject(s)
Action Potentials , Catheter Ablation , Heart Atria/surgery , Heart Rate , Ventricular Premature Complexes/surgery , Adult , Bundle of His/physiopathology , Catheter Ablation/adverse effects , Electrocardiography , Electrophysiologic Techniques, Cardiac , Feasibility Studies , Female , Heart Atria/physiopathology , Humans , Male , Middle Aged , Prospective Studies , Purkinje Fibers/physiopathology , Time Factors , Treatment Outcome , Ventricular Premature Complexes/diagnosis , Ventricular Premature Complexes/physiopathologyABSTRACT
Cardiac Purkinje cells (PCs) are implicated in lethal arrhythmias caused by cardiac diseases, mutations, and drug action. However, the pro-arrhythmic mechanisms in PCs are not entirely understood, particularly in humans, as most investigations are conducted in animals. The aims of this study are to present a novel human PCs electrophysiology biophysically-detailed computational model, and to disentangle ionic mechanisms of human Purkinje-related electrophysiology, pacemaker activity and arrhythmogenicity. The new Trovato2020 model incorporates detailed Purkinje-specific ionic currents and Ca2+ handling, and was developed, calibrated and validated using human experimental data acquired at multiple frequencies, both in control conditions and following drug application. Multiscale investigations were performed in a Purkinje cell, in fibre and using an experimentally-calibrated population of PCs to evaluate biological variability. Simulations demonstrate the human Purkinje Trovato2020 model is the first one to yield: (i) all key AP features consistent with human Purkinje recordings; (ii) Automaticity with funny current up-regulation (iii) EADs at slow pacing and with 85% hERG block; (iv) DADs following fast pacing; (v) conduction velocity of 160 cm/s in a Purkinje fibre, as reported in human. The human in silico PCs population highlights that: (1) EADs are caused by ICaL reactivation in PCs with large inward currents; (2) DADs and triggered APs occur in PCs experiencing Ca2+ accumulation, at fast pacing, caused by large L-type calcium current and small Na+/Ca2+ exchanger. The novel human Purkinje model unlocks further investigations into the role of cardiac Purkinje in ventricular arrhythmias through computer modeling and multiscale simulations.
Subject(s)
Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Biomarkers , Disease Susceptibility , Models, Biological , Purkinje Fibers/metabolism , Purkinje Fibers/physiopathology , Action Potentials , Arrhythmias, Cardiac/metabolism , Calcium/metabolism , Calcium Signaling , Electrophysiological Phenomena , Humans , Reproducibility of Results , Sodium/metabolismABSTRACT
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.MethodsâandâResults: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.
Subject(s)
Action Potentials , Arrhythmias, Cardiac/diagnosis , Bundle of His/physiopathology , Cardiac Catheterization/adverse effects , Electrophysiologic Techniques, Cardiac , Heart Rate , Heart Septal Defects, Ventricular/surgery , Purkinje Fibers/physiopathology , Adolescent , Adult , Arrhythmias, Cardiac/physiopathology , Cardiac Catheterization/instrumentation , Feasibility Studies , Female , Heart Septal Defects, Ventricular/diagnostic imaging , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Septal Occluder Device , Time Factors , Treatment Outcome , Young AdultABSTRACT
AIMS: His-Purkinje system pacing has been demonstrated as a synchronized ventricular pacing strategy via pacing His-Purkinje system directly, which can decrease the incidence of adverse cardiac structure alteration compared with right ventricular pacing (RVP). The purpose of this meta-analysis was to compare the effects of His-Purkinje system pacing and RVP in patients with bradycardia and cardiac conduction dysfunction. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from the establishment of databases up to 15 December 2019. Studies on long-term clinical outcomes of His-Purkinje system pacing and RVP were included. Chronic paced QRS duration, chronic pacing threshold, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), all-cause mortality, and heart failure hospitalization were collected for meta-analysis. RESULTS: A total of 13 studies comprising 2348 patients were included in this meta-analysis. Compared with RVP group, patients receiving His-Purkinje system pacing showed improvement of LVEF (mean difference [MD], 5.65; 95% confidence interval [CI], 4.38-6.92), shorter chronic paced QRS duration (MD, - 39.29; 95% CI, - 41.90 to - 36.68), higher pacing threshold (MD, 0.8; 95% CI, 0.71-0.89) and lower risk of heart failure hospitalization (odds ratio [OR], 0.65; 95% CI, 0.44-0.96) during the follow-up. However, no statistical difference existed in LVEDV, LVESV and all-cause mortality between the two groups. CONCLUSION: Our meta-analysis suggests that His-bundle pacing is more suitable for the treatment of patients with bradycardia and cardiac conduction dysfunction.
Subject(s)
Bradycardia/therapy , Bundle of His/physiopathology , Cardiac Conduction System Disease/therapy , Cardiac Pacing, Artificial , Heart Rate , Purkinje Fibers/physiopathology , Action Potentials , Aged , Bradycardia/diagnosis , Bradycardia/mortality , Bradycardia/physiopathology , Cardiac Conduction System Disease/diagnosis , Cardiac Conduction System Disease/mortality , Cardiac Conduction System Disease/physiopathology , Cardiac Pacing, Artificial/adverse effects , Cardiac Pacing, Artificial/mortality , Female , Humans , Male , Middle Aged , Risk Assessment , Risk Factors , Time Factors , Ventricular Function, Left , Ventricular Function, RightSubject(s)
Fever/complications , Syncope/etiology , Ventricular Fibrillation/etiology , Ventricular Premature Complexes/complications , Amiodarone/therapeutic use , Coronary Angiography , Drug Therapy, Combination , Electric Countershock , Electrocardiography , Female , Humans , Lidocaine/therapeutic use , Middle Aged , Pharyngitis/complications , Purkinje Fibers/physiopathology , Recurrence , Streptococcal Infections/complications , Tonsillitis/complications , Torsades de Pointes/etiology , Torsades de Pointes/physiopathology , Torsades de Pointes/therapy , Ventricular Fibrillation/drug therapy , Ventricular Fibrillation/physiopathology , Ventricular Fibrillation/therapy , Ventricular Premature Complexes/physiopathologyABSTRACT
OBJECTIVES: This study sought to evaluate the prevalence, mapping features, and ablation outcomes of non-scar-related ventricular tachycardia (NonScar-VT) and Purkinje-related VT (Purkinje-VT) in patients with structural heart disease. BACKGROUND: VT in structural heart disease is typically associated with scar-related myocardial re-entry. NonScar-VTs arising from areas of normal myocardium or Purkinje-VTs originating from the conduction system are less common. METHODS: We retrospectively analyzed 690 patients with structural heart disease who underwent VT ablation between 2013 and 2017. RESULTS: A total of 37 (5.4%) patients (16 [43%] with ischemic cardiomyopathy, 16 [43%] with nonischemic dilated cardiomyopathy, and 5 [14%] others) demonstrated NonScar/Purkinje-VTs, which represented the clinical VT in 76% of cases. Among the 37 VTs, 31 (84%) were Purkinje-VTs (28 bundle branch re-entrant VT). The remaining 6 (16%) VTs were NonScar-VTs and included 4 idiopathic outflow tract VTs. A total of 16 patients had prior history of VT ablations: empirical scar substrate modification was performed in 6 (38%) patients and residual inducibility of VT had not been assessed in 7 (44%). In all 37 patients, the NonScar/Purkinje-VT was successfully ablated. After a median follow-up of 18 months, the targeted NonScar/Purkinje-VT did not recur in any patients, and 28 (76%) of patients were free from any recurrent VT episodes. CONCLUSIONS: NonScar/Purkinje-VTs can be identified in 5.4% of patients undergoing VT ablation in the setting of structural heart disease. Careful effort to induce, characterize, and map these VTs is important because substrate-based ablation strategies would fail to eliminate these types of VT.
Subject(s)
Cardiomyopathies/complications , Catheter Ablation , Tachycardia, Ventricular , Aged , Cicatrix/physiopathology , Female , Humans , Male , Middle Aged , Prevalence , Purkinje Fibers/physiopathology , Retrospective Studies , Tachycardia, Ventricular/classification , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/epidemiology , Tachycardia, Ventricular/surgeryABSTRACT
Recently, four SCN5A mutations have been associated with Multifocal Ectopic Purkinje-related Premature Contractions (MEPPC), a rare cardiac syndrome combining polymorphic ventricular arrhythmia with dilated cardiomyopathy (DCM). Here, we identified a novel heterozygous mutation in SCN5A (c.611C>A, pAla204Glu) in a young woman presenting with polymorphic premature ventricular contractions (PVCs) and DCM. After failure of antiarrhythmic drugs and an attempt of radiofrequency catheter ablation showing three exit-sites of PVCs, all with presystolic Purkinje potentials, a treatment by hydroquinidine was tried, leading to an immediate and spectacular disappearance of all PVCs and normalization of cardiac function. Electrophysiological studies showed that Nav 1.5-A204E mutant channels exhibited a significant leftward shift of 8 mV of the activation curve, leading to a larger hyperpolarized window current when compared to wild-type. Action potential modeling using Purkinje fiber and ventricular cell models predicted an arrhythmogenic effect predominant in Purkinje fibers for the A204E mutation. Comparison with other MEPPC-associated Nav 1.5 mutations revealed a common electrophysiological pattern of abnormal voltage-dependence of activation leading to a larger hyperpolarized window current as a shared biophysical mechanism of this syndrome. These features of the mutant sodium channels are likely to be responsible for the hyperexcitability of the fascicular-Purkinje system observed in patients with MEPPC.