Purkinje-related Arrhythmias Academic research paper on "Clinical medicine"

Review Article

Purkinje-related Arrhythmias

Akihiko Nogami MD

Department of Heart Rhythm Management, Yokohama Rosai Hospital, Yokohama, Japan

The Purkinje system has been found to be responsible for the mechanism of some ventricular tachyarrhythmias. These ventricular tachyarrhythmias can be called Purkinje-related 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. (J Arrhythmia 2011; 27: 6-27)

Bundle branch reentry, Fascicular tachycardia, Idiopathic ventricular tachycardia, Polymorphic

Key words:

ventricular tachycardia, Ventricular fibrillation

Introduction

Johannes Evangelista Purkinje (Purkyne) (Figure 1) was born in Bohemia (now Czech Republic). In 1845, he discovered gelatinous fibers in the ventricular subendocardium. Later, they were called Purkinje fibers.1) However, he could not determine the function of that strange tissue and he thought it was muscular. In 1906, Sunao Tawara finally described its function as the conducting system (Figure 2).2) In the last two decades, there has been rapid progress in the treatment of ventricular arrhythmias and the Purkinje system has been found to be responsible for the mechanism of some ventricular tachyarrhythmias. These ventricu-

Figure 1 Johannes Evangelista Purkyne (1787-1869).

lar tachyarrhythmias can be called Purkinje-related arrhythmias, and are manifested as monomorphic

Address for correspondence: Akihiko Nogami MD, Department of Heart Rhythm Management, Yokohama Rosai Hospital, 3211 Kozukue, Kohoku, Yokohama, Kanagawa 222-0036, Japan. Tel: 045-474-8111 Fax: 045-474-8866 e-mail: akihiko-ind@umin.ac.jp

Figure 2 A macroscopic image of the left ventricle of the human heart. The anterior wall of the left ventricle was cut from just below the aortic valve toward the cardiac apex at the line between the anterior and posterior papillary muscles and opened toward the right and left. The entire course of the left bundle branch and its terminal ramifications are illustrated. From Tawara.2)

Table 1 Purkinje-related arrhythmias

Monomorphic VT

I. Verapamil-sensitive left fascicular VT

i. Left posterior type3-7'9'11-24'27'35»

ii. Left anterior type5'7'22'24'28»

iii. Upper septal type7»

II. Purkinje fiber-mediated VT post infarction27-29»

III. Bundle branch reentry VT

and Interfascicular reentry VT30-40»

IV. Focal Purkinje VT35'42'43»

Polymorphic VT/VF

I. Short-coupled variant of torsade de pointes

i. Left distal Purkinje origin47'63'64»

ii. Right distal Purkinje origin47'62»

II. Ischemic heart disease

i. Acute MI51'54'55'73»

ii. Remote MI or ischemic cardiomyopathy55-58»

III. Chronic myocarditis54»

IV. Amyloidosis53»

V. Nonischemic cardiomyopathy59»

VI. Aortic valve disease54»

VII. Brugada syndrome52»

VIII. Long-QT syndrome52»

IV. Catecholaminergic polymorphic VT

MI: myocardial infarction, VT: ventricular tachycardia, VF: ventricular fibrillation

ventricular tachycardia (VT) and polymorphic VT, including ventricular fibrillation (VF).

Classification

Table 1 shows the classification of Purkinje-related arrhythmias. 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. These VTs usually occur in specific locations and have specific QRS morphologies, whereas VTs associated with structural heart disease and not associated with the Purkinje system have a QRS morphology that tends to indicate the location of the scar. The mechanisms of left fascicular VT, Purkinje-related VT post infarction, BBR-VT, and interfascicular reentry VT are macroreentry, and that of focal Purkinje VT is abnormal automaticity (Table 2).

There has been growing evidence that the Purkinje network plays a pivotal role in both the initiation and perpetuation of VF. A triggering ventricular premature beat (VPB) could arise from either the right or left Purkinje system in patients with polymorphic VT or VF, and the catheter ablation of the trigger results in a very high cure rate of VF. Many investigators

Table 2 Purkinje-related monomorphic VTs

Tachycardia Mechanism Circuit limbs or origin Ablation target

Verapamil-sensitive left fascicular VT Macroreentry Slow conducting left septal fascicle and normal fascicles (or septal muscle) Diastolic abnormal Purkinje potential

Purkinje fiber-mediated VT post infarction Macroreentry Purkinje fibers and diseased muscle Diastolic Purkinje potential

BBR-VT Macroreentry Right and left bundle branches Right or left bundle branch

Interfascicular reentry Macroreentry Left anterior and posterior fascicles Left anterior or posterior fascicle

Focal Purkinje VT Abnormal automaticity Left or right distal Purkinje fibers The earliest presystolic Purkinje potential

BBR: bundle branch reentry, VT: ventricular tachycardia

also reported the successful ablation of Purkinje-related VF with an acute or remote myocardial infarction (MI). The same approach with good results has been reported in a small number of patients with other heart diseases.

Verapamil-sensitive fascicular VT

History

Verapamil-sensitive fascicular VT is the most common form of idiopathic left VT. It was first recognized as an electrocardiographic entity in 1979 by Zipes et al. who identified the characteristic diagnostic triad:3) (1) induction with atrial pacing, (2) right bundle branch block (RBBB) and a left-axis configuration, and (3) manifestation in patients without structural heart disease. In 1981, Belhassen et al. were the first to demonstrate the verapamil-sensitivity of this tachycardia, a fourth identifying feature.4) Ohe et al. reported another type of this tachycardia, with RBBB and right-axis deviation.5' In 1993, Nakagawa et al. reported that presystolic Purkinje potentials can be recorded during this VT and radiofrequency (RF) catheter ablation was successful at the site recording the early Purkinje potential.6) These findings supported the hypothesis that this VT originates from the Purkinje network of the left fascicles.

According to the QRS morphology, we classified verapamil-sensitive left fascicular VT into three subtypes (Table 1):7) (1) left posterior fascicular VT, whose QRS morphology exhibits an RBBB configuration and a superior axis (Figure 3A); (2) left anterior fascicular VT, whose QRS morphology exhibits an RBBB configuration and right-axis deviation

(Figure 3B); and (3) upper septal fascicular VT, whose QRS morphology exhibits a narrow QRS configuration and normal or right-axis deviation (Figure 3C). Left posterior fascicular VT is the most common type of verapamil-sensitive fascicular VT and may account for up to 90% of the cases, left anterior fascicular VT is uncommon (approximately 10%), and left upper septal fascicular VT is very rare (less than 1%).

Substrate and mechanism

Some data suggest that the tachycardia may originate from a false tendon or fibromuscular band in the left ventricle,8,9) although some evidence suggests that the opposite is true.10) We speculate that the Purkinje networks in the small anatomic structures (e.g., small fibromuscular bands, trabecu-lae carneae, and small papillary muscles) are important when considering the reentry circuit of verapamil-sensitive left posterior fascicular VT.

The mechanism of verapamil-sensitive left VT is reentry, because it can be induced, entrained, and terminated by ventricle or atrial stimulation. Many investigators reported the hypothesis that this VT is a reentrant VT that originates from the Purkinje network near the left posterior fascicle.3,5,11 Nakagawa et al. first reported the importance of Purkinje potentials in the ablation of this VT.6) Tsuchiya et al. also reported the significance of a late diastolic potential and emphasized the role of late diastolic and presystolic potentials in the VT circuit.12) However, the successful ablation sites identified by these two research groups were different. Whereas Nakagawa's ablation sites were at the apical-inferior septum of the left ventricle, Tsuchiya's ablation sites were at the basal septal

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Figure 3 Twelve-lead ECGs of verapamil-sensitive left fascicular VTs.

(A) A left posterior fascicular VT, whose QRS morphology exhibits a right bundle branch block (RBBB) configuration and superior axis;

(B) left anterior fascicular VT, whose QRS morphology exhibits an RBBB configuration and right-axis deviation; and (C) upper septal fascicular VT, whose QRS morphology exhibits a narrow QRS configuration and normal or right-axis deviation.

region close to the main trunk of the left bundle branch (LBB). To confirm its reentry circuit, my colleagues and I performed left ventricular septal mapping using an octapolar electrode catheter in 20 patients with left posterior fascicular VT (Figure 4A).13) In 15 of 20 patients, two distinct potentials, P1 and P2, were recorded during the VT at the midseptum (Figure 4B). Although the mid-diastolic potential (P1) was recorded earlier from the proximal rather than the distal electrodes, a fused presystolic Purkinje potential (P2) was recorded earlier from the distal electrodes. During sinus rhythm, recording at the same site demonstrated P2, which was recorded after the His-bundle potential and before the onset of the QRS complex; however, the sequence of P2 was the reverse of that seen during the VT.

The electrophysiological findings demonstrated that P1 is a critical potential in the circuit of the verapamil-sensitive left posterior fascicular VT and suggested the presence of a macroreentry circuit involving the abnormal Purkinje tissue with decre-mental properties and verapamil sensitivity. Many investigators proposed similar reentrant circuits.14,15 Ouyang et al. suggested that the reentry might be a small macroreentry circuit consisting of one ante-rograde Purkinje fiber with a Purkinje potential, one retrograde Purkinje fiber with a retrograde Purkinje potential, and the ventricular myocardium as the bridge.16)

Although P1 (a mid diastolic potential) has proved to be a critical potential in the VT circuit, whether

the left posterior fascicle or Purkinje fiber (P2) is involved in the retrograde limb of the reentrant circuit remains unclear.9,17,18) Recently, Morishima et al. reported a case with negative participation of the left posterior fascicle in the VT circuit.19) While selective capture of the left posterior fascicle by a sinus beat did not affect the cycle length of the VT, the post pacing interval after the entrainment from the left ventricular septal myocardium was equal to the cycle length of the VT. According to these findings, the retrograde limb of the circuit is the left ventricular septal myocardium itself, but not P2 (the left posterior fascicle or Purkinje fiber near the left posterior fascicle). P2 is the bystander of the VT circuit.

Mapping and ablation

RF catheter ablation may be considered a potential first-line therapy for patients with idiopathic VT, because these VTs can be eliminated by ablation in a high percentage of patients. Conventional left ventricular septal mapping using a multipolar electrode catheter is useful in patients with left posterior fascicular VT.13) Two distinct potentials, P1 and P2, can be recorded during the VT from the midseptum (see Figure 4B). Because the diastolic potential (P1) has been proven to be a critical potential in the VT circuit, this potential can be targeted to cure the tachycardia. Any P1 in the VT circuit can be targeted for catheter ablation. We usually target the apical third of the septum, to avoid the creation of left bundle branch block (LBBB) or atrioventricular block.

Figure 4 Mapping using an octapolar electrode catheter.

(A) Representation of an octapolar electrode catheter positioned at the left ventricular septum as viewed fluoroscopically in the right anterior oblique (RAO) and left anterior oblique (LAO) projections. The distance between electrodes 1 and 8 of the octapolar electrode catheter was approximately 25 mm. (B) During left posterior fascicular VT, a diastolic potential (P1) and presystolic Purkinje potential (P2) were recorded. While P1 was recorded earlier from the proximal rather than distal electrodes, P2 was recorded earlier from the distal rather than proximal electrodes. During sinus rhythm, recording at the same site demonstrated that the P2 was now recorded before the onset of the QRS complex and was the earliest on the proximal electrodes. H: His, HBE: His-bundle area, LV: left ventricle, RVOT: right ventricular outflow tract. From Nogami et al.13)

During the energy application, the P1-P2 interval gradually prolonged, and the VT terminated by block between P1 and P2. After the termination of the tachycardia, P1 was noted to occur after the QRS complex during sinus rhythm, whereas P2 was still observed before the QRS complex. When the distal segment of P1 is ablated, the P1 activation proceeds orthodromically around the circuit and subsequently blocks from a proximal to distal direction during sinus rhythm. The P1 that appears after the ablation

exhibits decremental properties during atrial pacing and/or ventricular pacing, and the intravenous administration of verapamil significantly prolongs the His-to-P1 interval during sinus rhythm.

Pace mapping at the successful ablation site is usually not good, because selective pacing of P1 is difficult and there is an antidromic activation of the proximal P1 potential. Pace mapping after a successful ablation is sometimes better than before ablation, because the antidromic activation of P1 is blocked.20)

The inability to reliably induce VT is a formidable obstacle to a successful ablation. Catheter mapping sometimes mechanically suppresses the conduction in the VT circuit ("bump" phenomenon). In such cases, a ventricular echo beat during sinus rhythm or atrial pacing is useful. If premature ventricular complexes with a similar QRS morphology to that observed during the VT are repeatedly seen, activation mapping can be performed. If no ventricular echo beats are inducible, the empiric anatomic approach can be an effective strategy for ablation of left posterior fascicular VT.21)

Figure 5 shows the position of the schematic fascicular VT circuits and the Purkinje potentials during sinus rhythm. The circuit of the left posterior fascicular VT is shown in Figure 5C. P1 and P2 can be recorded during the VT from the midseptum. This type of VT can be named a left posterior slow-fast type fascicular VT.

Uncommon Forms of Verapamil-sensitive Fascicular VT

The uncommon types of fascicular VT are a left anterior fascicular VT whose QRS morphology exhibits an RBBB configuration and right-axis deviation (Figure 3B)6,22) and an upper septal fascic-ular VT whose QRS morphology exhibits a relatively narrow QRS configuration and normal or right-axis deviation (Figure 3C).7) Upper septal fas-cicular VT is very rare.

With left anterior fascicular VT, the earliest ventricular activation is recorded from the antero-lateral left ventricle, and diastolic potentials are recorded from the midseptum. There have been several reports that described a left VT with an RBBB configuration, right-axis deviation, and different mechanisms. Crijns et al. reported a case of interfascicular reentrant VT with an RBBB configuration and right-axis deviation.23) In their patient, the VT circuit used the anterior fascicle as the anterograde limb and the posterior fascicle as the retrograde limb. Interfascicular VT usually has a His-bundle potential recorded in the diastolic phase during the VT, as well as posterior fascicular potentials. However, it may be difficult to distinguish between interfascicular VT and intrafascicular VT (verapamil-sensitive left anterior fascicular VT) by the surface ECG. The intracardiac recording of the left posterior fascicle is important. It is the retrograde limb in interfascicular VT, but a bystander in left anterior fascicular VT.

Some patients with left anterior fascicular VT also had a typical left posterior fascicular VT. Kottkamp et al. reported one patient who had two

left VT configurations with right- and left-axis deviation.24) In this patient, RF catheter ablation delivered to a single site between the left anterior and posterior fascicles successfully eliminated both VTs. This suggests that the anterior limb is the common pathway. The circuit of the left anterior fascicular VT is shown in Figure 5C. In this circuit, DP represents the activation potential in the proximal portion of the specialized Purkinje tissue with a decremental property. This type of VT can be named the left anterior slow-fast type fascicular VT.

Left upper septal fascicular VT is very rare and the most difficult type of fascicular VT.7) The differential diagnosis includes supraventricular tachycardias with bifascicular block aberrancy. With left upper septal fascicular VT, the retrograde activation of the His bundle is recorded before the onset of the QRS complex (Figure 6). If there is retrograde ventriculoatrial conduction during the tachycardia, it mimics atrioventricular nodal reentry tachycardia or atrioventricular reciprocating tachycardia. The response of these tachycardias to verapamil and the ability to initiate and entrain them by atrial pacing may also lead to diagnostic confusion. To avoid a misdiagnosis, recognition of the retrograde sequence of the His-bundle activation and measurement of a shorter His-to-ventricular (HV) interval during the tachycardia than in sinus rhythm is important. An earlier potential than the His-bundle potential is recorded from the left ventricular upper septum, where the left bundle potential is recorded during sinus rhythm. This VT can be slowed or terminated by the intravenous administration of verapamil; however, it is unresponsive to Valsalva maneuvers.

Figure 6 shows the intracardiac electrograms of the upper septal fascicular VT. A fused Purkinje potential was recorded at the left posterior fascicular (LPF) area during sinus rhythm (Figure 6A). Further, during VT, a recording at the same site also demonstrated a fused presystolic Purkinje potential which preceded the onset of the QRS by 20 ms (Figure 6B). The activation sequence of the Purkinje potentials in the LPF area is similar during sinus rhythm and the VT. That site is one of the exits during VT, because a fused presystolic ventricular potential was recorded. Further, another exit site during VT might be the left anterior fascicular area, because the QRS morphology during the VT is quite narrow and exhibits an inferior axis. This VT was successfully ablated at the left ventricular upper septum (Figure 6C,D). At that site, a left bundle potential was recorded during sinus rhythm and the

Figure 5 The position of fascicular VT circuits and the Purkinje potentials during sinus rhythm. (A) The tags in the CARTOMERGE image indicate the potentials of the left anterior fascicle (LAF), posterior fascicle (LPF), and distal Purkinje fibers during sinus rhythm. (B) In the left ventricular cavity, the anterior posterior papillary muscle (APM), posterior papillary muscle (PPM), and false tendons (FT) were observed (endoscopic view). (C) The circuits of the left posterior fascicular VT and left anterior fascicular VT are shown. The dotted lines indicate the ventricular myocardium as the proximal bridge between the diastolic and presystolic Purkinje potentials. The undulating line represents a zone of slow conduction. (D) The circuit of the left upper septal fascicular VT is shown. See the text for the discussion.

Purkinje potential preceded the QRS by 35 ms during the VT (Figure 6D).

The hypothesized VT circuit of left upper septal fascicular VT is depicted in Figure 5D. In this circuit, DP represents the activation potential of the specialized Purkinje tissue at the left ventricular upper septum. P represents the activation of the left fascicles or Purkinje fibers near the left fascicles.

Both the left anterior and posterior fascicles are the antegrade limbs of the reentrant circuit in VT. This explains why this VT exhibits a narrow QRS configuration and inferior axis. DP represents the common retrograde limb of the circuit in VT and can be considered an ablation target. This type of VT can be named a fast-slow type fascicular VT.

Figure 6 Intracardiac electrograms of a left upper septal fascicular VT. During the VT, there was a retrograde activation of the His-bundle. The activation sequence of the His-bundle potentials was the reverse of that during sinus rhythm. The HV interval is short during the VT. (A) During sinus rhythm, a fused Purkinje potential was recorded at the left posterior fascicular (LPF) area. (B) During the VT, a recording at the same site also demonstrated a fused Purkinje potential which preceded the onset of the QRS by 20 ms. The activation sequence of the Purkinje potentials is similar during sinus rhythm and the VT. (C) and (D) The VT was successfully ablated at the left ventricular upper septum. At that site, a left bundle branch (LF) potential was recorded during sinus rhythm and the potential preceded the QRS by 35 ms during the VT. The RF application eliminated the VT without making left bundle branch block or atrio-ventricular block. From Nogami et al.7)

Purkinje fiber-mediated VT post infarction

Earlier studies using canine infarction models showed that Purkinje fibers over the infarcted region remain almost structurally intact and were found to

be involved in both triggered and reentrant VT.25,26) Hayashi et al. first reported four post MI patients who presented with left posterior fascicular VT.27) Intravenous administration of verapamil terminated VT in one patient. Both diastolic and presystolic Purkinje potentials were sequentially recorded along the left

ventricular posterior septum during VT. The tachycardia could be entrained with atrial pacing and the diastolic Purkinje potentials were captured ortho-dromically. All patients were successfully ablated in the region of the distal fascicular potential. Morishima et al. described a verapamil-sensitive left anterior fascicular VT whose QRS morphology exhibited an RBBB configuration and right-axis deviation in a patient with a prior anteroseptal MI.28) Those VTs have several characteristic differences compared to the usual scar-related VT post infarction: (1) a relatively narrow QRS duration during VT, (2) verapamil-sensitivity, (3) presystolic or diastolic Purkinje potentials during VT, and (4) VT termination by a single or a few RF energy applications to that site. Bogun et al. studied 81 consecutive patients with monomorphic VT post MI.29) Nine patients were found to have a relatively narrow QRS (< 145 ms) VT, and the VT was successfully ablated at the site with presystolic or diastolic Purkinje potentials. They proposed a reentry circuit around an infero-septal scar and that surviving muscle bundles within the myocardium and Purkinje system were components of the reentry circuit. Although the preceding Purkinje potential was proven to be critical in the VT circuit, the other pathway is still unclear.

Bundle branch reentry and interfascicular reentry VT

Clinical features

A typical example of macroreentry in the bundle branches is BBR-VT.30,31) Usually, the reentry circuit propagates down the RBB and up the LBB producing a VT with an LBBB configuration. Induction of isolated BBR can occur as a normal electrophysiologic response; however, in patients with a conduction delay within the His-Purkinje system, macroreentry involving the right and left bundles can result in sustained BBR. In normal hearts, the rapid conduction and long refractory periods of the His-Purkinje system prevent sustained BBR usually by retrograde block in the LBB. Maintenance of BBR is critically dependent on the interplay between the conduction velocity and recovery of the tissue ahead of the reentrant impulse. Patients with BBR-VT commonly are seen with syncope, and the mechanism of the syncope is rapid ventricular rates, often 200 to 300 bpm. In patients with nonischemic dilated cardiomyopathy, BBR-VT may be responsible for up to 41% of inducible sustained monomorphic VTs.31)

Mechanism

The most common form of BBR presents with a typical LBBB pattern. This form depends on the retrograde block in the right bundle, due to a long refractory period, with slow retrograde conduction through the left bundle. A delay in the left bundle conduction provides sufficient time for recovery of the right bundle. Rarely, the reentrant circuit can be depolarized in the opposite direction, generating a QRS morphology with an RBBB configuration. Recently, Naruse et al. reported the electroanatomic mapping during the reverse common form of BBR (Figure 7).32) It has been well demonstrated that reentry in the His-Purkinje system is more likely to occur when extrastimuli are introduced to basic drives incorporating short to long cycle length changes as compared with constant cycle length drives.33) The abrupt cycle length prolongation may result in a more distal retrograde block in the His-Purkinje system, allowing more time for the excitability to recover in the antegrade direction.

Interfascicular reentry VT is a rare form of macroreentry between the left fascicles. The distal link between the fascicles occurs through the ventricular myocardium. The left anterior fascicle is usually the anterograde limb and the posterior fascicle the retrograde limb.34,35) Interfascicular tachycardia and BBR may present in the same patient.

Electrophysiologic study

A common finding with electrophysiology testing in patients with BBR is a prolongation of the HV interval and QRS complex duration. There are several diagnostic features suggestive of BBR-VT: (1) The QRS morphology during the tachycardia is a typical LBBB or RBBB pattern, consistent with ventricular activation through the appropriate bundle branch. (2) The induction of the tachycardia during ventricular extrastimulation depends on the achievement of a critical conduction delay in the His-Purkinje system. (3) The tachycardia can be terminated by spontaneous or pace-induced block in the His-Purkinje system, and rendered noninducible by ablation of the RBB or LBB. (4) During the tachycardia, the His-bundle, right bundle, or left bundle potentials precede each QRS complex with an appropriate sequence of the activation for the tachycardia QRS morphology with a stable potential-ventricle interval. (5) During the tachycardia, the HV interval is commonly longer than or equal to the HV interval during sinus rhythm.36) (6) Spontaneous variations in the V-V

Activation mapping covered the entire cycle length (CL) of the tachycardia (360 ms). During the tachycardia, the activation proceeds in an anterograde direction over the left posterior fascicle (LPF) and retrograde through the right bundle branch (RB). In this circuit, the left anterior fascicle (LAF) is a bystander, and there is a collision in the middle portion of the LAF. Modified from Naruse et al.32)

intervals are preceded by similar changes in the H-H intervals. (7) The tachycardia should be entrained from the right ventricular apex.37) Difference between the post pacing interval from the right ventricular apex and the tachycardia cycle length is less than 30 ms. (8) BBR-VT may exhibit concealed entrainment from the atrium if the atrioventricular nodal function is good.38)

The diagnostic criteria for left interfascicular reentry are as follows: (1) The QRS morphology during the tachycardia is an RBBB pattern, consistent with ventricular activation through the left anterior or posterior fascicle. The direction of the antegrade conduction in the left anterior or posterior fascicle determines the electrical axis.31,34) (2) The tachycardia can be terminated by spontaneous or pace-induced block in the left fascicular system, and rendered noninducible by ablation of the left anterior or posterior fascicle. (3) The left fascicular potential precedes each QRS complex during the tachycardia, and the His-bundle and right bundle follows the left fascicular activation. Variations in the R-R interval are preceded by the changes in the H-H interval. (3) The HV interval during the tachycardia is usually the same or shorter than the HV during sinus rhythm.

Catheter ablation

It is important to recognize BBR and interfascic-ular tachycardia because they can be cured with catheter ablation. The elimination of these tachycardias would decrease the need for pharmacologic antiarrhythmic therapy and the frequency of defibrillator shocks. Even though most patients demonstrate more conduction system disease in the left bundle, the right bundle is typically the target for ablation. In patients with complete antegrade block in the LBB, RBB ablation necessitates permanent pacing. However, in BBR-VT patients with LBBB during sinus rhythm, antegrade slow conduction over the LBB is present39 or the LBB is activated retrogradely (transseptal).34) To avoid the creation of complete atrioventricular block, the LBB should be targeted in such patients with LBBB during sinus rhythm and the BBR-VT.34)

Although ablation of the RBB will eliminate BBR, these patients have a high mortality rate. The most common cause of death was congestive heart fail-ure.40) Furthermore, this patient population has high-risk features for sudden cardiac death. Implantation of a dual-chamber defibrillator and perhaps a device that provides cardiac resynchronization therapy should be considered.

Focal Purkinje VT

Clinical and electrophysiological characteristics

Another type of Purkinje-related VT is focal tachycardia from the Purkinje system. This VT is classified as a propranolol-sensitive automatic VT.41) While this VT is usually observed in patients with ischemic heart disease,35) it is also observed in patients with structurally normal hearts.42'43) Focal Purkinje VT also arises from the right ventricle Purkinje system with an LBBB configuration.35 Focal Purkinje VT from the left ventricle can present with an RBBB configuration and either a left- or right-axis deviation on the 12-lead ECG, depending on the origin. It is difficult to distinguish a left focal Purkinje VT from reentrant fascicular VT by the 12-lead ECG. This VT can be induced by exercise and catecholamines (e.g., isoproterenol and phenylephr-ine); however, it cannot be induced or terminated by programmed ventricular stimulation. While this VT is responsive to lidocaine and beta-blockers, it is usually not responsive to verapamil. This can be used as a method to differentiate it from verapamil-sensitive fascicular VT. This VT is transiently suppressed by adenosine and overdrive pacing. The clinical and electrophysiological characteristics of this VT have not been well defined. Gonzalez et al. reported the electrophysiologic spectrum of Pur-kinje-related VT in 8 patients and showed the mechanism to be consistent with abnormal automa-ticity or triggered activity in 5 patients.42) The 12-lead ECG during VT in these patients exhibited RBBB with left-axis deviation. A distinct His deflection was recorded with a HV interval during VT that was shorter than that during sinus rhythm. The authors speculated that this VT arises from a fascicular focus at some distance from the myocar-dial site of the origin of the VT based on the varying ECG morphologies and responds poorly to catheter ablation.

Mapping and ablation

The ablation target of focal Purkinje VT is the earliest Purkinje activation during VT, while that of verapamil-sensitive fascicular VT is not the earliest Purkinje activation. Figure 8 shows the mapping and ablation of the focal VT from the distal Purkinje system of the left posterior fascicle. Presystolic Purkinje potentials were recorded from various sites in the left ventricle; however, the earliest Purkinje potential was recorded at the basal inferior wall (Figure 8A). The Purkinje potential preceded the QRS during VT by 70 ms, and the recording at the

same site demonstrated a fused Purkinje potential during sinus rhythm (Figure 8B,C). Pace mapping at this site produced an identical QRS complex, with an S-QRS interval of 70 ms, equal to the P-QRS interval during the VT. RF current delivered to this site suppressed the VT, while previous RF applications to other sites with a presystolic Purkinje potential were not effective.

The complications that have been associated with the catheter ablation of focal Purkinje VT have been LBBB and atrioventricular block. In verapamil-sensitive fascicular VTs, the creation of LBBB or atrioventricular block as a complication is quite rare because the ablation target is the diastolic "abnormal" Purkinje potential (P1) during VT and the abolition of the normal Purkinje potential (P2) is not needed to suppress the VT. On the other hand, the abolition of the Purkinje system is usually necessary to suppress the focal Purkinje VT. If the VT arises from a more proximal portion of the fascicle, there is the potential risk of creating LBBB or atrioventricular block by the ablation. Rodriguez et al. reported a case with focal Purkinje VT with an RBBB configuration and right-axis deviation in which left anterior fascicular block occurred after the ablation.43) Lopera et al. reported two focal Purkinje VT cases with ischemic heart disease in which complete atrioventricular block occurred after the successful ablation of the VT.35)

Purkinje-related polymorphic VT/VF

Although previous studies have shown that VF is perpetuated by reentry or spiral waves, recent data suggest the role of specific sources in triggering this arrhythmia.44-46 In 2002, Hai'ssaguerre et al. reported that idiopathic VF could be suppressed by catheter ablation of triggers originating from the Purkinje system.47) This idiopathic VF or polymorphic VT was associated with a short-coupling interval between ventricular premature beats (VPBs) and conducted complexes.48) The specialized conduction system of the Purkinje network, localized endocardially in the human heart, consists of a single branch on the right that penetrates a limited portion of the right ventricle, and at least 2 larger branches on the left that ramify more intricately to supply a greater area of the left ventricle.2,49,50 The Purkinje system may also play a role in post-infarction VF. In 2002, Bansch et al. reported that in 4 patients with combinations of repetitive VF, polymorphic VT, and monomorphic VT following an acute MI, Purkinje signals preceded every VPB, and ablation of the sites of the Purkinje signals eliminated all VPBs and no

III Vi

HRA 1-2 HBE 3-4 RVA 1-2 CS 9-10 CS 7-8 CS 5-6 CS 3-4 CS 1-2 ABL 1

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Figure 8 Focal Purkinje VT with an RBBB and left-axis deviation.

(A) Electroanatomic mapping during VT. The tags indicate the sites with the presystolic Purkinje potentials during VT. The earliest Purkinje potential was recorded at the basal inferior wall and RF current delivered to that site suppressed the VT (arrow). (B) The Purkinje potential preceded the QRS during the VT by 70 ms. (C) The recording at the same site demonstrated a fused Purkinje potential during sinus rhythm.

VT or VF recurred during the follow-up.51) Recent studies have shown that Purkinje fibers can initiate VF in some patients with other structural heart diseases: Brugada syndrome,52) Long-QT syndrome,5^ amyloidosis,53) chronic myocarditis,54) ischemic cardiomyopathy,54-58) nonischemic cardiomyopathy,59 and catecholaminergic polymorphic VT (Table 1).

Short-coupled variant of torsade de pointes

Ablation

Leenhardt et al. were the first to describe a syndrome of polymorphic VT associated with a short-coupling interval (245 ± 28 ms) between VPBs and conducted complexes in patients without ische-

mic or structural heart disease.48) This arrhythmia could not be provoked by isoproterenol, but the coupling interval lengthened in all patients after verapamil. Verapamil was the only drug apparently active on the arrhythmias; however, it did not prevent sudden death. Haissaguerre et al. then showed that the triggering VPB with a short-coupling interval could arise from either the right or left Purkinje system in 23 patients with polymorphic VT or VF.47) The interval from the Purkinje potential to the myocardial activation during sinus rhythm was 11 ± 5 ms, suggesting that the recordings were obtained from the distal Purkinje fibers. The Purkinje potential was recorded 38 ± 28 ms (range 10 to 150 ms) before the VPB. Ablation of the trigger resulted in a very high cure rate of 89%.

Figure 9 shows the electrocardiograms of our patient with short-coupled variant of torsade de pointes.60) In the electrophysiologic laboratory, non-sustained polymorphic VT with the same QRS morphology as the clinical polymorphic VT was repeatedly inducible by atrial pacing. The first VPB (VPB1) had an RBBB configuration with right-axis deviation. The second VPB (VPB2) was an RBBB pattern with a northwest axis. During the polymorphic VT, diastolic and presystolic Purkinje potentials were recorded from an octapolar electrode catheter placed at the left ventricular septum. The diastolic Purkinje potentials were recorded earlier from the proximal than distal electrodes, and fused presystolic Purkinje potentials were recorded earlier from the distal than the proximal electrodes (Figure 9A). During sinus rhythm, the recording at the same site demonstrated fused Purkinje potentials before the onset of the QRS. Radiofrequency (RF) energy was delivered to the site of electrodes 3-4. A diastolic Purkinje potential from this site preceded the onset of the first VPB by 15 ms and the second VPB by 60 ms. Electrograms recorded after the ablation revealed the abolition of the local Purkinje potential at the middle portion and a slight delay in the occurrence of the local ventricular electrogram during sinus rhythm (Figure 9B). The activation of the distal Purkinje system and septal muscle was delayed and reversed (retrograde), suggesting a collateral activation from the distal Purkinje network. After the ablation the polymorphic VT became noninducible, and only an isolated VPB was induced. The morphology of this VPB differed from that of the previous trigger VPBs (VPB1, VPB2) and intra-Purkinje block was also observed before this VPB. During a 10-year follow-up in which the patient received no drug therapy, no episodes of syncope or VF recurrence occurred.

Trigger VPBs in idiopathic VF can also arise from the right Purkinje system. Haissaguerre et al. reported that VPBs were elicited from the left ventricular septum in 10, from the anterior right ventricle in 9, and from both in 4 of their 23 patients with polymorphic VT or VF.47) While the trigger VPBs from the left distal Purkinje fiber could be ablated at left ventricular septum, the VPBs from the right distal Purkinje fiber were elicited at the right ventricular free wall. Saliba et al. and Kohsaka et al. also reported a successful ablation of trigger VPBs from the right distal Purkinje fiber.61,62) In both cases no Purkinje potentials were recorded before the normally conducted QRS during sinus rhythm. The distal right Purkinje potential might be buried in the local muscular activation during sinus rhythm.

Mechanism

In our patients, a rapid polymorphic VT was initiated by VPBs with very short coupling intervals. Further, a polymorphic VT with the same QRS morphology as the spontaneous polymorphic VT was inducible by burst atrial pacing (i.e., Purkinje stimulation) and was suppressed by verapamil. These observations suggest that the VF initiation might be caused by triggered activity from Purkinje tissue. However, suppression of VF was achieved with catheter ablation of the Purkinje network, not the earliest Purkinje activation in this patient. Therefore, we hypothesized that the reentry in the Purkinje system is essential for the initiation of VF. In the report by Haissaguerre et al., the electrocardiograms recorded after the ablation showed the abolition of the local Purkinje potential and a slight delay in the occurrence of the local ventricular electrogram.47) However, they did not determine how much of the complex Purkinje network was involved in each patient and the issue of multiple foci versus differing activation routes from limited foci remains unsolved. In our patient with the trigger VPB from the left Purkinje network (Figure 9), catheter mapping revealed that the constantly changing polymorphic QRS morphology resulted from the changing propagation in the Purkinje arborization and the polymorphic VT became noninducible after the catheter ablation of the Purkinje network. Knecht et al. reported that a recurrence of clinical VPBs after ablation was observed in 2 of 38 patients with idiopathic VF that no longer resulted in malignant ventricular arrhythmias despite an extended follow-up.63) They speculated that modulation of the Purkinje system and its surrounding tissue may be sufficient in some cases for avoiding initiating VF.

HRA HBE LV7-8 LV6-7 LV5-6 LV4-5 LV3-4 LV1-2

RAO 35°

III aVR aVL aVF

V1 V2 V3 V4 V5 V6 LV7-8 LV6-7 LV5-6 LV4-5 LV3-4 LV2-3

"Ww*-jMV

—--------pv

—A,-h

200 ms

Figure 9 Electrograms recorded before and after ablation of polymorphic VT. (A) During polymorphic VT, a diastolic Purkinje potential (Pd) and presystolic Purkinje potential (Pp) were recorded from the left ventricular septum. During sinus rhythm, fused Purkinje potentials (P) were recorded before the QRS onset. (B) Induction of the tachycardia after ablation. Electrograms recorded after ablation showed the abolition of the local Purkinje potential (P) at the middle portion and a slight delay in the occurrence of the local ventricular electrogram during sinus rhythm (arrow head). The polymorphic VT became noninducible and only an isolated VPB was inducible. The morphology of this VPB differed from that of the previous trigger VPB and intra-Purkinje block was also observed before this VPB (arrow). HBE: His-bundle electrogram, HRA: high right atrium, LAO: left anterior oblique view, LV: left ventricle, P: Purkinje potential during sinus rhythm, Pd: diastolic Purkinje potential, Pp: presystolic Purkinje potential, Sap: atrial pacing stimulus. Modified from Nogami et al.60)

Figure 10 The gating mechanism.

(A) The preparation consisited of a single free-running false tendon from the right bundle branch (RBB) to the free wall of the right ventricle (FWRV). (B) The changes in the action potential duration (APD) along the length of the preparation are paralleled by the changes in the local refractory period (RP). There is a progressive increase in the APD and RP to a maximum of 290 ms and a sharp fall as the conduction fibers approach the free wall. The functional refractory period of the preparation is the minimum coupling interval (S1-S2) which can result in excitation of the FW by the premature impulse applied to the RBB. The duration of the functional refractry period is determined by the duration of the local refractory period at the area of the maximum action potential duration, or gate. (C)-(F) Hypothetical patterns of normal and abnormal function of the gating mechanism. The diagram represents a false tendon with three branches serving the ventricular myocardium. Panels C and D demonstarate the normal situation in which the gates of all three branches have the same refractory period of 250 ms. In panel C, the premature impulse occurs 260 ms after the driving impulse (S1), and therefore finds all gates able to conduct the impulse. In panel D, the premature impulse occurs early enough to find all gates refractory, and the descending impulse is not conducted. In panel E, the gate of branch A is abnormally short and at the same S1S2 interval that caused block in all branches in panel D, the impulse is able to bypass the normal gates of the system and depolarize the myocardium. In panel F, the gate of branch A has an abnormally long refractry period and is not crossed by the premature impulse with the same S1S2 interval as that in panel C. Modified from Myerburg et al.49,66)

Possible mechanisms for the short-coupled variant of torsade de pointes include (1) spontaneous Ca2+ waves emanating from the Purkinje tissue or contiguous muscle, (2) phase 2 reentry in tightly coupled muscle-Purkinje junctions, and (3) marked conduction slowing and reflection in the distal Purkinje fibers.64) The effects of a Ca2+ infusion as well as verapamil tend to favor involvement of Ca2+ in the initiation of the trigger. Scheinman65) speculated that in patients with short-coupled VPBs, Ca2+ waves result in delayed afterdepolarizations, which lead to reentrant arrhythmias due to a defective gate function as proposed by Myerburg et al.48,66) Their experimental studies showed that the action potential duration and refractoriness of the peripheral Purkinje fibers gradually prolonged, with the maximal action potential duration occurring 2 to 3 mm proximal to the Purkinje-muscle junction. In addition, they found that these areas of maximal refractoriness

acted as gates for impulses propagated from above (Figure 10). They found that the "gates" were similar to multiple Purkinje strands, providing a "uniform functional limit for the propagation of premature impulses across the distal end of the conduction system". Moreover, approximately timed premature Purkinje or ventricular impulses could be confined either proximal or distal to the gate. A focal breakdown in the gating mechanism could result in a short-circuiting of the transmission across the gate, predisposing to reentrant circuits (Figure 10E). They also evaluated the influence of incised lesions in the left conducting system on the patterns of activation (Figure 11).67) When a vertical incision was added to the lower third of the septum so as to cut through the interconnecting subendocardial Purkinje fibers, the activation of the conducting system was delayed and reversed (retrograde), and the activation of the posterobasal septal muscle was markedly delayed

Figure 11 Influence of the lesions in the left conducting system on the patterns of activation.

(A) The preparation is of the left ventricle from the aortic ring to the begining of the lower third of the septal surface. The anterolateral papillary muscle is on the left, and posteromedial papillary muscle is on the right. The pairs of action potentials at levels I, II, III were recorded from the corresponding levels on the photographs. The first of each pair is recorded from conducting cells and the second from muscle cells. The numbers represent the intervals from the stimulus to the response at each site. (B) The activation is remapped after the incision across the posterior division of the left bundle branch. (C) Mapping after another incision made vertically through the interconnecting subendocardial Purkinje fibers. From Myerburg et al.67)

(Figure 11C). These electrograms are quite similar to the electrograms before and after the ablation in our patient (Figure 9B).

In 1998, Berenfeld and Jalife used a computerized 3-dimensional model to test the hypothesis that reentry involving the Purkinje muscle junction may be a mechanism of focal subendocardial activa-tion.68) In addition to the capacity for triggered activity, the differences between the Purkinje fibers and myocardium in the upstroke velocity, intra-cellular coupling, and action potential duration may provide the conditions for initiating or sustaining VF. And finally, the reentry was terminated if the Purkinje system was disconnected from the muscle before it reached a relative steady state of VF. Dosdall et al. demonstrated that the Purkinje system is active during early post-shock activation cycles using transmural and endocardial Purkinje activation mapping in pigs.69) In their second study,70) ablation of the Purkinje system by Lugol's solution hastened spontaneous VF termination. Pak et al. demonstrated the differences in the effect of Purkinje ablation and the distribution of the Purkinje network in dogs and swine.71) While the VF inducibility was decreased by catheter ablation targeting the left posterior papillary

muscle and left ventricular posteroseptum in dogs, the same ablation procedure did not reduce the VF inducibility in swine. The VF inducibility in swine was decreased only by a transmural cut-and-sew operation. In contrast to the canine Purkinje network, which is mostly localized to the subendocardium, the swine Purkinje network extends to the subepicardial layer with a higher density. Ideker and colleagues examined transmural activation mapping during long-duration VF in swine and canines, and documented that the difference in the Purkinje distribution had a significant impact on the transmural VF activation pattern.72 In pigs, the activation rate slows from 2 minutes to 10 minutes of VF, but continues at a similar rate at all six electrodes transmurally as the VF continues. In dogs, the activation rate slows near the epicardium more than near the endocardium. Conduction block in the dog first occurs toward the epicardium and progresses with time toward the endocardium. At 10 minutes of long-duration VF, no activations is present on the epicardium, while the endocardium continues to have a rapid activation in this canine recording. This transmural mapping during VF explains why the Purkinje network ablation from the endocardium in swine did not

reduce the VF inducibility in the experiment by Pak et al.71)

Long-term results after ablation

A multicenter study reported the long-term follow-up of 38 patients who underwent catheter ablation of VPB triggers for idiopathic VF.63) During a median follow-up of 63 months, 7 patients (18%) had recurrent VF. Five of the 7 patients underwent a repeat procedure with a successful ablation of the VPB triggers. Different VPBs were demonstrated in 4 of 5 patients, and an identical VPB was demonstrated in the remaining patient. However, these patients appear to represent a highly selected cohort, thereby rendering VF ablation a rarity.

Purkinje-related VF in ischemic heart disease

Ablation

In 2002, Bansch et al. reported successful catheter ablation of electrical storm (combinations of repetitive VF, polymorphic VT, and monomorphic VT) in 4 patients following an acute MI.51) Purkinje signals preceded every trigger VPB, and ablation of the sites of the Purkinje signals eliminated all VPBs and no VT or VF recurred during a follow-up of 16 ± 5 months. The coupling interval of the trigger VPBs varied from 270 to 380 ms (325 ± 45 ms) and the interval from the earliest Purkinje potential to the onset of the VPB was from 126 to 160 ms (139 ± 18 ms). Bode et al. and Enjoji et al. have also reported the successful ablation of the Purkinje-related VF with acute coronary syndrome.54,73) Many investigators demonstrated the same approach with good results in remote MI or ischemic cardiomyop-athy.55-58) Szumowski et al. and Marrouche et al. emphasized the important role of the Purkinje fibers along the border-zone of scar in the mechanism of polymorphic VT or VF in patients post MI.55,56)

Substrate

Although experimental studies have revealed that catheter ablation of the Purkinje system could terminate VF and prevent VF induction in ani-mals,71,74) the actual role of the Purkinje system and anatomical relationship to the endocavitary structures, such as the papillary muscles or fibromuscular bands, have not been described in humans. We examined autopsy specimens from a patient with ischemic cardiomyopathy who underwent RF catheter ablation of VF.58)

Catheter ablation was performed in a patient with ischemic cardiomyopathy, chronic renal failure on hemodialysis, and an implantable cardioverter

defibrillator (ICD). During the 3 weeks prior to admission, he experienced 35 episodes of VF, 6 episodes of sustained monomorphic VT, and 150 episodes of nonsustained polymorphic VT. Trigger VPB1 with an RBBB and superior axis morphology exclusively initiated VF or nonsustained polymorphic VT and trigger VPB2 with an RBBB and inferior axis morphology initiated sustained mono-morphic VT or nonsustained polymorphic VT. During VPB1 a diastolic Purkinje potential was recorded from the left ventricular mid-septum and preceded the onset of VPB1 by 20 ms. During a normally conducted QRS, a Purkinje potential was recorded before the onset of the QRS. RF energy applications to that site eliminated VPB1. The VF was totally suppressed after the ablation of VPB1. During sustained monomorphic VT, diastolic Purkinje potentials were recorded from the left ventricular inferior septum and preceded the onset of the QRS by 60 ms. An RF energy application to this site terminated the VT and the VT became noninducible. From the successful ablation site of VPB2 which initiated nonsustained polymorphic VT at the basal septum, a left bundle electrogram was recorded during sinus rhythm. During VPB2 the earliest Purkinje potential was recorded and preceded the onset of VPB2 by 70 ms. After the ablation, the VPB1, VPB2, monomorphic VT, VF, and non-sustained polymorphic VT were totally abolished. Unfortunately, he died from pneumonia one month later. No VT or VF was observed until his death.

Gross examination of the heart revealed several areas of the left ventricular septum exhibiting dense endocardial fibrosis corresponding to the sites of the RF energy deliveries (Figure 12A). Figure 12B shows the electroatomic voltage map. At the successful ablation sites for the sustained monomorphic VT and VPB2, fibromuscular bands connecting the posterior papillary muscle and ventricular septum were recognized (Figure 12C). Figure 12D-F shows the microscopic examination of the left ventricular septum and fibromuscular band which was connected to the posterior papillary muscle. In the center of the fibromuscular band, rows of Purkinje cells were recognized. In this case, it would appear that the Purkinje system in the fibromuscular band and posterior papillary muscle may have played an important role in the initiation and perpetuation of the VF associated with ischemic cardiomyopathy.

Mechanism

It is presumed that during MI the Purkinje fibers are relatively resistant to ischemia as they are supplied by cavital blood, and the amount of

Figure 12 Histopathologic findings.

(A) Gross examination of the heart revealed several areas of the left ventricular septum exhibiting dense endocardial fibrosis corresponding to the sites of the radiofrequency energy deliveries. (B) An electroatomic voltage map revealed a low voltage area on the left ventricular septum. The red tags indicate all the ablation sites. (C) At the successful ablation sites of the sustained monomorphic VT and VPB2, fibromuscular bands connecting the posterior papillary muscle and ventricular septum were recognized. (D) The proximal portion of the fibromuscular band connecting the posterior papillary muscle and ventricular septum was examined. (E) and (F) In the center of the fibromuscular band, Purkinje cells were recognized.

APM: anterior papillary muscle, LA: left atrium, MV: mitral valve, PPM: posterior papillary muscle, SMVT: sustained monomorphic ventricular tachycardia, VPC: ventricular premature contraction. From Nogami et al.58)

glycogen in Purkinje fibers is much higher than that in myocardial cells. These surviving Purkinje fibers crossing the border-zone of the MI demonstrate

heightened automaticity, triggered activity, and supernormal excitability, which, when coupled with prolongation of the action potential duration in this

region, may result in the necessary milieu for polymorphic VT/VF.68,75) The role of reentrant wavelets is discussed, as well as the concept of rotors with sustained electrical activity rotating around a functional barrier.44-46 Microreentry in small parts of the Purkinje network as the underlying mechanism of the VPBs, has been suggested by Janse and Kleber.76) However, detailed mapping and entrainment studies were impossible in the fast polymorphic VT/VF.

In patients with VF storm after an MI which was reported by Bansch et al., the coupling interval of trigger VPBs varied from 270 to 380 ms (325 ± 45 ms) and the interval from the earliest Purkinje potential to the onset of the VPB was 139 ± 18 ms.51) In contrast to these patients after an MI, the coupling interval of trigger VPBs was 280 ± 26 ms and the interval from the Purkinje potential to the onset of the VPB was 38 ± 28 ms in the patients without structural heart disease.47) This may be related to a conduction delay between the Purkinje fibers and the myocardial tissue in ischemic conditions or the difference in the origin in the Purkinje system.

Purkinje-related VF in other heart diseases

As with the idiopathic VF and ischemic VF, a similar mechanism of VF initiation and ablative therapy has been demonstrated in other heart diseases. Sinha et al. demonstrated the mapping and ablation of VF in 5 patients with nonischemic dilated cardiomyopathy.59 Electroatomic mapping identified scar along the posterior mitral annulus in all. The earliest site of the VPB activation was localized within the scar border zone and RF ablation was performed at this region targeting the Purkinje potentials around the scar border during sinus rhythm in four. Mlcochova et al. reported two patients with repetitive VF associated with cardiac amyloidosis.53 In one of the two patients the earliest activation was recorded at the area of the proximal posterior fascicle of the left bundle during the trigger VPB. Of interest, the left myocardial voltage map was relatively normal without any low-voltage areas.

Bode et al. reported two patients with chronic/ remote myocarditis and a patient after an aortic valve replacement.54) During the trigger VPB, one patient with chronic myocarditis had the earliest activation at the free wall of the right ventricle, and the other one at the basal midseptum of the left ventricle. A patient after an aortic valve replacement for severe aortic stenosis and regurgitation underwent a successful ablation of incessant VF at the mid-inferior

septum. The local ventricular electrograms at the successful ablation sites were preceded by Purkinje potentials, which were also recorded before the QRS during sinus rhythm.

In 2003, Hai'ssaguerre et al. described the role in the induction of VF in a small number of patients with Brugada syndrome or long-QT syndrome who had frequent VPBs.52) In my experience, Purkinje-like potentials were recorded from the right ventricular free wall during trigger VPBs in Brugada syndrome. However, the VPBs could not be eliminated by RF energy applications from the endocardium and the VF recurred shortly after the ablation.

Catecholaminergic polymorphic VT (CPVT) is a lethal familial disease characterized by episodic syncope or sudden cardiac death occurring during exercise or acute emotional stress in individuals without structural cardiac abnormalities.77) The underlying cause of these episodes is bidirectional VT, polymorphic VT, or VF. It is known to be associated with genetic mutations of the RyR2 or CASQ2 gene and CPVT is caused by an increased Ca2+ release through defective ryanodine receptor (RyR2) channels. Cerrone et al. demonstrated that the mechanism of CPVT was due to a focal origin in the Purkinje network in a knockin (RyR2) mouse model.78) They found that the single Purkinje cells generated delayed afterdepolarization-induced triggered activity at lower frequencies and levels of adrenergic stimulation than the wild-type.

Relationship between polymorphic VT and mon-omorphic VT

In the Purkinje-related arrhythmias, there are polymorphic VT/VF and monomorphic VT. However, the difference in the clinical and electro-physiological characteristics between polymorphic VT/VF and monomorphic VT has not been determined. In some ischemic patients with primary VF (i.e., VF not preceded by monomorphic VT), sustained monomorphic VT also occurred before and/or after successful VF ablation.51,54,58,73) Tsuchiya et al. reported a case which exhibited a transition from a Purkinje-related polymorphic VT to a monomorphic VT after the administration of class Ic drug.79) In their patient, the intravenous administration of pilsicainide provoked incessant nonsus-tained polymorphic VT and the polymorphic VT changed to monomorphic VT after an additional administration of pilsicainide. An RF current application to the Purkinje system at the left ventricular septum suppressed both the polymorphic and mono-morphic VTs. The effect of catheter ablation or

antiarrhythmic drugs might be associated with the "organization" of an unstable reentry circuit and the prolongation of the tachycardia cycle length.

Conclusions

Previous studies revealed that Purkinje-related arrhythmias are actually composed of multiple discrete subtypes that are best differentiated by their mechanism, morphology, basal heart disease, and the successful ablation site. Recognition of the heterogeneity of these arrhythmias and their unique characteristics should facilitate an appropriate diagnosis and therapy. Currently, there is no single hypothesis explaining the maintenance of VF. However, in patients with an electrical storm, catheter ablation of the triggering VPBs from the Purkinje system should be used as an electrical bailout therapy.

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