Purkinje Network Research Articles

Anatomical and molecular mapping of the left and right ventricular His–Purkinje conduction networks

Functioning of the cardiac conduction system depends critically on its structure and its complement of ion channels. Therefore, the aim of this study was to document both the structure and ion channel expression of the left and right ventricular His–Purkinje networks, as we have previously done for the sinoatrial and atrioventricular nodes. A three-dimensional (3D) anatomical computer model of the His–Purkinje network of the rabbit heart was constructed after staining the network by immunoenzyme labelling of a marker protein, middle neurofilament. The bundle of His is a ribbon-like structure and the architecture of the His–Purkinje network differs between the left and right ventricles. The 3D model is able to explain the breakthrough points of the action potential on the ventricular epicardium during sinus rhythm. Using quantitative PCR, the expression levels of the major ion channels were measured in the free running left and right Purkinje fibres of the rabbit heart. Expression of ion channels differs from that of the working myocardium and can explain the specialised electrical activity of the Purkinje fibres as suggested by computer simulations; the expression profile of the left Purkinje fibres is more specialised than that of the right Purkinje fibres. The structure and ion channel expression of the Purkinje fibres are highly specialised and tailored to the functioning of the system. The His–Purkinje network in the left ventricle is more developed than that in the right ventricle and this may explain its greater clinical importance.

Purkinje‐related Arrhythmias Part II: Polymorphic Ventricular Tachycardia and Ventricular Fibrillation

There has been growing evidence that the Purkinje network plays a pivotal role in both the initiation and perpetuation of ventricular fibrillation (VF). A triggering ventricular premature beat (VPB) with a short-coupling interval could arise from either the right or left Purkinje system in patients with polymorphic ventricular tachycardia (VT) or VF, and that can be suppressed by the catheter ablation of the trigger. A focal breakdown in the "gating mechanism" at the Purkinje system resulting in a short-circuiting of the transmission across the gate at the distal Purkinje network might predispose to reentrant circuits of polymorphic VT/VF. Many investigators also reported the successful ablation of Purkinje-related VF with an acute or remote myocardial infarction. The same approach with good short-term results has been reported in a small number of patients with other heart diseases (i.e., amyloidosis, chronic myocarditis, nonischemic cardiomyopathy). Catheter ablation of the triggering VPBs from the Purkinje system can be used as an electrical bailout therapy in patients with VF storm.

The Cardiac Conduction System

The human heart beats 2.5 billion times during a normal lifespan, a feat accomplished by cells of the cardiac conduction system (CCS). The functional components of the CCS can be broadly divided into the impulse-generating nodes and the impulse-propagating His-Purkinje system. Human diseases of the conduction system have been identified that alter impulse generation, impulse propagation, or both. CCS dysfunction is primarily due to acquired conditions such as myocardial ischemia/infarct, age-related degeneration, procedural complications, and drug toxicity. Inherited forms of CCS disease are rare, but each new mutation provides invaluable insight into the molecular mechanisms governing CCS development and function. Applying a multidisciplinary approach, which includes human genetic screening, biophysical analysis, and transgenic mouse technology, has yielded a broad array of gene families involved in maintaining normal CCS physiology (Figure 1). In this review, we discuss gene families that have been implicated in human CCS diseases of rhythm, conduction block, accessory conduction, and development (Table). We also investigate evolving therapeutic strategies that may serve as adjuvant or replacement therapy to current implantable pacemakers. Figure 1. Cardiac conduction system cell. Genes identified in human cardiac conduction system disease are highlighted. View this table: Table. Genetic Basis of Conduction System Disease The human sinoatrial node (SAN) is a crescent-shaped, intramural structure with its head located subepicardially at the junction of the right atrium and the superior vena cava and its tail extending 10 to 20 mm along the crista terminalis.26 The SAN has complex 3-dimensional tissue architecture with central and peripheral components made up of distinct ion channel and gap junction expression profiles.27 Central and peripheral cells have different action potential characteristics and conduction properties (Figure 2).27 Experimental and computational models have demonstrated that SAN heterogeneity is necessary to maintain normal automaticity and impulse conduction.28,–,30 Figure 2. Electrophysiological heterogeneity of the …

Role of Gap Junction Channels on Cardiac Memory

The phenomenon of cardiac memory refers to persistent response of the heart to an external pacing stimulus, where the response typically outlasts the stimulus. It is a fundamental tenet of neuroscience that synaptic modification is the basis of various forms of learning and memory. Drawing analogy with neural synapses and Gap Junctions (GJs) in the cardiac tissue, we had earlier hypothesized that dynamic, voltage-sensitive change in GJ conductance may be related to the phenomenon of cardiac memory. In this work we have coupled cardiac cells by GJ conductance. The GJ conductance is allowed to vary as a function of junctional voltage. Simulations show the cell pair and GJ system has two stable states: one at a high value of GJ conductance and another at a lower value. The system can be switched between the two states by an appropriate external input. Such bistable dynamics can support memory operations and most probably underlie the phenomenon of cardiac memory. There are three kinds of cell pairs are considered: (1) a Noble-Noble cell pair that represents adjacent cells in Purkinje network, (2) a pair of DiFranceso-Noble cells that represents adjacent SA nodal cells, and (3) a model of Noble cell coupled to Luo-Rudy cell model, which represents an interacting pair of a Purkinje fiber and a ventricular myocyte. Bistability is demonstrated in all the three cases and this bistability might be an underlying factor behind cardiac memory. Focused analysis of a pair of Noble cell models showed that bistability is obtained only when the properties of GJs “match” with the properties of the pair of cells that is coupled by the GJs. This study showed the role of GJ channels in cardiac memory.

Purkinje Fiber Network in Mammalian Hearts, as Revealed by Scanning Electron Microscopy

Purkinje Fiber Network in Mammalian Hearts, as Revealed by Scanning Electron Microscopy T. Shimada, T. Yamaguchi, H. Kawazato, N. Ono (Oita College of Medical Technology, Kanazawa Uni., Oita Uni.). It has been established that Purkinje fibers in mammalian hearts are different in cell size and ultrastructure among ungulates (first group), humans, monkeys and dogs (second group), and rodents (third group). In this study, the cytoarchitecture of a network of Purkinje fibers (Purkinje network) in three groups of mammals was studied by scanning electron microscopy (SEM). Purkinje networks in sheep, goats, human and dog hearts were demonstrated three-dimensionally by utilizing the NaOH digestion method. In the first group (sheep and goats), the Purkinje network composed of Purkinje strands showed a profile resembling a fishing-net. The cells were oval in shape and met side-to-side in addition to end-to-end contact. The Purkinje network in the second group (humans and dogs) showed a delicate and complicated configuration. Purkinje cells were usually cylindrical in shape and connected end-to-end, but were polygonal or stellate in shape at the bifurcations. Purkinje cells in the third group (rats) resembled in cytoarchitecture to ventricular myocytes, but were identified by a small diameter. From SEM analyses of hearts in various mammalian species, it may be suggested that the cell size and the cytoarchitecture in Purkinje networks reflect not only conducting function but also phylogeny.

Ventricular Fibrillation Triggered during Radiofrequency Energy Delivery for Verapamil-Sensitive Idiopathic Left Ventricular Tachycardia

Verapamil-sensitive idiopathic left ventricular tachycardia (VT) can be suppressed by radiofrequency ablation (RF) on the Purkinje network. RF delivered on the Purkinje fibers triggers premature ventricular contractions or repetitive ventricular response and disappear after cessation of RF. We present a case with idiopathic left VT who represented ventricular fibrillation (VF) during RF on the Purkinje network. Case: A 15-year-old male admitted our hospital because of recurrent sustained VT with QRS morphology of right bundle branch block and left axis deviation. Intravenous verapamil terminated VT. However, electrophysiologic study could not induce VT even if isoproterenol infusion. We delivered RF energy at the distal left posterior fascicular region where Purkinje potentials were recorded during sinus rhythm with pace-mapping QRS morphology mimicking VT-QRS. Shortly after RF delivery, polymorphic VT induced and degenerated into VF. RF deliveries around the VF site induced similar responses. Then, we created RF lesions on the Purkinje fibers more proximal to the VF-induced sites. No VT was documented 3 years after ablation. Conclusion: Purkinje network appears to have potential role for VF induction. RF ablations at the proximal site of the critical Purkinje network can prevent VT/VF occurrence in such case.

Familial Idiopathic Ventricular Fibrillation Linked to Chromosome 7q36 Harboring DPP6

Background: Until recently it was impossible to identify presymptomatic family members at risk for fatal events in familial idiopathic ventricular fibrillation (IVF). We uncovered a large IVF-family and linked their arrhythmic events to a new arrhythmia gene on chromosome 7q36: DPP6. Methods and Results: We studied 169 carriers and 195 non-carriers. ECGs and echocardiography were normal. All-cause mortality or IVF/resuscitation occurred in 67 carriers and 7 non-carriers (no IVF/resuscitation). At 62 years of age, 50% of carriers had an event (p<0.001), the youngest 16 years old, males earlier than females (56 vs. 72 years, p<0.001). IVF was always elicited by monomorphic short-coupled extrasystoles from the right ventricular apex/lower free wall and an origin in the Purkinje network was suspected. Expression-studies showed overexpression of DPP6 mRNA in carriers (p<0.01). Expression-studies in non-diseased explanted human hearts showed higher DPP6 mRNA expression in Purkinje fiber than in any other region (p<0.01). Conclusions: A new arrhythmia gene on chromosome 7q36, DPP6, is linked to familial IVF and shows a very malignant phenotype. Short-coupled extrasystoles from the right-ventricular apex/free wall, presumably originating from the Purkinje network, trigger IVF. For the first time, only genetic predisposition can be used as a risk-marker for future events in IVF.

Catheter Ablation of Ventricular Fibrillation: State of the Art

Catheter ablation of the triggering ventricular premature beats (VPBs) is feasible for idiopathic and ischemic ventricular fibrillation (VF) and can be used for a bailout therapy of VF storm. Also, it can reduce the number of the shock from an implantable defibrillator, one of the poor prognostic factors. In VF or polymorphic ventricular tachycardia (VT) from right ventricular outflow tract (RVOT), suppression of VF was achieved by catheter ablation at RVOT or pulmonary artery. In the short-coupled variant of torsade de pointes and ischemic VF, VF was suppressed by catheter ablation of the Purkinje network. Focal firing from Purkinje fiber and reentry at the Purkinje network may play an important role in the initiation and perpetuation of VF. The same approach with good short-term results has been reported in a small number of patients with other heart diseases (i.e., amyloidosis, chronic myocarditis, nonischemic cardiomyopathy, Brugada syndrome, Long-QT syndrome, and catecholaminergic polymorphic VT).

Purkinje-Related Ventricular Fibrillation

There has been growing evidence that the Purkinje network plays a pivotal role in both the initiation and perpetuation of ventricular fibrillation (VF). A triggering ventricular premature beat (VPB) with a short-coupling interval could arise from either the right or left Purkinje system in patients with polymorphic ventricular tachycardia (VT) or VF, and the catheter ablation of the trigger results in a very high cure rate of VF. A focal breakdown in the “gating mechanism” resulting in a short-circuiting of the transmission across the gate at the distal Purkinje network might predispose to reentrant circuits of polymorphic VT or VF. Many investigators also reported the successful ablation of Purkinje-related VF with an acute or remote myocardial infarction. The same approach with good short-term results has been reported in a small number of patients with other heart diseases (i.e. amyloidosis, chronic myocarditis, nonischemic cardiomyopathy, Brugada syndrome, Long-QT syndrome, and catecholaminergic polymorphic VT). Catheter ablation of the triggering VPBs from the Purkinje system can be used as an electrical bailout therapy in patients with VF storm, and is also useful for the reduction of implantable defibrillator shock.

Purkinje-related Arrhythmias

The Purkinje system has been found to be responsible for the mechanism of some ventricular tachyarrhythmias. These ventricular tachyarrhythmias can be called Purkinjerelated arrhythmias, and are manifested as monomorphic ventricular tachycardia (VT) and polymorphic VT, including ventricular fibrillation (VF). In monomorphic VTs, 4 distinct tachycardias have been found to be related to the Purkinje system: (1) verapamil-sensitive left fascicular VT, (2) Purkinje fiber-mediated VT post infarction, (3) bundle branch reentry (BBR) and interfascicular reentry VTs, and (4) focal Purkinje VT. In polymorphic VT and VF, the Purkinje system may also play an important role. The Purkinje network plays a pivotal role in both the initiation and perpetuation of VF. A triggering ventricular premature beat could arise from either the right or left Purkinje system, and the catheter ablation of the trigger results in a very high cure rate for VF. In patients with an electrical storm, catheter ablation of the triggering VPBs from the Purkinje system should be used as an electrical bailout therapy.

A Young Case of IntraFascicular Ventricular Tachycardia with Narrow QRS Complex

Introduction: Some previous reports demonstrated that ventricular tachycardia may rarely show narrow QRS complex. We experienced a young boy who had past history of Kawasaki disease with such a pattern of ventricular tachycardia. Case Presentation: A 14 year-old boy was transferred to our emergency department in a hemodynamically collapsed state. On 12-lead electrocardiograms, narrow QRS tachycardia with left posterior hemiblock morphology was recorded. We tried to terminate the tachycardia by intravenous infusion of medicine. At first, ATP was injected rapidly, the tachycardia was not terminated. We subsequently injected procainamide. The tachycardia was terminated. QRS complexes during sinus rhythm were similar to those during the tachycardia. Imaging examinations did not reveal structural heart disease on him. We performed electrophysiological study for diagnosis of the tachycardia. The tachycardia was easily induced by atrial extra stimulus and terminated by atrial burst pacing. The interval of His-right fascicular potentials was shorter than that of normal sinus rhythm. Therefore, the mechanism of the tachycardia was assumed to be microreentry rotating around proximal site of purkinje network, which means intrafascicular ventricular tachycardia. In other day, we tried catheter ablation, but the tachycardia was no more induced by any stimuli, so we could not have the procedure. The young patient was treated with oral administration of procainamide and remained asymptomatic.

198 Ablation of premature ventricular beats in post-ischemic intractable electrical storm

post-ischemic electrical storm (PIES) occurring shortly after the acute phase of myocardial infarction (MI) is a rare but potentially lethal phenomenon. Clinical and therapeutic options are poorly known. 14 pts (12 men, 61 ± 13 years old) underwent RF ablation for intractable PIES. PIES occurred 10 ± 5 days after MI (4 months in one pt). Mean EF was 28 ± 7%. Fast monomorphic VT (10 pts), FV (8 pts) or torsades de pointes (5 pts) recurred in each pt despite maximal anti-arrhythmic therapy (mean 22 ± 13 episodes). MI was inaugural anterior MI in each but 3 pts (subendocardial in 2, inferior in 1), with one vessel disease (left descending artery) in 8 pts (2 or 3 vessels in 6). When performed (4 pts), new PTCA did not control PIES. RF ablation was performed as a last chance solution, targetting ventricular premature beats arising from the left septal Purkinje network (in all patients the arrhythmia was of Purkinje origin, defined by a sharp spike Purkinje-potential preceding ventricular activation during sinus rhythm as well as during arrhythmia). Abolition of Purkinje potentials and of Purkinje premature beats led to resumption of electrical storm in 12/14 pts with 1 procedure (2 in one pt). The two pts with unsuccessful RF ablation died within a few hours from intractable heart failure and recurring arrhythmias. All other pts were implanted with an ICD (two pts had already been implanted before). During a 18 ± 19 months follow-up, 3 pts present with recurring isolated VT episodes found in ICD memories. Seven pts died from cardiac or non cardiac causes (7 ± 10 months). PIES is a rare but potentially lethal event occurring mainly in inaugural large anterior acute MI. RF ablation of initiating Purkinje-premature beats may be an efficient therapeutic solution despite the poor long-term prognosis of such patients.

E0551 Radiofrequency catheter ablation of ventricular tachycardia in patients with structural heart diseases using CARTO electroanatomic mapping system and a salineirrigated tip catheter

IntroductionThe aim of this study was to investigate the results of radiofrequency catheter ablation of ventricular tachycardia (VT) in patients with organic heart diseases utilising CARTO system and a saline-irrigated...

Incessant ventricular tachycardia due to spontaneous automaticity in the Purkinje network inducing reversible left ventricular dysfunction

This is a report of reversible left ventricular dysfunction due to incessant automaticity in the Purkinje network. The ideal site for ablation was determined by the presence of a spike, which suggested depolarization of some fascicle of the right bundle-branch of the His–Purkinje system or from an atrio-fascicular Mahaim fibre.

Realistic cardiac electrophysiology modelling: are we just a heartbeat away?

Realistic cardiac electrophysiology modelling: are we just a heartbeat away?

233 Indication, technique and results of Radio-frequency ablation of premature ventricular beats

radio-frequency (RF) ablation of premature ventricular beats (PVB) has been only reported as isolated cases or in short series. 34 successive pts (25 men, 53 ± 18 yo) underwent RF ablation of frequent or symptomatic isolated PVB at our institution from 2005 to 2009. Indication, technique and results were reported. 43 RF ablation of PVB was performed for post-ischemic electrical storm in 7 pts (6 men), for symptomatic PVB in 7 (3 men) and for suspected VPB-induced tachycardiomyopathy in 20 (16 men) with 1,2 procedure/pt. RF was performed in each case using pace mapping and activation mapping with conventional technique. RF ablation of PVB during intractable post-ischemic electrical storm was initially successful in each pt but fatal electrical storm recurred in 4 during the following days. PVB were targeted in the left septal Purkinje network. 10 procedures were performed in 7 pts for palpitations or syncope, leading to complete or partial clinical success in 6 (PVB reduction 9400 ± 12200 to 420 ± 610 /24h, NS). 25 procedures were performed for suspected VPB-induced tachycardiomyopathy in 20 pts leading to complete success in 9 pts and to significant decrease in VPB in 5 pts. Mean VPB/24h was 17800 ± 8600 before and 3410 ± 8150 after and 125 ± 230 at 11 ± 6 months follow-up (p=0,0005). EF increase from 41 ± 8 to 53 ± 7% (p<0,0001). Main locations of the PVB were RVOT, right or left aortic cusps, left basal septum, LVOT and laterobasal LV. Complications were asymptomatic mild pericardial effusion in one pt, transient AV block in one and transient ischemic stroke in one. RF ablation of PVB may be indicated if highly symptomatic, for electrical storm or for suspected tachycardiomyopathy with good although imperfect success rate

Bistable dynamics of cardiac cell models coupled by dynamic gap junctions linked to Cardiac Memory

In an earlier study, we suggested that adaptive gap junctions (GJs) might be a basis of cardiac memory, a phenomenon which refers to persistent electrophysiological response of the heart to external pacing. Later, it was also shown that the proposed mechanism of adaptation of GJs is consistent with known electrophysiology of GJs. In the present article, we show that a pair of cardiac cell models coupled by dynamic, voltage-sensitive GJs exhibits bistable behavior under certain conditions. Three kinds of cell pairs are considered: (1) a Noble-Noble cell pair that represents adjacent cells in Purkinje network, (2) a pair of DiFranceso-Noble cells that represents adjacent SA nodal cells, and (3) a model of Noble cell coupled to Luo-Rudy cell model, which represents an interacting pair of a Purkinje fiber and a ventricular myocyte. Bistability is demonstrated in all the three cases. We suggest that this bistability might be an underlying factor behind cardiac memory. Focused analysis of a pair of Noble cell models showed that bistability is obtained only when the properties of GJs "match" with the properties of the pair of cells that is coupled by the GJs. This novel notion of match between GJs and cardiac cell types might give an insight into specialized distributions of various connexin proteins in cardiac tissue.

Ventrikuläre Tachykardien mit Ursprung im spezifischen Reizleitungssystem

Ventricular tachycardias (VT) associated with the His-Purkinje system may occur in patients with and without organic heart disease. The former may encounter bundle branch reentrant VT, a macroreentrant VT utilizing the specific conduction system. It frequently occurs in patients with preexisting conduction disturbance such as complete left bundle branch block and may be eliminated by catheter ablation of the right bundle branch. After successful ablation, patient's prognosis depends on the presence or absence of structural heart disease.In patients without structural heart disease, VT with right bundle branch block pattern and superior axis, referred to as idiopathic left ventricular tachycardia, is observed. It is a reentrant VT utilizing the posterior left fascicle and the Purkinje network. The two treatment options include antiarrhythmic drug therapy with verapamil or curative catheter ablation.Another form of ventricular arrhythmia originating in the Purkinje network is idiopathic ventricular fibrillation (IVF). Focal triggers from the right and left ventricular Purkinje network induce premature ventricular contractions inducing IVF. This is amenable to catheter ablation leading to a significant reduction in ICD (implantable cardioverter defibrillator) interventions in sudden cardiac death survivors.

The extent of the specialized atrioventricular ring tissues

The so-called specialized tissues within the heart are the sinus node, the atrioventricular conduction system, and the Purkinje network. Further structures with the characteristics of specialized tissue are also found within the atrioventricular junction, although they are less well described. The purpose of this study was to demonstrate the location and extent of these atrioventricular ring specialized tissues, showing their relationship with the normal atrioventricular conduction system. We identified the tissues using histology combined with immunohistochemical labeling with connexin43 (Cx43), the major gap junction in heart, and HCN4, the major isoform of the funny channel. We observed rings of specialized tissue mainly in hearts from rats, mice, and guinea pigs, negative for Cx43 but positive for HCN4. Each ring takes its origin from an inferior extension of the atrioventricular node. The rightward ring runs around the vestibule of the tricuspid valve, whereas the leftward ring encircles the mitral valve. On returning toward the atrial septum, the tricuspid ring crosses over the penetrating part of the atrioventricular conduction system, reuniting with the mitral ring to form a superiorly located retroaortic node. The atrioventricular conduction system itself continues beyond the origin of the right and left bundle branches, forming an aortic ring that ascends toward the retroaortic node but fails to make contact because of the intervening area of aortic-to-mitral valvar fibrous continuity. Rings of conduction tissue take their origin from inferior extensions of the atrioventricular node, passing rightward and leftward to encircle the orifices of the tricuspid and mitral valves and reuniting to form an extensive retroaortic node. Thus, a ring with morphologic features justifying a definition of specialized conduction tissue surrounds the atrioventricular junctions, although its function has yet to be established.

Catheter ablation for patients with ventricular fibrillation

Ventricular fibrillation is a challenging arrhythmia for physicians, with only a limited number of treatment options available. Implantable cardioverter defibrillator therapy is the treatment of choice for patients for both primary and secondary prevention with the role of antiarrhythmic therapy aimed at reducing the number of recurrences. Catheter ablation is an accepted treatment for a number of atrial and ventricular arrhythmias, but until recently ventricular fibrillation was thought to be a bridge too far. The recent advances in ventricular fibrillation ablation will be reviewed. Recent work has demonstrated that the Purkinje network is critical in the triggering and maintenance of ventricular fibrillation. Catheter ablation targeting the ventricular ectopic(s) or Purkinje potentials responsible for triggering ventricular fibrillation or both has been shown to be both possible and efficacious in a number of conditions, ranging from the Brugada syndrome to ischaemic ventricular fibrillation to idiopathic ventricular fibrillation. Although there are relatively few reports of catheter ablation of ventricular fibrillation in the literature, the method appears robust as it is being repeated by a number of different groups around the world. Catheter ablation targeting ventricular ectopics and Purkinje potentials is a successful treatment for ventricular fibrillation. Although the long-term results of such procedures are awaited, the short-term results are very encouraging.