JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
8, 2018
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JACC Editor-in-Chief
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VOL. 72, NO.
ª 2018 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER
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
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 to
become more prevalent as our population
ages. Furthermore, cardiac pacing remains
the only definitive therapy for nonreversible bradyar-
therapy, there is continued debate regarding the
optimal ventricular pacing sites, particularly in the
ventricle. Initial ventricular-only pacing devices pro-
vided adequate rate support but were not synchro-
rhythmias. Despite years of successful pacing nized to atrial contraction, and led to negative
The views expressed in this paper by the American College of Cardiology’s (ACC) Electrophysiology Council do not necessarily
reflect the views of JACC or the ACC.
From the aGeisinger Heart Institute, Geisinger Commonwealth School of Medicine, Wilkes-Barre, Pennsylvania; bDivision of
Electrophysiology, Cleveland Clinic, Cleveland, Ohio; cKrannert Institute of Cardiology, Department of Medicine, Indiana Uni-
versity School of Medicine, Indianapolis, Indiana; dElectrophysiology Section, Division of Cardiology, University of Chicago,
Chicago, Illinois; eElectrophysiology Section, Division of Cardiology, Rush University Medical Center, Chicago, Illinois; fVanderbilt
Heart and Vascular Institute, Nashville, Tennessee; gDivision of Cardiology, Duke University, Durham, North Carolina; hDivision of
Electrophysiology, University of California San Francisco, California; iElectrophysiology Section, Division of Cardiology, American
University of Beirut, Beirut, Lebanon; jElectrophysiology Research Foundation, Warren, New Jersey; kRutgers’ Robert Wood
Johnson Medical School, New Brunswick, New Jersey; lElectrophysiology Section, Division of Cardiology, Albert Einstein College
of Medicine, New York, New York; mKansas City Heart Rhythm Institute, Overland Park, Kansas; and the nUniversity of Missouri,
Columbia, Missouri. Dr. Vijayaraman has served as a speaker for and received research support from Medtronic; has served as a
consultant for Medtronic, Boston Scientific, and Abbott; and has a patent pending for a His delivery tool. Dr. Chung has received
research support from Medtronic, Boston Scientific, and Abbott; and has served on the steering committee for EPIC Alliance and
Biotronik (uncompensated). Dr. Dandamudi has served as a speaker for, served as a consultant for, and received research support
from Medtronic. Dr. Upadhyay has received research support from Medtronic and Biotronik. Dr. Krishnan has received research
support from Abbott; and has served as a consultant for Zoll. Dr. Crossley has served as a speaker for, served as a consultant for,
and received research support from Medtronic; and has served as a consultant for Boston Scientific. Dr. Fisher has received
research support from Medtronic; has served as a consultant for Medtronic and MDT; and has received fellowship support from
Medtronic, Abbott, and Biotronik. All other authors have reported that they have no relationships relevant to the contents of this
paper to disclose.
Manuscript received March 16, 2018; revised manuscript received June 1, 2018, accepted June 4, 2018.
ISSN 0735-1097/$36.00 https://doi.org/10.1016/j.jacc.2018.06.017
928 Vijayaraman et al.
His Bundle Pacing
ABBREVIATIONS hemodynamic consequences including an
AND ACRONYMS increased risk of heart failure (HF) and atrial
fibrillation. Even atrioventricular (AV) syn-
AF = atrial fibrillation
chronized pacing delivered at the right ven-
AV = atrioventricular
tricular (RV) apex, however, was noted to
HBP = His bundle pacing
worsen contractile function in many pa-
HF = heart failure tients. Eventually, the connection between
HPCD = His-Purkinje the degree of right ventricular apical (RVA)
conduction disease
pacing and cardiac dysfunction became well
HV = His to ventricular
established (1). Pursuit of alternate pacing
electrogram interval
sites has included the RV septum, the RV
LBBB = left bundle branch
block
outflow tract, and the left ventricle (LV) (2).
Although biventricular pacing has unequivo-
LV = left ventricle/ventricular
cally improved HF outcomes and reduced
RBBB = right bundle branch
block mortality in patients with left bundle branch
RVP = right ventricular pacing
block (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 engage
the normal conduction through the His-Purkinje
conduction system. The concept of pacing the main
body of the bundle of His is not new. Early in-
vestigators described temporary His bundle pacing
(HBP) (4). Eventually the concept of directly pacing
the His bundle with a permanent pacemaker was
described (5). Although its electrophysiological role in
AV conduction makes the His bundle an attractive
site for physiological pacing, actual lead placement
can be technically challenging due to its anatomic
location and surrounding cardiac structures. In this
paper, we provide a comprehensive review of the
anatomy, physiology, implantation techniques, and
clinical role of permanent HBP.
ANATOMY OF THE HIS BUNDLE AND
PROXIMAL BUNDLE BRANCHES
A detailed knowledge of the anatomy of the His
bundle and proximal bundle branches is crucial for
understanding the anatomic basis of various con-
duction disorders as well as for approaching perma-
nent HBP. Wilhelm His Jr., a Swiss anatomist and
cardiologist, first described the His bundle structure
and its role in transmitting atrial impulses to the
ventricles in 1893. The Japanese pathologist, Sunao
Tawara, made seminal observations regarding the
cardiac conduction system in 1903 (6), revealing the
existence of the AV nodal structure and making
detailed observations of the His-Purkinje system
(HPS). Incredibly, based entirely on the anatomic
observations, he was able to surmise physiological
attributes of the HPS, including conduction
JACC VOL. 72, NO. 8, 2018
AUGUST 21, 2018:927–47
velocities. The His bundle forms an anatomical
continuation of the AV node, providing the connec-
tion for electrical signals from the AV node to reach
the right and left ventricles through the right and left
bundle branches, respectively (7).
The His bundle and the proximal branches initially
originate as part of the primitive interventricular
septum. During the second trimester of gestation,
the AV node connects with the proximal portion of
the developing His bundle. Failure of this junction to
develop leads to congenital complete heart block (7).
The His bundle extends inferiorly and leftward from
the AV node, directly past the posterior and inferior
margins of the membranous interventricular septum,
and remains undivided for a few millimeters. At the
crest of the muscular interventricular septum, the His
bundle starts to divide (Central Illustration, panel A)
into right and left bundle branches (8). The trunk of
the left bundle branch often splits into 3 fascicles
after the proximal 2 cm, and there are many sub-
endocardial ramifications and interconnections.
The proximal part of the His bundle rests on the right
atrial–LV portion of the membranous septum, and the
more distal His travels along the RV-LV portion of
the membranous septum, immediately below the
aortic root.
Recent macroscopic anatomic investigations (9)
have elucidated 3 common variations of the His
bundle relative to the membranous part of the ven-
tricular septum (Figure 1). In type I anatomy (46.7% of
105 cases), the His bundle consistently coursed along
the lower border of the membranous part of the
interventricular septum, but was covered with a thin
layer of myocardial fibers spanning from the muscular
part of the septum. In type II (32.4%), the His bundle
was apart from the lower border of the membranous
part of the interventricular septum and ran within the
interventricular muscle. In type III (21%), the His
bundle was immediately beneath the endocardium
and coursed onto the membranous part of the inter-
ventricular septum (naked AV bundle). Other reports
of anomalous His bundle locations include a pre-
dominantly left-sided course. These anatomical var-
iations of the His bundle may have clinical
implications for permanent HBP in terms of achieving
selective His bundle pacing (S-HBP) or nonselective
His bundle pacing (NS-HBP), in addition to potential
for injury to the His bundle resulting in transient or
persistent bundle branch block (BBB) or complete AV
block (10). Both the atrial and ventricular portions of
the His bundle can be accessed for permanent ven-
tricular pacing.
JACC VOL. 72, NO. 8, 2018 Vijayaraman et al. 929
AUGUST 21, 2018:927–47 His Bundle Pacing

C ENTR AL I LL U STRA T I O N 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.
930 Vijayaraman et al. JACC VOL. 72, NO. 8, 2018

His Bundle Pacing AUGUST 21, 2018:927–47

F I G U R E 1 Anatomic Variations of the His Bundle

(A) Type 1: The His bundle (AVB) runs under the membranous 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 the membranous part of the interventricular septum. (C) The type III
His bundle (arrow) is naked running beneath the endocardium with no surrounding myocardial fibers. AT ¼ attachment of septal tricuspid leaflet;
AVB ¼ atrioventricular bundle; AVN ¼ atrioventricular node; CS ¼ coronary sinus. Reprinted from Kawashima and Sasaki (9).

HBP: FROM BENCH TO BEDSIDE filaments contained within a single common cable.
The following observations were made by this group:
SEMINAL PHYSIOLOGICAL RECORDINGS OF THE HIS
1. The bulk of the His bundle is comprised of cells
BUNDLE. Using isolated perfused hearts and plunge
that eventually course into the left bundle
needles in animals, Alanís et al. (11) first described His
branches (only a small number enter the right
bundle electrograms in 1958. They are credited with
branch).
describing the His bundle as a “zone” of conduction
2. The cells that make up the His-Purkinje fibers are
and lacking decremental properties, in contrast to the
broader and shorter than the usual working
AV node. Scherlag et al. (12) are credited with devel-
myocardial cells with relatively few myofibrils.
oping the catheter-based approach in humans for
3. These cells are elongated and oblong in shape, and
recording the His bundle in 1969, which has essen-
make contact predominantly at their terminal ends
tially remained unchanged in the electrophysiology
and to a lesser extent across the lateral margins.
laboratory to date.
4. These cells are partitioned intricately by collagen
FUNCTIONAL LONGITUDINAL DISSOCIATION OF
fibers; in fact, longitudinal division of the His
THE HIS BUNDLE. Kaufmann and Rothberger (13) first
bundle by collagen makes it unique from a histo-
proposed the idea of functional longitudinal dissoci-
logical standpoint when compared with the AV
ation of the His bundle in 1919. According to this
node and the working myocardium.
theory, conduction fibers arose from the proximal
5. The collagen may minimize or even prevent lateral
portions of the common His bundle and were pre-
spread of the propagated impulse, while the com-
destined to the individual bundle branches. Several
partmentalized tissue with specialized intercel-
investigators studied this concept in both animal and
lular connections would facilitate rapid
human models. In 1971, James and Sherf (14)
longitudinal spread of the propagated impulse.
described the architecture of the His bundle using
both light microscopy and electron microscopy. Their An implication of these findings is that some
observations may explain the conduction properties patients with His-Purkinje conduction disease
that are seen in clinical practice with HBP (14). They (HPCD) may have relatively proximal disease, and
described the His bundle as multiple insulated that pacing distal to the site of block might
JACC VOL. 72, NO. 8, 2018 Vijayaraman et al. 931
AUGUST 21, 2018:927–47 His Bundle Pacing

F I G U R E 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).

overcome the block and narrow the QRS. Initial
work conducted by Narula (15) was instrumental in
demonstrating that patients with LBBB could be
corrected with pacing just distal to the presumed
site of block. These seminal observations paved the
way to confirming the feasibility of HBP even in
advanced His to ventricular electrogram interval
(HV) disease substrates (Figure 2).
HBP IN CLINICAL PRACTICE—HOW
STARTED. Credit goes to Deshmukh et al. (5) for
introducing permanent HBP in humans in 2000. They
studied the role of HBP in patients with HF and rapid
atrial fibrillation (AF), resulting in tachycardia-
induced cardiomyopathy. Between 2006 and 2011, a
handful of case reports and case series were pub-
lished which applied HBP in more general clinical
practice (16–20). These initial studies and observa-
tions have led to further exploration of the utility of
permanent HBP in patients requiring pacing and
device-paced HF therapy.
HBP LEAD IMPLANTATION TECHNIQUE
Permanent HBP was initially performed using stan-
dard pacing leads by reshaping the stylet or using a
deflectable stylet to precisely position the lead at a
site near the electrophysiology mapping catheter
IT ALL demonstrating the largest His deflection. This
approach was technically challenging and time
consuming. The development of a specialized pacing
lead (SelectSecure 3830, Medtronic, Minneapolis,
Minnesota) and sheaths (C315His, C304 SelectSite,
Medtronic) has made permanent HBP feasible in
routine clinical practice (21). It has been shown that
the His bundle region can be successfully located
using the pacing lead in >95% of patients (without a
mapping catheter) without significantly prolonging
932 Vijayaraman et al.
His Bundle Pacing
F I G U R E 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.
the procedure duration (22). The His bundle is
generally mapped using the pacing lead in a unipolar
fashion. The fixed-curve C315His sheath is more
effective than the deflectable C304 sheath for
implanting the HBP lead. This sheath has a proximal
curve directing the sheath to the tricuspid annulus,
while the secondary septal curve points the sheath
perpendicular to the myocardial surface allowing the
lead to be fixed securely (Figure 3). The implant
technique has been previously described (23). Once
venous access is obtained, the C315His sheath is
advanced over a guidewire and placed at the
tricuspid annulus (Online Video 1). The 3830 pacing
lead is then advanced to the tip of the sheath, and the
electrograms from this lead are simultaneously dis-
played in the EP recording system at a sweep speed
of 100 mm/s and the pacing system analyzer using a
jumper cable. If more prominent atrial electrograms
are noted, the sheath is rotated gently clockwise
allowing the lead to be moved slightly more ven-
tricularly. Once an atrial to ventricular electrogram
ratio of 1:2 or greater is noted, the sheath is pointed
toward the superior-anterior septum or midseptum
by minimal clockwise or counter-clockwise rotation,
respectively. Once a near-field His electrogram is
identified, pacing is performed at 5 V at 1 ms to assess
His capture. Twelve-lead electrocardiograms are dis-
played along with His electrograms during mapping
and pacing to facilitate accurate assessment of His
bundle capture and correction of bundle branch
blocks. Following identification of the His location,
the fluoroscopic image is saved as a reference. The
sheath is held steady, and the pacing lead is slowly
rotated clockwise approximately 5 times without
JACC VOL. 72, NO. 8, 2018
AUGUST 21, 2018:927–47
releasing the lead between rotations. This allows the
torque to be transmitted along the length of the lead
to the lead tip. If the lead is anchored well, it will
rotate back counterclockwise to release the excess
torque. 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 are
then checked in both unipolar and bipolar configu-
rations. HBP threshold is preferably tested at a pulse
width of 1 ms to allow for a lower capture voltage. In
most patients, a His bundle capture threshold
of #2.0 V at 1 ms is acceptable. In patients with
HPCD, a higher His bundle capture threshold may be
accepted provided the RV capture threshold is
significantly lower (NS-HBP). In these patients, it is
essential that attempts be made to map the distal His
bundle beyond the site of intra-Hisian block to ach-
ieve low His capture thresholds. A His bundle injury
current can often be recorded following lead fixation
in w40% of patients. To record the injury current, the
high-pass filter needs to be adjusted to 0.5 Hz from
30 Hz in the EP recording system (Figure 4). The
presence of a His bundle injury current has been
shown to predict excellent acute and long-term cap-
ture thresholds (24).
PRACTICAL CONSIDERATIONS. Permanent HBP can
be challenging due to the limited availability of
delivery tools, particularly in patients with an
enlarged right atrium and a displaced tricuspid
annular region or right pectoral implants. Modifi-
cations to implant techniques have recently been
described to achieve higher success in these pa-
tients (25).
JACC VOL. 72, NO. 8, 2018
AUGUST 21, 2018:927–47
PROCEDURAL OUTCOMES. In the original report by
Deshmukh et al. (5), the success of permanent HBP in
select patients with cardiomyopathy undergoing AV
node ablation was about 66% using traditional pacing
leads (5). Zanon et al. (26) reported an acute implant
success rate of 92% in 26 patients without underlying
HPCD while utilizing the 3830 pacing lead. In a sub-
sequent report by Sharma et al. (22), the acute HBP
implant success rate was 80% in a consecutive series
of 94 unselected patients (including patients with
HPCD) undergoing permanent pacemaker implanta-
tion. With increased procedural experience, the
feasibility of permanent HBP in all-comers, including
patients with infranodal AV block, was >90%. While
early studies reported significantly longer procedural
times, recent studies suggest similar fluoroscopy and
procedural times compared with right ventricular
pacing (RVP) (22).
Compared with high His bundle capture thresholds
reported with traditional pacing leads in early
studies, recent investigations show acceptable His
capture thresholds both at implant and during long-
term follow-up. In a study of 75 patients with
successful permanent HBP, Vijayaraman et al. (27)
reported His capture thresholds of 1.35  0.5 V at
0.5 ms at implant that remained stable during 5-year
follow-up (1.62  1.0 V at 0.5 ms). In another study
of AV node ablation and HBP in 42 patients, His
capture threshold at implant was 1.5  1.0 V at 0.5 ms
and remained unchanged during a median follow-up
of 20 months (28). In a study of 100 consecutive pa-
tients with advanced AV block, acute His capture
threshold at implant was 1.3  0.9 V at 0.5 ms and
slightly increased to 1.7  1.0 V at 0.5 ms during a
mean 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 regarding
the types of His bundle capture observed and pacing
threshold definitions. Recently, a multicenter HBP
collaborative working group proposed a refined set of
criteria to define HBP in patients with normal His-
Purkinje conduction and in those with HPCD (30).
The authors broadly defined 2 forms of His bundle
capture: selective capture, in which the His bundle is
the only tissue captured by the pacing stimulus; and
nonselective capture, in which there is fusion capture
of the His bundle and adjacent ventricular tissues
(Table 1). Various criteria for S-HBP or NS-HBP are
described in the following text.
SELECTIVE HBP. During S-HBP, ventricular activa-
tion occurs directly and completely over the HPS and
is accompanied by the following criteria:
Vijayaraman et al. 933
His Bundle Pacing
1. The pacing stimulus to QRS (S-QRS) onset interval
is equal to the native His-QRS onset interval
(H-QRS). However, in patients with HPCD, the
S-QRS interval can be shorter than the H-QRS
intervals, as in patients with BBB or HV block due to
capture of latent fascicular tissue.
2. The local ventricular electrogram on the pacing
lead will be discrete from the pacing artifact.
3. The paced QRS morphology is the same as the
native QRS morphology. In patients with HPCD, the
paced QRS duration may be narrower than the
native QRS with BBB or the escape rhythm.
4. Usually a single capture threshold (His capture) is
observed. However in patients with HPCD, 2 distinct
His capture thresholds—with and without correction
of underlying BBB—may be seen (Figure 5).
NONSELECTIVE HBP. During NS-HBP, there is
culmination of both His bundle and ventricular
capture.
1. The S-QRS interval is usually zero, as there is no
isoelectric interval between pacing stimulus and
QRS due to the presence of a pseudo-delta wave
(due to local myocardial capture).
2. The local ventricular electrogram is directly
captured by the pacing stimulus and is not seen as
a discrete component.
3. The paced QRS duration will usually be longer than
the native QRS duration by the H-QRS interval, and
the overall electrical axis of the paced QRS will be
concordant with the electrical axis of the intrinsic
QRS. In patients with HPCD, the paced QRS duration
may be narrower than the native QRS due to
correction of underlying BBB.
4. There will usually be 2 distinct capture thresholds
– right ventricular and His capture. The His capture
threshold may be lower or higher than the ven-
tricular capture threshold. The output difference
between the 2 thresholds (RV and His) is usually
small, and the final programmed output including
the safety margin would result in nonselective His
capture. In patients with HPCD, 3 distinct capture
thresholds may be observed in varying combination
(RV capture, His capture with correction of BBB, and
His capture without correction of BBB) (Figure 6).
Selective or nonselective capture of His bundle is
often dependent on the location of the pacing elec-
trode in relation to the His bundle, surrounding atrial
or ventricular tissue, and the amplitude of the pacing
output (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
934 Vijayaraman et al.
His Bundle Pacing
F I G U R E 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.
capture, possibly due to rapid conduction of the His-
Purkinje system relative to ventricular myocardial
conduction (33,34). The most important aspect of HBP
is to clearly document RV and His capture thresholds
along with BBB correction thresholds (where appli-
cable) for the purposes of follow-up and programming
final output settings.
HIS BUNDLE PACING FOR AV NODE
ABLATION AND ATRIOVENTRICULAR BLOCK
Ventricular pacing avoidance algorithms are often
employed in patients with first- or second-degree AV
block to prevent RV pacing. However, in complete AV
block, RV pacing is unavoidable. Various studies of
HBP in patients with AV block and AV node ablation
are shown in Table 2.
AV NODE ABLATION AND HBP. Deshmukh et al. (5)
originally reported the feasibility of permanent HBP
in 12 of 18 patients with atrial fibrillation undergoing
AV node ablation. In a subsequent series of 54 pa-
tients with AF and dilated cardiomyopathy undergo-
ing AV node ablation, direct (selective) HBP was
achieved in 39 patients with resultant improvement
in left ventricular ejection fraction (LVEF) from 23 
11% at baseline to 33  15% during a mean follow-up
of 42 months (35). In 2006, Occhetta et al. (36) re-
ported on the clinical advantage of para-Hisian pacing
compared with RVP in 16 of 18 patients undergoing
JACC VOL. 72, NO. 8, 2018
AUGUST 21, 2018:927–47
AV node ablation in a randomized, 6-month crossover
study. In this study, para-Hisian (nonselective) pac-
ing resulted in improved interventricular mechanical
delay, New York Heart Association (NYHA) functional
class, quality of life (QOL), 6-min walk, and mitral and
tricuspid regurgitation (36).
More recently, Huang et al. (28) reported on the
benefits of HBP combined with AV node ablation in 52
patients with symptomatic AF and HF. They were
successful 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 unchanged
compared with baseline (107.1  25.8 ms vs. 105.3 
23.9 ms). Vijayaraman et al. (37) have also published
work 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 in
functional class.
American College of Cardiology/American Heart
Association/Heart Rhythm Society AF practice
guidelines recommend that AV junction ablation
with permanent ventricular pacing is a reasonable
strategy to control heart rate in AF when pharma-
cological therapy is inadequate and rhythm control
cannot be achieved (Class IIa, Level of Evidence: B)
(38). Evidence from AV node ablation patients show
deleterious hemodynamic effects of RV pacing,
JACC VOL. 72, NO. 8, 2018 Vijayaraman et al. 935
AUGUST 21, 2018:927–47 His Bundle Pacing

T A B L E 1 Criteria for His Bundle Pacing

His-Purkinje Conduction Disease

Baseline Normal QRS With correction Without correction

Selective HBP  S-QRS ¼ H-QRS with isoelectric interval  S-QRS # H-QRS with isoelectric interval  S-QRS # or > H-QRS with isoelectric
 Discrete local ventricular electrogram in HBP  Discrete local ventricular electrogram in HBP interval
lead with S-V ¼ H-V lead  Discrete local ventricular electrogram
 Paced QRS ¼ native QRS  Paced QRS < native QRS in HBP lead
 Single capture threshold (His bundle)  2 distinct capture thresholds (HBP with BBB  Paced QRS ¼ native QRS
correction, HBP without BBB correction)  Single capture threshold (HBP with BBB)
Nonselective HBP  S-QRS < H-QRS (S-QRS usually 0, S-QRSend ¼  S-QRS < H-QRS (S-QRS usually 0, S-QRSend <  S-QRS < H-QRS (S-QRS usually 0) with
H-QRSend ) with or without isoelectric interval H-QRSend ) with or without isoelectric interval or without isoelectric interval (Pseudo-
(Pseudodelta wave þ/) (Pseudodelta wave þ/) delta wave þ/)
 Direct capture of local ventricular electro-  Direct capture of local ventricular electro-  Direct capture of local ventricular
gram in HBP lead by stimulus artifact (local gram in HBP lead by stimulus artifact electrogram in HBP lead by stimulus
myocardial capture)  Paced QRS # native QRS artifact
 Paced QRS > native QRS with normalization of  3 distinct capture thresholds possible (HBP  Paced QRS > native QRS
precordial and limb lead axes with respect to with BBB correction, HBP without BBB  2 distinct capture thresholds (HBP with
rapid dV/dt components of the QRS correction, RV capture) BBB, RV capture)
 2 distinct capture thresholds (His bundle
capture, 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.

especially in patients with reduced LVEF (39). HBP
may be particularly attractive in this population.
Whereas some centers may wait 2 to 4 weeks after
the initial device implant to perform AV node
ablation, other centers perform AV node ablation
during the initial pacemaker implant (23,37). The
ablation catheter is initially placed at the His
bundle location via femoral venous access and may
serve as a marker for HBP lead placement. AV node
ablation is performed after successful implantation
of the HBP lead. It may be prudent to obtain a
slightly distal His location for the HBP lead (very

F I G U R E 5 Selective His Bundle Pacing in LBBB

(Left) Baseline left bundle branch block (LBBB) with QRS duration of 150 ms. (Right) selective His bundle pacing (S-HBP) with correction of
LBBB (QRS 90 ms) at 1.4 V and loss of left bundle recruitment at 1.0 V. The local ventricular electrogram is discrete (arrows), suggesting
selective His capture.
936 Vijayaraman et al.
His Bundle Pacing
F I G U R E 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.
small atrial signal <0.5 mV and a larger ventricular
signal). The HBP lead electrodes may serve as an
excellent marker for the AV node ablation site. The
ablation catheter is then positioned at or below the
level of the ring electrode. Care is taken to avoid
any location closer to the distal electrode. It has
been shown that ablation closer to the tip electrode
may result in significant increase in His capture
thresholds (37). As soon as AV block is achieved
during the ablation, HBP is initiated at 0.5 to 1.0 V
above the His capture threshold. Any loss of His
capture should serve as a warning to stop ablating
immediately. If an excellent His capture threshold
(<1.5 V) or NS-HBP with RV capture threshold <1 V
is achieved, a back-up RVP lead can be avoided. In
patients with chronic AF, and in whom an RV back-
up pacing lead is desired, the HBP lead may be
connected to the atrial port of a dual-chamber de-
vice (pacer or ICD) and programmed to DVIR mode
to 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 with
infranodal block can be corrected with HBP. In a
recent series by Kronborg et al. (40), permanent HBP
was successful in 85% of patients with high-grade
AV block and narrow QRS complex. They achieved
S-HBP in 11% (4 of 38) and NS-HBP in 74% of pa-
tients (28 of 38). In this randomized study, patients
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were initially paced in either RV apex or HBP, and
crossed over to the opposite strategy after
12 months. They noted a significant improvement in
LVEF with HBP than with RVA pacing (55% vs. 50%).
Barba-Pichardo et al. (41) studied 182 patients with
AV block (84 narrow QRS and 98 wide QRS). They
attempted permanent HBP in only 68% of these pa-
tients due to high HBP thresholds during mapping.
Considering all patients with heart block, permanent
HBP was successfully achieved in only 32% (44 of 84
in narrow QRS and 15 of 98 in wide QRS) of patients.
Differences in methodology and tools used could
explain the low success rates in this study. In 2015,
Vijayaraman et al. (29) reported one of the largest
series of HBP in patients with AV block, achieving
HBP in 84% of 100 patients. Success was higher in
AV nodal block (93%) versus infranodal block (76%).
A small percentage of patients (5%) had elevated
thresholds on follow-up that required a lead revi-
sion. In this study, a high success rate for HBP was
achieved in patients with infranodal AV (HV) block
despite reporting only a small number of patients
with split-His potentials or a narrow QRS complex
(Figure 7). The postulated mechanisms for this
recruitment of distal His and bundle branches
in patients with intra-His block are: 1) longitudinal
dissociation in the His bundle with pacing adjacent
or distal to the site of delay/block; 2) virtual elec-
trode polarization effect; and/or 3) differential
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AUGUST 21, 2018:927–47 His Bundle Pacing

T A B L E 2 Permanent His Bundle Pacing in AV Node Ablation/AV Block

First Author, Follow-up Important

Year (Ref. #) Design (Months) N Indication Success (%) Characteristics Outcomes

Deshmukh et al., Observational 36 18 AV node ablation 66 Chronic AF, LVEF <40%, Improvement in LV dimensions,
2000 (5) QRS duration <120 ms NYHA functional class, and
LVEF
Deshmukh et al., Observational 42 54 AV node ablation 72 Chronic AF, LVEF <40%, Improved LVEF, NYHA functional
2004 (35) QRS duration <120 ms class, peak VO2
Occhetta et al., Randomized, 6 months, 12 18 AV node ablation 94 Chronic AF, QRS <120 ms Improvement in NYHA functional
2006 (36) crossover RVP vs. class, 6MWT, QOL, and
HBP hemodynamics
Huang et al., Observational 20 52 AV node ablation 81 Chronic AF, CHF Improvement in LV dimensions,
2017 (28) NYHA functional class, and
LVEF
Vijayaraman Observational 19 42 AV node ablation 95 Paroxysmal or persistent Improvement in NYHA functional
et al., 2017 AF, CHF class, LVEF
(37)
Barba-Pichardo Prospective >3 91 AV nodal 65 68 182 patients with AV block 5% lead failure
et al., 2010 Infranodal 26 57 mapped with EP
(41) catheter
Kronborg et al., Randomized crossover 24 38 AV nodal block 84 AV block, baseline narrow Improvement in LVEF, no
2014 (40) HBP vs. RVSP QRS, LVEF >40% significant improvement in
functional class, 6MWT, QOL
Pastore et al., Retrospective 12 148 AV nodal 100 High-grade AVB, HBP associated with lower risk of
2015 (58) Infranodal 48 Paroxysmal AF AF progression compared with
RV pacing
Vijayaraman Observational 19 100 AV nodal 46 93 High-grade AV block, no High success in infranodal block.
et al., 2015 Infranodal 54 76 back-up RV pacing Lead failure 5%
(29)

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.

source-sink relationships during
intrinsic impulse propagation. Interplay between the
strength of the excitatory impulse (the source) and
the electrical load represented by the tissue it must
excite (the sink) determines tissue excitability and
conduction.
PRACTICAL CONSIDERATIONS. Due to the unstable
nature of the escape rhythm in the infranodal AV
block, it would be prudent to place the atrial lead in
the RV to provide temporary back-up pacing during
His bundle mapping. Despite advanced AV block, the
His bundle can be easily located in patients with
infranodal block. In these patients, it is reasonable to
map 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 much
lower His capture threshold can be achieved. It is
preferable to aim for NS-HBP in this group so as to
have the safety of ventricular myocardial capture,
should conduction disease progress distally. In pa-
tients with AV nodal block, intravenous isuprel may
be necessary to increase junctional escape rates to
identify the His electrograms. In patients with no
stable escape rhythm, pace mapping can be per-
formed at the anatomical His bundle region to ach-
ieve successful HBP.
pacing versus HIS BUNDLE PACING FOR CARDIAC
RESYNCHRONIZATION THERAPY
Cardiac resynchronization therapy (CRT) with
coronary sinus (CS) lead placement has become
established as a first-line treatment for patients with
symptomatic class II to IV HF, LV systolic dysfunc-
tion, LBBB, and QRS duration $150 ms (42). Despite
the development of sophisticated tool sets to facili-
tate implant and intraprocedural strategies that have
evolved to consider mechanical and electrical delay
in LV lead targeting, rates of nonresponse to CRT
remain high—between 30% and 40% (43). In addition,
rates of implant failure for CRT range between 5% and
9%, in part due to high rates of CS lead dislodgement
(3% to 7% reported across major trials) (44). In light of
this, alternative strategies to achieve resynchroniza-
tion have gained momentum, including endocardial
LV lead pacing, “wireless” LV lead stimulation, and
permanent HBP. Among these, HBP may have a
theoretic advantage to conventional CRT, because it
restores the intrinsic electromechanical activation
sequence of the heart.
Although Narula reported in 1977 that HBP can
normalize LBBB during electrophysiology study (16),
it would be more than 20 years later that these initial
observations would be reproduced in patients
938 Vijayaraman et al.
His Bundle Pacing
F I G U R E 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.
undergoing HBP as part of a permanent pacing strat-
egy. Since the initial description by Moriña-Vásquez
et al. (45) in 2005, additional studies have further
confirmed the feasibility of permanent HBP to correct
bundle branch block. In the largely short-term and
midterm results reported from these studies, patients
have demonstrated improved functional
reduced mitral regurgitation, reduced dyssynchrony,
and improved LVEF after HBP on par with what has
been shown in CRT responders.
INITIAL CLINICAL DATA. To date, there have been 5
case series examining HBP for resynchronization
(Table 3). Barba-Pichardo et al. (46) were the first to
report on HBP among patients in whom CRT implant
was unsuccessful. Lustgarten et al. (47) attempted
HBP for CRT in 29 patients (28 with LBBB), and QRS
narrowing was achieved acutely in 21 (72%). The trial
protocol required Y-adapting the His and CS lead to
allow for crossover study, and permanent HBP could
not be achieved in 12 patients, with failure of con-
ventional CS LV lead placement in 1 patient. A total of
12 patients completed 12 months of follow-up and
crossover comparison. The study showed that pa-
tients appeared to benefit similarly when assigned to
HBP versus biventricular pacing. Although significant
improvement of NYHA functional class, QOL, 6-min
walk distance, and LVEF was noted for both HBP
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AUGUST 21, 2018:927–47
and biventricular pacing compared with baseline, the
study was not powered to detect differences between
the 2 strategies.
Ajijola et al. (48) reported on the first case series of
primary HBP (HBP lead in lieu of traditional LV lead)
in CRT-eligible patients (48). Among 21 patients (17
status, LBBB, 4 right bundle branch block [RBBB]), perma-
nent HBP was achieved in 16 patients (76%). The
majority of patients demonstrated QRS narrowing
with nonselective capture, with an average QRS
reduction of approximately 30%, but not to <120 ms
for the majority of patients. Most recently, Sharma
et al. (49) pooled data from 5 centers and compiled
the largest retrospective case series of CRT-eligible
patients thus far. They recognized 2 important co-
horts: Group I, patients in whom prior CRT had been
attempted but was unsuccessful and HBP was used as
a bail-out strategy; and Group II, primary HBP for
CRT-eligible patients (AV block, post-AV junction
ablation, underlying BBB, or patients undergoing
planned upgrade due to >40% RV pacing). Over a
mean follow-up period of 14 months, patients
demonstrated QRS narrowing, improvement in NYHA
functional 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%),
JACC VOL. 72, NO. 8, 2018
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F I G U R E 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.
and HBP was effective in this group (92% implant
success).
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 intraventricular
conduction delay and/or extensive LV scar remains
uncertain. In about 10% to 30% of patients, LBBB
may not be correctable by permanent HBP. Residual
intraventricular conduction delay due to scar or
peripheral conduction disease may persist. Can HBP
be combined with LV pacing, or is it possible to
reliably pace the proximal left bundle beyond the
site of block from the RV (50)? Whereas conven-
tional approaches to HBP suggest aiming for selec-
tive capture, NS-HBP may yield similar benefits
with better capture thresholds and R-wave sensing
(34,51). In light of high rates of nonresponse to
traditional CRT, there is clinical equipoise to justify
exploration of the role of HBP in CRT with ran-
domized studies (His-SYNC [His Bundle Pacing
Versus Coronary Sinus Pacing for Cardiac Resynch-
ronization Therapy] trial; NCT02700425; HOPE-HF
[The His Optimised Pacing Evaluated for Heart
Failure Trial]; NCT02671903). With current and
future trials, we can further clarify the role for HBP
Vijayaraman et al. 939
His Bundle Pacing
in pacing for patients with LBBB, RBBB, prolonged
PR intervals, or high expected degree of ventricular
pacing and underlying HF. Indeed, there may come
a time when a conventional CS or epicardial LV lead
is a bail out for HBP in the appropriately selected
patient.
ELECTRICAL SYNCHRONY AND
HEMODYNAMICS OF HBP
S-HBP VERSUS NS-HBP. The major clinical advantage
of HBP is that it can maintain electromechanical
synchrony (both intravascular and interventricular).
In S-HBP with normal HPS conduction, paced and
native 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 normalize
with improved mechanical synchrony (Figure 9). In
NS-HBP, where conduction through the HPS and pre-
excitation of septal myocardium are fused, one may
debate whether this would lead to some degree of
ventricular dyssynchrony. NS-HBP results in a
pseudo-delta wave that abruptly transitions to a steep
dV/dT when the His-Purkinje conduction reaches the
myocardium, with a timing approximating the HV
interval leading to QRS widening by a duration #HV
940 Vijayaraman et al. JACC VOL. 72, NO. 8, 2018

His Bundle Pacing AUGUST 21, 2018:927–47

T A B L E 3 His Bundle Pacing for CRT Indication

First Author Implant

(Ref. #) Year N Indication HBP Lead Success (%) Major Findings

Barba-Pichardo 2013 16 CRT implant failure Tendril 1488T, 56 QRS narrowing achieved in 13 of 16 patients with HBP, of
et al. (46) 1788TC, 1888TC whom 9 underwent implant. During mean follow-up of
31.3  21.5 months, NYHA functional class improved III/II
and LVEF improved from 29%/36% (<0.05)
Lustgarten et al. (47) 2015 29 Crossover study of HBP and Select-Secure 3830 59 QRS narrowing achieved in 21 of 29 patients with HBP, of
conventional CRT whom 17 patients underwent implant and 12 completed
follow-up. Both groups demonstrated significant
improvement 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 correction
achieved for all patients. They found that His bundle tip-RV
coil configuration demonstrated better capture thresholds
than 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). NYHA
functional class III/II (p < 0.001), and LVEF improved
from 27  10% to 41  13% (p < 0.001)
Sharma et al. (49) 2017 106 CRT implant failure (Group I) Select-Secure 3830 90 QRS narrowing achieved across all patients with implant
and primary HBP (Group II) success (157  33 ms to 117  18 ms; p ¼ 0.0001).
Underlying BBB was present in 48 patients and implant
success was 92% in this group (33 of 36 LBBB and 11 of 12
non-LBBB). Among all patients NYHA functional class
2.8  0.5/1.8  0.6 (p ¼ 0.0001) and LVEF improved from
30  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.

interval. The LV total activation time did not
differ significantly during NS-HBP compared with
S-HBP or intrinsic activation (52). However, during
biventricular pacing, the activation pattern is entirely
different, with early activation occurring in the LV
epicardium (Figure 10).
Hemodynamic improvements appear to be compa-
rable with both S-HBP and NS-HBP. Catanzariti et al.
(53) reported echocardiographic measurements in 23
patients implanted with S-HBP or NS-HBP and RVA
pacing leads (53). Compared with RVA pacing, S-HBP
or NS-HBP was associated with lower interventricular
dyssynchrony, intraventricular dyssynchrony, and
better myocardial performance index with no differ-
ences between S-HBP and NS-HBP. Lustgarten et al.
(47) demonstrated that both S- and NS-HBP advanced
LV activation time, confirming engagement of the HPS
with more rapid activation of the LV (Figure 11).
ACUTE STUDIES OF HBP
HBP VERSUS RVP. Acute electrophysiology studies
have reported favorable hemodynamics during HBP
compared with RVP. In 31 patients with narrow QRS
undergoing an electrophysiological study, Ji et al.
(54) reported no significant difference in LV circum-
ferential strain, radial strain, twist, and mechanical
dyssynchrony comparing His and RA pacing, whereas
RV outflow tract and RVA pacing worsened these
parameters. Pastore et al. (55) studied tissue Doppler
imaging echocardiography in 29 patients with S-HBP
and 15 with NS-HBP (55). RVA and RV outflow tract
septum pacing showed variable effects on LV elec-
tromechanical activation, with longer electrome-
chanical latency and intra-LV dyssynchrony
compared with pacing from the His bundle region.
HBP VERSUS LV OR BIVENTRICULAR PACING. A
comparison of HBP to LV or biventricular pacing may
help establish whether HBP can substitute for LV
pacing in CRT-eligible patients. In an acute temporary
HBP 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 (which
increased by about 4 mm for both biventricular pac-
ing and HBP with AV shortening/optimization)
compared with intrinsic rhythm, suggesting
improved acute hemodynamic function. Padeletti
et al. (57) studied acute hemodynamics using pres-
sure volume loops in HF patients with LBBB.
Compared with AAI pacing, biventricular and LV-only
pacing improved systolic function and LV synchrony
at individually optimized AV delays, while His-LV
pacing 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 the
patients studied.
JACC VOL. 72, NO. 8, 2018 Vijayaraman et al. 941
AUGUST 21, 2018:927–47 His Bundle Pacing

F I G U R E 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.

F I G U R E 1 0 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.
942 Vijayaraman et al. JACC VOL. 72, NO. 8, 2018

His Bundle Pacing AUGUST 21, 2018:927–47

F I G U R E 1 1 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.

ECHOCARDIOGRAPHIC HEMODYNAMICS class, brain natriuretic peptide, mean LVEF, or LV

AND FUNCTIONAL STUDIES WITH volumes. However, myocardial perfusion score, Short
PERMANENT HBP Form-36 physical and mental status, mitral regurgita-
tion, and mechanical dyssynchrony were significantly
Compared with RVA pacing, HBP has been associated better with HBP than during RVA pacing. One-half of
with improved fractional shortening, dP/dt, LVEF, and the patients had dyssynchrony with RVA pacing,
myocardial performance index (Tei index). Also, whereas none had dyssynchrony during HBP.
improvement in interventricular electromechanical
delay, intraventricular dyssynchrony, systolic- HBP IN CRT. HBP has potential theoretical benefits

diastolic electromechanical delay, LV isovolumetric over CS or epicardial LV pacing. Electrically, CS/LV

contraction and relaxation times, and LV ejection time
have been demonstrated (20,30,35,36,53,55,58,59).
These studies are summarized in Table 4. In 12 patients
undergoing pacemaker implantation with preserved
His bundle conduction, Zanon et al. (19) performed
HBP for 3 months and then crossed over to RVA pacing.
Myocardial scintigraphy, QOL, clinical evaluation,
echocardiography, and brain natriuretic peptide were
assessed. There was no differences in NYHA functional
pacing still results in myocardial activation with
inherent degrees of dyssynchrony that may attenuate
the beneficial effects in patients with ischemic car-
diomyopathy, non-LBBB QRS morphologies, and
certain lead positions, such as apically or over-scarred
areas. In CRT candidates with wide QRS durations,
success rates for electrical synchronization with QRS
narrowing during HBP range from 70% to 92%
(47–49). HBP resulted in a narrower QRS than
JACC VOL. 72, NO. 8, 2018 Vijayaraman et al. 943
AUGUST 21, 2018:927–47 His Bundle Pacing

T A B L E 4 Hemodynamics of Permanent HBP

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

Catanzariti et al., 24 23 (96%) 7.5 months  Compared with RVA pacing, selective or nonselective HBP is associated with
2006 (53) lower interventricular dyssynchrony, intraventricular dyssynchrony, MR, and
better myocardial performance index (Tei index)
 No difference between selective or nonselective HBP
Zanon et al., 12 3-month HBP crossover  Patients with preserved HPS conduction
2008 (19) to RVA pacing  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., 26 20 SHBP 34 months  Patients with HBP and backup RVA lead
2013 (20) 6 NSHBP Crossover at end to RVA  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 V
vs. 06 V at 05 ms), but stable from implant
Kronborg et al., 38 84% HBP 12-month crossover, HBP  Narrow QRS <120 ms c AVB, LVEF >40%
2014 (40) vs. RVSP  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., 37 3-month crossover from  Compared with HBP, RVA pacing increased systolic-diastolic electromechanical
2014 (58) HBP to RVA pacing delay, intra-LV dyssynchrony, LV isovolumetric contraction, and relaxation
times; 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., 23 NSHBP 11 HBP vs. RVSP  Mechanical synchrony parameters were significantly better during HBP compared
2017 (33) SHBP 12 Intrapatient with RV septal pacing with no significant difference between S-HBP or NS-HBP
RVSP 23

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-systolic
diameter; 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.

biventricular pacing and required shorter implant
times compared with LV leads (47). These studies
showed significant improvements in NYHA functional
class, QOL, LV end-diastolic diameter, and LVEF.
Recently, 2 observational studies showed that HBP
can improve echocardiographic and clinical outcomes
in 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 to
adversely affect medium-term HPS conduction. A
study of 20 HBP patients at the time of generator
change (mean follow-up 70  24 months) showed no
differences in HV intervals and QRS duration, and
demonstrated trends toward improvement in LVEF
and LV end-diastolic diameter (p ¼ 0.06), with
consistent 1:1 His-Purkinje conduction with decre-
mental pacing to 500 ms (60). Published data on long-
term clinical outcomes of HBP are scarce. Recently
Vijayaraman et al. (27) reported
echocardiographic outcomes during 5-year follow-up
in an observational, case-control study of HBP
compared with RVP. HBP was associated with a sig-
nificant reduction in the combined endpoint of HF
hospitalization 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 HBP
group (55  8% vs. 57  6%; p ¼ 0.13), whereas a
significant decline was noted in RVP (57  7% vs. 52 
11%; p ¼ 0.002). Pacing-induced cardiomyopathy was
significantly lower in HBP compared with RVP (2% vs.
22%; p ¼ 0.04). Abdelrahman et al. (61) compared 332
consecutive patients undergoing HBP with 433 pa-
tients with RVP in an observational cohort study. The
combined endpoint of all-cause mortality, time to
first HFH (heart failure hospitalization), or upgrade to
biventricular pacing was significantly reduced with
HBP (25% vs. 32%; HR: 0.71; 95% confidence interval
[CI]: 0.534 to 0.944; p ¼ 0.02). This difference was
primarily in patients with ventricular pacing >20%
(25% in HBP vs. 36% in RVP; HR: 0.65; 95% CI: 0.456
clinical and to 0.927; p ¼ 0.02) (Central Illustration panel B). The
944 Vijayaraman et al.
His Bundle Pacing
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 partly
be explained by elimination of ventricular dyssyn-
chrony and reduction in HF. Additional factors, such
as 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 a
known marker of arrhythmic risk and may potentially
contribute to reducing mortality (62). Although this
observational study is hypothesis generating, ran-
domized controlled trials are necessary to confirm
potential mortality benefits attributable to HBP.
HBP: CLINICAL CHALLENGES
AND TROUBLESHOOTING
CAPTURE THRESHOLDS. The His bundle region is in
the central fibrous body minimally surrounded by
myocardial tissue. Unless the lead tip penetrates the
fibrous insulation of the His bundle or is in close
proximity, the His capture thresholds can be signifi-
cantly higher than traditional RV capture thresholds.
In some patients, the His bundle may be located
deeper and the helix may not be long enough to
achieve acceptable His thresholds. In our experience,
HBP can consistently be achieved in >95% of patients
with normal His-Purkinje conduction. However, His
capture thresholds >2 V at 1 ms may be seen in w10%
of patients at implant. We accept these values at
implant, provided there is nonselective capture with
significantly lower RV capture thresholds. Addition-
ally, in some patients, His bundle capture threshold
may progressively increase during follow-up.
Vijayaraman et al. (27) reported that His capture
thresholds remained relatively stable during 5-year
follow-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 in
chronic pacing threshold >1 V from baseline was
noted in 9 patients in HBP compared with 6 patients
in RVP (12% vs. 6%; p ¼ 0.04) (27).
LEAD REVISIONS. One of the early concerns of HBP
was the risk for lead failure. Many operators routinely
implanted a back-up RV pacing lead. Recent reports
show that HBP leads are relatively stable, and routine
placement of a back-up RV pacing lead is not neces-
sary in most patients (22,27,29,60). In a recent study
by Vijayaraman et al. (29), acute loss of capture
occurred in 2 of 100 patients with AV block and HBP.
Lead revisions were required in 3 additional patients
at 2 to 6 months post-implant due to progressive
JACC VOL. 72, NO. 8, 2018
AUGUST 21, 2018:927–47
increases in capture threshold for a lead revision rate
of 5% (29). In a long-term study of 75 patients with
HBP, lead revisions were required in 5 patients (6.7%),
4 of whom underwent successful lead replacement at
the His bundle region even as late as 5 years after the
initial implant (27). Acute increase in HBP threshold or
loss 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-up
is less clear. It is likely that due to the anatomical
proximity of the loop of the HBP lead, the tricuspid
valve motion causes slow unhinging of the lead. The
possibility of local fibrosis and exit block cannot be
excluded. The 3830 pacing lead has a helix length of
only 1.8 mm and the depth of the His bundle relative to
the endocardial surface is variable. Because of the
paucity of excitable tissue surrounding the His bundle
in the central fibrous body, micro-dislodgement of the
lead can lead to significant increase in His bundle
capture threshold compared to RV myocardium. In a
recent study of lead extraction, Vijayaraman et al. (63)
reported that 21 of 22 leads in the His bundle location
could successfully be removed without any injury to
the conduction system following a mean lead dwell
time 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 with
longer-term HBP is unknown.
BATTERY DEPLETION. Early investigators’ enthu-
siasm for HBP waned due to high His capture
thresholds and back-up RV lead requirement, which
leads to premature battery depletions necessitating
early generator changes. Recent studies have
demonstrated that the majority of patients undergo-
ing HBP do well without need for early generator
changes (27,60,61). In patients undergoing CRT with
HBP, capture thresholds required to correct underly-
ing BBB are often higher, and early battery depletion
can still be a major obstacle. Further improvements in
battery technology with development of long-lasting
His bundle–specific pacing systems capable of deliv-
ering high output would be necessary.
SENSING. The electrogram obtained from the HBP
lead may demonstrate atrial, His, and ventricular
signals depending on the location of the tip elec-
trode above or below the tricuspid valve plane and
orientation of the ring electrode. The ventricular
electrogram amplitudes tend to be significantly
smaller than traditional RV sensing. In patients with
selective HBP with a lead tip above the valve plane,
the ventricular electrogram amplitude may be lower
than 1 to 2 mV along with relatively larger atrial
electrogram. It is critical to program the ventricular
JACC VOL. 72, NO. 8, 2018
AUGUST 21, 2018:927–47
sensing parameters appropriately compared with
traditional RV parameters. Although unipolar elec-
trogram amplitudes are often better than bipolar
signals, oversensing and inhibition can be an issue.
Development of dedicated sensing algorithms
capable of blanking far-field atrial electrograms and
modifying the interelectrode distance and electrode
characteristics of pacing lead may be necessary to
optimize His-specific pacing systems.
DEVICE FOLLOW-UP. During follow-up, assessment
of His bundle capture using multilead ECG (preferably
12-lead) is recommended. At 3-month follow-up, the
pacing output is programmed to at least 1 V above the
His capture threshold, as confirmed with multilead
ECG rather than at twice-safety margin, to conserve
battery life. In patients with BBB, 3 different capture
thresholds may be noted (Figures 2, 5, and 10)
depending on selective or nonselective His capture
with correction (RV, right bundle or left bundle, and
complete His bundle capture). Similar to early
biventricular pacing, attention to local electrogram in
the pacing electrode and 12-lead ECG may elucidate
selective versus nonselective capture. Utility of
automatic threshold testing features is limited in
HBP. In patients with selective HBP, due to lack of
evoked potentials, this feature may fail to detect the
true His capture threshold. On the contrary, in pa-
tients with nonselective HBP, this feature will detect
myocardial capture threshold rather than His bundle
capture. Development of automatic threshold algo-
rithms to accurately identify His capture thresholds
would be an important next step to extend battery
longevity. Importantly, additional training of the
device clinic personnel is necessary to ensure appro-
priate programming during follow-up.
FUTURE DIRECTIONS
Despite recent advances and interest in HBP, several
unanswered questions and concerns remain (64).
Although permanent HBP may be an attractive op-
tion for physiological pacing in several groups of
patients, its reliability and long-term performance
are yet to be fully validated in large prospective
studies. Particularly relevant are patients with
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ACKNOWLEDGMENT The authors thank Ms. Avani
Pugazhendhi for her help in editing the video.
ADDRESS FOR CORRESPONDENCE: Dr. Pugazhendhi
Vijayaraman, Cardiac Electrophysiology, Geisinger
Heart Institute, 1000 E Mountain Boulevard, MC 36-
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KEY WORDS cardiac resynchronization
therapy, heart failure, permanent His bundle
pacing, right ventricular pacing
A PPE NDI X For a supplemental video,
please see the online version of this paper.