his bundle pacingdescribed the architecture of the his bundle using both light microscopy and...

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Dr. Valentin Fuster.

J O U R N A L O F T H E AM E R I C A N C O L L E G E O F C A R D I O L O G Y V O L . 7 2 , N O . 8 , 2 0 1 8

ª 2 0 1 8 B Y T H E AM E R I C A N C O L L E G E O F C A R D I O L O G Y F O UN DA T I O N

P U B L I S H E D B Y E L S E V I E R

THE PRESENT AND FUTURE

COUNCIL PERSPECTIVES

His Bundle Pacing
Pugazhendhi Vijayaraman, MD,a Mina K. Chung, MD,b Gopi Dandamudi, MD,c Gaurav A. Upadhyay, MD,d
Kousik Krishnan, MD,e George Crossley, MD,f Kristen Bova Campbell, PHARMD,g Byron K. Lee, MD,h

Marwan M. Refaat, MD,i Sanjeev Saksena, MD,j,k John D. Fisher, MD,l Dhananjaya Lakkireddy, MD,m,n

on behalf of the ACC’s Electrophysiology Council

ABSTRACT

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Traditional right ventricular (RV) pacing for the management of bradyarrhythmias has been pursued successfully for

decades, although there remains debate regarding optimal pacing site with respect to both hemodynamic and clinical

outcomes. The deleterious effects of long-term RV apical pacing have been well recognized. This has generated interest

in approaches providing more physiological stimulation, namely, His bundle pacing (HBP). This paper reviews the

anatomy of the His bundle, early clinical observations, and current approaches to permanent HBP. By stimulating the His-

Purkinje network, HBP engages electrical activation of both ventricles and may avoid marked dyssynchrony. Recent

studies have also demonstrated the potential of HBP in patients with underlying left bundle branch block and cardio-

myopathy. HBP holds promise as an attractive mode to achieve physiological pacing. Widespread adaptation of this

technique is dependent on enhancements in technology, as well as further validation of efficacy in large randomized

clinical trials. (J Am Coll Cardiol 2018;72:927–47) © 2018 by the American College of Cardiology Foundation.

T he need for cardiac pacing continues tobecome more prevalent as our populationages. Furthermore, cardiac pacing remains

the only definitive therapy for nonreversible bradyar-rhythmias. Despite years of successful pacing

N 0735-1097/$36.00

e views expressed in this paper by the American College of Cardiology’s

ect the views of JACC or the ACC.

m the aGeisinger Heart Institute, Geisinger Commonwealth School of

ctrophysiology, Cleveland Clinic, Cleveland, Ohio; cKrannert Institute of

rsity School of Medicine, Indianapolis, Indiana; dElectrophysiology Sect

icago, Illinois; eElectrophysiology Section, Division of Cardiology, Rush Un

art and Vascular Institute, Nashville, Tennessee; gDivision of Cardiology, D

ctrophysiology, University of California San Francisco, California; iElectrop

iversity of Beirut, Beirut, Lebanon; jElectrophysiology Research Founda

nson Medical School, New Brunswick, New Jersey; lElectrophysiology Se

Medicine, New York, New York; mKansas City Heart Rhythm Institute, Ove

lumbia, Missouri. Dr. Vijayaraman has served as a speaker for and receive

sultant for Medtronic, Boston Scientific, and Abbott; and has a patent pe

earch support from Medtronic, Boston Scientific, and Abbott; and has ser

tronik (uncompensated). Dr. Dandamudi has served as a speaker for, serv

m Medtronic. Dr. Upadhyay has received research support from Medtron

pport from Abbott; and has served as a consultant for Zoll. Dr. Crossley ha

d received research support from Medtronic; and has served as a consu

earch support from Medtronic; has served as a consultant for Medtronic

dtronic, Abbott, and Biotronik. All other authors have reported that they h

per to disclose.

nuscript received March 16, 2018; revised manuscript received June 1, 20

therapy, there is continued debate regarding theoptimal ventricular pacing sites, particularly in theventricle. Initial ventricular-only pacing devices pro-vided adequate rate support but were not synchro-nized to atrial contraction, and led to negative

https://doi.org/10.1016/j.jacc.2018.06.017

(ACC) Electrophysiology Council do not necessarily

Medicine, Wilkes-Barre, Pennsylvania; bDivision of

Cardiology, Department of Medicine, Indiana Uni-

ion, Division of Cardiology, University of Chicago,

iversity Medical Center, Chicago, Illinois; fVanderbilt

uke University, Durham, North Carolina; hDivision of

hysiology Section, Division of Cardiology, American

tion, Warren, New Jersey; kRutgers’ Robert Wood

ction, Division of Cardiology, Albert Einstein College

rland Park, Kansas; and the nUniversity of Missouri,

d research support from Medtronic; has served as a

nding for a His delivery tool. Dr. Chung has received

ved on the steering committee for EPIC Alliance and

ed as a consultant for, and received research support

ic and Biotronik. Dr. Krishnan has received research

s served as a speaker for, served as a consultant for,

ltant for Boston Scientific. Dr. Fisher has received

and MDT; and has received fellowship support from

ave no relationships relevant to the contents of this

18, accepted June 4, 2018.

https://doi.org/10.1016/j.jacc.2018.06.017

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ABBR EV I A T I ON S

AND ACRONYMS

AF = atrial fibrillation

AV = atrioventricular

HBP = His bundle pacing

HF = heart failure

HPCD = His-Purkinje

conduction disease

HV = His to ventricular

electrogram interval

LBBB = left bundle branch

block

LV = left ventricle/ventricular

RBBB = right bundle branch

block

RVP = right ventricular pacing

Vijayaraman et al. J A C C V O L . 7 2 , N O . 8 , 2 0 1 8

His Bundle Pacing A U G U S T 2 1 , 2 0 1 8 : 9 2 7 – 4 7

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hemodynamic consequences including anincreased risk of heart failure (HF) and atrialfibrillation. Even atrioventricular (AV) syn-chronized pacing delivered at the right ven-tricular (RV) apex, however, was noted toworsen contractile function in many pa-tients. Eventually, the connection betweenthe degree of right ventricular apical (RVA)pacing and cardiac dysfunction became wellestablished (1). Pursuit of alternate pacingsites has included the RV septum, the RVoutflow tract, and the left ventricle (LV) (2).Although biventricular pacing has unequivo-cally improved HF outcomes and reducedmortality in patients with left bundle branchblock (LBBB) and severe LV systolic dysfunc-tion (3), its role in patients with preserved LV

systolic function remains unresolved.From first principles, an ideal physiological

approach to ventricular stimulation should engagethe normal conduction through the His-Purkinjeconduction system. The concept of pacing the mainbody of the bundle of His is not new. Early in-vestigators described temporary His bundle pacing(HBP) (4). Eventually the concept of directly pacingthe His bundle with a permanent pacemaker wasdescribed (5). Although its electrophysiological role inAV conduction makes the His bundle an attractivesite for physiological pacing, actual lead placementcan be technically challenging due to its anatomiclocation and surrounding cardiac structures. In thispaper, we provide a comprehensive review of theanatomy, physiology, implantation techniques, andclinical role of permanent HBP.

ANATOMY OF THE HIS BUNDLE AND

PROXIMAL BUNDLE BRANCHES

A detailed knowledge of the anatomy of the Hisbundle and proximal bundle branches is crucial forunderstanding the anatomic basis of various con-duction disorders as well as for approaching perma-nent HBP. Wilhelm His Jr., a Swiss anatomist andcardiologist, first described the His bundle structureand its role in transmitting atrial impulses to theventricles in 1893. The Japanese pathologist, SunaoTawara, made seminal observations regarding thecardiac conduction system in 1903 (6), revealing theexistence of the AV nodal structure and makingdetailed observations of the His-Purkinje system(HPS). Incredibly, based entirely on the anatomicobservations, he was able to surmise physiologicalattributes of the HPS, including conduction

velocities. The His bundle forms an anatomicalcontinuation of the AV node, providing the connec-tion for electrical signals from the AV node to reachthe right and left ventricles through the right and leftbundle branches, respectively (7).

The His bundle and the proximal branches initiallyoriginate as part of the primitive interventricularseptum. During the second trimester of gestation,the AV node connects with the proximal portion ofthe developing His bundle. Failure of this junction todevelop leads to congenital complete heart block (7).The His bundle extends inferiorly and leftward fromthe AV node, directly past the posterior and inferiormargins of the membranous interventricular septum,and remains undivided for a few millimeters. At thecrest of the muscular interventricular septum, the Hisbundle starts to divide (Central Illustration, panel A)into right and left bundle branches (8). The trunk ofthe left bundle branch often splits into 3 fasciclesafter the proximal 2 cm, and there are many sub-endocardial ramifications and interconnections.The proximal part of the His bundle rests on the rightatrial–LV portion of the membranous septum, and themore distal His travels along the RV-LV portion ofthe membranous septum, immediately below theaortic root.

Recent macroscopic anatomic investigations (9)have elucidated 3 common variations of the Hisbundle relative to the membranous part of the ven-tricular septum (Figure 1). In type I anatomy (46.7% of105 cases), the His bundle consistently coursed alongthe lower border of the membranous part of theinterventricular septum, but was covered with a thinlayer of myocardial fibers spanning from the muscularpart of the septum. In type II (32.4%), the His bundlewas apart from the lower border of the membranouspart of the interventricular septum and ran within theinterventricular muscle. In type III (21%), the Hisbundle was immediately beneath the endocardiumand coursed onto the membranous part of the inter-ventricular septum (naked AV bundle). Other reportsof anomalous His bundle locations include a pre-dominantly left-sided course. These anatomical var-iations of the His bundle may have clinicalimplications for permanent HBP in terms of achievingselective His bundle pacing (S-HBP) or nonselectiveHis bundle pacing (NS-HBP), in addition to potentialfor injury to the His bundle resulting in transient orpersistent bundle branch block (BBB) or complete AVblock (10). Both the atrial and ventricular portions ofthe His bundle can be accessed for permanent ven-tricular pacing.

CENTRAL ILLUSTRATION His Bundle Pacing: Conduction System and Outcomes

Vijayaraman, P. et al. J Am Coll Cardiol. 2018;72(8):927–47.

(A) Schematic representation of the His-Purkinje conduction system. The membranous septum is indicated in yellow. Image courtesy of K.

Shivkumar, MD, PhD, UCLA Cardiac Arrhythmia Center, Wallace A. McAlpine MD collection. Reproduced with permission. (B) Clinical out-

comes of HBP. Kaplan-Meyer survival curves demonstrating a statistically significant reduction in the primary endpoint (composite endpoint

of all-cause mortality, HFH, or upgrade to biventricular pacing) with His bundle pacing (HBP) compared with right ventricular pacing (RVP)

in all patients and in patients with ventricular pacing (VP) >20%. Reprinted from Abdelrahman et al. (62). AVN ¼ atrioventricular node;

CS ¼ coronary sinus; HB ¼ His bundle; IVC ¼ inferior vena cava; LBB ¼ left bundle branch; LV ¼ left ventricle; PA ¼ pulmonary artery;

RA ¼ right atrium; RBB ¼ right bundle branch; SVC ¼ superior vena cava.

J A C C V O L . 7 2 , N O . 8 , 2 0 1 8 Vijayaraman et al.A U G U S T 2 1 , 2 0 1 8 : 9 2 7 – 4 7 His Bundle Pacing

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FIGURE 1 Anatomic Variations of the His Bundle

(A) Type 1: The His bundle (AVB) runs under themembranous part of the interventricular septum (MS). (B) The type II His bundle runs within the

muscular part of the interventricular muscle apart from the lower border of themembranous part of the interventricular septum. (C) The type III

His bundle (arrow) is naked running beneath the endocardiumwith no surroundingmyocardial fibers. AT¼ attachment of septal tricuspid leaflet;

AVB ¼ atrioventricular bundle; AVN ¼ atrioventricular node; CS ¼ coronary sinus. Reprinted from Kawashima and Sasaki (9).



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HBP: FROM BENCH TO BEDSIDE

SEMINAL PHYSIOLOGICAL RECORDINGS OF THE HIS

BUNDLE. Using isolated perfused hearts and plungeneedles in animals, Alanís et al. (11) first described Hisbundle electrograms in 1958. They are credited withdescribing the His bundle as a “zone” of conductionand lacking decremental properties, in contrast to theAV node. Scherlag et al. (12) are credited with devel-oping the catheter-based approach in humans forrecording the His bundle in 1969, which has essen-tially remained unchanged in the electrophysiologylaboratory to date.

FUNCTIONAL LONGITUDINAL DISSOCIATION OF

THE HIS BUNDLE. Kaufmann and Rothberger (13) firstproposed the idea of functional longitudinal dissoci-ation of the His bundle in 1919. According to thistheory, conduction fibers arose from the proximalportions of the common His bundle and were pre-destined to the individual bundle branches. Severalinvestigators studied this concept in both animal andhuman models. In 1971, James and Sherf (14)described the architecture of the His bundle usingboth light microscopy and electron microscopy. Theirobservations may explain the conduction propertiesthat are seen in clinical practice with HBP (14). Theydescribed the His bundle as multiple insulated

filaments contained within a single common cable.The following observations were made by this group:

1. The bulk of the His bundle is comprised of cellsthat eventually course into the left bundlebranches (only a small number enter the rightbranch).

2. The cells that make up the His-Purkinje fibers arebroader and shorter than the usual workingmyocardial cells with relatively few myofibrils.

3. These cells are elongated and oblong in shape, andmake contact predominantly at their terminal endsand to a lesser extent across the lateral margins.

4. These cells are partitioned intricately by collagenfibers; in fact, longitudinal division of the Hisbundle by collagen makes it unique from a histo-logical standpoint when compared with the AVnode and the working myocardium.

5. The collagen may minimize or even prevent lateralspread of the propagated impulse, while the com-partmentalized tissue with specialized intercel-lular connections would facilitate rapidlongitudinal spread of the propagated impulse.

An implication of these findings is that somepatients with His-Purkinje conduction disease(HPCD) may have relatively proximal disease, andthat pacing distal to the site of block might

FIGURE 2 Longitudinal Dissociation Within the His Bundle

Fibers within the His bundle are already pre-destined to become the right bundle branch (RBB) and left bundle branch (LBB), as depicted in the figure. (A) Pacing at 2 V

results in capture of local ventricular tissue and His (both RBB and LBB fibers), which is considered nonselective HBP. There is minimal delta wave on the surface

electrocardiogram (ECG) (blue circles). However, ventricular capture is evidenced by the absence of local electrogram in the His bundle pacing (HBP) lead. (B) Pacing at

1.5 V results in selective His (RBB and LBB) capture (no delta wave, as in orange circles) with loss of ventricular capture (arrow shows discrete local electrogram in the

HBP lead). (C) Pacing at 1.0 V demonstrates capture of RBB fibers alone with LBB block pattern (arrow shows the discrete local electrogram with different

morphology). Reprinted with permission from Sharma et al. (49).


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overcome the block and narrow the QRS. Initialwork conducted by Narula (15) was instrumental indemonstrating that patients with LBBB could becorrected with pacing just distal to the presumedsite of block. These seminal observations paved theway to confirming the feasibility of HBP even inadvanced His to ventricular electrogram interval(HV) disease substrates (Figure 2).

HBP IN CLINICAL PRACTICE—HOW IT ALL

STARTED. Credit goes to Deshmukh et al. (5) forintroducing permanent HBP in humans in 2000. Theystudied the role of HBP in patients with HF and rapidatrial fibrillation (AF), resulting in tachycardia-induced cardiomyopathy. Between 2006 and 2011, ahandful of case reports and case series were pub-lished which applied HBP in more general clinicalpractice (16–20). These initial studies and observa-tions have led to further exploration of the utility of

permanent HBP in patients requiring pacing anddevice-paced HF therapy.

HBP LEAD IMPLANTATION TECHNIQUE

Permanent HBP was initially performed using stan-dard pacing leads by reshaping the stylet or using adeflectable stylet to precisely position the lead at asite near the electrophysiology mapping catheterdemonstrating the largest His deflection. Thisapproach was technically challenging and timeconsuming. The development of a specialized pacinglead (SelectSecure 3830, Medtronic, Minneapolis,Minnesota) and sheaths (C315His, C304 SelectSite,Medtronic) has made permanent HBP feasible inroutine clinical practice (21). It has been shown thatthe His bundle region can be successfully locatedusing the pacing lead in >95% of patients (without amapping catheter) without significantly prolonging

FIGURE 3 SelectSecure 3830 Pacing Lead and the C315 His Sheath Used to Deliver the Lead

Full description of how to perform HBP using the 3830 pacing lead and C315His sheath is available in Online Video 1.



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the procedure duration (22). The His bundle isgenerally mapped using the pacing lead in a unipolarfashion. The fixed-curve C315His sheath is moreeffective than the deflectable C304 sheath forimplanting the HBP lead. This sheath has a proximalcurve directing the sheath to the tricuspid annulus,while the secondary septal curve points the sheathperpendicular to the myocardial surface allowing thelead to be fixed securely (Figure 3). The implanttechnique has been previously described (23). Oncevenous access is obtained, the C315His sheath isadvanced over a guidewire and placed at thetricuspid annulus (Online Video 1). The 3830 pacinglead is then advanced to the tip of the sheath, and theelectrograms from this lead are simultaneously dis-played in the EP recording system at a sweep speedof 100 mm/s and the pacing system analyzer using ajumper cable. If more prominent atrial electrogramsare noted, the sheath is rotated gently clockwiseallowing the lead to be moved slightly more ven-tricularly. Once an atrial to ventricular electrogramratio of 1:2 or greater is noted, the sheath is pointedtoward the superior-anterior septum or midseptumby minimal clockwise or counter-clockwise rotation,respectively. Once a near-field His electrogram isidentified, pacing is performed at 5 V at 1 ms to assessHis capture. Twelve-lead electrocardiograms are dis-played along with His electrograms during mappingand pacing to facilitate accurate assessment of Hisbundle capture and correction of bundle branchblocks. Following identification of the His location,the fluoroscopic image is saved as a reference. Thesheath is held steady, and the pacing lead is slowlyrotated clockwise approximately 5 times without

releasing the lead between rotations. This allows thetorque to be transmitted along the length of the leadto the lead tip. If the lead is anchored well, it willrotate back counterclockwise to release the excesstorque. Once the lead is fixed, the sheath is with-drawn to the high right atrium until an adequate loop(slack) is formed. Sensing and pacing thresholds arethen checked in both unipolar and bipolar configu-rations. HBP threshold is preferably tested at a pulsewidth of 1 ms to allow for a lower capture voltage. Inmost patients, a His bundle capture thresholdof #2.0 V at 1 ms is acceptable. In patients withHPCD, a higher His bundle capture threshold may beaccepted provided the RV capture threshold issignificantly lower (NS-HBP). In these patients, it isessential that attempts be made to map the distal Hisbundle beyond the site of intra-Hisian block to ach-ieve low His capture thresholds. A His bundle injurycurrent can often be recorded following lead fixationin w40% of patients. To record the injury current, thehigh-pass filter needs to be adjusted to 0.5 Hz from30 Hz in the EP recording system (Figure 4). Thepresence of a His bundle injury current has beenshown to predict excellent acute and long-term cap-ture thresholds (24).

PRACTICAL CONSIDERATIONS. Permanent HBP canbe challenging due to the limited availability ofdelivery tools, particularly in patients with anenlarged right atrium and a displaced tricuspidannular region or right pectoral implants. Modifi-cations to implant techniques have recently beendescribed to achieve higher success in these pa-tients (25).

http://jaccjacc.acc.org/video/2018/0609_VID1.mp4

http://jaccjacc.acc.org/video/2018/0609_VID1.mp4


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PROCEDURAL OUTCOMES. In the original report byDeshmukh et al. (5), the success of permanent HBP inselect patients with cardiomyopathy undergoing AVnode ablation was about 66% using traditional pacingleads (5). Zanon et al. (26) reported an acute implantsuccess rate of 92% in 26 patients without underlyingHPCD while utilizing the 3830 pacing lead. In a sub-sequent report by Sharma et al. (22), the acute HBPimplant success rate was 80% in a consecutive seriesof 94 unselected patients (including patients withHPCD) undergoing permanent pacemaker implanta-tion. With increased procedural experience, thefeasibility of permanent HBP in all-comers, includingpatients with infranodal AV block, was >90%. Whileearly studies reported significantly longer proceduraltimes, recent studies suggest similar fluoroscopy andprocedural times compared with right ventricularpacing (RVP) (22).

Compared with high His bundle capture thresholdsreported with traditional pacing leads in earlystudies, recent investigations show acceptable Hiscapture thresholds both at implant and during long-term follow-up. In a study of 75 patients withsuccessful permanent HBP, Vijayaraman et al. (27)reported His capture thresholds of 1.35 � 0.5 V at0.5 ms at implant that remained stable during 5-yearfollow-up (1.62 � 1.0 V at 0.5 ms). In another studyof AV node ablation and HBP in 42 patients, Hiscapture threshold at implant was 1.5 � 1.0 V at 0.5 msand remained unchanged during a median follow-upof 20 months (28). In a study of 100 consecutive pa-tients with advanced AV block, acute His capturethreshold at implant was 1.3 � 0.9 V at 0.5 ms andslightly increased to 1.7 � 1.0 V at 0.5 ms during amean follow-up of 19 months (29).

DEFINITIONS OF S- AND NS-HBP. A lack of unifor-mity of terminology in the published data for per-manent HBP has contributed to confusion regardingthe types of His bundle capture observed and pacingthreshold definitions. Recently, a multicenter HBPcollaborative working group proposed a refined set ofcriteria to define HBP in patients with normal His-Purkinje conduction and in those with HPCD (30).The authors broadly defined 2 forms of His bundlecapture: selective capture, in which the His bundle isthe only tissue captured by the pacing stimulus; andnonselective capture, in which there is fusion captureof the His bundle and adjacent ventricular tissues(Table 1). Various criteria for S-HBP or NS-HBP aredescribed in the following text.

SELECTIVE HBP. During S-HBP, ventricular activa-tion occurs directly and completely over the HPS andis accompanied by the following criteria:

1. The pacing stimulus to QRS (S-QRS) onset intervalis equal to the native His-QRS onset interval(H-QRS). However, in patients with HPCD, theS-QRS interval can be shorter than the H-QRSintervals, as in patients with BBB or HV block due tocapture of latent fascicular tissue.

2. The local ventricular electrogram on the pacinglead will be discrete from the pacing artifact.

3. The paced QRS morphology is the same as thenative QRS morphology. In patients with HPCD, thepaced QRS duration may be narrower than thenative QRS with BBB or the escape rhythm.

4. Usually a single capture threshold (His capture) isobserved. However in patients with HPCD, 2 distinctHis capture thresholds—with and without correctionof underlying BBB—may be seen (Figure 5).

NONSELECTIVE HBP. During NS-HBP, there isculmination of both His bundle and ventricularcapture.

1. The S-QRS interval is usually zero, as there is noisoelectric interval between pacing stimulus andQRS due to the presence of a pseudo-delta wave(due to local myocardial capture).

2. The local ventricular electrogram is directlycaptured by the pacing stimulus and is not seen asa discrete component.

3. The paced QRS duration will usually be longer thanthe native QRS duration by the H-QRS interval, andthe overall electrical axis of the paced QRS will beconcordant with the electrical axis of the intrinsicQRS. In patients with HPCD, the paced QRS durationmay be narrower than the native QRS due tocorrection of underlying BBB.

4. There will usually be 2 distinct capture thresholds– right ventricular and His capture. The His capturethreshold may be lower or higher than the ven-tricular capture threshold. The output differencebetween the 2 thresholds (RV and His) is usuallysmall, and the final programmed output includingthe safety margin would result in nonselective Hiscapture. In patients with HPCD, 3 distinct capturethresholds may be observed in varying combination(RV capture, His capture with correction of BBB, andHis capture without correction of BBB) (Figure 6).

Selective or nonselective capture of His bundle isoften dependent on the location of the pacing elec-trode in relation to the His bundle, surrounding atrialor ventricular tissue, and the amplitude of the pacingoutput (31,32). Although one might intuitively antic-ipate selective capture to be preferable over NS-HBP,published data indicate that there is little hemody-namic and clinical difference between the 2 forms of

FIGURE 4 His Bundle Injury Current

The electrograms from the His bundle pacing lead at a high-pass filter setting of 0.5 Hz demonstrate the presence of an injury current at the

His bundle (dashed arrow) and ventricle (solid arrow). His bundle electrogram with high-pass filter setting of 30Hz is shown (*). (Right)

Nonselective His bundle pacing with correction of underlying right bundle branch block.



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capture, possibly due to rapid conduction of the His-Purkinje system relative to ventricular myocardialconduction (33,34). The most important aspect of HBPis to clearly document RV and His capture thresholdsalong with BBB correction thresholds (where appli-cable) for the purposes of follow-up and programmingfinal output settings.

HIS BUNDLE PACING FOR AV NODE

ABLATION AND ATRIOVENTRICULAR BLOCK

Ventricular pacing avoidance algorithms are oftenemployed in patients with first- or second-degree AVblock to prevent RV pacing. However, in complete AVblock, RV pacing is unavoidable. Various studies ofHBP in patients with AV block and AV node ablationare shown in Table 2.

AV NODE ABLATION AND HBP. Deshmukh et al. (5)originally reported the feasibility of permanent HBPin 12 of 18 patients with atrial fibrillation undergoingAV node ablation. In a subsequent series of 54 pa-tients with AF and dilated cardiomyopathy undergo-ing AV node ablation, direct (selective) HBP wasachieved in 39 patients with resultant improvementin left ventricular ejection fraction (LVEF) from 23 �11% at baseline to 33 � 15% during a mean follow-upof 42 months (35). In 2006, Occhetta et al. (36) re-ported on the clinical advantage of para-Hisian pacingcompared with RVP in 16 of 18 patients undergoing

AV node ablation in a randomized, 6-month crossoverstudy. In this study, para-Hisian (nonselective) pac-ing resulted in improved interventricular mechanicaldelay, New York Heart Association (NYHA) functionalclass, quality of life (QOL), 6-min walk, and mitral andtricuspid regurgitation (36).

More recently, Huang et al. (28) reported on thebenefits of HBP combined with AV node ablation in 52patients with symptomatic AF and HF. They weresuccessful in achieving permanent HBP in 42 (81%)patients with resultant improvement in LV end-diastolic dimensions, LVEF, and functional class.The QRS duration during HBP remained unchangedcompared with baseline (107.1 � 25.8 ms vs. 105.3 �23.9 ms). Vijayaraman et al. (37) have also publishedwork on the feasibility of AV node ablation and per-manent HBP. Successful HBP was achieved in 40 of 42(95%) patients with improvement in LVEF from 43 �13% to 50 � 11% (p ¼ 0.01) along with improvement infunctional class.

American College of Cardiology/American HeartAssociation/Heart Rhythm Society AF practiceguidelines recommend that AV junction ablationwith permanent ventricular pacing is a reasonablestrategy to control heart rate in AF when pharma-cological therapy is inadequate and rhythm controlcannot be achieved (Class IIa, Level of Evidence: B)(38). Evidence from AV node ablation patients showdeleterious hemodynamic effects of RV pacing,

TABLE 1 Criteria for His Bundle Pacing

Baseline Normal QRS

His-Purkinje Conduction Disease

With correction Without correction

Selective HBP � S-QRS ¼ H-QRS with isoelectric interval� Discrete local ventricular electrogram in HBP

lead with S-V ¼ H-V� Paced QRS ¼ native QRS� Single capture threshold (His bundle)

� S-QRS # H-QRS with isoelectric interval� Discrete local ventricular electrogram in HBP

lead� Paced QRS < native QRS� 2 distinct capture thresholds (HBP with BBB

correction, HBP without BBB correction)

� S-QRS # or > H-QRS with isoelectricinterval

� Discrete local ventricular electrogramin HBP lead

� Paced QRS ¼ native QRS� Single capture threshold (HBP with BBB)

Nonselective HBP � S-QRS < H-QRS (S-QRS usually 0, S-QRSend ¼H-QRSend) with or without isoelectric interval(Pseudodelta wave þ/�)

� Direct capture of local ventricular electro-gram in HBP lead by stimulus artifact (localmyocardial capture)

� Paced QRS > native QRS with normalization ofprecordial and limb lead axes with respect torapid dV/dt components of the QRS

� 2 distinct capture thresholds (His bundlecapture, RV capture)

� S-QRS < H-QRS (S-QRS usually 0, S-QRSend <

H-QRSend) with or without isoelectric interval(Pseudodelta wave þ/�)

� Direct capture of local ventricular electro-gram in HBP lead by stimulus artifact

� Paced QRS # native QRS� 3 distinct capture thresholds possible (HBP

with BBB correction, HBP without BBBcorrection, RV capture)

� S-QRS < H-QRS (S-QRS usually 0) withor without isoelectric interval (Pseudo-delta wave þ/�)

� Direct capture of local ventricularelectrogram in HBP lead by stimulusartifact

� Paced QRS > native QRS� 2 distinct capture thresholds (HBP with

BBB, RV capture)

Reprinted with permission from Vijayaraman et al. (30).

BBB ¼ bundle branch block; dV/dt ¼ rate of change in voltage; H-QRS ¼ His-QRS; H-V ¼ His-ventricular; RV ¼ right ventricle; S-QRS ¼ stimulus-QRS; S-V ¼ stimulus-ventricular.


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especially in patients with reduced LVEF (39). HBPmay be particularly attractive in this population.Whereas some centers may wait 2 to 4 weeks afterthe initial device implant to perform AV nodeablation, other centers perform AV node ablationduring the initial pacemaker implant (23,37). The

FIGURE 5 Selective His Bundle Pacing in LBBB

(Left) Baseline left bundle branch block (LBBB) with QRS duration of 150

LBBB (QRS 90 ms) at 1.4 V and loss of left bundle recruitment at 1.0 V

selective His capture.

ablation catheter is initially placed at the Hisbundle location via femoral venous access and mayserve as a marker for HBP lead placement. AV nodeablation is performed after successful implantationof the HBP lead. It may be prudent to obtain aslightly distal His location for the HBP lead (very

ms. (Right) selective His bundle pacing (S-HBP) with correction of

. The local ventricular electrogram is discrete (arrows), suggesting

FIGURE 6 Nonselective His Bundle Pacing in RBBB

The 12-lead ECG and intracardiac electrograms from the right atrial (RA) and HBP leads are shown. With pacing at 1.5 V, there is nonselective

HBP (right ventricle [RV], right and left bundle capture), at 1.2 V, there is loss of RV capture, and at 1.0 V there is loss of left bundle capture in

this patient with underlying right bundle branch block (RBBB). Abbreviations as in Figure 2.



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small atrial signal <0.5 mV and a larger ventricularsignal). The HBP lead electrodes may serve as anexcellent marker for the AV node ablation site. Theablation catheter is then positioned at or below thelevel of the ring electrode. Care is taken to avoidany location closer to the distal electrode. It hasbeen shown that ablation closer to the tip electrodemay result in significant increase in His capturethresholds (37). As soon as AV block is achievedduring the ablation, HBP is initiated at 0.5 to 1.0 Vabove the His capture threshold. Any loss of Hiscapture should serve as a warning to stop ablatingimmediately. If an excellent His capture threshold(<1.5 V) or NS-HBP with RV capture threshold <1 Vis achieved, a back-up RVP lead can be avoided. Inpatients with chronic AF, and in whom an RV back-up pacing lead is desired, the HBP lead may beconnected to the atrial port of a dual-chamber de-vice (pacer or ICD) and programmed to DVIR modeto avoid sensing from the HBP lead.

AV BLOCK AND HBP. While the feasibility of per-manent HBP in patients with AV nodal block is ex-pected, surprisingly high numbers of patients withinfranodal block can be corrected with HBP. In arecent series by Kronborg et al. (40), permanent HBPwas successful in 85% of patients with high-gradeAV block and narrow QRS complex. They achievedS-HBP in 11% (4 of 38) and NS-HBP in 74% of pa-tients (28 of 38). In this randomized study, patients

were initially paced in either RV apex or HBP, andcrossed over to the opposite strategy after12 months. They noted a significant improvement inLVEF with HBP than with RVA pacing (55% vs. 50%).Barba-Pichardo et al. (41) studied 182 patients withAV block (84 narrow QRS and 98 wide QRS). Theyattempted permanent HBP in only 68% of these pa-tients due to high HBP thresholds during mapping.Considering all patients with heart block, permanentHBP was successfully achieved in only 32% (44 of 84in narrow QRS and 15 of 98 in wide QRS) of patients.Differences in methodology and tools used couldexplain the low success rates in this study. In 2015,Vijayaraman et al. (29) reported one of the largestseries of HBP in patients with AV block, achievingHBP in 84% of 100 patients. Success was higher inAV nodal block (93%) versus infranodal block (76%).A small percentage of patients (5%) had elevatedthresholds on follow-up that required a lead revi-sion. In this study, a high success rate for HBP wasachieved in patients with infranodal AV (HV) blockdespite reporting only a small number of patientswith split-His potentials or a narrow QRS complex(Figure 7). The postulated mechanisms for thisrecruitment of distal His and bundle branchesin patients with intra-His block are: 1) longitudinaldissociation in the His bundle with pacing adjacentor distal to the site of delay/block; 2) virtual elec-trode polarization effect; and/or 3) differential

TABLE 2 Permanent His Bundle Pacing in AV Node Ablation/AV Block

First Author,Year (Ref. #) Design

Follow-up(Months) N Indication Success (%)

ImportantCharacteristics Outcomes

Deshmukh et al.,2000 (5)

Observational 36 18 AV node ablation 66 Chronic AF, LVEF <40%,QRS duration <120 ms

Improvement in LV dimensions,NYHA functional class, andLVEF

Deshmukh et al.,2004 (35)

Observational 42 54 AV node ablation 72 Chronic AF, LVEF <40%,QRS duration <120 ms

Improved LVEF, NYHA functionalclass, peak VO2

Occhetta et al.,2006 (36)

Randomized, 6months,crossover RVP vs.HBP

12 18 AV node ablation 94 Chronic AF, QRS <120 ms Improvement in NYHA functionalclass, 6MWT, QOL, andhemodynamics

Huang et al.,2017 (28)

Observational 20 52 AV node ablation 81 Chronic AF, CHF Improvement in LV dimensions,NYHA functional class, andLVEF

Vijayaramanet al., 2017(37)

Observational 19 42 AV node ablation 95 Paroxysmal or persistentAF, CHF

Improvement in NYHA functionalclass, LVEF

Barba-Pichardoet al., 2010(41)

Prospective >3 91 AV nodal 65Infranodal 26

6857

182 patients with AV blockmapped with EPcatheter

5% lead failure

Kronborg et al.,2014 (40)

Randomized crossoverHBP vs. RVSP

24 38 AV nodal block 84 AV block, baseline narrowQRS, LVEF >40%

Improvement in LVEF, nosignificant improvement infunctional class, 6MWT, QOL

Pastore et al.,2015 (58)

Retrospective 12 148 AV nodal 100Infranodal 48

High-grade AVB,Paroxysmal AF

HBP associated with lower risk ofAF progression compared withRV pacing

Vijayaramanet al., 2015(29)

Observational 19 100 AV nodal 46Infranodal 54

9376

High-grade AV block, noback-up RV pacing

High success in infranodal block.Lead failure 5%

AF ¼ atrial fibrillation; AV node ¼ atrioventricular; CHF ¼ congestive heart failure; ejection fraction; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association; QOL; Quality of life;RVSP ¼ right ventricle septal pacing; 6MWT ¼ 6 min walk test.


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source-sink relationships during pacing versusintrinsic impulse propagation. Interplay between thestrength of the excitatory impulse (the source) andthe electrical load represented by the tissue it mustexcite (the sink) determines tissue excitability andconduction.

PRACTICAL CONSIDERATIONS. Due to the unstablenature of the escape rhythm in the infranodal AVblock, it would be prudent to place the atrial lead inthe RV to provide temporary back-up pacing duringHis bundle mapping. Despite advanced AV block, theHis bundle can be easily located in patients withinfranodal block. In these patients, it is reasonable tomap the distal His potential beyond the site of block,especially in patients demonstrating 2:1 AV conduc-tion or stable escape rhythm (Figure 8), where a muchlower His capture threshold can be achieved. It ispreferable to aim for NS-HBP in this group so as tohave the safety of ventricular myocardial capture,should conduction disease progress distally. In pa-tients with AV nodal block, intravenous isuprel maybe necessary to increase junctional escape rates toidentify the His electrograms. In patients with nostable escape rhythm, pace mapping can be per-formed at the anatomical His bundle region to ach-ieve successful HBP.

HIS BUNDLE PACING FOR CARDIAC

RESYNCHRONIZATION THERAPY

Cardiac resynchronization therapy (CRT) withcoronary sinus (CS) lead placement has becomeestablished as a first-line treatment for patients withsymptomatic class II to IV HF, LV systolic dysfunc-tion, LBBB, and QRS duration $150 ms (42). Despitethe development of sophisticated tool sets to facili-tate implant and intraprocedural strategies that haveevolved to consider mechanical and electrical delayin LV lead targeting, rates of nonresponse to CRTremain high—between 30% and 40% (43). In addition,rates of implant failure for CRT range between 5% and9%, in part due to high rates of CS lead dislodgement(3% to 7% reported across major trials) (44). In light ofthis, alternative strategies to achieve resynchroniza-tion have gained momentum, including endocardialLV lead pacing, “wireless” LV lead stimulation, andpermanent HBP. Among these, HBP may have atheoretic advantage to conventional CRT, because itrestores the intrinsic electromechanical activationsequence of the heart.

Although Narula reported in 1977 that HBP cannormalize LBBB during electrophysiology study (16),it would be more than 20 years later that these initialobservations would be reproduced in patients

FIGURE 7 Intra-Hisian AV Block

The electrograms from the His bundle pacing (HBP) lead demonstrate atrial (A) and split His potentials (H and Hʹ), evidence for Wenckebach

type conduction delay in between the split His potentials in a patient with intra-Hisian AV block and narrow QRS. Selective His capture with

QRS morphology identical to the native complexes is seen during HBP. Note “‘AH” dissociation secondary to noncapture of the proximal His at

low output.



938

undergoing HBP as part of a permanent pacing strat-egy. Since the initial description by Moriña-Vásquezet al. (45) in 2005, additional studies have furtherconfirmed the feasibility of permanent HBP to correctbundle branch block. In the largely short-term andmidterm results reported from these studies, patientshave demonstrated improved functional status,reduced mitral regurgitation, reduced dyssynchrony,and improved LVEF after HBP on par with what hasbeen shown in CRT responders.

INITIAL CLINICAL DATA. To date, there have been 5case series examining HBP for resynchronization(Table 3). Barba-Pichardo et al. (46) were the first toreport on HBP among patients in whom CRT implantwas unsuccessful. Lustgarten et al. (47) attemptedHBP for CRT in 29 patients (28 with LBBB), and QRSnarrowing was achieved acutely in 21 (72%). The trialprotocol required Y-adapting the His and CS lead toallow for crossover study, and permanent HBP couldnot be achieved in 12 patients, with failure of con-ventional CS LV lead placement in 1 patient. A total of12 patients completed 12 months of follow-up andcrossover comparison. The study showed that pa-tients appeared to benefit similarly when assigned toHBP versus biventricular pacing. Although significantimprovement of NYHA functional class, QOL, 6-minwalk distance, and LVEF was noted for both HBP

and biventricular pacing compared with baseline, thestudy was not powered to detect differences betweenthe 2 strategies.

Ajijola et al. (48) reported on the first case series ofprimary HBP (HBP lead in lieu of traditional LV lead)in CRT-eligible patients (48). Among 21 patients (17LBBB, 4 right bundle branch block [RBBB]), perma-nent HBP was achieved in 16 patients (76%). Themajority of patients demonstrated QRS narrowingwith nonselective capture, with an average QRSreduction of approximately 30%, but not to <120 msfor the majority of patients. Most recently, Sharmaet al. (49) pooled data from 5 centers and compiledthe largest retrospective case series of CRT-eligiblepatients thus far. They recognized 2 important co-horts: Group I, patients in whom prior CRT had beenattempted but was unsuccessful and HBP was used asa bail-out strategy; and Group II, primary HBP forCRT-eligible patients (AV block, post-AV junctionablation, underlying BBB, or patients undergoingplanned upgrade due to >40% RV pacing). Over amean follow-up period of 14 months, patientsdemonstrated QRS narrowing, improvement in NYHAfunctional class, and LVEF. Implant success was high(95 of 106 patients, 90%) and lead-related complica-tion rate was overall low (7 of 95 patients, 7.3%).Importantly, BBB was present in 48 patients (45%),

FIGURE 8 Mapping the Distal His Bundle in Infranodal AV Block Following Transcatheter Aortic Valve Replacement

Fluoroscopic location of the His bundle pacing lead and corresponding intracardiac electrogram in the proximal and distal His bundle location

are shown. The distance between the 2 locations in relation to the prosthetic valve clearly demonstrates the site of block to be very discrete.

(Right) The narrow His-paced QRS morphology.


939

and HBP was effective in this group (92% implantsuccess).

OPEN QUESTIONS AND FUTURE DIRECTIONS.

Although HBP demonstrates early promising results,appropriate patient selection remains to be defined.The use of HBP in patients with intraventricularconduction delay and/or extensive LV scar remainsuncertain. In about 10% to 30% of patients, LBBBmay not be correctable by permanent HBP. Residualintraventricular conduction delay due to scar orperipheral conduction disease may persist. Can HBPbe combined with LV pacing, or is it possible toreliably pace the proximal left bundle beyond thesite of block from the RV (50)? Whereas conven-tional approaches to HBP suggest aiming for selec-tive capture, NS-HBP may yield similar benefitswith better capture thresholds and R-wave sensing(34,51). In light of high rates of nonresponse totraditional CRT, there is clinical equipoise to justifyexploration of the role of HBP in CRT with ran-domized studies (His-SYNC [His Bundle PacingVersus Coronary Sinus Pacing for Cardiac Resynch-ronization Therapy] trial; NCT02700425; HOPE-HF[The His Optimised Pacing Evaluated for HeartFailure Trial]; NCT02671903). With current andfuture trials, we can further clarify the role for HBP

in pacing for patients with LBBB, RBBB, prolongedPR intervals, or high expected degree of ventricularpacing and underlying HF. Indeed, there may comea time when a conventional CS or epicardial LV leadis a bail out for HBP in the appropriately selectedpatient.

ELECTRICAL SYNCHRONY AND

HEMODYNAMICS OF HBP

S-HBP VERSUS NS-HBP. The major clinical advantageof HBP is that it can maintain electromechanicalsynchrony (both intravascular and interventricular).In S-HBP with normal HPS conduction, paced andnative QRS duration and morphology are identical,and electromechanical synchrony will be unaffected.In S-HBP with underlying BBB and complete correc-tion, electrical synchrony would likely normalizewith improved mechanical synchrony (Figure 9). InNS-HBP, where conduction through the HPS and pre-excitation of septal myocardium are fused, one maydebate whether this would lead to some degree ofventricular dyssynchrony. NS-HBP results in apseudo-delta wave that abruptly transitions to a steepdV/dT when the His-Purkinje conduction reaches themyocardium, with a timing approximating the HVinterval leading to QRS widening by a duration #HV

https://www.clinicaltrials.gov/ct2/show/NCT02700425?term=NCT02700425&rank=1

https://www.clinicaltrials.gov/ct2/show/NCT02671903

TABLE 3 His Bundle Pacing for CRT Indication

First Author(Ref. #) Year N Indication HBP Lead

ImplantSuccess (%) Major Findings

Barba-Pichardoet al. (46)

2013 16 CRT implant failure Tendril 1488T,1788TC, 1888TC

56 QRS narrowing achieved in 13 of 16 patients with HBP, ofwhom 9 underwent implant. During mean follow-up of31.3 � 21.5 months, NYHA functional class improved III/IIand LVEF improved from 29%/36% (<0.05)

Lustgarten et al. (47) 2015 29 Crossover study of HBP andconventional CRT

Select-Secure 3830 59 QRS narrowing achieved in 21 of 29 patients with HBP, ofwhom 17 patients underwent implant and 12 completedfollow-up. Both groups demonstrated significantimprovement in NYHA functional class, 6-min walk, QOL,and LVEF compared with baseline.

Su et al. (50) 2015 16 CRT implant failure Select-Secure 3830 100 Specific degree of QRS narrowing not reported, but correctionachieved for all patients. They found that His bundle tip-RVcoil configuration demonstrated better capture thresholdsthan bipolar configuration

Ajijola et al. (48) 2017 21 Primary HBP Select-Secure 3830 76 QRS narrowing achieved in all 16 patients with implant success(180 � 23 ms to 129 � 13 ms; p < 0.0001). NYHAfunctional class III/II (p < 0.001), and LVEF improvedfrom 27 � 10% to 41 � 13% (p < 0.001)

Sharma et al. (49) 2017 106 CRT implant failure (Group I)and primary HBP (Group II)

Select-Secure 3830 90 QRS narrowing achieved across all patients with implantsuccess (157 � 33 ms to 117 � 18 ms; p ¼ 0.0001).Underlying BBB was present in 48 patients and implantsuccess was 92% in this group (33 of 36 LBBB and 11 of 12non-LBBB). Among all patients NYHA functional class2.8�0.5/1.8�0.6 (p¼0.0001) and LVEF improved from30 � 10% to 43 � 13% (p ¼ 0.0001).

BBB ¼ bundle branch block; CRT ¼ cardiac resynchronization therapy; LBBB ¼ left bundle branch block; LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association; QOL ¼ quality of life;RV ¼ right ventricle.



940

interval. The LV total activation time did notdiffer significantly during NS-HBP compared withS-HBP or intrinsic activation (52). However, duringbiventricular pacing, the activation pattern is entirelydifferent, with early activation occurring in the LVepicardium (Figure 10).

Hemodynamic improvements appear to be compa-rable with both S-HBP and NS-HBP. Catanzariti et al.(53) reported echocardiographic measurements in 23patients implanted with S-HBP or NS-HBP and RVApacing leads (53). Compared with RVA pacing, S-HBPor NS-HBP was associated with lower interventriculardyssynchrony, intraventricular dyssynchrony, andbetter myocardial performance index with no differ-ences between S-HBP and NS-HBP. Lustgarten et al.(47) demonstrated that both S- and NS-HBP advancedLV activation time, confirming engagement of the HPSwith more rapid activation of the LV (Figure 11).

ACUTE STUDIES OF HBP

HBP VERSUS RVP. Acute electrophysiology studieshave reported favorable hemodynamics during HBPcompared with RVP. In 31 patients with narrow QRSundergoing an electrophysiological study, Ji et al.(54) reported no significant difference in LV circum-ferential strain, radial strain, twist, and mechanicaldyssynchrony comparing His and RA pacing, whereasRV outflow tract and RVA pacing worsened these

parameters. Pastore et al. (55) studied tissue Dopplerimaging echocardiography in 29 patients with S-HBPand 15 with NS-HBP (55). RVA and RV outflow tractseptum pacing showed variable effects on LV elec-tromechanical activation, with longer electrome-chanical latency and intra-LV dyssynchronycompared with pacing from the His bundle region.

HBP VERSUS LV OR BIVENTRICULAR PACING. Acomparison of HBP to LV or biventricular pacing mayhelp establish whether HBP can substitute for LVpacing in CRT-eligible patients. In an acute temporaryHBP versus biventricular pacing study by Sohaib et al.(56), 14 patients with systolic HF, prolonged PR>200 ms, and narrow QRS <140 ms or RBBB demon-strated improvement in blood pressure (whichincreased by about 4 mm for both biventricular pac-ing and HBP with AV shortening/optimization)compared with intrinsic rhythm, suggestingimproved acute hemodynamic function. Padelettiet al. (57) studied acute hemodynamics using pres-sure volume loops in HF patients with LBBB.Compared with AAI pacing, biventricular and LV-onlypacing improved systolic function and LV synchronyat individually optimized AV delays, while His-LVpacing improved indexes at all AV delays. One ma-jor shortcoming of this study, however, is that tem-porary HBP did not narrow the LBBB in any of thepatients studied.

FIGURE 9 3D Vectorcardiogram in LBBB and During His Bundle Pacing

The 12-lead ECG and corresponding 3-dimensional (3D) vectorcardiograms at baseline with LBBB and during HBP with correction of LBBB are

shown. Note the normalization of activation pattern with HBP. Courtesy of Terry D. Bauch, Geisinger Heart Institute. Abbreviations as in

Figures 2, 5, and 6.

FIGURE 10 Electrical Synchrony of His Bundle Pacing

From left to right, ECG Imaging epicardial activation maps for intrinsic QRS, selective His bundle pacing, nonselective His bundles pacing and biventricular pacing (BVP)

in a single patient with a normal QRS duration and morphology. Above are maps of the right ventricle (RV) and below of the left ventricle (LV). The color scale on the

left indicates the activation times. Selective HBP activates both ventricles identically to intrinsic rhythm. Nonselective HBP pacing activates the LV identical to selective

HBP and intrinsic rhythm but on the RV maps there is evidence of early (red) activation in the basal and mid ventricle, indicate capture of local right ventricular

myocardium alongside the bundle of His. Biventricular pacing activates the heart with an entirely different pattern with earliest activation (red) in the LV. Courtesy of

Ahran Arnold and Zachary Whinnett, Imperial College London, United Kingdom.


941

FIGURE 11 Cardiac Resynchronization During HBP

The 12-lead ECG and intracardiac electrograms from the HBP, right ventricular (RV), and left ventricular (LV) leads are shown at sweep speed of 100 mm/s. At baseline,

the QRS duration is 195 ms with His-LV interval of 230 ms. During nonselective HBP at 3 V, despite a QRS duration of 180 ms, the stimulus-LV interval is decreased to

160 ms. During selective HBP at 2 V, the QRS duration is 125 ms with stimulus-LV interval of 160 ms, proving the recruitment of left fascicles. At 1 V and selective HBP,

the QRS duration is now 195 ms with LV activation delayed to 230 ms, with the loss of recruitment of left fascicles. Abbreviations as in Figure 2.



942

ECHOCARDIOGRAPHIC HEMODYNAMICS

AND FUNCTIONAL STUDIES WITH

PERMANENT HBP

Compared with RVA pacing, HBP has been associatedwith improved fractional shortening, dP/dt, LVEF, andmyocardial performance index (Tei index). Also,improvement in interventricular electromechanicaldelay, intraventricular dyssynchrony, systolic-diastolic electromechanical delay, LV isovolumetriccontraction and relaxation times, and LV ejection timehave been demonstrated (20,30,35,36,53,55,58,59).These studies are summarized in Table 4. In 12 patientsundergoing pacemaker implantation with preservedHis bundle conduction, Zanon et al. (19) performedHBP for 3months and then crossed over to RVA pacing.Myocardial scintigraphy, QOL, clinical evaluation,echocardiography, and brain natriuretic peptide wereassessed. Therewas no differences in NYHA functional

class, brain natriuretic peptide, mean LVEF, or LVvolumes. However, myocardial perfusion score, ShortForm-36 physical and mental status, mitral regurgita-tion, and mechanical dyssynchrony were significantlybetter with HBP than during RVA pacing. One-half ofthe patients had dyssynchrony with RVA pacing,whereas none had dyssynchrony during HBP.

HBP IN CRT. HBP has potential theoretical benefitsover CS or epicardial LV pacing. Electrically, CS/LVpacing still results in myocardial activation withinherent degrees of dyssynchrony that may attenuatethe beneficial effects in patients with ischemic car-diomyopathy, non-LBBB QRS morphologies, andcertain lead positions, such as apically or over-scarredareas. In CRT candidates with wide QRS durations,success rates for electrical synchronization with QRSnarrowing during HBP range from 70% to 92%(47–49). HBP resulted in a narrower QRS than

TABLE 4 Hemodynamics of Permanent HBP

First Author,Year (Ref. #) N Acute Success Follow-Up Results

Catanzariti et al.,2006 (53)

24 23 (96%) 7.5 months � Compared with RVA pacing, selective or nonselective HBP is associated withlower interventricular dyssynchrony, intraventricular dyssynchrony, MR, andbetter myocardial performance index (Tei index)

� No difference between selective or nonselective HBP

Zanon et al.,2008 (19)

12 3-month HBP crossoverto RVA pacing

� Patients with preserved HPS conduction� Myocardial scintigraphy, QoL, clinical evaluation, echo, BNP� Perfusion score, Short Form-36 physical and mental status significantly better

during HBP than during RVAP� No difference in NYHA functional class, BNP, mean LVEF, LV volumes� Less MR and mechanical dyssynchrony during HBP� One-half of RVAP had dyssynchrony, none during HBP

Catanzariti et al.,2013 (20)

26 20 SHBP6 NSHBP

34 monthsCrossover at end to RVA

� Patients with HBP and backup RVA lead� At last follow-up, mean paced QRSd NS from baseline at implant� At mean of 346 months, pacing switched to RVA with decrease in LVEF 57.3% to

50.1%, increase in MR, worsened interventricular delay, and tissue Doppler im-aging asynchrony index, although no change in myocardial performance index

� Higher pacing thresholds on the His bundle compared with RVA lead (mean 18 Vvs. 06 V at 05 ms), but stable from implant

Kronborg et al.,2014 (40)

38 84% HBP 12-month crossover, HBPvs. RVSP

� Narrow QRS <120 ms c AVB, LVEF >40%� HBP preserved LVEF and mechanical synchrony (time to peak systolic velocity

between opposite basal segments) compared with RVSP� No difference in NYHA functional class, 6MWT, QoL, or complications� Mean threshold higher in HBP than RVSP leads

Pastore et al.,2014 (58)

37 3-month crossover fromHBP to RVA pacing

� Compared with HBP, RVA pacing increased systolic-diastolic electromechanicaldelay, intra-LV dyssynchrony, LV isovolumetric contraction, and relaxationtimes; LV ejection time was shorter

� HBP had better myocardial performance index and diastolic function, lower PASP� RVA pacing had higher LA volumes pre-atrial contraction and minimal volume

with reduction in passive emptying fraction and total emptying fraction� Hisian area compared with RVA pacing resulted in a more physiological LV

electromechanical activation/relaxation and consequently better LA function

Zhang et al.,2017 (33)

23 NSHBP 11SHBP 12RVSP 23

HBP vs. RVSPIntrapatient

� Mechanical synchrony parameters were significantly better during HBP comparedwith RV septal pacing with no significant difference between S-HBP or NS-HBP

BNP ¼ brain natriuretic peptide; HBP ¼ His bundle pacing; LV ¼ left ventricle; LVEDD ¼ left ventricular end-diastolic diameter; LVEF ¼ left ventricular ejection fraction; LVESD ¼ left ventricular end-systolicdiameter; NS-HBP ¼ nonselective His bundle pacing; QoL ¼ quality of life; RVA ¼ right ventricular apical; RVSP ¼ right ventricular septal pacing; S-HBP ¼ selective His bundle pacing.


943

biventricular pacing and required shorter implanttimes compared with LV leads (47). These studiesshowed significant improvements in NYHA functionalclass, QOL, LV end-diastolic diameter, and LVEF.Recently, 2 observational studies showed that HBPcan improve echocardiographic and clinical outcomesin patients who failed traditional LV lead implanta-tion and in CRT nonresponders (48,49).

MEDIUM-TERM OUTCOMES

The presence of an HBP lead does not appear toadversely affect medium-term HPS conduction. Astudy of 20 HBP patients at the time of generatorchange (mean follow-up 70 � 24 months) showed nodifferences in HV intervals and QRS duration, anddemonstrated trends toward improvement in LVEFand LV end-diastolic diameter (p ¼ 0.06), withconsistent 1:1 His-Purkinje conduction with decre-mental pacing to 500 ms (60). Published data on long-term clinical outcomes of HBP are scarce. RecentlyVijayaraman et al. (27) reported clinical and

echocardiographic outcomes during 5-year follow-upin an observational, case-control study of HBPcompared with RVP. HBP was associated with a sig-nificant reduction in the combined endpoint of HFhospitalization or mortality in patients with >40%ventricular pacing (32% vs. 53%; hazard ratio [HR]:1.9; p ¼ 0.04). LVEF remained unchanged in the HBPgroup (55 � 8% vs. 57 � 6%; p ¼ 0.13), whereas asignificant decline was noted in RVP (57 � 7% vs. 52 �11%; p ¼ 0.002). Pacing-induced cardiomyopathy wassignificantly lower in HBP compared with RVP (2% vs.22%; p ¼ 0.04). Abdelrahman et al. (61) compared 332consecutive patients undergoing HBP with 433 pa-tients with RVP in an observational cohort study. Thecombined endpoint of all-cause mortality, time tofirst HFH (heart failure hospitalization), or upgrade tobiventricular pacing was significantly reduced withHBP (25% vs. 32%; HR: 0.71; 95% confidence interval[CI]: 0.534 to 0.944; p ¼ 0.02). This difference wasprimarily in patients with ventricular pacing >20%(25% in HBP vs. 36% in RVP; HR: 0.65; 95% CI: 0.456to 0.927; p ¼ 0.02) (Central Illustration panel B). The



944

incidence of HFH was significantly reduced in HBP(12.4% vs. 17.6%; HR: 0.63; 95% CI: 0.430 to 0.931;p ¼ 0.02). There was a trend toward reduced mor-tality in HBP (17.2% vs. 21.4%; p ¼ 0.06). The mech-anisms by which HBP may reduce mortality can partlybe explained by elimination of ventricular dyssyn-chrony and reduction in HF. Additional factors, suchas reduction in dispersion of ventricular repolariza-tion, may play a role. In addition to QRS narrowing,HBP also reduces T peak to T end duration, which is aknown marker of arrhythmic risk and may potentiallycontribute to reducing mortality (62). Although thisobservational study is hypothesis generating, ran-domized controlled trials are necessary to confirmpotential mortality benefits attributable to HBP.

HBP: CLINICAL CHALLENGES

AND TROUBLESHOOTING

CAPTURE THRESHOLDS. The His bundle region is inthe central fibrous body minimally surrounded bymyocardial tissue. Unless the lead tip penetrates thefibrous insulation of the His bundle or is in closeproximity, the His capture thresholds can be signifi-cantly higher than traditional RV capture thresholds.In some patients, the His bundle may be locateddeeper and the helix may not be long enough toachieve acceptable His thresholds. In our experience,HBP can consistently be achieved in >95% of patientswith normal His-Purkinje conduction. However, Hiscapture thresholds >2 V at 1 ms may be seen in w10%of patients at implant. We accept these values atimplant, provided there is nonselective capture withsignificantly lower RV capture thresholds. Addition-ally, in some patients, His bundle capture thresholdmay progressively increase during follow-up.Vijayaraman et al. (27) reported that His capturethresholds remained relatively stable during 5-yearfollow-up of 75 patients (1.35 � 0.9 V at implant vs.1.62 � 1.00 V at 0.5 ms; p < 0.05). An increase inchronic pacing threshold >1 V from baseline wasnoted in 9 patients in HBP compared with 6 patientsin RVP (12% vs. 6%; p ¼ 0.04) (27).

LEAD REVISIONS. One of the early concerns of HBPwas the risk for lead failure. Many operators routinelyimplanted a back-up RV pacing lead. Recent reportsshow that HBP leads are relatively stable, and routineplacement of a back-up RV pacing lead is not neces-sary in most patients (22,27,29,60). In a recent studyby Vijayaraman et al. (29), acute loss of captureoccurred in 2 of 100 patients with AV block and HBP.Lead revisions were required in 3 additional patientsat 2 to 6 months post-implant due to progressive

increases in capture threshold for a lead revision rateof 5% (29). In a long-term study of 75 patients withHBP, lead revisions were required in 5 patients (6.7%),4 of whom underwent successful lead replacement atthe His bundle region even as late as 5 years after theinitial implant (27). Acute increase in HBP threshold orloss of capture is most likely due to inadequate fixa-tion of the HBP lead. The mechanism for delayed in-crease in HBP threshold during longer-term follow-upis less clear. It is likely that due to the anatomicalproximity of the loop of the HBP lead, the tricuspidvalve motion causes slow unhinging of the lead. Thepossibility of local fibrosis and exit block cannot beexcluded. The 3830 pacing lead has a helix length ofonly 1.8 mm and the depth of the His bundle relative tothe endocardial surface is variable. Because of thepaucity of excitable tissue surrounding the His bundlein the central fibrous body, micro-dislodgement of thelead can lead to significant increase in His bundlecapture threshold compared to RV myocardium. In arecent study of lead extraction, Vijayaraman et al. (63)reported that 21 of 22 leads in the His bundle locationcould successfully be removed without any injury tothe conduction system following a mean lead dwelltime of 26 � 18 months. A new HBP lead could suc-cessfully be implanted in 10 of 13 patients. Nonethe-less, the impact of lead extraction in patients withlonger-term HBP is unknown.

BATTERY DEPLETION. Early investigators’ enthu-siasm for HBP waned due to high His capturethresholds and back-up RV lead requirement, whichleads to premature battery depletions necessitatingearly generator changes. Recent studies havedemonstrated that the majority of patients undergo-ing HBP do well without need for early generatorchanges (27,60,61). In patients undergoing CRT withHBP, capture thresholds required to correct underly-ing BBB are often higher, and early battery depletioncan still be a major obstacle. Further improvements inbattery technology with development of long-lastingHis bundle–specific pacing systems capable of deliv-ering high output would be necessary.

SENSING. The electrogram obtained from the HBPlead may demonstrate atrial, His, and ventricularsignals depending on the location of the tip elec-trode above or below the tricuspid valve plane andorientation of the ring electrode. The ventricularelectrogram amplitudes tend to be significantlysmaller than traditional RV sensing. In patients withselective HBP with a lead tip above the valve plane,the ventricular electrogram amplitude may be lowerthan 1 to 2 mV along with relatively larger atrialelectrogram. It is critical to program the ventricular


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sensing parameters appropriately compared withtraditional RV parameters. Although unipolar elec-trogram amplitudes are often better than bipolarsignals, oversensing and inhibition can be an issue.Development of dedicated sensing algorithmscapable of blanking far-field atrial electrograms andmodifying the interelectrode distance and electrodecharacteristics of pacing lead may be necessary tooptimize His-specific pacing systems.

DEVICE FOLLOW-UP. During follow-up, assessmentof His bundle capture using multilead ECG (preferably12-lead) is recommended. At 3-month follow-up, thepacing output is programmed to at least 1 V above theHis capture threshold, as confirmed with multileadECG rather than at twice-safety margin, to conservebattery life. In patients with BBB, 3 different capturethresholds may be noted (Figures 2, 5, and 10)depending on selective or nonselective His capturewith correction (RV, right bundle or left bundle, andcomplete His bundle capture). Similar to earlybiventricular pacing, attention to local electrogram inthe pacing electrode and 12-lead ECG may elucidateselective versus nonselective capture. Utility ofautomatic threshold testing features is limited inHBP. In patients with selective HBP, due to lack ofevoked potentials, this feature may fail to detect thetrue His capture threshold. On the contrary, in pa-tients with nonselective HBP, this feature will detectmyocardial capture threshold rather than His bundlecapture. Development of automatic threshold algo-rithms to accurately identify His capture thresholdswould be an important next step to extend batterylongevity. Importantly, additional training of thedevice clinic personnel is necessary to ensure appro-priate programming during follow-up.

FUTURE DIRECTIONS

Despite recent advances and interest in HBP, severalunanswered questions and concerns remain (64).Although permanent HBP may be an attractive op-tion for physiological pacing in several groups ofpatients, its reliability and long-term performanceare yet to be fully validated in large prospectivestudies. Particularly relevant are patients with

infranodal, intra-Hisian AV block and BBB, wherelong-term safety of HBP has not been well studied.In such patients, should a backup RV lead be placedwith HBP? What happens to the His bundle when itis traumatized by the screw on the tip of the lead inthe long term? Can a second His Bundle pacing leadbe placed successfully if the earlier lead fails in thelong run? Considerable effort needs to go intoimproving the design and structure of the lead andthe delivery tools to allow for easier implantationand stabilization of the lead. Beyond implant, whatare the implications of extracting a chronic HBPlead? And beyond pacing hemodynamics, what is theimpact of HBP on arrhythmia? Does HBP reduce therisk of ventricular tachyarrhythmias in the presenceof myocardial scar? These and other questionsremain.

What is certain is that this technique holds poten-tial and requires further validation in larger studieswith longer follow-up. It is also clear that collectiveand collaborative efforts from physician scientists,industry partners, scientific societies, and regulatoryauthorities will be required to successfully developthis technology and advance our understanding ofthe physiology of pacing.

CONCLUSIONS

HBP is an attractive mode of physiological pacingwith significant promise for future applications inpatients who are traditional candidates for RV pacingas well as CRT. Widespread adaptation of this tech-nique is dependent on the improvement of tools andfurther validation of its efficacy in large randomizedclinical trials.

ACKNOWLEDGMENT The authors thank Ms. AvaniPugazhendhi for her help in editing the video.

ADDRESS FOR CORRESPONDENCE: Dr. PugazhendhiVijayaraman, Cardiac Electrophysiology, GeisingerHeart Institute, 1000 E Mountain Boulevard, MC 36-10, Wilkes-Barre, Pennsylvania 18711. E-mail:[email protected] OR [email protected]. Twitter: @Hisdoc1, @GeisingerHealth.

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KEY WORDS cardiac resynchronizationtherapy, heart failure, permanent His bundlepacing, right ventricular pacing

APPENDIX For a supplemental video,please see the online version of this paper.
























































































his bundle pacingdescribed the architecture of the his bundle using both light microscopy and...

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