The conduction system, comprising the bundle branches, its fascicles and Purkinje fibres, is a source of ventricular arrhythmias. Both re-entrant and focal mechanisms operate. The specialised conduction system originates from the atrioventricular node as the His bundle, and after passing through the membranous septum, subdivides into the right and left bundle branches. The right bundle branch (RBB) courses along the right ventricular septum until it reaches the moderator band. The left bundle branch (LBB), which arborises much more proximally into two main trunks – the left superior and inferior fascicles – and then along its course, gives off an extensive network of subfascicular fibres.1 The superior and inferior fascicles course, respectively, towards the lateral and septal papillary muscles, coordinating their contraction and ensuring synchronous activation of the left ventricular myocardium and mitral valvular apparatus. A septal fascicle may arise separately from the LBB or as a sub-branch of the left superior or inferior fascicle and insert into the mid-septum. Distally, the fascicles arborise into Purkinje fibres that are composed of longitudinally arranged Purkinje cells insulated from ventricular myocytes by connective tissue.
In addition to their structural differences, the electrical properties of Purkinje cells are unique when compared with cardiac myocytes. The action potential of a Purkinje cell demonstrates a more rapid upstroke and a higher amplitude when compared with ventricular myocytes.2 In addition, increased expression of connexin proteins allows for enhanced longitudinal cell-to-cell communication.3,4 Both of these factors contribute to increased conduction velocity in the Purkinje network, threefold that of typical cardiomyocytes.5
The papillary muscles, in contrast to the cardiac conduction system, serve a primarily structural role as outcroppings of myocardium within the ventricular cavity that attach to the leaflets of atrioventricular valve leaflets via the chordae tendineae. They provide tension on the valve leaflets during systole causing coordinated valve closure. The left ventricular papillary muscles are one of the more common non-outflow tract origins of premature ventricular contractions.
Fascicular Ventricular Arrhythmias
Arrhythmias originating from the specialised cardiac conduction system can be due to either triggered activity, likely due to altered cellular calcium handling, or re-entry within the conduction system due to its insulated nature and anisotropic conduction properties.6
Ventricular tachycardia involving the conduction system can be classified into three groups: bundle branch re-entry, fascicular re-entry and non-re-entrant fascicular ventricular tachycardia (VT). The Purkinje system can also play a role in the initiation and perpetuation of polymorphic ventricular arrhythmias and ventricular fibrillation. These arrhythmias can occur in both structurally normal and abnormal hearts.
Bundle Branch Re-entry Ventricular Tachycardia
Bundle branch re-entry (BBR) VT (BBRVT) is a macroreentrant arrhythmia in which propagation occurs antegrade over one common bundle, across the septal myocardium and retrograde over the contralateral bundle. As this typically requires conduction system delay to sustain re-entry, this rhythm is very uncommon in the absence of structural heart disease. The RBB is most often the antegrade limb of the circuit. This produces a surface QRS with a typical LBB block conduction pattern. The RBB-V interval will be equivalent to or greater than that observed during sinus rhythm. An atypical form of BBRVT can also occur where conduction occurs antegrade over the LBB and retrograde via the RBB, which will produce a QRS with typical RBB block morphology. Here, since the RBB is activated retrograde, the RBB-V interval will typically be negative. In both scenarios, the H-V interval is most commonly longer during BBRVT than during sinus rhythm due to conduction delay, but theoretically may be shorter if the site of His recording is significantly proximal to the turnaround site of the bifurcation of the RBB and LBB.7
Interruption of conduction over the RBB will render VT non-inducible, and most commonly, antegrade conduction will be present over the LBB, even if not clearly observed at baseline. In some cases, LBB conduction may only be present in the retrograde direction, and complete heart block can result. Regardless of the subtype of BBRVT, as the apical interventricular septal myocardium is involved in the re-entry circuit, entrainment from the right ventricular apex can be a useful discriminating tool, as the postpacing interval minus tachycardia cycle length will typically be <30 ms.8 Figure 1 illustrates a case of the atypical form of BBR in a patient with baseline conduction system disease.
Fascicular Re-entry
The most common form of fascicular arrhythmia in the structurally normal heart is idiopathic fascicular re-entry. This form of VT was classically described to occur in the absence of structural heart disease, have a right bundle and left superior axis, and be induced with atrial pacing.9 Further, Belhassen et al. demonstrated that this VT was uniquely sensitive to verapamil; thus, its common moniker, verapamil-sensitive idiopathic VT.10
Re-entrant fascicular ventricular tachycardia remains an incompletely understood entity where the entirety of the circuit is yet to be defined. However, based on the QRS morphology, this form of VT can be divided into four subtypes based on the VT exit site: left inferior subtype, left superior subtype, septal subtype and reverse subtype.11 In all cases, the circuit is thought to involve an insulated Purkinje fibre, the local ventricular myocardium and an unsolved slowly conducting component of the circuit serving as the upper turnaround point. Verapamil sensitivity is felt to be dependent on the amount of the circuit within the fascicular system.
The left inferior subtype is by far the most common form of fascicular re-entry, accounting for 70–80% of reported cases. The exit site for this circuit is from a distal portion of the left inferior fascicle, and the QRS has a right bundle and left superior axis.
The left superior subtype accounts for 10–15% of cases, and has an exit site from the left superior fascicle resulting in a right bundle and right inferior axis.
The remaining subtypes are exceedingly rare. The septal subtype of fascicular ventricular tachycardia involves a re-entrant circuit with retrograde conduction over the septal fascicle, and antegrade activation simultaneously over the left superior and inferior fascicles, leading to a QRS morphology very similar to sinus rhythm. Theoretically, neither ablation of the left superior or inferior fascicles alone should interrupt the septal fascicular VT circuit.
Non-idiopathic Fascicular Re-entry
In patients with conduction system disease, a form of fascicular re-entry may be observed where conduction occurs antegrade over one of the left-sided fascicles, most commonly the superior fascicle, and retrograde via the inferior fascicle. In this condition, in contrast to BBRVT, the H-V is less than that observed during sinus rhythm (SR), often by >40 ms due to the turnaround site for VT being quite distal to the His deflection, unlike BBR, where most commonly the H-V observed during VT is greater than during SR.12 The left anterior fascicle (LAF) is typically the antegrade limb and can easily be discerned from the QRS morphology (RB right axis deviation pattern).13 The F-V time at successful ablation sites in the antegrade limb of the circuit should be equivalent or longer during VT than SR, as the pattern of conduction should be the same with the possibility of distal conduction delay. Sites where the F-V interval is shorter during VT than during SR represent bystanders. In contrast to BBR, the RB is a bystander in this circuit and, as such, ablation of the common RB will not affect the circuit. Ablation of either the LAF or left posterior fascicle is required; typically, the antegrade limb (most often the LAF) is targeted.
Mapping Fascicular Arrhythmias
As a general principle, for all types of VT involving the fascicular system, mapping the earliest recorded fascicular site is a good place to start. At sites in the antegrade limb of the circuit, the F-V interval during VT should be greater than or equal to the F-V interval during sinus rhythm. If the F-V interval observed during VT is less than that during SR, the site cannot be involved in the antegrade limb of the circuit (Figures 2 and 3). Overdrive pacing from sites of interest can be extremely helpful. In re-entrant forms, entrainment should be observed with a postpacing interval minus tachycardia cycle length near zero if the fascicular potential can be captured. In some cases, the postpacing interval minus tachycardia cycle length may be negative if a distal component of the circuit (ventricular myocardium near the exit) is also capture, and the postpacing interval is measured to the fascicular potential. Finally, due to the re-entrant mechanism, it is possible in these cases to observe orthodromic capture of the upstream conduction system when pacing downstream sites (Supplementary Figure 1).
Nogami et al. described discrete potentials in the distal segments of the re-entrant fascicular tachycardia, with the P1 potential representing anterograde activation and a P2 potential from the retrograde distal conduction system not thought to be involved in the circuit (Figure 4).11 Since the antegrade limb of the fascicular re-entry circuit is felt to represent an insulated distal fascicular fibre, the P1-V interval during SR is quite short or even negative, while during VT, the P1-V should be long. Notably, these potentials may be very difficult to record using a large electrode, such as on an ablation catheter.14 These potentials are recorded using multipolar catheters placed along the long axis of the left inferior or superior fascicle, and with smaller electrodes for improved signal resolution. In their series, P1 potentials were recorded in 60% of patients. When these are evident, a turnaround point, indicated by the latest P1 potential intersecting with the P2 potential, is ideal for ablation. Because of its distal position in the circuit, targeting these later potentials prevents damage to the proximal LBB. In the septal type of fascicular re-entry, a diastolic fascicular potential may be observed at the site of the septal fascicle; the F-V interval at this site during VT should, again, be greater than observed during sinus rhythm.
Non-re-entrant Fascicular Ventricular Tachycardia/Premature Ventricular Contraction
Focal arrhythmias from the fascicular system can also occur. While these are most frequently seen in patients with structural heart disease, they may also occur in its absence.15,16 It is impossible to distinguish between non-re-entrant and re-entrant forms of fascicular VT based on the ECG alone. Clinically, focal fascicular VT does not typically respond to verapamil. During electrophysiological evaluation, it should not be induced with programmed stimulation, but may be provoked by catecholamines or rapid pacing. They are usually manifested as salvos of premature ventricular contractions (PVCs) or repetitive tachycardia. When sustained, they are distinguished from re-entrant arrhythmia by the inability to reset or entrain.
Making the distinction between focal and re-entrant fascicular VT is critical to the success of catheter ablation for these arrhythmias. In contrast to fascicular re-entry, ablation for an automatic focus will not be successful if the involved fascicle is empirically transected at any point along its course; rather, the focal site of origin must be targeted. For this reason, the earliest site of fascicular activity must be mapped and ablated. Empiric ablation is highly discouraged, as proximal ablation may result in increased difficulty with subsequent mapping efforts due to loss of antegrade fascicular signals.
Papillary Muscle Arrhythmias
One potential reason papillary muscles are a common site of premature ventricular contraction origin may be due to the dense population of specialised conduction tissue within these structures. In one series, at 45% of successful ablation sites on the papillary structure, a fascicular pre-potential was able to be identified,suggesting that in some cases these PVCs may simply be originating from the fascicular system at its distal terminus within the papillary complex.17
Success rates for ablation of papillary muscle PVCs are relatively low compared with other idiopathic PVC sites, in the 50–80% range.18–23 The activation time at sites of successful PVC suppression on the papillary muscle is typically 20–40 ms pre-QRS onset.17,22,23
Successful ablation of PVCs originating from the papillary muscle often involves rather extensive energy delivery. In one series from a highly experienced centre, nearly one-quarter of cases required >20 lesions to achieve acute success.22 This need for multiple ablations may be due to a multitude of factors, but three stand out. First, the regions of the papillary muscles are the thickest areas of the left ventricle, and it may be that the origin of a papillary muscle PVC is deep within the muscular structure. As such, extensive lesion delivery is needed to achieve adequate depth to reach the site of origin.
Second, it is possible that the activation pattern of the endocardial surface in the region of the papillary muscles may not serve as a reliable surrogate for the site of closest proximity to the site of origin. Work using a beating heart model has shown that an intramural site of origin may lead to displaced sites of earliest surface activation.24,25 Furthermore, if the site of origin involves the fascicular system, it is possible that the site of earliest myocardial activation may be remote from the site of initiation due to the insulated properties of these fibres. These factors may lead to imprecision in mapping the exact site of origin, again, potentially leading to more extensive ablation prior to success.
Third, and in the authors’ opinion, the most likely reason extensive ablation is often required, is that due to the highly mobile nature of the papillary muscle structure, many energy applications do not actually result in significant tissue heating due to inconsistent catheter tissue coupling. In our experience, and in that of other centres, contact-force sensing is generally not helpful in this scenario, as the anatomy of the papillary muscle rarely allows for a catheter to be forcefully advanced onto the structure without becoming displaced.22 For this reason, measures that allow one to assess whether tissue heating is occurring are critical to success.
Currently, the only two measures available that reflect lesion formation in the tissue are impedance decline and characteristic tissue changes on intracardiac echocardiography. Calculated values that have been correlated with lesion formation in other cardiac chambers or other areas of the ventricle may not hold true when targeting a 3D complex structure, such as the papillary muscle. For this reason, we will often continue to apply radiofrequency energy at a site of suspected papillary PVC origin until the targeted tissue becomes echogenic on intracardiac echocardiography (Supplementary Figure 2 and Supplementary Video 1). When catheter stability is an issue, focal cryoablation may prove useful.26,27 Other tools that may enhance constant catheter tissue coupling, such as a deformable lattice-tipped catheter may also prove useful. It will be interesting to see whether pulsed-field ablation, which is dependent on constant tissue proximity to maintain field strength rather than catheter–tissue coupling for current delivery, proves to be superior for targeting papillary muscle-based arrhythmias. Preclinical work suggests that pulsed-field ablation lesions at these sites may be larger and deeper than radiofrequency lesions.28
In addition to its utility in assessing lesion formation, intracardiac echocardiography may also be useful in identifying structural abnormalities of the papillary complexes. In one series, 39 of 43 patients with papillary muscle ventricular arrhythmia (VA) were found to have increased echogenicity of the papillary muscles. In this series, 44% of these hyperechoic sites harboured the VA site of origin.23 Other imaging modalities, such as cardiac MRI and cardiac CT, may also be used to characterise the papillary muscle anatomy and identify structural abnormalities. In this same series, when papillary calcification was observed, these locations were observed with a VA site of origin 100% of the time.
Importantly, despite extensive ablation to the papillary muscles, the development of significant valvular dysfunction is quite rare.19 However, caution should be taken with extensive ablation at the interface of the papillary muscle with the left ventricular wall, as the authors have observed the development of intramural haematomas at this site.29
Mapping the Papillary Muscles
First, a point on nomenclature. The papillary muscles of the left ventricle are complex structures and may have anatomical variability across individuals. For clarity of communication, we will think of the papillary muscles as mountains of myocardium arising from the left ventricular wall. The apex of the papillary muscle is the point where the muscle is smallest and the chordae tendineae attach. This can be confusing, because the apex of the papillary muscle is the point that is the least ‘apical’ relative to the left ventricle. For this reason, many refer to this as the tip of the muscle. The broadest portion of the muscle, where it joins the left ventricle will be referred to as the base of the muscle; again, this can be misleading, as this region is the least ‘basal’ aspect of the papillary muscle relative to the left ventricle.
Because the papillary muscle structure is made of multiple peaks and valleys, mapping these structures can be complex. As a result of this structural complexity, we recommend the use of a linear mapping catheter to allow for the many points on these complex structures to be interrogated. Mapping catheters with a large footprint simply are not able to be wedged into the crevasses that may harbour the site of critical activation. Further, when mapping the site of origin of VA arising from the papillary muscles, the usage of intracardiac echocardiography is critical. The structural complexity of the papillary muscle complex can be very difficult, if not impossible, to display on current electroanatomic mapping systems. To overcome this challenge, the operator must catalogue the anatomical position of the mapping catheter at each site sampled. At each site sampled, it is helpful to ask where on the papillary complex the catheter is relative to the papillary apices, and whether the catheter lies on the septal or lateral aspect of the structure. Within these parameters, the earliest site of activation is identified, and then targeted for ablation based on electroanatomic mapping and constant surveillance under intracardiac echocardiography. Often, when radiofrequency energy is applied, acceleration of ectopy can often be observed and may serve as a confirmatory sign of energy application at the proper location.30 In some scenarios, high-fidelity cardiac CT imaging may be integrated with the electroanatomic mapping system to better characterise and display this complex anatomy.31
ECG Characteristics
All PVCs and VT arising from the left-sided conduction system or the left ventricular papillary muscles will exhibit a right bundle morphology in lead V1. VAs arising from the papillary muscle may be more likely to present as PVCs alone, rather than both PVCs and VT.32
VAs originating from the inferior papillary muscle and left posterior fascicle will have a RB pattern in V1 and a left superior QRS axis (Supplementary Figure 2). VAs from the inferior papillary will typically exhibit an R>r´ morphology in V1, whereas VA from the left posterior fascicle will tend to have a r<R´ morphology. These both can be differentiated from VAs arising from the inferior mitral annulus, as they will exhibit a positive to negative precordial transition, whereas VA from the mitral annulus will tend to have a positive QRS morphology across the precordium.
VAs originating from the superior papillary muscle and LAF will have a RB pattern in V1 and a right inferior axis. VA arising from the superior fascicular system will tend to have a narrower QRS (often <130 ms) and, again, is more likely to demonstrate an r<R´ morphology when compared with those with a superior papillary origin (Supplementary Figure 3).
Idiopathic VF
The term, ‘idiopathic VF’ (IVF), describes the occurrence of recurrent VF in patients without discernible heart disease, including genetic arrhythmia syndromes. The exact mechanism is not fully defined. Purkinje fibres act as triggers, and in the maintenance of VF in several disease states and in patients with IVF.33 Purkinje tissue and regions of Purkinje–muscle junctions are more prone to triggered automaticity. Isolated Purkinje fibres in structures, such as the right ventricular moderator band and false tendons, are commonly implicated in IVF.34,35 Certain genetic mutations, notably the Dutch haplotype DPP6 and the IRX3 genes, have been associated with IVF.
Catheter ablation targeting culprit regions of the Purkinje network has moderate to high success in preventing recurrent VF and ICD shocks. When initiating PVCs are documented, targeting the appropriate regions based on QRS morphology and pace mapping is possible (Supplementary Figure 4). The ongoing presence of initiating PVCs allows for more targeted mapping and ablation. In the absence of PVCs, when IVF is the likely diagnosis, systematic mapping of the endocardium and epicardium may identify small areas of structural abnormalities not identified by imaging.36 Use of drugs, such as isoproterenol and sodium channel blockers, has variable success in inducing Purkinje-mediated arrhythmias in the electrophysiology laboratory.
Purkinje potentials recorded during sinus rhythm precede the onset of PVCs or VF (Supplementary Figure 5). In the case of the right ventricular moderator band or false tendons, intracardiac echocardiography is useful in confirming contact. We have used a cryoballoon for ablation on the moderator band when catheter stability is poor.37 Often, ablation at sites adjacent to the earliest Purkinje potential can prevent recurrences due to local re-entry (Figure 5). Dissociating the Purkinje fibres from the local myocardium can be successful in preventing recurrence of VF, even if PVCs are not fully suppressed.36
Conclusion
Arrhythmias originating from the cardiac conduction system and papillary structures can occur in patients with and without structural heart disease. When the conduction system is involved, highly detailed mapping and careful electrophysiological evaluation are often the key to success. In the case of papillary arrhythmias, excessive myocardial thickness and effective lesion formation are common issues. Finally, the Purkinje system can play a role in the initiation and perpetuation of ventricular fibrillation, both in the setting of structural disease and the normal heart.38
Clinical Perspective
- Conduction system-associated arrhythmias can occur in patients with and without heart disease.
- Ablation of conduction system-related arrhythmias requires careful electrophysiological evaluation with particular attention paid to the relationship of conduction system activation during ventricular tachycardia and during sinus rhythm.
- Ablation of papillary muscle premature ventricular contractions may be challenging due to the muscular structure’s thickness and mobility, often requiring extensive energy delivery and precise mapping techniques. Intracardiac echocardiography can be essential for success.
- The conduction system may be implicated in the initiation and perpetuation of idiopathic ventricular fibrillation. Ablation of the implicate regions may be effective in reducing recurrence.