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Synchronous ventricular pacing with direct capture of the atrioventricular conduction system: Functional anatomy, terminology, and challenges
Author’s Accepted Manuscript Synchronous ventricular pacing with direct capture of the atrioventricular conduction system: Functional anatomy, terminology, and challenges Siva K. Mulpuru, Yong-Mei Cha, Samuel J. Asirvatham www.elsevier.com/locate/buildenv
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S1547-5271(16)30614-2 http://dx.doi.org/10.1016/j.hrthm.2016.08.005 HRTHM6809
To appear in: Heart Rhythm Received date: 10 June 2016 Cite this article as: Siva K. Mulpuru, Yong-Mei Cha and Samuel J. Asirvatham, Synchronous ventricular pacing with direct capture of the atrioventricular conduction system: Functional anatomy, terminology, and challenges, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2016.08.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Conduction System Pacing
Synchronous ventricular pacing with direct capture of the atrioventricular conduction system: Functional anatomy, terminology, and challenges
Siva K Mulpuru MD1, FHRS, Yong-Mei Cha MD1, FHRS, Samuel J Asirvatham MD1,2, FHRS
1. Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 2. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN Brief running title: Selective conduction system pacing Conflicts of interest: S. J. Asirvatham receives no significant honoraria and is a consultant with Abiomed, Atricure, Biosense Webster, Biotronik, Boston Scientific, Medtronic, Spectranetics, St. Jude, Sanofi-Aventis, Wolters Kluwer, Elsevier, Zoll. None for S.K. Mulpuru and Y. M Cha Corresponding Author: Samuel J. Asirvatham, MD Professor of Medicine, Division of Cardiovascular Diseases 200 First Street SW Rochester, MN 55905 Email: [email protected] Phone number: 507-293-3376 Fax number: 507-255-2550
1
Conduction System Pacing
Abstract: Right ventricular apical pacing is associated with an increased incidence of heart failure, atrial fibrillation, and overall mortality. As a result, pacing the ventricles in a manner that closely mimics normal atrioventricular conduction with an intact His-Purkinje system has been explored. Recently, the sustainable benefits of selective His bundle stimulation have been demonstrated and proposed as the preferred method of ventricular stimulation for appropriate patients. Ideally, conduction system pacing should be selective without myocardial capture, overcome distal bundle-branch block when present, and not compromise tricuspid valve function. Contemporary literature on conduction system pacing is confusing largely because of inconsistent terminology and, at times, anatomically inaccurate terms used interchangeably for nonsynonomous anatomic sites.
In this review, we discuss the functional anatomy of the
atrioventricular conduction access with specific emphasis on terminology, relationship to the membranous septum, tricuspid valve tissue, and proximity to atrial or ventricular myocardium. The potential benefits of each specific site as well as associated unique difficulties with those sites are described. Key Words: cardiac pacing; ventricular synchrony; His bundle; AV node; conduction system
2
Conduction System Pacing
Introduction The human cardiac conduction system is admirably suited to deliver coordinated electrical impulses that result in synchronous and mechanically efficient ventricular myocardial contraction. It follows that single site myocardial stimulation being fundamentally different from the facilitated multisite endocardial breakthrough with conduction system stimulation results in abnormal physiology. Indeed, chronic right ventricular apical pacing (RVAP) is associated with increased risk of death 1, 2, heart failure, hospitalization 3, and the development of persistent atrial fibrillation
4, 5
. These clinical adverse effects have been directly linked to the
abnormal electrical activation sequence and resulting mechanical ventricular dyssynchrony. (Supplemental material for expanded discussion on pathophysiology of adverse effects due to RV apical pacing) Biventricular pacing and cardiac resynchronization therapies (CRT) are superior to RVAP in patients with reduced ejection fraction 6.
However, optimal lead location and anatomic
limitations to consistently place the lead at the most beneficial sites as well as the fundamental disengagement of the intrinsic cardiac conduction system limit the utility of CRT. Alternate ventricular myocardial pacing sites have thus been investigated either for single site or part of a biventricular pacing system. Nevertheless, any small number of direct myocardial stimulation sites is unlikely to mimic the normal efficiency of the intrinsic conduction system. Ideal cardiac stimulation with pacing would involve direct and sole capture of the proximal conduction system without ventricular or atrial myocardial sensing or capture, not effect valvular function, and overcome distal bundle-branch and Purkinje pathology that results in bundlebranch block or electromechanical uncoupling. Significant efforts towards this ideal goal have recently been made. However, confusion in the literature exists with variably used terminology, 3
Conduction System Pacing
inexact appreciation of the precise portion of the anatomic conduction system being stimulated, and whether or not distal Purkinje disease can be overcome with proximal conduction tissue pacing. In this review, we discuss the functional anatomy of the conduction system, attempt to clarify the existing nomenclature with regard to specific sites of stimulation, and further discuss the impact of lead orientation and pacing output. Also presented are some of the advantages, disadvantages, and specific challenges associated with each possible approach toward ideal conduction system pacing. Anatomy and physiology of the atrioventricular conduction system Electrical excitation from the sinus node reaches the atrioventricular (AV) node largely through nonspecialized, atrial myocardial tissue. Because of naturally occurring anatomic obstacles to conduction in the atrium such as the fossa ovalis and, in part, the Eustachian ridge, the wave front approaches the AV node through an anterior and posterior path and inserts into similarly positioned extensions of the AV node constituting the fast and slow pathways. The AV node and slow pathway myocardium are located within the triangle of Koch. This triangle is formed by the tendon of Todaro up to the anterior and superior limit of the septal leaflet, the septal leaflet of the tricuspid valve insertion margin, and an imaginary line connecting the two at the floor of the coronary sinus. The compact AV node occupies a variable position near the epicenter of this triangle and is thus an atrial structure being posterior (atrial) to the septal leaflet of the tricuspid valve. The penetrating bundle of His, usually referred to simply as the His bundle (HB), is a ventricular structure and is located within the membranous portion of the ventricular septum (Figure 1A). The HB is surrounded by connective tissue from the central fibrous body, which constitutes an
4
Conduction System Pacing
insulating layer to the chord-like bundle.
The membranous septum itself is formed as a
conjunction of two valve leaflet commissures; on the right, the commissure between the anterior and septal leaflets of the tricuspid valve are immediately adjacent and opposite on the left with the commissure of the right and noncoronary sinuses of Valsalva of the aortic valve. Thus, surrounding the HB, there is no myocardial tissue (Figure 1B), and the His bundle itself is a chord-like structure measuring up to 20 mm in length and 4 mm in diameter
7, 8
.
The major
connections between the cells of the HB are end-to-end intra-collated discs giving rise to its typical property of rapid longitudinal conduction. The penetrating HB that emerges on the muscular crest of the interventricular septum to continue as the bundle branches. Noteworthy is that there is no ventricular myocardial proximity around the HB itself as it penetrates through the membranous septum and after a variable length divides between the right and left bundles. Occasionally, the HB divides on the left side of the septum, and when this occurs, the right bundle may emerge at the base of the septal papillary muscle 8. The proximal bundle branches, like the HB, are surrounded by connective tissue which is a direct continuation of the fibrous body. The relationship of the penetrating HB to tricuspid valve tissue is important to clarify. Since the penetrating HB is located on the membranous septum and the membranous septum in turn is made up in part of tricuspid valve tissue, anatomically, any conduction system location proximal to tricuspid valve tissue and thus the membranous septum would not be the HB. Of more functional and practical relevance, however, is the question of whether the HB can be stimulated without affecting tricuspid valve function.
This certainly can be accomplished since the
membranous septum is in part proximal to the free and mobile tricuspid valve leaflets, and in
5
Conduction System Pacing
addition, the more distal membranous septum can be reached via the commissure between the free septal and anterior leaflets of the tricuspid valve. The compact AV node located in the atrium within the triangle of Koch serves as the gateway of electrical conduction to the ventricles. The compact AV node, in addition to its characteristically slow conduction, also exhibits decremental properties. However, the transition between the compact AV node and HB is not abrupt, and atrial portions of the conduction system (distal most narrowed portion of the AV node) may have functional properties similar to the penetrating bundle of His. Indeed, linkage analysis has confirmed that the HB and the most inferior portion of the compact AV node are both derived from the ventricular myocardium 9. (Supplemental material for expanded discussion on physiology of normal conduction) Nomenclature Non-apical RVP sites have been reasonably classified into generally accepted terms including the outflow tract, inflow septal, and apical sites 10(Figure 2). However, inexact and interchangeable use of non-synonymous terms with regard to commonly described conduction system pacing (Figure 3) has given rise to significant confusion.
“Para-Hisian”/ “Peri-Hisian” pacing. These terms have been variably used to describe stimulation in or near the HB presumably including targeted HB capture as well as the proximal bundle-branches and surrounding myocardium11-13
HB pacing.
Anatomic HB pacing would involve the stimulatory electrode making
contact with the penetrating HB as it traverses through the membranous septum. No surrounding ventricular myocardium is present in this location, and sole conduction system capture would be anticipated. 6
Conduction System Pacing
AV nodal pacing. An electrode placed in the center of the triangle of Koch would stimulate the compact AV node. The proximate atrial myocardium may or may not be captured, and no direct ventricular myocardial capture would be anticipated.
AV septal pacing. Because the septal leaflet of the tricuspid valve is inserted more apical compared to the mitral valve, a portion of the interventricular septum has left ventricular myocardium on one side and right atrial myocardium on the other. This structure is called the AV septum 14. Pacing at this site stimulates ventricular myocardium and may, in addition, sense or capture the right atrial myocardium. No specific capture of the conduction system would be routinely expected with AV septal pacing.
Proximal bundle-branch capture.
Here, the target for pacing is one or both of the
proximal bundle-branches located on the crest of the interventricular septum after the division of the HB.
Stimulation would be expected to occur of the ventricular
myocardium at the crest, but sole right and/or left bundle capture may occur depending on the exact position of the stimulatory cathode.
Distal AV nodal/transitional tissue stimulation. The transitional zone that constitutes the terminal, relatively linear portion of the compact AV node prior to it being named the penetrating HB on the membranous system can also be successfully stimulated with conduction system capture. Characteristics of stimulation at this site may be similar and indistinguishable from penetrating HB capture with minimal or no detectable decrement seen.
Given the confusing and variably used terms all essentially attempting to selectively pace the conduction system to reproduce a normal QRS morphology and without ventricular myocardial capture, we propose the use of the term selective conduction system pacing when such a name is 7
Conduction System Pacing
meant to be fulfilled. Because of the juxtaposition of tissues with very different conduction properties, the exact stimulated structure and resulting excitation wave front may be exquisitely dependent on the pacing output, dimensions and type of the stimulatory electrodes, and the orientation of the cathode and anode relative to the approximated conduction tissue and surrounding myocardium (Figure 4). Ideally, for selective conduction system pacing, a very small bipole with both anode and cathode secured to the targeted conduction tissue with stimulation at sufficiently low output is used. Distal electrode unipolar stimulation has been used with success to achieve the desired result of sole conduction system stimulation. However, with larger electrodes and the antenna of the unipolar pacing vector, the potential for intermittent, undesirable myocardial stimulation exists. Presently available leads have a definite separation between the active helix serving as a cathode and the more proximal anode. The orientation and pacing output have significant interaction with variable resulting excitation patterns (Table 1). (Supplemental material for expanded discussion on effects of bipole orientation to structures captured) We now briefly review the characteristics, advantages, and disadvantages of each of the sites that have been described (Table 2). Pacing the penetrating bundle of His Selective pacing of the HB as it courses through the membranous septum is accomplished by screwing in the cathode through the fibrous sheath around the HB. Pacing results in QRS morphology similar to a normally conducted beat.
If the electrode is exactly on the HB,
thresholds will be low and acceptable, but nearby locations on the fibrous skeleton of the heart
8
Conduction System Pacing
could still allow HB capture but with high thresholds and the potential for far-field ventricular myocardial capture from far-field capture or anodal stimulation. Advantages
Given that there is no myocardium on the membranous septum, sole conduction system capture is the norm with maximized engagement of the His-Purkinje network and resulting normal mechanical contraction.
Because the membranous septum is formed at the commissure of the septal and anterior tricuspid leaflets, a lead placed in this location should not cause any disturbance of tricuspid valve closure and thus not result in tricuspid regurgitation despite the ventricular location of the membranous septum. Further, despite the fact that the tricuspid valve tissue forms in part in the membranous septum, the free margin of the attachment of the leaflets of the tricuspid valve are distal to portions of the membranous septum, and pacing at that site can stimulate the HB without interfering with tricuspid valve closure.
Again, because of no myocardium on the membranous septum, a distal HB electrogram can be recorded prior to screwing in the electrode to allow electrical sensing confirmation of the bundle of His site in addition to its characteristic anatomic location.
Disadvantages
The membranous septum is a relatively thin structure with its thickness being potentially less than that of the length of a standard helix. Thus, perforation with potential shunt or exposure of the helix tip to the left-sided circulation remain unwanted possibilities.
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Conduction System Pacing
Precise localization into the bundle is needed to achieve acceptable thresholds. Whereas peri-Hisian stimulatory location or lead tip location would give consistent conduction system pacing only at higher output with possible simultaneous ventricular capture.
Attempts at screwing in the lead into the HB, particularly if repeated attempts are needed or when extracting the lead, may result in complete AV block or bundle-branch block (supplemental figure 1) in patients who otherwise may have normal conduction.
Pacing the AV node The compact AV node may be stimulated with the cathode secured in the middle of the triangle of Koch atrial to the septal leaflet of the tricuspid valve. Advantages
Sole conduction system capture with QRS similar to conducted beats.
No potential for ventricular myocardial capture.
No potential for promoting tricuspid regurgitation.
Disadvantages
Proximal AV nodal capture would result in significant decrement and possible Mobitz I block to the ventricle at higher pacing rates.
Depending on the output and lead orientation as well as the set AV paced interval, atrial myocardial sensing and/or capture may complicate pacing from this location.
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Conduction System Pacing
Pacing the distal AV node transitional zone Pacing at this site would be essentially indistinguishable from penetrating bundle of His capture. However, the electrode will be atrial to the line of attachment of the septal leaflet and thus in the apex of the triangle of Koch. Advantages
Sole conduction system pacing.
Advantage over compact AV nodal pacing would be that no decrement would be expected.
No potential for ventricular myocardial capture.
No potential for causing or worsening tricuspid valve dysfunction.
Disadvantages
More likely to be affected by far-field atrial sensing or capture than pacing the penetrating bundle of His.
Pacing the proximal bundle branches The cathode secured on the crest of the ventricular septum may capture the right bundle-branch alone. The resulting QRS would be nearly identical to conducted rhythm since a very short conduction time would be required to enter the left bundle concurrently with antegrade right bundle activation. Pacing at this site may also capture the left bundle or both bundles together depending on the type and how superficial the branching on the crest is in a given heart (Figure 5).
11
Conduction System Pacing
Advantages
No risk of membranous septal perforation.
Relatively larger target.
Could potentially capture the conduction tissue distal to the level of bundle-branch block, thus normalizing conduction even in a patient with bundle-branch block during conducted rhythm.
Disadvantage
Exact type of activation will be dependent on pacing output and amount of local myocardial capture.
Some, but likely insignificant potential for promoting tricuspid valve regurgitation (could course through the commissure and thus not affect coaptation).
AV septal pacing is not a type of attempted conduction system pacing and is discussed briefly under alternate ventricular myocardial pacing (see below). Overcoming left bundle-branch block A principle reason for attempting synchronous pacing particularly in heart failure patients is because of the dyssynchrony from preexisting left bundle-branch block and other infra-Hisian conduction abnormalities. Can pacing the HB proximal to the site of block overcome such infraHisian abnormality?
In patients with very proximal bundle-branch block, stimulation by
physical electrode (pacing lead) that captures the bundles distal to the level of the block may, in part, normalize the QRS (Figure 6). For block that is within the HB or very proximal in the bundle branches, since fibers destined to be the right or left bundle are histologically 12
Conduction System Pacing
differentiated more proximally 15, capture may improve conduction. However, in most patients with left bundle-branch block, the disease and fibrosis is more distal than the HB/left bundle junction and thus more problematic in terms of proximal capture normalizing conduction. However, some proximal disease is usually present as well and associated with a decrease in the number of conducting cells proximally available to produce a sufficient upstream voltage gradient (source) to successfully depolarize through the diseased distal left bundle-branch
16, 17
.
Virtual electrode polarization effect has been postulated as one mechanism for recruitment of blocked bundle branches18. Indeed recent studies using HB pacing leads in patients with AV block have demonstrated higher rates of His-Purkinje recruitment even in patients with lower levels of conduction block
19, 20
. This recruitment or restoring of a normal QRS by His pacing
even in the absence of intact distal His-Purkinje activation by optimizing the source sink relationship is a major goal that requires study on route to allow selective conduction system pacing to be a clear method of choice over single-site or biventricular myocardial stimulation21, 22
.
Present experience with conduction system pacing Several investigators reported experience with selective conduction system pacing over the last two decades. Deshmukh et al. described “His bundle” pacing in 18 patients with chronic atrial fibrillation undergoing single-chamber pacemaker implantation23. Electrophysiology catheter guided HB mapping was performed, and consistent capture was demonstrated among 14 patients. A Sweet Tip bipolar lead (Model 4269, Cardiac Pacemakers, Inc. St. Paul, MN) with active fixation was placed with long axis parallel to the HB axis. Permanent “His bundle” pacing was feasible in 12 out of 14 patients in whom HB was mapped with the catheter. Notably, pacing was
13
Conduction System Pacing
performed in a bipolar configuration. “His bundle” pacing was associated with improvement in left ventricular dimensions, functional status, cardiothoracic ratio, and ejection fraction. Lustgarten et al. described experience of “direct His Bundle pacing” among 10 patients eligible for CRT.24 Electrophysiology catheter-guided mapping of the HB was performed, and the lead (Select Secure model 3830, Medtronic Inc., Minneapolis, MN) was placed in the HB position. Notably, pacing was performed in both unipolar and bipolar configurations. The lead was then unscrewed and fixed in the atrium. All patients underwent implantation of right ventricular high voltage lead and a coronary sinus lead. Among 7 out of 10 patients, “direct His Bundle pacing” resulted in QRS narrower than biventricular pacing or native conduction. The authors postulated that the narrowing in QRS complex is due to capture of latent His-Purkinje system. “Direct His bundle pacing” was associated with shorter lead implantation time when compared to coronary sinus leads. Subsequent crossover study of 29 patients (12 patients completed crossover) at one year demonstrated improvements in ejection fraction, functional status, 6-minute walk distance with CRT, and “His bundle pacing”25 Barba-Picardo et al. described their experience with “His Bundle pacing” among 182 patients with AV conduction abnormalities or left bundle-branch block that improved with “His Bundle pacing”.19 Electrophysiology catheter was used for conduction system mapping. An active fixation lead (Tendril Model 1488T and 1788 TC, St Jude, Sylmar, CA, USA) was used in all patients. Pacing threshold less than 2.5V @1.0ms and 1:1 conduction up to 100 bpm were deemed necessary for permanent lead fixation. “His Bundle pacing” using electrophysiology catheter improved conduction disturbance in 133 (73%) out of 182 patients. Conduction improvement was frequently seen in patients with narrow complex QRS (97%) when compared to wide complex QRS (52%). Permanent lead fixation was feasible in 59 patients (65%). Lead 14
Conduction System Pacing
dislodgement and increase in thresholds occurred in less than 5% of patients included in the study. The group subsequently described feasibility of Hisian resynchronization in 9 out of 16 patients with cardiomyopathy and unsuccessful coronary sinus lead placement26. Kronberg et al. compared “His or paraHisian pacing” to right ventricular septal pacing in a prospective, randomized, double-blinded crossover trial of 38 patients with AV block, narrow QRS, and left ventricular ejection fraction >40%27. Select Secure lead (model 3830, Medtronic Inc., Minneapolis, MN) was used for “His or para Hisian pacing”. Ejection fraction and indices of mechanical synchrony were preserved in “His or para Hisian” arm, and there was no difference in functional status, 6-minute walk test, quality of life, and device-related complications when compared to the septal pacing arm. Zanon et al. described the largest experience with Select Secure lead placement in the HB region28. The success rate was 72% (220 out of 308 patients). A significant number of patients (41%) had right ventricular apical lead as back-up. Twelve patients had lead-related events in the cohort. Sharma et al. described the most recent experience with “His Bundle pacing” among patients undergoing dual-chamber pacemaker implantations29. Notably, mapping of the HB region was performed using the pacing lead. Select Secure lead (model 3830, 69 cm, Medtronic Inc., Minneapolis, MN) was delivered through fixed curve sheath (C315HIS, Medtronic Inc.) “His Bundle pacing” was feasible in 75 out of 94 (80%) patients. Fluoroscopy times were similar, although procedure times were a bit longer among patients that underwent “His bundle pacing” when compared to patients with right ventricular apical pacing. Three patients developed loss of capture and elevated thresholds. Heart failure hospitalizations were less frequent among patients that underwent “His Bundle pacing”. Among patients with AV block, “His Bundle Pacing” was
15
Conduction System Pacing
feasible in 84% of the patients and can normalize AV conduction (93% with AV nodal block vs. 76% with infranodal block)20. Recognized challenges and potential complications Extraction experience is limited in patients with Select Secure leads. Small studies from pediatric patients suggest lower complications and high complete extraction rates30. However, they have limited experience in extracting the lead from the HB position. Lack of the lumen to insert a locking stylet and non-retractable helix makes the lead a less attractive option for extraction in adults.
The Tensi-lock design of the inner cable provides reasonable support during the
extraction procedure. Development of adhesions along the lead will prevent transmission of counterclockwise torque to unscrew the lead from the membranous septum. It is conceivable that during the extraction process, there can be injury to the HB with development of new conduction abnormalities. There is a potential to leave a small membranous ventricular septal defect (Gerbode type LV/RA shunt) during the extraction process. The aortic valve is supported by the central fibrous body. It is conceivable that damage to the central fibrous body can result in structural abnormalities of the aortic valve. AV node ablation, if required in patients, with a HB pacing lead can be challenging. The smaller caliber of the lead near a mobile annulus raises concerns for lead dislodgement in pacemaker-dependent patients. Supplemental material for expanded discussion on technical aspects of HB pacing (supplemental figure 2) and alternative site pacing to restore synchrony (supplemental figure 3).
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Conduction System Pacing
Future directions Important improvements in the present understanding, techniques, tools, and documentation of benefit with regard to conduction system pacing are required to fully realize the potential of this exciting and highly promising technology. Consistent nomenclature As explained above, the confusing and, at times, anatomically inexact use of various terms related to the concept of promoting normal electromechanical pacing has made it difficult to compare small case series or for operators to clearly appreciate what the target site to secure the pacing lead is. We suggest the use of the term selective conduction system pacing whenever QRS morphology similar to conducted beats and a stimulus-to-QRS onset delay is obtained towards the goal of normal electrical conduction and mechanical function. The similarities and goal although disparate locations such as the distal compact AV node, the penetrating HB, or the proximal bundle branches may all effectively create the same result. The similarities in outcome and benefit outweigh the precise differences. However, as noted above, each individual location despite the similar result has its own unique challenges and potential for complication. Lead design and delivery tools Potentially innovative lead design where a closely spaced bipole possibly within the helix itself or with the ring electrode very close to the deployed helix yet minimizing the risk for septal perforation may be advantageous if not a requirement for consistent conduction system-only pacing
31-33
. The ideal delivery tool should allow consistent and reproducible selective
conduction system capture with optimal lead stability. A combined fluoroscopic and mapping
17
Conduction System Pacing
approach without the availability of tools designed entirely for this purpose make the procedure challenging. Documentation of benefit Larger trials specifically looking at lead stability, chronic pacing thresholds benefit for ventricular function, overcoming distal His-Purkinje disease, and translation to decreased hospitalization and cardiovascular mortality are needed to fully appreciate the exact degree of benefit with selective conduction system pacing. Conclusion Selective conduction system pacing is a highly promising and likely major advance in how we pace the heart. The likely normalized electromechanical activation will both prevent and possibly improve electrical and hemodynamic cardiac function. Important pioneering work has placed this previously obscure method of pacing appropriately in the limelight largely through the meticulous work of a few insightful groups of investigators19, 24-26, 29, 34-41. With clarification of terminology, larger studies, and improved tools, we may well have a new norm for cardiac stimulation.
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Conduction System Pacing
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Sharma PS, Huizar J, Ellenbogen KA, Tan AY. Recruitment of bundle branches with permanent His bundle pacing in a patient with advanced conduction system disease: What is the mechanism? Heart Rhythm Feb 2016;13:623-625. Barba-Pichardo R, Morina-Vazquez P, Fernandez-Gomez JM, Venegas-Gamero J, HerreraCarranza M. Permanent His-bundle pacing: seeking physiological ventricular pacing. Europace Apr 2010;12:527-533. Vijayaraman P, Naperkowski A, Ellenbogen KA, Dandamudi G. Electrophysiologic Insights Into Site of Atrioventricular BlockLessons From Permanent His Bundle Pacing. JACC: Clinical Electrophysiology 2015;1:571-581. Joyner RW, Sugiura H, Tan RC. Unidirectional block between isolated rabbit ventricular cells coupled by a variable resistance. Biophys J Nov 1991;60:1038-1045. Rohr S, Kucera JP, Fast VG, Kleber AG. Paradoxical improvement of impulse conduction in cardiac tissue by partial cellular uncoupling. Science Feb 7 1997;275:841-844. Deshmukh P, Casavant DA, Romanyshyn M, Anderson K. Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation. Circulation Feb 29 2000;101:869-877. Lustgarten DL, Calame S, Crespo EM, Calame J, Lobel R, Spector PS. Electrical resynchronization induced by direct His-bundle pacing. Heart Rhythm Jan 2010;7:15-21. Lustgarten DL, Crespo EM, Arkhipova-Jenkins I, Lobel R, Winget J, Koehler J, Liberman E, Sheldon T. His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: A crossover design comparison. Heart Rhythm Jul 2015;12:1548-1557. Barba-Pichardo R, Manovel Sanchez A, Fernandez-Gomez JM, Morina-Vazquez P, VenegasGamero J, Herrera-Carranza M. Ventricular resynchronization therapy by direct His-bundle pacing using an internal cardioverter defibrillator. Europace Jan 2013;15:83-88. Kronborg MB, Mortensen PT, Poulsen SH, Gerdes JC, Jensen HK, Nielsen JC. His or para-His pacing preserves left ventricular function in atrioventricular block: a double-blind, randomized, crossover study. Europace Aug 2014;16:1189-1196. Zanon F, Svetlich C, Occhetta E, Catanzariti D, Cantu F, Padeletti L, Santini M, Senatore G, Comisso J, Varbaro A, Denaro A, Sagone A. Safety and performance of a system specifically designed for selective site pacing. Pacing Clin Electrophysiol Mar 2011;34:339-347. Sharma PS, Dandamudi G, Naperkowski A, Oren JW, Storm RH, Ellenbogen KA, Vijayaraman P. Permanent His-bundle pacing is feasible, safe, and superior to right ventricular pacing in routine clinical practice. Heart Rhythm Feb 2015;12:305-312. Shepherd E, Stuart G, Martin R, Walsh MA. Extraction of SelectSecure leads compared to conventional pacing leads in patients with congenital heart disease and congenital atrioventricular block. Heart Rhythm Jun 2015;12:1227-1232. Henz BD, Friedman PA, Bruce CJ, Okumura Y, Johnson SB, Danielsen A, Packer DL, Asirvatham SJ. Synchronous ventricular pacing without crossing the tricuspid valve or entering the coronary sinus--preliminary results. J Cardiovasc Electrophysiol Dec 2009;20:1391-1397. Asirvatham SJ, Bruce CJ, Danielsen A, Johnson SB, Okumura Y, Kathmann E, Packer DL, Friedman PA. Intramyocardial pacing and sensing for the enhancement of cardiac stimulation and sensing specificity. Pacing Clin Electrophysiol Jun 2007;30:748-754. de Voogt W, van Hemel N, Willems A, Visser J, Chitre Y, Bornzin G, Helland J. Far-field R-wave reduction with a novel lead design: experimental and human results. Pacing Clin Electrophysiol Aug 2005;28:782-788. Shan P, Su L, Chen X, Xu L, Ni X, Huang W. Direct His-Bundle Pacing Improved Left Ventricular Function and Remodelling in a Biventricular Pacing Nonresponder. Can J Cardiol Nov 10 2015.
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Conduction System Pacing 35. 36.
37.
38.
39.
40.
41.
Slawuta A, Mazur G, Malecka B, Gajek J. Permanent His bundle pacing - An optimal treatment method in heart failure patients with AF and narrow QRS. Int J Cardiol Jul 1 2016;214:451-452. Vijayaraman P, Dandamudi G, Worsnick S, Ellenbogen KA. Acute His-Bundle Injury Current during Permanent His-Bundle Pacing Predicts Excellent Pacing Outcomes. Pacing Clin Electrophysiol May 2015;38:540-546. Catanzariti D, Maines M, Manica A, Angheben C, Varbaro A, Vergara G. Permanent His-bundle pacing maintains long-term ventricular synchrony and left ventricular performance, unlike conventional right ventricular apical pacing. Europace Apr 2013;15:546-553. Kronborg MB, Poulsen SH, Mortensen PT, Nielsen JC. Left ventricular performance during paraHis pacing in patients with high-grade atrioventricular block: an acute study. Europace Jun 2012;14:841-846. Kronborg MB, Mortensen PT, Gerdes JC, Jensen HK, Nielsen JC. His and para-His pacing in AV block: feasibility and electrocardiographic findings. J Interv Card Electrophysiol Sep 2011;31:255262. Manovel A, Barba-Pichardo R, Tobaruela A. Electrical and mechanical cardiac resynchronisation by novel direct his-bundle pacing in a heart failure patient. Heart Lung Circ Dec 2011;20:769772. Zanon F, Bacchiega E, Rampin L, Aggio S, Baracca E, Pastore G, Marotta T, Corbucci G, Roncon L, Rubello D, Prinzen FW. Direct His bundle pacing preserves coronary perfusion compared with right ventricular apical pacing: a prospective, cross-over mid-term study. Europace May 2008;10:580-587.
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Figure Legends Figure 1A: The compact AV node (1) converges into a transitional zone (2) before continuing as the His bundle (3) at the apex of Koch’s triangle. The HB penetrates the membranous septum and continues as bundle branches (4) on the summit of muscular septum. Panel B shows sagittal histological sections of the membranous septum stained with Masson’s trichome. The HB is surrounded by fibrous tissue without any myocardial tissue. The proximal part of the septal tricuspid leaflet is plastered to the underlying ventricular myocardium (Published with permission of the Publisher. Original source: Sánchez-Quintana D, Picazo-Angelín B, Cabrera A, Murillo M, Cabrera JA. Koch's Triangle and the Atrioventricular Node in Ebstein's Anomaly: Implications for Catheter Ablation. Rev Esp Cardiol. 2010;63(6):660-7. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier España S.L. All rights reserved) CFBcentral fibrous body, TV tricuspid valve, MV mitral valve, TT tendon of Todaro
Figure 2: Pacing site nomenclature. RAO view showing 1. Outflow tract, 2. RV anterior wall, 3. RV apex positions. LAO view showing 4. Septal position. Four chamber view showing 5. AV septal lead position.
Figure 3: Pacing the proximal conduction system beyond the AV node can be achieved by placing a lead on the membranous septum or on the muscular septum near the vicinity of proximal right bundle. RA- Right atrium, AO- Aorta, AV- Atrioventricular, MS – Membranous septum, IV inter ventricular septum, RV- Right ventricle, LV- Left ventricle.
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Figure 4: It is uncommon to see pure Hisian capture in the electrophysiology lab due to variation of the bipoles axis to the HB axis. Para-Hisian pacing maneuver showing His and ventricular capture for the first 2 beats (Panel A). The last 2 beats are narrow, with isoelectric interval between stimulus to QRS and a far-field released ventricular electrogram (arrow). One of the electrodes commonly captures the surrounding myocardium resulting His + local ventricular myocardial capture (Panel B). The issue of bipoles axis change is overcome by active fixation of the pacing lead on the conduction system Figure 5: Panel A shows selective conduction system capture with resulting narrow QRS complex. Note that there is an isoelectric interval which is similar to the HV interval. Panel B illustrates placement of lead on the proximal right bundle-branch in a patient with wide QRS. With high output, the QRS complex is narrow due to recruitment of both bundle branches. At low output, QRS resembles native conduction. If the patient has native bundle-branch block as depicted in Figure 6, a wide QRS with isoelectric interval can be expected with selective conduction system capture. Panel C shows intracardiac electrograms in a patient with selective conduction system pacing lead during threshold testing. At high output, we notice normalization of QRS. This is frequently fusion of basal ventricular pacing and conduction system capture. In the middle of the strip we note one non-captured beat. As the output is reduced, the QRS resembles non-captured beat indicating conduction system capture. CS- conduction system, NCNon capture, VP- ventricular pace, RV right ventricle.
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Figure 6: Selective conduction system pacing in a patient with baseline right bundle-branch block. At low output, we capture the conduction system selectively with QRS resembling native conduction. Isoelectric interval is noted in lead V1. At high output, we recruit the blocked right bundle resulting in narrowing of QRS complex. Notice that the stimulus to QRS is simultaneous due to local myocardial capture.
Table1: Effects of pacing mode, output and electrode orientation on tissues captured. Site
Advantages
Disadvantages
Pacing Output High
Para Hisian/ Peri Hisian
Conduction system capture with engagement of local myocardium
QRS morphology is a fusion of conduction system and basal ventricular pacing
His Bundle
Conduction system capture with maximal engagement of HPS No potential for TR His Bundle recording aides as a good target for lead placement. Conduction system capture No potential for TR or ventricular capture
Membranous septal perforation Potential for creating new conduction system disturbances
Low
Mobitz Type 1 block to ventricle at higher pacing rates Atrial sensing and or capture
Low
Sole conduction system capture Minimal or no decrement No potential for TR or ventricular capture Capture of the ventricular myocardium with sense/capture of the
Concurrent atrial sensing/capture
Low
Conduction system is frequently disengaged
Low
AV node
Distal AV node transitional zone
AV septum
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Proximal Bundle Branches
right atrium No potential for TR No risk of membranous septum perforation Relatively larger target Pacing distal to block results in normalization of conduction
Insignificant potential Low/High for TR
Table 2: Advantages and disadvantages of various selective conduction system pacing sites. Pacing Mode Unipolar
Orientation At an angle- perpendicular
Bipolar
Cathode- at an angleperpendicular Anode- Floating
Bipolar
Cathode- parallel or purpendicular Anode- contact with myocardium
Possible effect Minimal effect of orientation on the tissue captured Bigger antenna often raises the possibility of oversensing All practical purposes similar to unipolar pacing High thresholds for selective conduction system capture can be expected when the cathode is screwed into the central fibrous body Low thresholds for selective conduction system capture when cathode is screwed on the proximal conduction system. Low output pacingbasal ventricular capture High output- Selective conduction system capture and basal ventricular capture High thresholds for selective conduction system capture can be 25
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expected when the cathode is screwed into the central fibrous body High output pacing when the cathode is screwed into the proximal conduction system may lead to concurrent atrial capture.
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PII: DOI: Reference:
S1547-5271(16)30614-2 http://dx.doi.org/10.1016/j.hrthm.2016.08.005 HRTHM6809
To appear in: Heart Rhythm Received date: 10 June 2016 Cite this article as: Siva K. Mulpuru, Yong-Mei Cha and Samuel J. Asirvatham, Synchronous ventricular pacing with direct capture of the atrioventricular conduction system: Functional anatomy, terminology, and challenges, Heart Rhythm, http://dx.doi.org/10.1016/j.hrthm.2016.08.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Conduction System Pacing
Synchronous ventricular pacing with direct capture of the atrioventricular conduction system: Functional anatomy, terminology, and challenges
Siva K Mulpuru MD1, FHRS, Yong-Mei Cha MD1, FHRS, Samuel J Asirvatham MD1,2, FHRS
1. Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 2. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN Brief running title: Selective conduction system pacing Conflicts of interest: S. J. Asirvatham receives no significant honoraria and is a consultant with Abiomed, Atricure, Biosense Webster, Biotronik, Boston Scientific, Medtronic, Spectranetics, St. Jude, Sanofi-Aventis, Wolters Kluwer, Elsevier, Zoll. None for S.K. Mulpuru and Y. M Cha Corresponding Author: Samuel J. Asirvatham, MD Professor of Medicine, Division of Cardiovascular Diseases 200 First Street SW Rochester, MN 55905 Email: [email protected] Phone number: 507-293-3376 Fax number: 507-255-2550
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Abstract: Right ventricular apical pacing is associated with an increased incidence of heart failure, atrial fibrillation, and overall mortality. As a result, pacing the ventricles in a manner that closely mimics normal atrioventricular conduction with an intact His-Purkinje system has been explored. Recently, the sustainable benefits of selective His bundle stimulation have been demonstrated and proposed as the preferred method of ventricular stimulation for appropriate patients. Ideally, conduction system pacing should be selective without myocardial capture, overcome distal bundle-branch block when present, and not compromise tricuspid valve function. Contemporary literature on conduction system pacing is confusing largely because of inconsistent terminology and, at times, anatomically inaccurate terms used interchangeably for nonsynonomous anatomic sites.
In this review, we discuss the functional anatomy of the
atrioventricular conduction access with specific emphasis on terminology, relationship to the membranous septum, tricuspid valve tissue, and proximity to atrial or ventricular myocardium. The potential benefits of each specific site as well as associated unique difficulties with those sites are described. Key Words: cardiac pacing; ventricular synchrony; His bundle; AV node; conduction system
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Introduction The human cardiac conduction system is admirably suited to deliver coordinated electrical impulses that result in synchronous and mechanically efficient ventricular myocardial contraction. It follows that single site myocardial stimulation being fundamentally different from the facilitated multisite endocardial breakthrough with conduction system stimulation results in abnormal physiology. Indeed, chronic right ventricular apical pacing (RVAP) is associated with increased risk of death 1, 2, heart failure, hospitalization 3, and the development of persistent atrial fibrillation
4, 5
. These clinical adverse effects have been directly linked to the
abnormal electrical activation sequence and resulting mechanical ventricular dyssynchrony. (Supplemental material for expanded discussion on pathophysiology of adverse effects due to RV apical pacing) Biventricular pacing and cardiac resynchronization therapies (CRT) are superior to RVAP in patients with reduced ejection fraction 6.
However, optimal lead location and anatomic
limitations to consistently place the lead at the most beneficial sites as well as the fundamental disengagement of the intrinsic cardiac conduction system limit the utility of CRT. Alternate ventricular myocardial pacing sites have thus been investigated either for single site or part of a biventricular pacing system. Nevertheless, any small number of direct myocardial stimulation sites is unlikely to mimic the normal efficiency of the intrinsic conduction system. Ideal cardiac stimulation with pacing would involve direct and sole capture of the proximal conduction system without ventricular or atrial myocardial sensing or capture, not effect valvular function, and overcome distal bundle-branch and Purkinje pathology that results in bundlebranch block or electromechanical uncoupling. Significant efforts towards this ideal goal have recently been made. However, confusion in the literature exists with variably used terminology, 3
Conduction System Pacing
inexact appreciation of the precise portion of the anatomic conduction system being stimulated, and whether or not distal Purkinje disease can be overcome with proximal conduction tissue pacing. In this review, we discuss the functional anatomy of the conduction system, attempt to clarify the existing nomenclature with regard to specific sites of stimulation, and further discuss the impact of lead orientation and pacing output. Also presented are some of the advantages, disadvantages, and specific challenges associated with each possible approach toward ideal conduction system pacing. Anatomy and physiology of the atrioventricular conduction system Electrical excitation from the sinus node reaches the atrioventricular (AV) node largely through nonspecialized, atrial myocardial tissue. Because of naturally occurring anatomic obstacles to conduction in the atrium such as the fossa ovalis and, in part, the Eustachian ridge, the wave front approaches the AV node through an anterior and posterior path and inserts into similarly positioned extensions of the AV node constituting the fast and slow pathways. The AV node and slow pathway myocardium are located within the triangle of Koch. This triangle is formed by the tendon of Todaro up to the anterior and superior limit of the septal leaflet, the septal leaflet of the tricuspid valve insertion margin, and an imaginary line connecting the two at the floor of the coronary sinus. The compact AV node occupies a variable position near the epicenter of this triangle and is thus an atrial structure being posterior (atrial) to the septal leaflet of the tricuspid valve. The penetrating bundle of His, usually referred to simply as the His bundle (HB), is a ventricular structure and is located within the membranous portion of the ventricular septum (Figure 1A). The HB is surrounded by connective tissue from the central fibrous body, which constitutes an
4
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insulating layer to the chord-like bundle.
The membranous septum itself is formed as a
conjunction of two valve leaflet commissures; on the right, the commissure between the anterior and septal leaflets of the tricuspid valve are immediately adjacent and opposite on the left with the commissure of the right and noncoronary sinuses of Valsalva of the aortic valve. Thus, surrounding the HB, there is no myocardial tissue (Figure 1B), and the His bundle itself is a chord-like structure measuring up to 20 mm in length and 4 mm in diameter
7, 8
.
The major
connections between the cells of the HB are end-to-end intra-collated discs giving rise to its typical property of rapid longitudinal conduction. The penetrating HB that emerges on the muscular crest of the interventricular septum to continue as the bundle branches. Noteworthy is that there is no ventricular myocardial proximity around the HB itself as it penetrates through the membranous septum and after a variable length divides between the right and left bundles. Occasionally, the HB divides on the left side of the septum, and when this occurs, the right bundle may emerge at the base of the septal papillary muscle 8. The proximal bundle branches, like the HB, are surrounded by connective tissue which is a direct continuation of the fibrous body. The relationship of the penetrating HB to tricuspid valve tissue is important to clarify. Since the penetrating HB is located on the membranous septum and the membranous septum in turn is made up in part of tricuspid valve tissue, anatomically, any conduction system location proximal to tricuspid valve tissue and thus the membranous septum would not be the HB. Of more functional and practical relevance, however, is the question of whether the HB can be stimulated without affecting tricuspid valve function.
This certainly can be accomplished since the
membranous septum is in part proximal to the free and mobile tricuspid valve leaflets, and in
5
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addition, the more distal membranous septum can be reached via the commissure between the free septal and anterior leaflets of the tricuspid valve. The compact AV node located in the atrium within the triangle of Koch serves as the gateway of electrical conduction to the ventricles. The compact AV node, in addition to its characteristically slow conduction, also exhibits decremental properties. However, the transition between the compact AV node and HB is not abrupt, and atrial portions of the conduction system (distal most narrowed portion of the AV node) may have functional properties similar to the penetrating bundle of His. Indeed, linkage analysis has confirmed that the HB and the most inferior portion of the compact AV node are both derived from the ventricular myocardium 9. (Supplemental material for expanded discussion on physiology of normal conduction) Nomenclature Non-apical RVP sites have been reasonably classified into generally accepted terms including the outflow tract, inflow septal, and apical sites 10(Figure 2). However, inexact and interchangeable use of non-synonymous terms with regard to commonly described conduction system pacing (Figure 3) has given rise to significant confusion.
“Para-Hisian”/ “Peri-Hisian” pacing. These terms have been variably used to describe stimulation in or near the HB presumably including targeted HB capture as well as the proximal bundle-branches and surrounding myocardium11-13
HB pacing.
Anatomic HB pacing would involve the stimulatory electrode making
contact with the penetrating HB as it traverses through the membranous septum. No surrounding ventricular myocardium is present in this location, and sole conduction system capture would be anticipated. 6
Conduction System Pacing
AV nodal pacing. An electrode placed in the center of the triangle of Koch would stimulate the compact AV node. The proximate atrial myocardium may or may not be captured, and no direct ventricular myocardial capture would be anticipated.
AV septal pacing. Because the septal leaflet of the tricuspid valve is inserted more apical compared to the mitral valve, a portion of the interventricular septum has left ventricular myocardium on one side and right atrial myocardium on the other. This structure is called the AV septum 14. Pacing at this site stimulates ventricular myocardium and may, in addition, sense or capture the right atrial myocardium. No specific capture of the conduction system would be routinely expected with AV septal pacing.
Proximal bundle-branch capture.
Here, the target for pacing is one or both of the
proximal bundle-branches located on the crest of the interventricular septum after the division of the HB.
Stimulation would be expected to occur of the ventricular
myocardium at the crest, but sole right and/or left bundle capture may occur depending on the exact position of the stimulatory cathode.
Distal AV nodal/transitional tissue stimulation. The transitional zone that constitutes the terminal, relatively linear portion of the compact AV node prior to it being named the penetrating HB on the membranous system can also be successfully stimulated with conduction system capture. Characteristics of stimulation at this site may be similar and indistinguishable from penetrating HB capture with minimal or no detectable decrement seen.
Given the confusing and variably used terms all essentially attempting to selectively pace the conduction system to reproduce a normal QRS morphology and without ventricular myocardial capture, we propose the use of the term selective conduction system pacing when such a name is 7
Conduction System Pacing
meant to be fulfilled. Because of the juxtaposition of tissues with very different conduction properties, the exact stimulated structure and resulting excitation wave front may be exquisitely dependent on the pacing output, dimensions and type of the stimulatory electrodes, and the orientation of the cathode and anode relative to the approximated conduction tissue and surrounding myocardium (Figure 4). Ideally, for selective conduction system pacing, a very small bipole with both anode and cathode secured to the targeted conduction tissue with stimulation at sufficiently low output is used. Distal electrode unipolar stimulation has been used with success to achieve the desired result of sole conduction system stimulation. However, with larger electrodes and the antenna of the unipolar pacing vector, the potential for intermittent, undesirable myocardial stimulation exists. Presently available leads have a definite separation between the active helix serving as a cathode and the more proximal anode. The orientation and pacing output have significant interaction with variable resulting excitation patterns (Table 1). (Supplemental material for expanded discussion on effects of bipole orientation to structures captured) We now briefly review the characteristics, advantages, and disadvantages of each of the sites that have been described (Table 2). Pacing the penetrating bundle of His Selective pacing of the HB as it courses through the membranous septum is accomplished by screwing in the cathode through the fibrous sheath around the HB. Pacing results in QRS morphology similar to a normally conducted beat.
If the electrode is exactly on the HB,
thresholds will be low and acceptable, but nearby locations on the fibrous skeleton of the heart
8
Conduction System Pacing
could still allow HB capture but with high thresholds and the potential for far-field ventricular myocardial capture from far-field capture or anodal stimulation. Advantages
Given that there is no myocardium on the membranous septum, sole conduction system capture is the norm with maximized engagement of the His-Purkinje network and resulting normal mechanical contraction.
Because the membranous septum is formed at the commissure of the septal and anterior tricuspid leaflets, a lead placed in this location should not cause any disturbance of tricuspid valve closure and thus not result in tricuspid regurgitation despite the ventricular location of the membranous septum. Further, despite the fact that the tricuspid valve tissue forms in part in the membranous septum, the free margin of the attachment of the leaflets of the tricuspid valve are distal to portions of the membranous septum, and pacing at that site can stimulate the HB without interfering with tricuspid valve closure.
Again, because of no myocardium on the membranous septum, a distal HB electrogram can be recorded prior to screwing in the electrode to allow electrical sensing confirmation of the bundle of His site in addition to its characteristic anatomic location.
Disadvantages
The membranous septum is a relatively thin structure with its thickness being potentially less than that of the length of a standard helix. Thus, perforation with potential shunt or exposure of the helix tip to the left-sided circulation remain unwanted possibilities.
9
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Precise localization into the bundle is needed to achieve acceptable thresholds. Whereas peri-Hisian stimulatory location or lead tip location would give consistent conduction system pacing only at higher output with possible simultaneous ventricular capture.
Attempts at screwing in the lead into the HB, particularly if repeated attempts are needed or when extracting the lead, may result in complete AV block or bundle-branch block (supplemental figure 1) in patients who otherwise may have normal conduction.
Pacing the AV node The compact AV node may be stimulated with the cathode secured in the middle of the triangle of Koch atrial to the septal leaflet of the tricuspid valve. Advantages
Sole conduction system capture with QRS similar to conducted beats.
No potential for ventricular myocardial capture.
No potential for promoting tricuspid regurgitation.
Disadvantages
Proximal AV nodal capture would result in significant decrement and possible Mobitz I block to the ventricle at higher pacing rates.
Depending on the output and lead orientation as well as the set AV paced interval, atrial myocardial sensing and/or capture may complicate pacing from this location.
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Pacing the distal AV node transitional zone Pacing at this site would be essentially indistinguishable from penetrating bundle of His capture. However, the electrode will be atrial to the line of attachment of the septal leaflet and thus in the apex of the triangle of Koch. Advantages
Sole conduction system pacing.
Advantage over compact AV nodal pacing would be that no decrement would be expected.
No potential for ventricular myocardial capture.
No potential for causing or worsening tricuspid valve dysfunction.
Disadvantages
More likely to be affected by far-field atrial sensing or capture than pacing the penetrating bundle of His.
Pacing the proximal bundle branches The cathode secured on the crest of the ventricular septum may capture the right bundle-branch alone. The resulting QRS would be nearly identical to conducted rhythm since a very short conduction time would be required to enter the left bundle concurrently with antegrade right bundle activation. Pacing at this site may also capture the left bundle or both bundles together depending on the type and how superficial the branching on the crest is in a given heart (Figure 5).
11
Conduction System Pacing
Advantages
No risk of membranous septal perforation.
Relatively larger target.
Could potentially capture the conduction tissue distal to the level of bundle-branch block, thus normalizing conduction even in a patient with bundle-branch block during conducted rhythm.
Disadvantage
Exact type of activation will be dependent on pacing output and amount of local myocardial capture.
Some, but likely insignificant potential for promoting tricuspid valve regurgitation (could course through the commissure and thus not affect coaptation).
AV septal pacing is not a type of attempted conduction system pacing and is discussed briefly under alternate ventricular myocardial pacing (see below). Overcoming left bundle-branch block A principle reason for attempting synchronous pacing particularly in heart failure patients is because of the dyssynchrony from preexisting left bundle-branch block and other infra-Hisian conduction abnormalities. Can pacing the HB proximal to the site of block overcome such infraHisian abnormality?
In patients with very proximal bundle-branch block, stimulation by
physical electrode (pacing lead) that captures the bundles distal to the level of the block may, in part, normalize the QRS (Figure 6). For block that is within the HB or very proximal in the bundle branches, since fibers destined to be the right or left bundle are histologically 12
Conduction System Pacing
differentiated more proximally 15, capture may improve conduction. However, in most patients with left bundle-branch block, the disease and fibrosis is more distal than the HB/left bundle junction and thus more problematic in terms of proximal capture normalizing conduction. However, some proximal disease is usually present as well and associated with a decrease in the number of conducting cells proximally available to produce a sufficient upstream voltage gradient (source) to successfully depolarize through the diseased distal left bundle-branch
16, 17
.
Virtual electrode polarization effect has been postulated as one mechanism for recruitment of blocked bundle branches18. Indeed recent studies using HB pacing leads in patients with AV block have demonstrated higher rates of His-Purkinje recruitment even in patients with lower levels of conduction block
19, 20
. This recruitment or restoring of a normal QRS by His pacing
even in the absence of intact distal His-Purkinje activation by optimizing the source sink relationship is a major goal that requires study on route to allow selective conduction system pacing to be a clear method of choice over single-site or biventricular myocardial stimulation21, 22
.
Present experience with conduction system pacing Several investigators reported experience with selective conduction system pacing over the last two decades. Deshmukh et al. described “His bundle” pacing in 18 patients with chronic atrial fibrillation undergoing single-chamber pacemaker implantation23. Electrophysiology catheter guided HB mapping was performed, and consistent capture was demonstrated among 14 patients. A Sweet Tip bipolar lead (Model 4269, Cardiac Pacemakers, Inc. St. Paul, MN) with active fixation was placed with long axis parallel to the HB axis. Permanent “His bundle” pacing was feasible in 12 out of 14 patients in whom HB was mapped with the catheter. Notably, pacing was
13
Conduction System Pacing
performed in a bipolar configuration. “His bundle” pacing was associated with improvement in left ventricular dimensions, functional status, cardiothoracic ratio, and ejection fraction. Lustgarten et al. described experience of “direct His Bundle pacing” among 10 patients eligible for CRT.24 Electrophysiology catheter-guided mapping of the HB was performed, and the lead (Select Secure model 3830, Medtronic Inc., Minneapolis, MN) was placed in the HB position. Notably, pacing was performed in both unipolar and bipolar configurations. The lead was then unscrewed and fixed in the atrium. All patients underwent implantation of right ventricular high voltage lead and a coronary sinus lead. Among 7 out of 10 patients, “direct His Bundle pacing” resulted in QRS narrower than biventricular pacing or native conduction. The authors postulated that the narrowing in QRS complex is due to capture of latent His-Purkinje system. “Direct His bundle pacing” was associated with shorter lead implantation time when compared to coronary sinus leads. Subsequent crossover study of 29 patients (12 patients completed crossover) at one year demonstrated improvements in ejection fraction, functional status, 6-minute walk distance with CRT, and “His bundle pacing”25 Barba-Picardo et al. described their experience with “His Bundle pacing” among 182 patients with AV conduction abnormalities or left bundle-branch block that improved with “His Bundle pacing”.19 Electrophysiology catheter was used for conduction system mapping. An active fixation lead (Tendril Model 1488T and 1788 TC, St Jude, Sylmar, CA, USA) was used in all patients. Pacing threshold less than 2.5V @1.0ms and 1:1 conduction up to 100 bpm were deemed necessary for permanent lead fixation. “His Bundle pacing” using electrophysiology catheter improved conduction disturbance in 133 (73%) out of 182 patients. Conduction improvement was frequently seen in patients with narrow complex QRS (97%) when compared to wide complex QRS (52%). Permanent lead fixation was feasible in 59 patients (65%). Lead 14
Conduction System Pacing
dislodgement and increase in thresholds occurred in less than 5% of patients included in the study. The group subsequently described feasibility of Hisian resynchronization in 9 out of 16 patients with cardiomyopathy and unsuccessful coronary sinus lead placement26. Kronberg et al. compared “His or paraHisian pacing” to right ventricular septal pacing in a prospective, randomized, double-blinded crossover trial of 38 patients with AV block, narrow QRS, and left ventricular ejection fraction >40%27. Select Secure lead (model 3830, Medtronic Inc., Minneapolis, MN) was used for “His or para Hisian pacing”. Ejection fraction and indices of mechanical synchrony were preserved in “His or para Hisian” arm, and there was no difference in functional status, 6-minute walk test, quality of life, and device-related complications when compared to the septal pacing arm. Zanon et al. described the largest experience with Select Secure lead placement in the HB region28. The success rate was 72% (220 out of 308 patients). A significant number of patients (41%) had right ventricular apical lead as back-up. Twelve patients had lead-related events in the cohort. Sharma et al. described the most recent experience with “His Bundle pacing” among patients undergoing dual-chamber pacemaker implantations29. Notably, mapping of the HB region was performed using the pacing lead. Select Secure lead (model 3830, 69 cm, Medtronic Inc., Minneapolis, MN) was delivered through fixed curve sheath (C315HIS, Medtronic Inc.) “His Bundle pacing” was feasible in 75 out of 94 (80%) patients. Fluoroscopy times were similar, although procedure times were a bit longer among patients that underwent “His bundle pacing” when compared to patients with right ventricular apical pacing. Three patients developed loss of capture and elevated thresholds. Heart failure hospitalizations were less frequent among patients that underwent “His Bundle pacing”. Among patients with AV block, “His Bundle Pacing” was
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feasible in 84% of the patients and can normalize AV conduction (93% with AV nodal block vs. 76% with infranodal block)20. Recognized challenges and potential complications Extraction experience is limited in patients with Select Secure leads. Small studies from pediatric patients suggest lower complications and high complete extraction rates30. However, they have limited experience in extracting the lead from the HB position. Lack of the lumen to insert a locking stylet and non-retractable helix makes the lead a less attractive option for extraction in adults.
The Tensi-lock design of the inner cable provides reasonable support during the
extraction procedure. Development of adhesions along the lead will prevent transmission of counterclockwise torque to unscrew the lead from the membranous septum. It is conceivable that during the extraction process, there can be injury to the HB with development of new conduction abnormalities. There is a potential to leave a small membranous ventricular septal defect (Gerbode type LV/RA shunt) during the extraction process. The aortic valve is supported by the central fibrous body. It is conceivable that damage to the central fibrous body can result in structural abnormalities of the aortic valve. AV node ablation, if required in patients, with a HB pacing lead can be challenging. The smaller caliber of the lead near a mobile annulus raises concerns for lead dislodgement in pacemaker-dependent patients. Supplemental material for expanded discussion on technical aspects of HB pacing (supplemental figure 2) and alternative site pacing to restore synchrony (supplemental figure 3).
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Future directions Important improvements in the present understanding, techniques, tools, and documentation of benefit with regard to conduction system pacing are required to fully realize the potential of this exciting and highly promising technology. Consistent nomenclature As explained above, the confusing and, at times, anatomically inexact use of various terms related to the concept of promoting normal electromechanical pacing has made it difficult to compare small case series or for operators to clearly appreciate what the target site to secure the pacing lead is. We suggest the use of the term selective conduction system pacing whenever QRS morphology similar to conducted beats and a stimulus-to-QRS onset delay is obtained towards the goal of normal electrical conduction and mechanical function. The similarities and goal although disparate locations such as the distal compact AV node, the penetrating HB, or the proximal bundle branches may all effectively create the same result. The similarities in outcome and benefit outweigh the precise differences. However, as noted above, each individual location despite the similar result has its own unique challenges and potential for complication. Lead design and delivery tools Potentially innovative lead design where a closely spaced bipole possibly within the helix itself or with the ring electrode very close to the deployed helix yet minimizing the risk for septal perforation may be advantageous if not a requirement for consistent conduction system-only pacing
31-33
. The ideal delivery tool should allow consistent and reproducible selective
conduction system capture with optimal lead stability. A combined fluoroscopic and mapping
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approach without the availability of tools designed entirely for this purpose make the procedure challenging. Documentation of benefit Larger trials specifically looking at lead stability, chronic pacing thresholds benefit for ventricular function, overcoming distal His-Purkinje disease, and translation to decreased hospitalization and cardiovascular mortality are needed to fully appreciate the exact degree of benefit with selective conduction system pacing. Conclusion Selective conduction system pacing is a highly promising and likely major advance in how we pace the heart. The likely normalized electromechanical activation will both prevent and possibly improve electrical and hemodynamic cardiac function. Important pioneering work has placed this previously obscure method of pacing appropriately in the limelight largely through the meticulous work of a few insightful groups of investigators19, 24-26, 29, 34-41. With clarification of terminology, larger studies, and improved tools, we may well have a new norm for cardiac stimulation.
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Sharma PS, Huizar J, Ellenbogen KA, Tan AY. Recruitment of bundle branches with permanent His bundle pacing in a patient with advanced conduction system disease: What is the mechanism? Heart Rhythm Feb 2016;13:623-625. Barba-Pichardo R, Morina-Vazquez P, Fernandez-Gomez JM, Venegas-Gamero J, HerreraCarranza M. Permanent His-bundle pacing: seeking physiological ventricular pacing. Europace Apr 2010;12:527-533. Vijayaraman P, Naperkowski A, Ellenbogen KA, Dandamudi G. Electrophysiologic Insights Into Site of Atrioventricular BlockLessons From Permanent His Bundle Pacing. JACC: Clinical Electrophysiology 2015;1:571-581. Joyner RW, Sugiura H, Tan RC. Unidirectional block between isolated rabbit ventricular cells coupled by a variable resistance. Biophys J Nov 1991;60:1038-1045. Rohr S, Kucera JP, Fast VG, Kleber AG. Paradoxical improvement of impulse conduction in cardiac tissue by partial cellular uncoupling. Science Feb 7 1997;275:841-844. Deshmukh P, Casavant DA, Romanyshyn M, Anderson K. Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation. Circulation Feb 29 2000;101:869-877. Lustgarten DL, Calame S, Crespo EM, Calame J, Lobel R, Spector PS. Electrical resynchronization induced by direct His-bundle pacing. Heart Rhythm Jan 2010;7:15-21. Lustgarten DL, Crespo EM, Arkhipova-Jenkins I, Lobel R, Winget J, Koehler J, Liberman E, Sheldon T. His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy patients: A crossover design comparison. Heart Rhythm Jul 2015;12:1548-1557. Barba-Pichardo R, Manovel Sanchez A, Fernandez-Gomez JM, Morina-Vazquez P, VenegasGamero J, Herrera-Carranza M. Ventricular resynchronization therapy by direct His-bundle pacing using an internal cardioverter defibrillator. Europace Jan 2013;15:83-88. Kronborg MB, Mortensen PT, Poulsen SH, Gerdes JC, Jensen HK, Nielsen JC. His or para-His pacing preserves left ventricular function in atrioventricular block: a double-blind, randomized, crossover study. Europace Aug 2014;16:1189-1196. Zanon F, Svetlich C, Occhetta E, Catanzariti D, Cantu F, Padeletti L, Santini M, Senatore G, Comisso J, Varbaro A, Denaro A, Sagone A. Safety and performance of a system specifically designed for selective site pacing. Pacing Clin Electrophysiol Mar 2011;34:339-347. Sharma PS, Dandamudi G, Naperkowski A, Oren JW, Storm RH, Ellenbogen KA, Vijayaraman P. Permanent His-bundle pacing is feasible, safe, and superior to right ventricular pacing in routine clinical practice. Heart Rhythm Feb 2015;12:305-312. Shepherd E, Stuart G, Martin R, Walsh MA. Extraction of SelectSecure leads compared to conventional pacing leads in patients with congenital heart disease and congenital atrioventricular block. Heart Rhythm Jun 2015;12:1227-1232. Henz BD, Friedman PA, Bruce CJ, Okumura Y, Johnson SB, Danielsen A, Packer DL, Asirvatham SJ. Synchronous ventricular pacing without crossing the tricuspid valve or entering the coronary sinus--preliminary results. J Cardiovasc Electrophysiol Dec 2009;20:1391-1397. Asirvatham SJ, Bruce CJ, Danielsen A, Johnson SB, Okumura Y, Kathmann E, Packer DL, Friedman PA. Intramyocardial pacing and sensing for the enhancement of cardiac stimulation and sensing specificity. Pacing Clin Electrophysiol Jun 2007;30:748-754. de Voogt W, van Hemel N, Willems A, Visser J, Chitre Y, Bornzin G, Helland J. Far-field R-wave reduction with a novel lead design: experimental and human results. Pacing Clin Electrophysiol Aug 2005;28:782-788. Shan P, Su L, Chen X, Xu L, Ni X, Huang W. Direct His-Bundle Pacing Improved Left Ventricular Function and Remodelling in a Biventricular Pacing Nonresponder. Can J Cardiol Nov 10 2015.
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Slawuta A, Mazur G, Malecka B, Gajek J. Permanent His bundle pacing - An optimal treatment method in heart failure patients with AF and narrow QRS. Int J Cardiol Jul 1 2016;214:451-452. Vijayaraman P, Dandamudi G, Worsnick S, Ellenbogen KA. Acute His-Bundle Injury Current during Permanent His-Bundle Pacing Predicts Excellent Pacing Outcomes. Pacing Clin Electrophysiol May 2015;38:540-546. Catanzariti D, Maines M, Manica A, Angheben C, Varbaro A, Vergara G. Permanent His-bundle pacing maintains long-term ventricular synchrony and left ventricular performance, unlike conventional right ventricular apical pacing. Europace Apr 2013;15:546-553. Kronborg MB, Poulsen SH, Mortensen PT, Nielsen JC. Left ventricular performance during paraHis pacing in patients with high-grade atrioventricular block: an acute study. Europace Jun 2012;14:841-846. Kronborg MB, Mortensen PT, Gerdes JC, Jensen HK, Nielsen JC. His and para-His pacing in AV block: feasibility and electrocardiographic findings. J Interv Card Electrophysiol Sep 2011;31:255262. Manovel A, Barba-Pichardo R, Tobaruela A. Electrical and mechanical cardiac resynchronisation by novel direct his-bundle pacing in a heart failure patient. Heart Lung Circ Dec 2011;20:769772. Zanon F, Bacchiega E, Rampin L, Aggio S, Baracca E, Pastore G, Marotta T, Corbucci G, Roncon L, Rubello D, Prinzen FW. Direct His bundle pacing preserves coronary perfusion compared with right ventricular apical pacing: a prospective, cross-over mid-term study. Europace May 2008;10:580-587.
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Figure Legends Figure 1A: The compact AV node (1) converges into a transitional zone (2) before continuing as the His bundle (3) at the apex of Koch’s triangle. The HB penetrates the membranous septum and continues as bundle branches (4) on the summit of muscular septum. Panel B shows sagittal histological sections of the membranous septum stained with Masson’s trichome. The HB is surrounded by fibrous tissue without any myocardial tissue. The proximal part of the septal tricuspid leaflet is plastered to the underlying ventricular myocardium (Published with permission of the Publisher. Original source: Sánchez-Quintana D, Picazo-Angelín B, Cabrera A, Murillo M, Cabrera JA. Koch's Triangle and the Atrioventricular Node in Ebstein's Anomaly: Implications for Catheter Ablation. Rev Esp Cardiol. 2010;63(6):660-7. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier España S.L. All rights reserved) CFBcentral fibrous body, TV tricuspid valve, MV mitral valve, TT tendon of Todaro
Figure 2: Pacing site nomenclature. RAO view showing 1. Outflow tract, 2. RV anterior wall, 3. RV apex positions. LAO view showing 4. Septal position. Four chamber view showing 5. AV septal lead position.
Figure 3: Pacing the proximal conduction system beyond the AV node can be achieved by placing a lead on the membranous septum or on the muscular septum near the vicinity of proximal right bundle. RA- Right atrium, AO- Aorta, AV- Atrioventricular, MS – Membranous septum, IV inter ventricular septum, RV- Right ventricle, LV- Left ventricle.
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Figure 4: It is uncommon to see pure Hisian capture in the electrophysiology lab due to variation of the bipoles axis to the HB axis. Para-Hisian pacing maneuver showing His and ventricular capture for the first 2 beats (Panel A). The last 2 beats are narrow, with isoelectric interval between stimulus to QRS and a far-field released ventricular electrogram (arrow). One of the electrodes commonly captures the surrounding myocardium resulting His + local ventricular myocardial capture (Panel B). The issue of bipoles axis change is overcome by active fixation of the pacing lead on the conduction system Figure 5: Panel A shows selective conduction system capture with resulting narrow QRS complex. Note that there is an isoelectric interval which is similar to the HV interval. Panel B illustrates placement of lead on the proximal right bundle-branch in a patient with wide QRS. With high output, the QRS complex is narrow due to recruitment of both bundle branches. At low output, QRS resembles native conduction. If the patient has native bundle-branch block as depicted in Figure 6, a wide QRS with isoelectric interval can be expected with selective conduction system capture. Panel C shows intracardiac electrograms in a patient with selective conduction system pacing lead during threshold testing. At high output, we notice normalization of QRS. This is frequently fusion of basal ventricular pacing and conduction system capture. In the middle of the strip we note one non-captured beat. As the output is reduced, the QRS resembles non-captured beat indicating conduction system capture. CS- conduction system, NCNon capture, VP- ventricular pace, RV right ventricle.
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Figure 6: Selective conduction system pacing in a patient with baseline right bundle-branch block. At low output, we capture the conduction system selectively with QRS resembling native conduction. Isoelectric interval is noted in lead V1. At high output, we recruit the blocked right bundle resulting in narrowing of QRS complex. Notice that the stimulus to QRS is simultaneous due to local myocardial capture.
Table1: Effects of pacing mode, output and electrode orientation on tissues captured. Site
Advantages
Disadvantages
Pacing Output High
Para Hisian/ Peri Hisian
Conduction system capture with engagement of local myocardium
QRS morphology is a fusion of conduction system and basal ventricular pacing
His Bundle
Conduction system capture with maximal engagement of HPS No potential for TR His Bundle recording aides as a good target for lead placement. Conduction system capture No potential for TR or ventricular capture
Membranous septal perforation Potential for creating new conduction system disturbances
Low
Mobitz Type 1 block to ventricle at higher pacing rates Atrial sensing and or capture
Low
Sole conduction system capture Minimal or no decrement No potential for TR or ventricular capture Capture of the ventricular myocardium with sense/capture of the
Concurrent atrial sensing/capture
Low
Conduction system is frequently disengaged
Low
AV node
Distal AV node transitional zone
AV septum
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Proximal Bundle Branches
right atrium No potential for TR No risk of membranous septum perforation Relatively larger target Pacing distal to block results in normalization of conduction
Insignificant potential Low/High for TR
Table 2: Advantages and disadvantages of various selective conduction system pacing sites. Pacing Mode Unipolar
Orientation At an angle- perpendicular
Bipolar
Cathode- at an angleperpendicular Anode- Floating
Bipolar
Cathode- parallel or purpendicular Anode- contact with myocardium
Possible effect Minimal effect of orientation on the tissue captured Bigger antenna often raises the possibility of oversensing All practical purposes similar to unipolar pacing High thresholds for selective conduction system capture can be expected when the cathode is screwed into the central fibrous body Low thresholds for selective conduction system capture when cathode is screwed on the proximal conduction system. Low output pacingbasal ventricular capture High output- Selective conduction system capture and basal ventricular capture High thresholds for selective conduction system capture can be 25
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expected when the cathode is screwed into the central fibrous body High output pacing when the cathode is screwed into the proximal conduction system may lead to concurrent atrial capture.
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