Europace (2025) 27, euaf050 EHRA DOCUMENT

https://doi.org/10.1093/europace/euaf050

European Society of Cardiology (ESC) clinical

consensus statement on indications for
conduction system pacing, with special
contribution of the European Heart Rhythm

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Association of the ESC and endorsed by the
Asia Pacific Heart Rhythm Society, the
Canadian Heart Rhythm Society, the Heart
Rhythm Society, and the Latin American Heart
Rhythm Society
Michael Glikson , FESC (Chair)1,2*, Haran Burri , FEHRA, FESC (Chair)3*,
Amr Abdin 4, Oscar Cano 5,6, Karol Curila 7, Jan De Pooter 8,
Juan C. Diaz , (LAHRS Representative)9, Inga Drossart , (ESC Patient Forum
Representative)10,11, Weijian Huang , (APHRS Representative)12,
Carsten W. Israel 13, Marek Jastrzębski 14, Jacqueline Joza ,
(CHRS Representative)15, Jarkko Karvonen 16, Daniel Keene 17,
Christophe Leclercq , FESC, FEHRA18, Wilfried Mullens 19,
Margarida Pujol-Lopez 20, Archana Rao 21, Kevin Vernooy , FESC, FEHRA22,
Pugazhendhi Vijayaraman , (HRS Representative)23, Francesco Zanon 24,
and Yoav Michowitz , (Document Coordinator)1,2*

Document Reviewers: Jens Cosedis Nielsen, (Review Coordinator)25, Lucas Boersma26,27,

Carina Blomström-Lundqvist28,29, Mads Brix Kronborg25, Mina K. Chung30, Hung Fat Tse31,
Habib Rehman Khan32, Francisco Leyva33,34, Ulises Rojel-Martinez35, Marcin Ruciński10,36, and Niraj Varma37
1
Jesselson Integrated Heart Center, Shaare Zedek Medical Center, 12 Shmuel Beit Street, 9103102, Jerusalem, Israel; 2Faculty of Medicine, Hebrew
University, Jerusalem, Israel; 3Cardiac Pacing Unit, Cardiology Department, University Hospital of Geneva, Geneva, Switzerland; 4Internal Medicine
Clinic III, Cardiology, Angiology and Intensive Care Medicine, Saarland University Hospital, Homburg/Saar, Germany; 5Unidad de Arritmias, Hospital
Universitari i Politècnic La Fe, Valencia, Spain; 6Centro de Investigaciones Biomédicas en RED en Enfermedades Cardiovasculares (CIBERCV),
Madrid, Spain; 7Cardiocenter, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady, Prague, Czech Republic;
8
Department of Cardiology, Ghent University Hospital, Ghent, Belgium; 9Clínica Las Vegas, Universidad CES, Medellín, Colombia; 10ESC Patient
Forum, Sophia Antipolis, France; 11European Society of Cardiology, Sophia Antipolis, France; 12Department of Cardiology, The First Affiliated
Hospital of Wenzhou Medical University, Wenzhou, China; 13Department of Medicine-Cardiology, Diabetology and Nephrology, Bethel-Clinic,

* Corresponding authors. E-mail address: [email protected] (Y.M.); Tel: +972 2 6555975. E-mail address: [email protected] (M.G.); Tel: +41 22 373 72 00. E-mail address: haran.burri@
hug.ch (H.B.)
© the European Society of Cardiology 2025.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/),
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cited. For commercial re-use, please contact [email protected]
2 M. Glikson et al.

Bielefeld, Germany; 14First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University, Medical College,
Krakow, Poland; 15Department of Medicine, McGill University Health Centre, Montreal, Canada; 16Heart and Lung Center, Helsinki University
Hospital, Helsinki, Finland; 17National Heart and Lung Institute, Imperial College London, London, UK; 18Service de Cardiologie et Maladies
Vasculaires, Université de Rennes, CHU Rennes, INSERM, LTSI—UMR 1099, F-35000 Rennes, France; 19Hasselt University, Ziekenhuis Oost-
Limburg, Genk, Belgium; 20Institut Clínic Cardiovascular (ICCV), Hospital Clínic, Universitat de Barcelona, Institut d’Investigacions Biomèdiques
August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; 21Liverpool Heart and Chest Hospital, Liverpool, UK; 22Department of Cardiology,
Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands; 23Geisinger
Commonwealth School of Medicine, Geisinger Heart Institute, Wilkes-Barre, PA, USA; 24Santa Maria della Misericordia Hospital, Rovigo, Italy;
25
Department of Cardiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 26Cardiology
Department, St. Antonius Hospital, Nieuwegein, The Netherlands; 27Cardiology Department, Amsterdam UMC, Amsterdam, The Netherlands;
28
Department of Cardiology, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 29Department of
Medical Science, Uppsala University, Uppsala, Sweden; 30Cardiac Pacing & Electrophysiology, Department of Cardiovascular Medicine, Heart,
Vascular & Thoracic Institute, Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland Clinic
Lerner College of Medicine of Case western Reserve University, Cleveland, OH, USA; 31Cardiology Division, Department of Medicine, Queen

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Mary Hospital, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR; 32Western University, London
Ontario, Canada; 33Aston Medical School, Aston University, Aston Triangle, Birmingham, UK; 34University Hospitals Birmingham, Queen Elizabeth,
Mindelsohn Way, Birmingham, UK; 35Arrhythmias ad Pacing Service, Cardiology Division, Department of Medicine, South Medical Center, Puebla,
Mexico; 36European Association of Patient with Cardiovascular Diseases, Serce na Banacha – Poland; and 37Cardiac Pacing & Electrophysiology, Heart
and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
Received 3 March 2025; accepted after revision 10 March 2025; online publish-ahead-of-print 31 March 2025

Abstract Conduction system pacing (CSP) is being increasingly adopted as a more physiological alternative to right ventricular and
biventricular pacing. Since the 2021 European Society of Cardiology pacing guidelines, there has been growing evidence
that this therapy is safe and effective. Furthermore, left bundle branch area pacing was not covered in these guidelines
due to limited evidence at that time. This Clinical Consensus Statement provides advice on indications for CSP, taking
into account the significant evolution in this domain.
...................................................................................................................................................
Keywords Conduction system pacing • His bundle pacing • Left bundle branch area pacing • Cardiac resynchronization therapy •
Biventricular pacing • Indications

His-optimized and left bundle branch pacing-optimized cardiac

Table of contents resynchronization therapy........................................................................................ 18
Preamble ............................................................................................................................ 3 Delineation and rationale .................................................................................... 18
Definition of categories of advice and areas of uncertainty........................ 3 Published data and practical considerations ................................................ 18
Scientific background—an update .......................................................................... 4 Upgrade to conduction system pacing ............................................................... 20
Differences between conduction system pacing methods .......................... 4 Patient education and shared decision-making ............................................... 22
His bundle pacing vs. left bundle branch area pacing ..................................... 5 Future perspectives..................................................................................................... 22
Criteria for His bundle capture .......................................................................... 8 Conclusions .................................................................................................................... 23
Criteria for left bundle branch area pacing.................................................... 8 Supplementary material............................................................................................. 24
Success rates, procedural outcomes, and complications of His Funding.............................................................................................................................. 24
bundle pacing and left bundle branch area pacing ...................................... 9 Data availability.............................................................................................................. 24
Conduction system pacing for atrioventricular block with left References ..................................................................................................................... 24
ventricular ejection fraction > 40% ........................................................................ 9
Conduction system pacing for atrioventricular block in reduced left Abbreviations
ventricular ejection fraction (≤40%) ................................................................... 11 AF atrial fibrillation
Conduction system pacing in atrioventricular node ablation ................... 12 APHRS Asian Pacific Heart Rhythm Association
Conduction system pacing in sinus node dysfunction ................................. 15 AV atrioventricular
Conduction system pacing for heart failure without bradycardia AVN atrioventricular node
pacing indication ........................................................................................................... 15 AVNA atrioventricular node ablation
His bundle pacing .................................................................................................... 15 BiV-CRT biventricular cardiac resynchronization therapy
Left bundle branch area pacing ......................................................................... 16 BiVP biventricular pacing
Conduction system pacing in non-left bundle branch pacing BNP brain natriuretic peptide
patients ........................................................................................................................ 16 CHRS Canadian Heart Rhythm Society
Conduction system pacing in patients with left ventricular ejection CI confidence interval
fraction 36–50%....................................................................................................... 16 CSP conduction system pacing
Conduction system pacing cardiac resynchronization therapy in CSP-CRT conduction system pacing cardiac
non-responders to biventricular cardiac resynchronization resynchronization therapy
therapy......................................................................................................................... 17 CRT-D cardiac resynchronization therapy defibrillator
Clinical implications ................................................................................................ 17 EHRA European Heart Rhythm Association
ESC/EHRA clinical consensus statement 3

ESC European Society of Cardiology examples of the extensive use of CSP. The European Heart Rhythm
HBP His bundle pacing Association (EHRA) published a consensus document on CSP implant­
HF heart failure ation to standardize the technique.10 The 2024 updated EHRA core
HFH heart failure hospitalization curriculum now includes CSP in its syllabus.11 This emphasizes the im­
HFmrEF heart failure and mildly reduced ejection portance of proper training and patient selection for CSP.
fraction Recently, the Heart Rhythm Society (HRS) guidelines on physiologic­
HFpEF heart failure with preserved ejection fraction al pacing have expanded the indications for CSP.12 Given the increasing
HFrEF heart failure with reduced ejection fraction published evidence and consensus among European experts on the
HOT-CRT His-optimized cardiac resynchronization likely benefits of CSP and to reconcile the European recommendations
therapy on pacing and cardiac resynchronization with current practice, we
HR hazard ratio decided to update advice on indications for CSP.
HRS Heart Rhythm Society This document represents a collaborative effort of the ESC and EHRA,
ICD implantable cardioverter–defibrillator as well as EHRA’s sister societies: the Asia Pacific Heart Rhythm Society
LAHRS Latin America Heart Rhythm Society (APHRS), Canadian Heart Rhythm Society (CHRS), HRS, and Latin

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LBBAP left bundle branch area pacing American Heart Rhythm Society (LAHRS). It follows the principles of
LBBB left bundle branch block the ESC and EHRA scientific document committees in terms of evaluating
LBBP left bundle branch pacing evidence and providing advice. All advice was submitted to anonymous
LFP left fascicular pacing voting and had to be approved by >70% of the writing group to be imple­
LOT-CRT left bundle branch optimized CRT mented (the patient representative did not vote, due to the technical na­
LV left ventricular ture of the advices). The authors include early CSP adopters (all of whom
LVEF left ventricular ejection fraction have extensive experience with BiV-CRT), experts in CRT who primarily
LVSP left ventricular septal pacing perform biventricular pacing (BiVP), non-implanting HF specialists, and a
ms millisecond patient representative (I.D.). We thus aim to provide a balanced and con­
NIVCD non-specific intra-ventricular conduction delay sensual view, from multiple perspectives.
nsHBP non-selective His bundle pacing
NYHA New York Heart Association
PICM pacing-induced cardiomyopathy
QoL quality of life
Definition of categories of advice
QRSd QRS duration and areas of uncertainty
RCT randomized clinical trials
RBBB right bundle branch block Definition Categories of advice Icons
RBBP right bundle branch pacing
RV right ventricular Evidence or general agreement that a given Advice TO DO
measure is clinically useful and appropriate
RVP right ventricular pacing
RWPT R-wave peak time Evidence or general agreement that a given May be appropriate
sHBP selective His bundle pacing measure may be clinically useful and TO DO
appropriate
SND sinus node dysfunction
TAVI transcatheter aortic valve implantation Evidence or general agreement that a given Advice NOT TO DO
TR tricuspid valve regurgitation measure is not appropriate or harmful

V volt No advice can be given because of lack of Areas of uncertainty

data or inconsistency of data. The topic is
important to be addressed

Preamble
Type of supporting evidence Strength of evidence Icons
Conduction system pacing (CSP) is an overarching term including His
Published data$
bundle pacing (HBP) as well as left bundle branch area pacing (LBBAP). >1 high quality RCT
Meta-analysis of high quality RCT
This is a relatively new area of pacing that is continuing to gain popularity
among pacing specialists as being more physiological than the traditional
High quality RCT
form of right ventricular pacing (RVP), as well as emerging as an alterna­ >1 moderate quality RCT
tive to biventricular cardiac resynchronization therapy (BiV-CRT) in Meta-analysis of moderate quality RCT

cases of heart failure (HF) with conduction system disease.

When the 2021 European Society of Cardiology (ESC) guidelines on
pacing1 were being formulated, CSP had already been investigated for High quality, large observational studies

several years, mainly in the form of HBP in cases of atrioventricular

(AV) block, for pacing in the setting of AV nodal ablation and as a sub­
Expert opinion*#
stitute for BiV-CRT in selected patients. At that point, most of the in­ Strong consensus

formation on HBP was observational with short-term follow-up, and >90% of writing group supports advice

there were only two small randomized controlled pilot trials that in­ >90% agree

cluded more than one centre.2–5 A conservative approach towards Consensus

HBP was therefore taken, and no recommendations regarding >70% of writing group supports advice

LBBAP were formulated due to limited available data at that time. >70% agree

$ The reference for the published data that fulfil the criteria is indicated in the table of advice, if applicable
Ever since the publication of the 2021 guidelines, the use of CSP has
*Expert opinion also takes into account randomized, nonrandomized, observational or registry studies with limitations of
greatly evolved, mainly with LBBAP,6 due to perceived greater ease of design or execution, case series, meta -analyses of such studies, physiological or mechanistic studies in human subjects

implantation and superior electrical parameters compared with HBP. # For areas of uncertainty:strong consensus that the topic is relevant and important to be addressed
by future trials
Recent European surveys7,8 and the recent MELOS registry9 are
4 M. Glikson et al.

Among the first studies to report detrimental outcome associated

with RVP, in both patients with and without pre-existing HF, were the
DAVID and MOST trials.18–20 The clinical entity of pacing-induced car­
Advice: CSP implantation and Strength of evidence
diomyopathy (PICM) was introduced over the following years, which af­
training
.................................................................. fects 10–20% of patients who receive RVP.21,22 It is difficult to ascertain
Advice TO DO which patients will develop PICM, despite some predictors having been
described [e.g. paced QRS duration (QRSd)23]. In addition, there is no
Conduction system pacing implantation
evidence of clinical benefit of alternative pacing sites such as RV septal pa­
should be performed by physicians who cing over RV apical pacing.24 For these reasons, pacing strategies such as
have undergone adequate training and BiVP or CSP have been developed to avoid or to attenuate PICM.
who have acquired the necessary skills
>90% agree
to perform the procedure safely and
effectively, with systematic evaluation of Differences between conduction

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type of pacing that is achieved [e.g.
selective vs. non-selective HBP (nsHBP),
system pacing methods
LBBP, left fascicular pacing (LFP), left Capture of the conduction system is present with HBP, proximal right
ventricular septal pacing (LVSP), etc.] bundle branch pacing (RBBP), left bundle branch pacing (LBBP), and
LFP. For the purposes of this document and in the interest of simplifi­
cation, proximal RBBP is not distinguished from HBP, and LFP is not dis­
tinguished from LBBP. Although CSP implies capture of the conduction
Scientific background—an update system,10 for the purposes of this document we also included LVSP as
being part of CSP.
In 1925, Wiggers first highlighted the potential detrimental effects of Left bundle branch area pacing includes LBBP, LFP, and LVSP.10
RVP due to the asynchronous activation of the ventricles.13 Following Capture of the conduction system may be either selective (with exclu­
the advent of cardiac pacing in the late 1950s, numerous observations sive capture of conduction tissue) or non-selective (with concurrent
have since underscored the progressive sequence of harm. This process capture of conductive tissue and local myocardium). With HBP, ap­
begins at the molecular level and extends to macroscopic changes, such proximately two-thirds of patients have nsHBP at programmed out­
as asynchronous hypertrophy, leading to a progressive decline in left put,25,26 while LBBP, LFP, and RBBP are almost always non-selective
ventricular (LV) function (Figure 1). This decline is associated with in­ due to more surrounding myocardial tissue.27–29 Previous studies
creased episodes of HF and, consequently, higher mortality.15 showed that despite the differences in QRSd, ventricular synchrony
Evidence suggests that pacing at any myocardial site within the right during nsHBP is similar to selective HBP (sHBP) and much more physio­
ventricle (RV), not just the apex, is associated with detrimental haemo­ logical than RV septal pacing.30–33 Also, no difference in clinical out­
dynamic effects.16 The slow electrical propagation through the myocar­ comes between nsHBP and sHBP has been observed.25
dium can lead to ventricular mechanical dyssynchrony,17 LV During LVSP, the conduction tissue is not captured; however, capturing
dysfunction, and HF, particularly in patients who require a high percent­ myocytes close to the left septal endocardium leads to more synchronous
age of pacing.18 ventricular activation than during RVP.16,34,35 Both LBBP and LVSP have

Asynchronous electrical activation

Dyscoordinated contraction

Reduced pump function

Longer
Increased conduction
Rightward shift P–V relation wall stress pathlength
Neurohumoral Molecular/
activation cellular
Regional Ventricular dilatation changes
differences
mechanical
work
Hypertrophy

Asymmetric
hypertrophy

Figure 1 Relationship between asynchronous ventricular activation leading to reduced pump function. P–V, pressure volume. Reproduced, with
permission, from Vernooy et al.14
ESC/EHRA clinical consensus statement 5

Activation time (ms)

0 10 20 30 40 50 60 70 80 90 100

RVAP BiVP LVSP

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54 77 54 59 53 37
40 65 40 54 60 43
59 22 55 45 87 59 22 54 44 44 71 23 48 50
45 45 74 45 45 38 76 65 30 57
25 28 55 25 28 50 74 43 56

24 29 58 24 29 52 73 39 55
42 25 48 51 79 42 25 47 50 36 79 61 30 43 55
56 61 94 56 58 47 77 28 55
43 73 43 55 61 41
58 85 56 58 56 41

nsLBBP sLBBP sHBP

53 37 73 45 43 45
60 39 71 40 37 40
71 23 34 47 90 44 49 44 42 49
76 58 30 44 58 34 44 36 34 39 34 44
85 42
67 34 36 68 34 36 29 32 36

65 31 36 65 33 36 29 31 56
77 30 31 45 78 39 45 38 38 45
77 56 28 50 56 31 50 45 34 31
87 43 43 55
61 38 67 38 42 38
56 41 71 44 50 44

Figure 2 Computer-simulated three-dimensional activation maps following different pacing strategy and their corresponding segmental activation
time in bullseye form. Reproduced with permission from Meiburg et al.38

similar ECG characteristics and paced QRSd,36 but they differ in their ven­ His bundle pacing vs. left bundle
tricular activation patterns.37 Whereas LVSP produces less interventricu­
lar dyssynchrony than LBBP (due to delayed LV activation, which branch area pacing
nevertheless occurs before RV activation), the latter is associated with bet­
ter LV synchrony (due to more rapid and homogenous LV activation) (see Conduction system pacing utilizing HBP and LBBAP has been utilized for the
Figures 2 and 3).36 It is still a matter of debate whether capture of the left- management of both bradycardia and HF indications. While HBP provides ex­
sided conduction system impacts clinical outcomes. Most probably, this cellent synchronous biventricular activation, LBBAP preserves or restores
makes little difference in patients without documented structural heart intra-ventricular LV synchrony, with both modalities providing comparable
disease,36 but some observational studies have reported worse outcomes mechanical performance of the heart.30,31,34,36,38,42–46 The clinical impact of
for patients with HF with LVSP compared with LBBP.39,40 Another open RV dyssynchrony or delayed activation induced by LBBAP is currently unclear.
question is whether LBBP is superior to LFP, as suggested by a small ob­ While there are no high-quality long-term randomized comparisons
servational study in patients with HF.41 between HBP and LBBAP,42,47–55 observational data comparing HBP
6 M. Glikson et al.

RVSP LVSP

V1 V1

V2 V2

V3 V3

V4 V4

V5 V5
V8–V1
V6 V1–V8 V6 delay = –11 ms

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delay = 52 ms
V7 V7

V8 V8
0 50 100 150 200 0 50 100 150 200
t (ms) t (ms)

HBP LBBP

V1 V1

V2 V2

V3 V3

V4 V4

V5 V5
V1–V8
delay = 5 ms V8–V1
V6 V6 delay = –23 ms

V7 V7

V8 V8
–50 0 50 100 150 0 50 100 150 200
t (ms) t (ms)

Figure 3 Examples of ventricular dyssynchrony assessed by ultra-high-frequency ECG (sampled at 5 KHz and evaluating the 150–1000 hz spectrum
of the QRS complex, with V1–V8 electrodes placed in standard positions). In each of the UHF-ECG maps, time is visualized on the x-axis, and chest leads
are visualized on the y-axis. Local activations under the specific leads are connected by a black line. The difference between V1 and V8 activations (white
circles) indicates interventricular electrical dyssynchrony, whereas the width of the coloured band informs of local activation duration. Note that all CSP
methods, as well as LVSP, are associated with less interventricular dyssynchrony than RVSP. CSP, conduction system pacing; ECG, electrocardiogram;
HBP, His bundle pacing; LBBP, left bundle branch pacing; LVSP, left ventricular septal pacing; RVSP, right ventricular septal pacing.

and LBBAP indicate that the success rates, capture thresholds, sensing Despite certain challenges associated with HBP (achieving favourable
amplitude, and lead complication rates are more favourable with electrical parameters, difficulty in correcting distal conduction dis­
LBBAP, while acute haemodynamic improvement and clinical outcomes ease),25,56,58,70–74 employment of the implant technique outlined in
including LVEF, HF, and mortality outcomes appear overall compar­ the EHRA CSP consensus document (e.g. ensuring torque buildup, cur­
able.46,47,51,56–58 The only randomized trial comparing HBP and rent of injury of the His potential, stability testing, etc.) and application
LBBAP was a small crossover study in 23 patients who underwent of strict implant criteria (e.g. capture threshold of ≤1.5 V/0.5 ms and
AVN ablation followed by 6 months of pacing in each modality, without sensing >2 mV) may allow stable and effective HBP delivery.
any significant differences in LVEF.59 Implantation at the distal His bundle offers several advantages com­
The more favourable electrical parameters and perceived ease of im­ pared with the proximal His bundle: lower thresholds, larger R-wave
plantation have led to preferential adoption of LBBAP over HBP in clin­ sensing, less P-wave oversensing, nsHBP with septal myocardial capture
ical practice over the past years.6–8,51,56 There are nevertheless as backup in case of loss of HB capture, and less interference with sub­
inherent advantages and disadvantages with both CSP techniques sequent AV node ablation (AVNA).75,76
(see Table 1), which makes it worthwhile to encourage acquiring profi­ The learning curve for HBP implantation is sometimes perceived to
ciency with HBP as well as LBBAP. be unduly prolonged. However, in a multicentre report, a success rate
ESC/EHRA clinical consensus statement 7

Table 1 Comparison of HBP vs. LBBAP

HBP LBBAP
..............................................................................................................................................
Pacing threshold and May be high (ideally accept only if pacing threshold ≤1.5V/ Low (usually ≤1.5V/0.5 ms)
energy consumption 0.5ms)
Sensing Usually smaller R waves, P wave far-field oversensing (accept R waves comparable to RV leads (usually >4 mV), no P wave
only if R waves >2 mV with far-field P waves <0.5 mV) far-field oversensing
Guidance at implantation Clear physiological landmarks (His EGM and paced QRS Predominantly anatomical and surrogate ECG markers (e.g.
similar to intrinsic QRS or with bundle branch correction, RWPT, QRS transition with decrementing output often
QRS transition with decrementing output if nsHBP) absent)
Proof of conduction Very clear definition, easy documentation in close to 100% of More difficult, combination of different EGM and ECG

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system capture implants parameters with often uncertain confirmation of
conduction system capture
QRS duration Identical to native narrow QRS in sHBP; nsHBP is wider Wider than native narrow QRS
Use of ST segment for Equal to intrinsic ischaemia diagnosis in sHBP (STE, STD) ST segment deviation and ischaemia diagnosis feasible in
ischaemia diagnosis60–62 proximal LBBP
AV node ablation after May be challenging, with risk of threshold increase in proximal Easy, no risk of threshold increase
device implantation HBP implantation, and higher risk of recurrence of AV
conduction
Requirement for backup Advised in specific subgroups of patients (AV node ablation, Usually not required
lead pacemaker dependency, high capture threshold, poor
sensing)
Loss of conduction system Easy to assess (paced QRS morphology resembles intrinsic or More difficult to assess (QRS transitions with decrementing
capture48 with bundle branch correction, QRS transition with output infrequently encountered, requirement for digital
decrementing output in case of nsHBP). callipers for RWPT measurements)
Reported to be up to 23.5% Reported to be up to 13.5%
Late Threshold Increase Not uncommon ∼10–14% Unusual
Long-term data Available Accumulating
Complications (1) Long-term threshold increase/loss of capture (1) Septal perforation
(2) Ventricular undersensing (2) Permanent RBBB up to 6.3%
(3) P wave oversensing (3) Permanent CHB in patients with LBBB
(4) Lead micro/macrodislodgment (4) Loss of conduction system capture (mainly due to
microdislodgment)
(5) Lead macrodislodgment
(6) Tricuspid regurgitation
(7) Septal haematoma
(8) Coronary vessel trauma/fistula
(9) Myocardial infarction
(10) Lead fracture
Pacemaker-lead induced Rare; none in atrial/proximal HBP63 Up to 33%64
tricuspid regurgitation
Synchronization in narrow Biventricular synchrony30,42 Similar LV synchrony but less favourable RV synchrony36
QRS
Resynchronization in More favourable (also with nsHBP without correction of Less favourable67
RBBB RBBB)65,66
Resynchronization in LV resynchronization but at higher thresholds and lower LV resynchronization with very low thresholds and greater
LBBB success2,68 success69
Extractability Relatively easy, with minimal complications, similar to RV lead May potentially be complex and challenging (long-term data
extraction are lacking for the time being)

ECG, electrocardiogram; EGM, electrogram; HBP, His bundle pacing; LBBAP, left bundle branch area pacing; nsHBP, non-selective His bundle pacing; RWPT, R-wave peak time; sHBP,
selective His bundle pacing; STD, ST segment depression; STE, ST segment elevation.
8 M. Glikson et al.

Table 2 Preferred pacing modality of HBP or LBBAP according to indication (assuming expertise of the operator with both techniques, and
acceptable electrical parameters)

HBP may be preferred LBBAP may be preferred Either HBP or LBBAP suitable
..............................................................................................................................................
Tricuspid valve dysfunction/prosthesis/transcatheter repair.63,64,79 Scheduled AVN ablation53 Heart failure indication
Infra-nodal AV block80 Nodal AV block
Bailout in case of unsuccessful/unsatisfactory LBBAP Previous or scheduled TAVI or aortic valve surgery
(e.g. in patients with septal scar81) Bailout in case of unsuccessful/unsatisfactory HBP

Table based upon expert opinion of the writing group. Nodal AV block = supra-Hisian block; infra-nodal block = intra- or infra-Hisian block. Definite diagnosis of level of block may be
obtained by mapping the His with the pacing lead, which is routinely performed for HBP.
AV, atrioventricular; AVN, atrioventricular node; HBP, His bundle pacing; LBBAP, left bundle branch area pacing; TAVI, transcatheter aortic valve implantation.

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of 87% was achieved after 40 cases.70 In another report from three cen­ Criteria for His bundle capture
tres, the success rate flattened after ∼30–40 cases.77 However, HBP Confirming HB capture during the implantation procedure is clinically
success was defined as a threshold of ≤ 3.5V/1ms, and required num­ important since myocardial pacing in the para-Hisian area actually cor­
bers are likely to be higher to achieve lower capture thresholds. responds to right ventricular septal pacing (RVSP) and leads to dyssyn­
Conversely, LBBAP may seem to be relatively easy and with a high suc­ chronous ventricular activation (unlike nsHBP, where conduction
cess rate, even for beginners. However, many implantations in inexperi­ system capture is achieved in addition to myocardial capture).30,32
enced hands represent only deep septal pacing rather than true LBBAP. Confirmation of HBP in patients with narrow QRS is straightforward
Even in experienced centres, success may be met in only 92% of patients because QRS complex morphology and duration are the same as spon­
with bradycardia and is even lower in patients with HF (82%), although taneous complexes during sHBP with an isoelectric interval corre­
these figures included the learning curves of the operators.9 The learning sponding to the HV interval, or only slightly different with a
curve for successful LBBAP implantation has been reported to flatten pseudo-delta wave during nsHBP.65,73 It is more complex in case of
after 50–100 patients in a single-centre report with one main oper­ nsHBP with uncorrected bundle branch block, where the QRS com­
ator.78 In another single-centre study with three operators, LBBAP im­ plexes may be even wider than with intrinsic rhythm.65
plantation success was evaluated for the first 126 cases and was 79% for The gold standard for confirming HB capture is to demonstrate tran­
the first 42 patients and increased to 90% for the following 42 cases and sitions in QRS morphology with decrementing output (from nsHBP to
to 95% for the last tertile. In the multicentre MELOS registry,9 success either sHBP or to myocardial capture, or loss of correction of bundle
rate continued to increase over the first 270 cases, with fluoroscopy branch block) .65,73 Transitions are absent in 5–10% of patients (e.g.
time and V6RWPT reaching a plateau after approximately 110 cases. due to near-identical thresholds between the HB and myocytes), and
Therefore, the learning curve for LBBAP may not be shorter than for in those cases, other methods of confirmation have to be used (such
HBP, and each technique presents its own set of challenges. as programmed stimulation, which leverages differences in refractory
There may be instances where one pacing modality is preferred periods between tissues).65,88–90 QRS morphology criteria have also
(Table 2). been described and are detailed in the recent EHRA consensus docu­
The capture thresholds are higher and success rates of HBP are low­ ment on CSP implantation.10
er among patients with bundle branch block, infra-nodal AV block, and
those with aortic valve replacement.25,71,80,82–84 It is preferable to opt
for LBBAP in patients with significant aortic valve disease, as transcath­ Criteria for left bundle branch area pacing
eter aortic valve implantation (TAVI) or aortic valve surgery may com­ Left bundle branch area pacing consists of LBBP and LVSP with both being
promise HBP lead function. As discussed in the following sections, associated with better ventricular synchrony and LV haemodynamics than
patients with infra-nodal AV block or those requiring AV nodal ablation RVP.16,33–35,37,91 For evaluation of LBBAP, correct positioning of the V1
are better served with LBBAP than with HBP. chest electrode is essential as the terminal r′/R′ deflection may be missed
A final consideration is the potential worsening of tricuspid valve regur­ if the electrode is placed too high. In some cases, LBBAP without a termin­
gitation (TR), observed in up to one-third of patients undergoing LBBAP, al r′/R′-wave in V1 can be observed,10 presumably due to rapid transseptal
particularly in a basal position.64,79,85 However, this finding requires valid­ activation, or right ventricular activation occurring via rapid retrograde
ation in large studies. Notably, this issue does not appear to be as prevalent conduction to the HB and down the RBB, or slow propagation via dis­
with HBP, although sheath and lead manipulation at the level of the valve eased LBB, resulting in simultaneous biventricular activation, which is
may risk entanglement in the subvalvular apparatus.63 The His bundle probably the dominant mechanism in patients with HF. Other causes
may be paced from the atrial aspect of the tricuspid valve (thereby avoiding for absence of a terminal r′/R′ in V1 are anodal capture with bipolar pa­
the valve altogether) or from the ventricular aspect as it courses in proximity cing,92 or fusion with intrinsic conduction.
to the commissure between the septal and anterosuperior leaflets.86 In in­ A number of criteria have been described in the EHRA consensus
stances where the tricuspid valve needs to be spared, such as patients with a document on CSP implantation to confirm conduction system capture
history of tricuspid valve surgery or transcatheter repair, HBP is prefer­ in LBBP, the gold standard of which is transitions in QRS morphology
rable.87 Long-term evolution of TR with CSP needs to be further studied. during decremental output with unipolar pacing (i.e. with transitions
In general, implanters may use the CSP modality that best suits them. from non-selective LBBP to LVSP or to selective LBBP).10 The accuracy
However, CSP implanting centres should ideally be able to perform of R-wave peak time (RWPT) criteria is uncertain, especially in patients
both HBP and LBBAP and should also be able to perform BiVP implant­ with low septal and/or apical lead placements,93,94 as these pacing loca­
ation (as CSP is not always successful). Being proficient with all techni­ tions can produce V6RWPT shortening and V6–V1 interpeak interval
ques offers the operator an alternative for a bailout solution in case the prolongation without conduction system capture and can cause mis­
initial technique is unsuccessful or suboptimal. classification of LVSP as LBBP. In addition to pacing site, the
ESC/EHRA clinical consensus statement 9

V6RWPT depends upon heart size and conduction velocity (e.g. with
misclassification of LBBP as LVSP due to long V6RWPT in patients
Conduction system pacing for
with slow conduction or dilated hearts). It is therefore important to atrioventricular block with left
realize that none of the V6RWPT cut-offs (or for the V6–V1 interpeak
interval) are 100% accurate for diagnosing conduction system capture ventricular ejection fraction > 40%
and there is little information on the optimal cut-offs in patients with In patients with high-grade AV block and normal systolic function, BiVP
HF. Also, a terminal r/R wave in V1 may occasionally be visible when has been shown to preserve LVEF during follow-up compared with a
pace mapping from the RV septum and is therefore per se not diagnos­ significant decline in patients who had been randomized to RVP (with­
tic of LBBAP.95 out, however, any differences in clinical outcome).97,98 Biventricular pa­
The criteria for LVSP are as follows: (i) deep septal deployment of cing nevertheless bypasses the His–Purkinje system, inevitably resulting
the pacing lead together with (ii) terminal r′/R′-wave in lead V1, without in ventricular dyssynchrony38,43,99 (see Figures 2 and 4). As BiVP re­
criteria for conduction system capture.10 quires a more complex implantation procedure which coincides with
a higher risk of complications,100 it has not been recommended as an
alternative to RVP in patients with AV block and LVEF >40% in the

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2021 ESC pacing guidelines.1 According to these guidelines, HBP may
Success rates, procedural outcomes, and be considered for treating these patients, who were anticipated to
complications of His bundle pacing and left have >20% ventricular pacing, without giving any recommendation
for LBBAP due to the limited amount of data available at that time.
bundle branch area pacing More recently, the 2023 HRS/APHRS/LAHRS guidelines on physio­
A meta-analysis of 15 observational studies involving 2491 patients logical pacing stated that LBBAP may be useful (along with CRT) in
found that LBBAP had significantly higher success rates compared AV block patients with LVEF 36–50% and that it may be considered
with HBP (91.1 vs. 80.9%; P < 0.001), along with significantly lower in those with LVEF >50%.12
lead-related complications over follow-up, which included lead failure, In patients with AV block in whom ventricular pacing is anticipated to
inactivation for elevated thresholds and dislodgment (1.1 vs. 4.3%; be infrequent (<20%), strategies that minimize ventricular pacing are
P = 0.003).96 The meta-analysis also found no significant difference in appropriate, similar to what is outlined in the 2021 ESC pacing guide­
lead dislodgement rates between CSP and traditional RVP.96 lines.1,101 However, as the course of evolution of the conduction disor­
In a multicentre study involving 870 subjects, of whom 849 were fol­ ders in these patients may be unforeseeable, CSP may be an option in
lowed for 6 months, CSP lead implantation was successful in 768 patients proficient centres to provide a physiological means of delivering pacing
(90%), with a success rate of 95% for LBBAP and 88% for HBP (P = therapy in case ventricular pacing burden increases.
0.002).58 The two pacing modalities had no significant differences in pro­ Over the past years, various studies have compared either HBP
cedural or fluoroscopy duration. However, the threshold at implantation and/or LBBAP with RVP in patients with AV block (most of whom
was higher for HBP (1.44 ± 1.03 V at 0.71 ± 0.33 ms) than for LBBAP had mildly reduced to normal LVEF) and showed that this emerging
(0.69 ± 0.39 V at 0.46 ± 0.15 ms, P < 0.001). At 6-month follow-up, pacing strategy seems very promising. Unfortunately, so far only a
HBP continued to have a higher threshold than LBBAP (1.59 ± 0.97 V few small randomized clinical trials (RCTs) have compared CSP
at 0.67 ± 0.31 ms vs. 0.79 ± 0.33 V at 0.44 ± 0.13 ms; P < 0.001). An in­ with RVP in patients with bradycardia and near-normal LVEF, none
crease in the pacing threshold of more than 1 V at 6 months was ob­ of which have long-term follow-up. One early trial showed in 38 pa­
served in 3 of 208 patients (1.4%) with LBBAP and 55 of 418 patients tients that HBP preserved LVEF and mechanical synchrony as com­
(13.2%) with HBP (P < 0.001). Serious adverse events related to the im­
pared to RVP after 12 months.4 A recent RCT in 92 patients also
plantation procedure or the CSP lead occurred in 5 of 251 patients
showed superiority of HBP over RVP, with a higher LVEF and lower
(2.0%) with LBBAP and 25 of 598 patients (4.2%) with HBP (P = 0.11).
levels of TGFβ1 during follow-up.102 Two small RCTs focusing on
ECG parameters compared LBBP with RVP and showed that LBBP re­
sulted in significant narrower QRS duration than RVP.103,104 In another
study, however, in 50 randomized patients, the LVEF was not significantly
different between LBBP and RVP after 12 months.105 Nevertheless, glo­
Advice: HBP vs. LBBAP Strength of evidence bal longitudinal strain, QRS duration, as well as echocardiographic mea­
.................................................................. surements of dyssynchrony were significantly better during LBBP as
Advice TO DO compared to RVP. In the single-centre STAY study, 70 patients with
It is advised that CSP implantation centres AV block, LVEF > 40% (mean ∼60%), and an expected high ventricular
should ideally be capable of performing
pacing burden (mean ∼91%) were randomized to either RVP or CSP
(9 HBP, 17 LBBP, and 10 LVSP).106 Over a 6-month follow-up, RVP
both HBP and LBBAP, and should be
was associated with a significant decrease in LVEF {mean difference,
able to perform BiVP implantation
>90% agree
−5.8% [95% confidence interval (CI), −9.6 to −2%]; P < 0.01} and in­
crease in LV end-diastolic diameter [mean difference 3.2 mm (95% CI,
In patients with significant aortic valve
0.1–6.2); P = 0.04]. In addition, HF-related admissions were higher in
disease (which may require future
the RVP group (22.6 vs. 5.1%; P = 0.03).
intervention), infra-nodal AV block or Besides the few small short-term RCTs that show superiority of CSP
AVNA, it is advised that LBBAP is over RVP in patients with AV block, larger observational studies have
preferred over HBP25,71,80,82–84 been performed (for which data should be interpreted with caution
In patients requiring sparing of the tricuspid due to the inherent caveats of non-randomized studies). In a compari­
valve (e.g. after tricuspid valve surgery or
son of 304 patients with HBP at one hospital with 433 patients receiving
RVP at a sister hospital,26 a significant reduction in the primary endpoint
transcatheter repair), it is advised that
with HBP (all-cause mortality, HF hospitalizations (HFH), or need for
HBP is preferred over LBBAP63 upgrade to BiVP) was found after a mean follow-up of ∼2 years
(with a requirement for lead revision in 4.2% of patients with HBP
10 M. Glikson et al.

A Left bundle branch block Left bundle branch pacing

QRS 162 ms QRS 132 ms

LVAT 90 ms LVAT 60 ms

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B Right ventricular pacing Left bundle branch pacing

QRS 164 ms QRS 131 ms

LVAT 115 ms LVAT 69 ms

C Left bundle branch block Biventricular pacing

QRS 194 ms QRS 126 ms

LVAT 108 ms LVAT 74 ms

Figure 4 Electrocardiographic imaging (ECGi) with examples of LVAT shortening and change of activation pattern with CSP and BiVP. All 3 cases
show long LVAT with delayed activation of the left ventricle (blue or purple during intrinsic rhythm with left bundle branch block or with right ven­
tricular pacing. With CSP and BiVP, all showed decrease in LVAT and faster activation of the left ventricle (green or red). (A) Maps with an imageless
ECGi technology and (B) and (C) maps with ECGi that requires computed tomography. BiVP, biventricular pacing; CSP, conduction system pacing;
LVAT, left ventricular activation time.

due to high thresholds). The same group also reported improved out­ (LVEF was not reported but was presumably preserved overall).51
come of the same primary endpoint in 321 patients with LBBAP com­ All-cause mortality at 6 months was lower in the CSP group (HR
pared with 382 patients with RVP after a mean follow-up of 1.6 0.66; P < 0.0001) as was HFH (HR 0.70; P = 0.02). Other observational
years.107 Among patients with ventricular pacing >20%, LBBAP was as­ studies showed that the incidence of HFH and need for an upgrade to
sociated with a significant reduction in mortality [7.8 vs. 15%; hazard ra­ BiVP was significantly lower in patients undergoing LBBP as compared
tio (HR) 0.59; P = 0.03] and HFH (3.7 vs. 10.5%; HR 0.38; P = 0.004) as to those receiving RVP.109,110 Also, for other populations such as AV
compared to RVP. Another series reported similar results in 628 pa­ block after TAVI111,112 and for patients with AV block and HF with pre­
tients who received RVP compared with 231 patients received CSP served ejection fraction,113 LBBP seems to be a better alternative com­
(95 HBP and 136 LBBAP), with a reduction in HFH in patients with pared with RVP.
>20% ventricular pacing in a multivariable-adjusted model, with a HR Meta-analyses of the few randomized trials and larger observational co­
of 0.40 (95% CI, 0.17–0.95).108 These studies did not specifically target horts comparing CSP with RVP in patients with AV block showed that
a population with AV block and LVEF >40%, but ∼50–65% of patients CSP was significantly superior in preserving LVEF, shortening paced
had AV block and the mean LVEF was >50%. Reduced mortality was QRS duration, and reducing rates of HFH.114–116 On the contrary, RVP
also reported in a large population-based study in patients with dual- was associated with higher implantation success rate and shorter proced­
chamber pacemakers using data from Medicare claims in 6197 patients ure/fluoroscopy duration and had fewer lead complications.
with CSP (4738 LBBAP and 1459 HBP) compared with 16 989 patients While awaiting the results of the ongoing larger RCTs in patients
with RVP, roughly half of whom had an AV block indication for pacing with AV block and mildly reduced to normal LVEF (>40%) requiring
ESC/EHRA clinical consensus statement 11

frequent (>20%) ventricular pacing, both HBP and LBBP might be con­ block and LVEF < 35%, and refer the reader to the recommendations
sidered as alternatives to RVP in these patients. It has nevertheless been for treating HF.12
shown that HBP implantation is less successful in infra-nodal block com­ There is a paucity of evidence regarding CSP in AV block patients
pared with nodal block (76 vs. 93%, P < 0.05).80 A backup lead may be with LVEF < 40%. Randomized trials comparing conduction system pa­
useful to avoid asystole in HBP patients with AV block, particularly if the cing cardiac resynchronization therapy (CSP-CRT) to BiV-CRT typically
block is infra-nodal or in case of sensing issues.1,10,117 Left bundle branch do not indicate the percentages of patients with AV block, but these
area pacing may be a more effective and reliable form of pacing in these presumably are low3,68,122–124 (see Supplementary material online,
instances and has been shown to require fewer lead revisions, yield low­ Table S1). Randomized trials involving CSP as a treatment modality focus­
er pacing thresholds, greater R-wave amplitudes, and similar paced QRS ing on patients with AV block and LVEF < 40% have not been performed
duration compared with HBP in patients with AV block.47,118 to date. Patients with AV nodal ablation or upgrades are separate entities
and are discussed in following sections. Likewise, most observational
studies on CSP do not separately report outcomes of patients with
AV block and LVEF < 40%. They mostly included patients with LVEF <
Conduction system pacing for 50% and a mix of indications for CRT, AVNA, or device upgrade and a

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atrioventricular block in reduced minority of patients with AV block, without separate reporting of results
in these subgroups9,40,49,69,125–135 (see Supplementary material online,
left ventricular ejection fraction Table S1). Patients included in observational studies dedicated to CSP
in AV block had an average LVEF of >50%.80,118
(≤40%) A small (n = 50) observational case–control matched study evalu­
Current ESC pacing guidelines state, based on several RCTs,119–121 that ated the benefits of CSP in patients with LVEF ≤45% who were candi­
BiV-CRT rather than RVP is recommended for patients with HF with re­ dates for CRT due to either AV block or an upgrade from RVP.130
duced EF (HFrEF, LVEF ≤40%) who have AV block and an indication for Conduction system pacing (with either HBP or LBBP) and BiVP re­
ventricular pacing, regardless of New York Heart Association (NYHA) sulted in similar echocardiographic response and LVEF improvement
class and QRS duration, in order to reduce morbidity; this includes pa­ at 6-month follow-up; decreased mitral regurgitation and improved
tients with AF.1 The largest relevant trial is BLOCK HF,119 which included functional class were observed with CSP.
208 patients who had LVEF < 35% (30% of the total cohort of the trial). In patients with HF, CSP implant success rate is lower compared with
HOBIPACE120 and COMBAT121 (which both only included patients with bradycardia indication.9 In the specific population with complete AV
LVEF < 40%) totalled 90 patients together. Therefore, the evidence for block and LVEF ≤40% (n = 77), an 88.3% implant success rate has
the efficacy of BiVP in the context of AV block is relatively scarce com­ been reported.136 Owing to the pros and cons of CSP and of BiVP
pared with that of BiV-CRT for treating HF. for treating AV block in patients with LVEF < 40%, it is a matter of de­
The 2023 HRS/APHRS/LAHRS guidelines on physiological pacing do bate whether one or the other pacing modality should be preferred.
not give any specific recommendations for pacing in patients with AV This is particularly the case in patients with a narrow QRS,137 where

AVB

Anticipated VP < 20% Anticipated VP ≥20%

LVEF LVEF LVEF

≤40% 41–50% > 50%

RVP CSP*
+MVP +MVP BiVP† CSP* RVP RVP, BiVP†, CSP* CSP* or RVP

Wide/
non-physiological
* In case of infra-nodal block, LBBAP is the
paced QRS with
preferred CSP modality, or HBP with a backup lead
BiVP or CSP
† CSP advised if coronary sinus lead implantation fails

HOT/LOT-CRT

Advice TO DO; May be appropriate TO DO; Advice NOT DO DO

Figure 5 Summary of CSP indications in AVB. AVB, atrioventricular block; BiVP, biventricular pacing; CSP, conduction system pacing; HBP, His bundle
pacing; HOT/LOT-CRT, His-optimized or left bundle-optimized cardiac resynchronization therapy; LBBAP, left bundle branch area pacing; LVEF, left
ventricular ejection fraction; MVP, minimized ventricular pacing; RVP, right ventricular pacing.
12 M. Glikson et al.

BiVP circumvents the His–Purkinje system and delivers myocardial pa­

cing. Conduction system pacing may provide a more physiological form
Conduction system pacing in
of pacing with similar dyssynchrony and strain correction over time.138 atrioventricular node ablation
Even patients with AV block with a wide QRS rhythm may benefit from
CSP, as it has been shown that 96% of AV block lies at the nodal or In patients with rapidly conducted and symptomatic atrial tachyarrhyth­
intra-Hisian level, and is therefore amenable to correction with CSP mias refractory to medical or ablative therapy, AVNA is an established
(which was successful in 97% of patients).118 therapeutic strategy. In patients with atrial fibrillation (AF), the combined
Trials studying CSP in AV block and LVEF <40% are ongoing and vary in effects of loss of AV synchrony, beat-to-beat irregularity, and rapid ven­
the patient population recruited, and usually also include a CRT indication tricular rates can lead to a reduction in cardiac output with adverse car­
(e.g. Left vs. Left, CONSYST-CRT 2, etc.). The LVEF cut-off differs but diac remodelling, and HF symptoms. These patients may benefit from a
generally includes patients with LVEF <40% as a subset. The interventions ‘pace-and-ablate’ strategy (Figure 6).140–143 In a recent network
broadly compare CSP with RVP or BiVP depending on the patient cohort meta-analysis comparing AF therapies including pharmacological treat­
(c.f. Figure 11 and supplementary material online, Table S9). ment and different AF ablation modalities (radiofrequency, cryoballoon,
A summary for CSP indications in AV block, as opposed to BiVP and to and surgical ablation), the ‘pace-and-ablate’ strategy showed a consistent

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RVP, is shown in Figure 5 (for HOT/LOT-CRT, see relevant section). trend compared with other treatments in reducing cardiovascular and all-
cause mortality, re-hospitalization, and stroke.144
The combination of AVNA and conventional RVP has shown to be
effective in controlling heart rate and regularizing ventricular response.
Overall, quality of life (QoL), cardiac symptoms, exercise tolerance, and
Advice: CSP for AV block Strength of evidence LVEF were significantly improved with AVNA + RVP in observational
.................................................................. and randomized studies in comparison with pharmacological rate con­
Advice TO DO trol (see Supplementary material online, Table S2).145–160 However,
In patients with AV block in whom BiVP is concerns about the potential deleterious effects of RVP have led to
desired, it is advised to implant CSPa as a
the emergence of BiVP as an alternative modality for patients undergo­
ing AVNA. Multiple studies including RCTs comparing BiVP with RVP
rescue strategy if coronary sinus lead
have shown variable benefits of BiVP in terms of QoL, 6-min walking dis­
implantation fails139 tance, and/or LVEF in patients undergoing AVNA (see Supplementary
>90% agree
May be appropriate TO DO material online, Table S3).161–169 In the APAF-CRT mortality trial,169
It may be appropriate to implant CSPa in 133 elderly patients with severely symptomatic permanent AF, narrow
patients with LVEF >40% with an QRS (≤110 ms), and at least one HFH during the previous year were ran­
anticipated ventricular pacing burden
domly assigned to AVNA + BiVP vs. pharmacological rate control. A sig­
nificant absolute mortality reduction of 18% was obtained with AVNA +
>20%.4,26,51,102–106,108,114–116
BiVP at 4-year follow-up [11% mortality in the AVNA + BiVP group vs.
It may be appropriate to implant CSPa in 29% in the pharmacological rate control group (HR 0.26, 95% CI
lieu of BiVP in patients with AV block 0.10–0.65)].
and LVEF <40% with an anticipated The different available pacing modalities for combination with AVNA
ventricular pacing burden >20%130,132 are outlined in Table 3. Conduction system pacing appears to be an ef­
In patients with AV block and infrequent
fective method for pace-and-ablate therapy due to its ability to maintain
normal ventricular activation in this pacing-dependent group who are at
(<20%) anticipated ventricular pacing, it
risk of developing PICM, particularly if the baseline QRS is narrow. This
may be appropriate to implant CSPa in approach is further supported by previously reported positive out­
combination with minimized ventricular comes of BiVP in this setting.
>90% agree
pacing strategies, in order to provide The 2021 ESC guidelines on cardiac pacing and cardiac resynchroni­
physiological ventricular pacing in case zation therapy (CRT) stated that the ‘pace-and-ablate’ strategy using
the conduction disorder progresses HBP with an additional RV backup lead may be considered.1 Since its
publication, new data exploring the ‘pace-and-ablate’ strategy using
It may be appropriate to choose CSPa as
both HBP and LBBAP have become available. Most of the currently
opposed to BiVP as a primary strategy,
published studies have an observational and retrospective design,
taking into account operator with limited prospective and randomized data, and have included most­
experience, in the presence of specific ly patients with baseline impaired LVEF and HF.5,76,170–184 Overall, CSP
>90% agree
patient populations where a simpler was associated with a similar improvement in LVEF, NYHA, and QoL
device is desired (e.g. frail patients, parameters when compared with BiVP but was superior to RVP (see
patients with limited life expectancy, or Supplementary material online, Table S4). A single-centre retrospective
those requiring a smaller device) study included 223 patients who underwent AVNA and who received
either CSP (n = 110, HBP 84, LBBAP 46) or RVP (n = 113).179 After a
Advice NOT TO DO
mean follow-up of 27 ± 19 months, LVEF significantly increased in both
It is advised to avoid RV pacing inpatients groups but the combined primary outcome of time to death or HFH
with AV block, LVEF <40%, and was significantly reduced with CSP (48% for CSP vs. 62% for RV myo­
frequent (>20%) anticipated ventricular cardial pacing, HR 0.61, 95% CI 0.42–0.89, P < 0.01), although patients
pacing119–121 in the RVP group were sicker with significantly lower baseline LVEF and
wider baseline QRS duration. In the ALTERNATIVE-AF trial,177 50 pa­
a
The decision for implanting HBP vs. LBBAP can be based on the relevant advice tients with persistent AF and LVEF ≤40% with QRS < 120ms or RBBB
Table and Table 2. In patients undergoing HBP, a backup lead may be useful, underwent AVNA and sequentially received 9 months of treatment
particularly if the block is infra-nodal or in case of sensing issues. with both HBP and BiVP in a randomized, crossover trial.
Improvement in LVEF was significantly greater with HBP compared
ESC/EHRA clinical consensus statement 13

Atrial fibrillation promotes:

1 Loss of AV synchrony*
• Loss of atrial contribution to filling

2 Irregularity
• Decreases net coronary perfusion
• Creates inefficient mechanics (failure of contractility adaptation)
to beat-to-beat changes in ventricular filling)
• Impaired Ca2+ homeostasis with reduction in systolic Ca2+ release Pace and ablate with CSP

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• Reduces diastolic filling time addresses irregularity and
• Increases sympathetic nerve activity may promote sinus rhythm*
Negatively
• Increases mitral regurgitation in a small proportion
influences

QOL
3 Rapid ventricular rates EF
• Induces ischaemia, ATP depletion, oxidative stress, RAS activation Hospitalizations

Cardiac output Cardiac remodelling Heart failure

Figure 6 Haemodynamic consequences of AF and potential benefits of the ‘pace-and-ablate’ therapy. AF, atrial fibrillation; ATP, adenosine triphos­
phate; AV, atrioventricular; CSP, conduction system pacing; EF, ejection fraction; QOL, quality of life; RAS, renin-angiotensin system. Reproduced, with
permission, from Joza et al.140.

Table 3 Comparison of the different pacing modalities for the ‘pace-and-ablate’ strategy

RV pacing BiV-CRT HBP LBBAP

..............................................................................................................................................
Implant technique Easy May be complex May be complex May be complex
LV synchrony Impaired Preserved/restored Preserved/restored Preserved/restored
LVEF Impaired Preserved/restored Preserved/restored Preserved/restored
Pacing threshold Low High High Low
Lead-related complications Low Intermediate High Low
Battery longevity Long Shorter Shorter Long
AVN ablation Easy Easy Challenging Easy
Risk of rise in capture threshold due to AVN ablation No No Yes No
Risk of recurrence of AV conduction at follow-up Low Low Intermediate Low
Backup lead advised No No Yes No

with BiVP, with similar improvement in NYHA class, LV end-diastolic Notably, CSP allows the use of a more straightforward device with
diameter, and B-type natriuretic peptide levels. In a retrospective study, less hardware in the venous system and usually a relatively simple pro­
the outcomes of 68 patients with permanent AF and uncontrolled cedure in experienced hands. As a result, in the presence of specific pa­
heart rate undergoing AVNA and LBBAP were compared with a con­ tient populations where a simpler device or procedure is desirable (e.g.
trol group including both RVP (n = 44) and BiVP (n = 24) using propen­ older and frail patients or those requiring a smaller device), CSP could
sity matching.183 Patients with LBBAP had a higher LVEF improvement be chosen over BiV-CRT.
and a lower 1-year rate of the composite score of HFH or mortality, Direct comparisons between HBP and LBBAP in patients undergoing
whereas AVNA procedure data and complications were comparable. AVNA are scarce. Improvement in LVEF was similar between the two
14 M. Glikson et al.

pacing modalities in a series of 162 patients with propensity-matched The risk of threshold rise due to AVNA rises exponentially when the
groups52 and in a small randomized crossover study with 23 pa­ ablation site is <6mm from the HBP lead tip and is not mitigated by
tients.59 A prospective, multicentre study reported the incidence cryoablation.184 Due to the risk of threshold rise and loss of capture,
of device-related complications in patients undergoing AVNA and the 2021 ESC pacing guidelines stated that a backup lead should be con­
implantation of either BiVP (n = 263) or CSP (HBP n = 68, LBBAP sidered in HBP patients who are planned for AVNA1 (a backup LBBAP
n = 42).181 At 12-month follow-up, the risk of device-related compli­ lead is an option185). Notably, a backup lead may be considered accord­
cations was comparable (5.7% for BiVP, 4.4% for HBP, and 2.4% for ing to the HRS document on physiological pacing.12 Experienced opera­
LBBAP, P = 0.65) as was the risk of HFH (2.7, 1.5, and 2.4%, respect­ tors who perform HBP implantation and AVNA in the same session
ively, P = 0.85). However, compared with BiVP and HBP, LBBAP was may opt to not implant a backup lead. However, a backup lead may
associated with shorter procedural and fluoroscopy times, lower pa­ otherwise be useful in the interest of patient safety.
cing thresholds, and longer estimated residual battery longevity. Due to the potential issues with HBP in the setting of AVNA (difficult
Similar findings were reported in 164 patients who underwent either ablation with risk of rise in capture thresholds and recurrence of AV
HBP (n = 68) or LBBAP (n = 96) and AVNA, with shorter mean pace­ conduction, requirement for a backup lead, etc.), LBBAP is the pre­
maker implantation and AVNA times for LBBAP.182 Higher acute and ferred CSP option.

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12-month follow-up complete AV block rates were also obtained Ongoing large, multicentre, RCTs are currently evaluating the role of
with LBBAP in comparison with HBP with a comparable improve­ CSP in patients undergoing AVNA in comparison with RVP (included in
ment in NYHA class and LVEF. A significant rise in the pacing thresh­ the patient population of PROTECT-HF, NCT05815745), pharmaco­
old > 1V occurred in 11% of HBP patients (with one patient logical treatment (PACE-FIB,186 NCT05029570 and RAFT P&A study,
undergoing lead revision) with no such cases among LBBAP patients. NCT06299514) or AF ablation (ABACUS, NCT06207383). They will
The relatively short follow-up in these two studies should be noted provide the definite answers as to superiority of one treatment modality
when commenting on long-term safety. In a multicentre series of over another.
98 AVNA patients with CSP (48 HBP, 50 LBBAP), a > 1V rise in cap­ A summary of indications for CSP in the setting of AVNA, as op­
ture threshold was noted in 14.5% patients with HBP, without any posed to BiVP and RVP, is shown in Figure 7 (for HOT/LOT-CRT,
lead issues in the LBBAP patients.53 see relevant section).

AVNA

LVEF ≤40% LVEF 41–50% LVEF >50%

BiVP CSP* BiVP CSP* CSP* RVP

Wide/non-
physiological paced
QRS with BiVP or CSP

HOT/LOT-CRT

*LBBAP preferred, or HBP with backup lead

Failed coronary sinus lead
implantation
Advice TO DO; May be appropriate TO DO

CSP

Figure 7 Indications for CSP in patients scheduled for AVNA. AVNA, atrioventricular nodal ablation; BiVP, biventricular pacing; CSP, conduction
system pacing; HBP, His bundle pacing; HOT/LOT-CRT, His-optimized or left bundle-optimized cardiac resynchronization therapy; LBBAP, left bundle
branch area pacing; LVEF, left ventricular ejection fraction; RVP, right ventricular pacing.
ESC/EHRA clinical consensus statement 15

be useful. The physio-VP AF study (NCT05367037) is randomizing pa­

tients with SND or second-degree AV block to either CSP or RVP with
minimized ventricular pacing.
Advice: CSP for AVNA Strength of evidence
.................................................................. Sinus node dysfunction and AF often coexist with 40–70% of patients
Advice TO DO
with SND having a history of atrial arrhythmias at the time of diagno­
sis.191 Some of these patients may later require AVNA, and in this in­
It is advised that CSP is implanted as a stance, having a CSP lead from the onset may be desirable. In a
rescue strategy if coronary sinus lead recent analysis using Medicare data in patients with dual-chamber pace­
implantation fails makers, as many as 37% of patients implanted with CSP had SND as the
indication for pacing.51
>90% agree Due to the paucity of data, it was decided not to formulate advice on
May be appropriate TO DO this topic for the time being.
It may be appropriate that patients
Conduction system pacing for

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undergoing HBP as a primary strategy
for ‘ablate-and-pace’ therapy receive a
‘backup’ ventricular lead in the interest
heart failure without bradycardia
of safety, taking into account operator
>90% agree pacing indication
experience and whether the procedures Left bundle branch block causes interventricular dyssynchrony and de­
are performed concomitantly or in a layed activation of the LV, which negatively impacts cardiac function, es­
staged manner1,117 pecially in patients with HFrEF.192 Landmark clinical trials have clearly
In patients scheduled for AVNA, it may be demonstrated that BiV-CRT enhances QoL, reduces LV remodelling,
appropriate that LBBAP is preferred
and decreases cardiovascular events such as hospitalizations and mor­
tality in patients with impaired LV function and LBBB, and this effect is
over HBP to simplify the ablation, avoid
less pronounced in patients with a less wide QRS and non-LBBB.193,194
increase in capture thresholds and The efficacy of BiV-CRT stems from correcting the delayed LV electric­
>90% agree
recurrence of AV conduction, and avoid al activation through pacing, which involves leads placed in the RV and
requirement for a backup lead an appropriate branch of the coronary sinus to deliver epicardial LV
In patients with an LVEF >40% undergoing stimulation. However, despite significant advancements in delivery
AVNA, it may be appropriate to implant tools and leads, BiVP is not always feasible.195 Challenges in coronary
sinus cannulation, a lack of suitable coronary sinus tributaries, high pa­
CSP in lieu of RVP or BiVP in order to
cing threshold, or phrenic nerve capture hinder successful implantation
preserve LV function and improve HF in ∼5–10% of cases.73,195 Additionally, one-third of patients do not re­
symptoms.5,76,172,173,175,179–181,183 spond to BiV-CRT, with the rate of non-responders remaining consist­
In patients with an LVEF ≤ 40% undergoing ent over time, particularly among patients with non-LBBB or QRS
AVNA, it may be appropriate to implant complexes < 150 ms.66,196,197 Given these challenges, alternative pacing
CSP in lieu of BiVP in order to improve modalities to deliver CRT have been explored. In recent years, CSP has
gained attention as a potential alternative to BiVP by restoring resynchro­
LV function and HF
nized ventricular activation.3,123,198–200 Cardiac resynchronization therapy
symptoms170,171,174,176,178
with CSP has been employed either as the initial therapy for CRT,12 in
In the presence of specific patient cases when BiVP is not possible and as a rescue approach.1,12,201
populations where a simpler device is
desired (e.g. frail patients, patients with His bundle pacing
limited life expectancy, or those His bundle pacing and LBBAP restore LV synchrony to a greater extent,
>90% agree
requiring a smaller device), it may be with superior acute haemodynamic response, compared with BiVP.42
appropriate to choose CSP instead of Permanent HBP was first reported as an alternative to BiVP for CRT
BiVP as a primary strategy, taking into in 2013.201 In a randomized crossover study of 29 patients referred
account operator experience for CRT, all implanted with an HBP lead and a coronary sinus lead, signifi­
cant QRS narrowing was observed in 21 of the 29 patients (72%), and
HBP delivered an equivalent clinical response to BiVP over 6 months.3
The His Bundle Pacing vs. Coronary Sinus Pacing for Cardiac
Resynchronization Therapy (His-SYNC) pilot trial was the first prospect­
Conduction system pacing in sinus ive, randomized controlled trial aiming to assess the feasibility and efficacy
node dysfunction of HBP as a first-line strategy compared with BiV-CRT.2 Among the 41
patients enrolled, HBP demonstrated superior QRS narrowing with a
There is good evidence that in patients with sinus node dysfunction trend to greater improvement in LVEF compared with BiV-CRT.
(SND), unnecessary RVP should be minimized to avoid AF and HF, par­ However, the study was limited by high crossover rates towards the
ticularly if systolic function is impaired or borderline.20,187 This may be BiV-CRT group, mainly due to the inability to correct the QRS complex
achieved by programming long AV intervals or specific algorithms, because of non-specific intra-ventricular conduction delays.
which may, however, lead to long PR intervals with AV dyssyn­ The Direct His pacing as an Alternative to BiVP in Symptomatic
chrony.101,188,189 Atrial pacing significantly lengthens PR intervals190 HFrEF Patients with True LBBB (His-Alternative) trial randomized 50
and may even result in AV block due to decremental conduction during patients to HBP vs. BiV-CRT.68 In the HBP group, 72% achieved suc­
rate-adaptive pacing. Implanting the atrial lead first in these patients al­ cessful LBBB correction, and HBP provided comparable clinical and
lows for evaluation of AV conduction to help decide whether CSP may echocardiographic improvements, though with higher pacing
16 M. Glikson et al.

thresholds. When LBBB correction can be achieved with HBP, it is a 0.3–10.9; P = 0.039). The HOT-CRT trial124 included 100 patients
reasonable alternative to BiV-CRT, especially when effective CRT can­ with LVEF < 50% and an indication for CRT and randomized patients
not be achieved with an LV/coronary sinus lead (see Supplementary to either CSP-CRT (39 LBBAP, 5 LBBAP + coronary sinus pacing, 4
material online, Table S5). HBP, and 2 crossover) or BiV-CRT (41 BiVP and 9 crossover). The pri­
Despite these encouraging preliminary results, technical difficulties in mary endpoint was improvement in LVEF at 6 months, which was
achieving the target pacing site, unsatisfactory electrical lead para­ greater with CSP-CRT compared with BiV-CRT (12.4 ± 7.3 vs. 8.0 ±
meters, especially regarding increases in pacing thresholds over time, 10.1%, P = 0.02). Complications were more frequent in the BiV-CRT
and the inability to correct infra-Hisian or more distal conduction dis­ group, mainly driven by rises in coronary sinus lead pacing threshold
ease limit the adoption of HBP as a standard alternative to conventional and phrenic nerve capture (see Supplementary material online,
BiV-CRT.71,202,203 Table S5).
In patients with HFrEF, impaired LV filling due to AV dyssynchrony In a meta-analysis of seven randomized controlled trials comparing
resulting from prolonged PR intervals may contribute to pump fail­ 200 CSP-CRT patients with 208 BiV-CRT patients, CSP-CRT was su­
ure.188 The HOPE-HF study204 was a randomized double-blind cross­ perior in terms of improvement in NYHA class and LVEF, with no sig­
over study in 167 patients with HFrEF, PR > 200 ms (average 249 ms) nificant differences in HF hospizalization and mortality over limited

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and either QRS <140 ms or RBBB and found no meaningful benefit of follow-up time.210
HBP over backup ventricular pacing. Therefore, there is currently insuf­
ficient evidence that CSP-CRT is indicated solely for the purpose of Conduction system pacing in non-left
correcting slight PR prolongation in patients with HF.
bundle branch pacing patients
Patients with HF and non-LBBB present a significant challenge in clinical
Left bundle branch area pacing practice, as data from large BiV-CRT clinical trials do not indicate fa­
With the above-mentioned limitations of HBP, LBBAP might address vourable outcomes for these patients.211 According to the 2021 ESC
these issues by capturing the conduction system more distally, with guidelines, BiVP should be considered for patients with non-LBBB
more stable pacing parameters. Following the encouraging results in and a QRS duration >150 ms, and a Class IIb recommendation for
bradycardia indications,115,205 LBBP was investigated in patients with those with a QRS duration of 130–150 ms, without any indication
HF and CRT indications.206 Observational data suggest than conduction for CSP.1 The 2023 HRS/APHRS/LAHRS guidelines attribute a Class
system capture with LBBP (rather than LVSP) impacts clinical outcome 2b indication for CSP in patients with non-LBBB with NYHA III–IV +
in patients with CRT indications,39,40 but this deserves further study as QRS 120–149 ms, as well as NYHA II + QRS ≥150 ms.12
results are heterogenous.207 His bundle pacing has been shown to achieve electrical resynchroniza­
In a cohort of 325 patients with LVEF < 50% and an indication for tion and improve clinical outcomes in a small multicentre observational
CRT, LBBP was successfully achieved in 85% of patients.69 This was asso­ study with 37 patients with right bundle branch block (RBBB) and re­
ciated with a significant reduction in QRS duration (from 152 ± 32 to duced LVEF.66 Similarly, data from some observational studies indicate
137 ± 22 ms, P < 0.01) and an improvement in LVEF at 6-month follow- that LBBAP is a feasible alternative for delivering CRT or physiological
up (from 33 ± 10 to 44 ± 11%, P < 0.01). Additionally, data suggest that ventricular pacing in patients with RBBB, HF, and LV dysfunction.67,208
patients with RBBB may benefit from LBBP, with QRS narrowing, a re­ The number of patients with non-specific intra-ventricular conduction
duction in interventricular mechanical delay,208 and an increase in LVEF.67 delay (NIVCD) who have been studied with LBBAP is very small, and
In a large retrospective study of 1778 CRT patients, LBBP was com­ treatment efficacy in this patient subgroup has not been reported separ­
pared to BiVP.134 After a mean follow-up of 33 ± 16 months, time to ately.69 No randomized trial has yet assessed the benefit of CSP-CRT
death or HFH was superior in the LBBP group (HR 1.5, 95% CI 1.2– compared with BiV-CRT in this population, and further studies are
1.8, P < 0.001) with significantly reduced HFH and a trend in improved needed to establish its advantages. Observational data on LBBAP com­
survival. At follow-up, NYHA and LVEF were also significantly superior bined with coronary sinus pacing, known as left bundle branch-optimized
with LBBAP. The results were consistent in patients with LBBB (a sub­ CRT (LOT-CRT), have shown encouraging results in patients with
group which is most likely to respond to BiVP). NIVCD and are discussed later.212,213
The MELOS study, a large observational registry on LBBP outcomes,
reported a lead implantation success rate of 82.2% for HF indications Conduction system pacing in patients with
and an overall complication rate of 11.7%, including both acute and
late complications.9 This rate is comparable to previously reported left ventricular ejection fraction 36–50%
data for BiVP implantations. Specifically, 8.3% of the complications Indications for BiV-CRT in patients with an LVEF ≤35% are well estab­
were related to the LBBP lead, including 3.7% of acute LV perforations, lished. However, the criteria for patients with HF with an LVEF of 36
which were managed by lead repositioning and were not associated −50% are less clear. In a substudy of the multicentre PROSPECT study,
with adverse clinical consequences. patients with NYHA functional Class III−IV status and a QRS duration
There are currently three published modest size randomized con­ >130 ms who had an LVEF >35% and underwent BiV-CRT, experi­
trolled trials with limited follow-up duration comparing LBBAP and enced significant clinical benefits, as well as structural improvements
BiV-CRT. The LEVEL-AT study included 70 patients with HF with compared with baseline.214 A recent randomized crossover trial in
LVEF < 35%, LBBB >130 ms, or non-LBBB >150 ms.123 Patients 76 patients with LVEF 35–50% and LBBB showed significant improve­
were randomized 1:1 to CSP (4 HBP, 31 LBBAP) or to BiVP. ment in LVEF and ventricular remodelling after 6 months of CRT.215
Conduction system pacing was non-inferior in terms of reduction of There is also scant evidence of CSP efficacy in HF patients with LVEF
LV activation time (LVAT) measured by ECG imaging (the primary end­ > 35%, who do not have an indication for pacing. Most studies on CSP
point), HFH or mortality (combined endpoint), LV remodelling (LV in patients with HF and mildly reduced ejection fraction (HFmrEF) also
end-systolic volume), improvement in NYHA, and QRS shortening. included a mix of patients with AV block or PICM. A meta-analysis216
The LBBP-RESYNC trial included 40 patients in sinus rhythm with non- and some additional series217–219 reported together <300 HFmrEF pa­
ischaemic cardiomyopathy and LBBB (i.e. at high likelihood of respond­ tients without a pacing indication, the largest of these being I-CLAS219
ing to BiV-CRT), randomized to either LBBP or BiVP.209 At 6-month which included 168 such patients. Although the results were not re­
follow-up, LBBP was associated with a significantly greater improve­ ported separately for this specific subgroup of patients with HFmrEF
ment in LVEF compared with BiVP (mean difference: 5.6%; 95% CI: and LBBB, 260 patients with CSP had significantly lower composite
ESC/EHRA clinical consensus statement 17

outcome of death or HFH compared with 75 patients who had re­ upgrading to LBBAP is both feasible and effective, with significant clinical
ceived BiVP (HR 0.49, P = 0.006). However, randomized, large pro­ improvements being observed.220 This makes LBBAP a potential pacing
spective studies are needed to evaluate the effects of CSP-CRT on strategy, albeit with limited evidence at this point, for patients who do
patients with HF and an LVEF >35%. not respond to traditional BiV-CRT and remain with wide QRS despite
it. Randomized studies are needed to assess the efficacy and safety of
this strategy in CRT non-responder patients.
Conduction system pacing cardiac
resynchronization therapy in
non-responders to biventricular cardiac Clinical implications
resynchronization therapy Conduction system pacing cardiac resynchronization therapy , particu­
A substantial number of patients do not respond to CRT (in terms of larly with LBBP, has increasingly gained support as an alternative to con­
symptoms and/or ventricular remodelling). Among the different causes, ventional BiV-CRT due to encouraging initial results (even compared
a suboptimal resynchronization with BiVP can be responsible for non- with patients with the highest likelihood of responding favourably to

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response, especially in patients with remaining QRS prolongation des­ BiV-CRT), simpler (and more economical) pacing systems, and enthu­
pite BiVP. To optimize the quality of cardiac resynchronization, CSP has siasm generated by new pacing techniques. However, the lack of data
emerged as a potential solution. A multicentre international observa­ from large randomized studies refrains routine adoption of this ap­
tional study tested the hypothesis of whether LBBAP could be a viable proach over BiV-CRT in daily clinical practice. While awaiting results
alternative in 44 BiV-CRT non-responders with a mean QRS duration from ongoing large randomized controlled trials assessing the role of
of 150 ± 22 ms with BiVP, at a median of 5.1 years after the original im­ CSP in patients with HF (see section below), CSP-CRT may be used
plant. This strategy was associated with a significant shortening of QRS as an alternative to BiV-CRT in selected patients. This is particularly ap­
duration, improvements in NYHA functional class, and improved echo­ plicable as rescue therapy when effective CRT cannot be achieved due
cardiographic parameters (LVEF and LV end-systolic and end-diastolic to the inability to place a coronary sinus lead in a suitable, stable loca­
volumes). However, death or hospitalization due to HF occurred in tion, or in non-responders to BiV-CRT.139 Another option is combining
30% of patients at 1-year follow-up.139 CSP and coronary sinus-based CRT, which is covered below.
Another non-randomized, prospective, multicentre, case–control A summary of indication for CSP-CRT, as opposed to BiV-CRT, is
study evaluated the feasibility, clinical efficacy, and outcomes of upgrad­ shown in Figure 8 (for PICM and HOT/LOT-CRT, see later correspond­
ing to LBBAP in 48 BiV-CRT non-responders. The results indicated that ing sections).

CRT indication

LBBB Non-LBBB PICM* Non-response to BiV-CRT

LVEF LVEF LVEF LVEF

≤35% 36–50% ≤35% 36–50%

BiVP BiVP
BiVP CSP or CSP BiVP CSP or CSP BiVP CSP CSP

Wide/non-physiological paced QRS with BiVP or CSP

HOT/LOT-CRT

Failed coronary sinus lead implantation *Various definitions exist for PICM
Most evidence is for BiVP with LVEF ≤ 35%

CSP Advice TO DO May be appropriate TO DO

Advice NOT DO DO Areas of uncertainty

Figure 8 Indication for CSP-CRT. BiV-CRT, biventricular pacing cardiac resynchronization therapy; BiVP, biventricular pacing; CSP, conduction sys­
tem pacing; HOT/LOT-CRT, His-optimized or left bundle-optimized cardiac resynchronization therapy; LBBB, left bundle branch block; LVEF, left ven­
tricular ejection fraction; PICM, pacing-induced cardiomyopathy.
18 M. Glikson et al.

wall in patients with HF may result not only from a discrete lesion in the
left bundle branch that can be bypassed/corrected by CSP, but also
from widespread delay, distal focal lesion(s) in the conduction system,
Advice: CSP-CRT Strength of evidence
.................................................................. electrical uncoupling, myocardial scar, and functional conduction block.
Advice TO DO
In patients with wider QRS, non-typical LBBB and more advanced HF,
both mechanisms (focal proximal lesion and distal delay) often coexist.
In candidates for BiVP in whom coronary Analysis of V6RWPT—an electrocardiographic marker of LV lateral
sinus lead implantation is unsuccessful, wall activation time, indicates that such conduction delay cannot be cor­
CSP is advised as rescue therapy.139,201 rected by CSP alone.223 In patients with narrow QRS complexes or iso­
May be appropriate TO DO lated RBBB, the V6RWPT during LBBP closely follows the intrinsic
native activation times and remains within the norm for the V6 intrinsic
For patients with LVEF ≤ 35%, LBBB with
deflection time (i.e. 50–60 ms). This value plus the left bundle branch
QRS ≥130 ms, and Class II–IV HF latency of 20–30 ms yields physiologically paced V6RWPT values of
symptoms despite GDMT, CSP may be 70–90 ms. However, in patients with wide baseline QRS complexes

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appropriate as an alternative to BiVP to due to LBBB or NIVCD, V6RWPT values during confirmed left bundle
improve LVEF, exercise capacity, and branch capture are often non-physiological (>90 ms), suggesting that
symptoms and to reduce despite proximal LBB capture, additional LV conduction delay remained
HFH9,68,123,134,209,210 and coronary sinus pacing may be required to correct this.223
Furthermore, in a significant percentage of patients in whom LBBP is
In non-responders to BiV-CRT, it may be
attempted, only LVSP is achieved,9 resulting in a potentially important
appropriate to implant CSP to improve additional delay in LV lateral wall activation.
HF symptoms and LVEF139,220 On the contrary, conventional BiV-CRT is also limited in its ability to
>90% agree
fully restore physiological LV activation. This is due to several factors:
potentially desynchronizing effects of myocardial pacing with the RV
In the presence of specific patient
lead, localized non-physiological epicardial LV pacing, latency, and sub­
populations where a simpler device is optimal LV lead position (paraseptal/apical) due to unfavourable cardiac
desired (e.g. frail patients, patients with venous anatomy and/or LV scar. Failure of BiV-CRT to restore physio­
limited life expectancy, or those logic activation may manifest as QRS prolongation rather than narrow­
requiring a smaller device), it may be ing. This is observed in one-third of BiV-CRT patients and is associated
appropriate to choose CSP instead of
>90% agree with a poor prognosis compared with patients with narrowing of QRS
BiVP as a primary strategy, taking into
after BiV-CRT.224
The combination of CSP and coronary sinus pacing/RVP (Figure 9) may
account operator experience
address some of the limitations of both techniques, providing more
Areas of uncertainty physiological LV activation and thus a narrower QRS and a more efficient
For patients with a CRT indication and form of CRT. Although more data from long-term RCTs are needed, this
non-LBBB, the clinical impact of CSP is approach may be pursued in difficult cases with suboptimal electrocar­
uncertain66,67,208 diographic results of CSP or coronary sinus pacing-based CRT at im­
plantation. Furthermore, His-optimized and left bundle branch
>90% agree
pacing-optimized cardiac resynchronization therapy (HOT/LOT-CRT)
is an option in patients who do not respond clinically to BiV-CRT or
For patients with HF and LVEF >35% to CSP-CRT and in whom the paced QRS is considered suboptimal.
without an indication for ventricular
pacing, the clinical impact of CSP is
Published data and practical
uncertain
>90% agree considerations
His-optimized and left bundle branch pacing-optimized cardiac resyn­
chronization therapy has been evaluated in a number of observational
studies.99,212,213,221,222,226,227 These studies were primarily multicentre
and prospective, with sample sizes ranging from 19 to 112, included pa­
His-optimized and left bundle tients with a mean LVEF <30% and compared HOT/LOT-CRT with
branch pacing-optimized cardiac BiVP, LBBAP, or HBP. The principal outcomes and conclusions of these
studies are presented in more detail in Supplementary material online,
resynchronization therapy Table S6. All studies showed superior electrical resynchronization (QRS
narrowing or LVAT reduction) and some also superior echocardio­
Delineation and rationale graphic or haemodynamic outcomes when LOT-CRT was compared
Two hybrid pacing modalities combining CSP and coronary sinus pacing to BiVP and/or CSP alone. The absence of studies examining mortality
were recently introduced: His bundle-optimized CRT (HOT-CRT)221 with long-term follow-up and randomized trials represents a significant
and left bundle branch-optimized CRT (LOT-CRT).222 In the setting limitation to the current understanding of the benefits and risks of hy­
of sHBP without correction of RBBB, RVP may be used to correct brid pacing approach for CRT. A further significant practical limitation is
RV electrical dyssynchrony and potentially also qualify as the lack of uniform criteria for the addition of a coronary sinus lead to a
HOT-CRT.99 The rationale for adding a coronary sinus lead to a CSP CSP-based CRT system and the increased complexity of the proced­
lead (or vice versa, depending on the initial CRT strategy) stems from ure. The prevailing expert opinion is that there is no necessity to add
the limitations of CSP-CRT, and BiV-CRT and the not infrequently ob­ a coronary sinus lead to a CSP-based CRT system if the obtained paced
served suboptimal electrical, echocardiographic, and clinical outcomes QRS already indicates a physiological, i.e. fast and synchronous LV acti­
with each of these CRT modalities. Delayed activation of the LV lateral vation. If the paced QRS is not deemed satisfactory (based on criteria
ESC/EHRA clinical consensus statement 19

BiV-CRT LOT-CRT LOT-CRT

(RVP + CS) (LBBAP + BiVP) (LBBAP + CS)

HOT-CRT HOT-CRT HOT-CRT

(HBP + BiVP) (HBP + RVP in RBBB) (HBP + CS)

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Figure 9 Schematic illustration of ventricular activation wavefronts BiV-CRT, HOT-CRT, and LOT-CRT. Approximate activation by the right ven­
tricular lead is indicated in blue, by the conduction system pacing lead in green, and by the coronary sinus lead in red. Adapted with permission from
Zweerink et al.225 BiV-CRT, biventricular pacing cardiac resynchronization therapy; BiVP, biventricular pacing; CS, coronary sinus pacing; HBP, His bun­
dle pacing; HOT-CRT, His bundle pacing-optimized cardiac resynchronization therapy; LOT-CRT, left bundle branch-optimized cardiac resynchroniza­
tion therapy; RBBB, right bundle branch block; RVP, right ventricular pacing.

The selection of LOT-CRT over HOT-CRT or vice versa is currently

Table 4 Criteria used to determine whether HOT/LOT-CRT based on the operator’s preference, experience, and ability to imple­
may be required after having implanted a CSP lead ment HBP and LBBP, as well as on case-dependent anatomical and
physiological factors that influence the feasibility of HBP and LBBAP.
Paced QRS width It is important to note, however, that LOT-CRT usually offers superior
Presence of conduction system capture pacing parameters and normal sensing without compromising arrhyth­
V6 or aVL RWPT mia detection in cardiac resynchronization therapy defibrillator
(CRT-D) systems, while HOT-CRT may provide superior QRS nar­
V6V1 interpeak interval
rowing due to the direct recruitment of the right bundle branch in
Paced QRS notching the setting of LBBB.
QRS axis (normal vs. axis deviation) Patients with permanent AF cannot benefit from algorithms which
Anatomical position of LBBAP lead (basal, mid, or apical) adjust AV delays to promote fusion between intrinsic conduction and
ventricular pacing, used in BiV-CRT.228 In these patients, HOT-CRT
Absence or minimal acute haemodynamic response to pacing
with HBP (usually using the off-label configuration of connecting the
lead to the unused atrial channel of the generator) combined with cor­
LBBAP, left bundle branch area pacing; RWPT, R-wave peak time.
onary sinus and/or RV pacing may be used to deliver controlled and
constant fusion pacing by adjusting AV delay, even in patients in
whom bundle branch block remains uncorrected by HBP.99,225
Although there are no dedicated randomized studies on HOT/
outlined in Table 4), there may be benefit from the HOT/LOT-CRT ap­ LOT-CRT, it is pertinent to note that, unlike CSP-CRT, these pacing
proach (Figure 10). modalities do not deviate too much from conventional BiV-CRT as
A recent randomized study investigating CSP-based vs. BiVP-based they also include a coronary sinus lead (which is considered the dom­
CRT strategies used that criterion and determined that LOT-CRT inant factor in conventional resynchronization) and a septal pacing
was necessary for 10% of CRT candidates in the CSP-CRT arm.124 lead (due to non-selective septal capture during HBP or LBBAP). In con­
The multicentre CSPOT study, which specifically addresses this ques­ trast to CSP-CRT, the HOT/LOT-CRT approach does not replace key
tion, found that the haemodynamic benefit of LOT-CRT over LBBAP BiV-CRT components, but builds on them. Therefore, it is anticipated
was present when there was distal conduction disease, as indicated that favourable major endpoint results from CRT trials will be main­
by a longer QRS duration (>171 ms, which was the mean value for tained with HOT/LOT-CRT. Nevertheless, operator experience and
the group) or when the obtained QRS was suboptimal (lacking a ter­ patient risk need to be carefully taken into account, particularly when
minal r wave in lead V1). When both these conditions were met, the evaluating upgrade procedures. Randomized clinical trials are still
benefit of LOT-CRT was most pronounced, with a 14.5% greater im­ needed to determine the safety of a more complex procedure and
provement in LV dP/dtmax and a 20.8 ms shorter QRS duration than whether the superior electrical resynchronization translates into hard
during LBBAP.213 outcomes such as mortality and hospitalization for HF.
20 M. Glikson et al.

Baseline BiVP LBBP LOT-CRT

25
V1

V2

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V3

V4

V5

V6

Figure 10 Superior electrical resynchronization with LOT-CRT compared with BiVP. Note the presence of QRS notching with BiVP and LBBP,
which disappears with LOT-CRT. BiVP, biventricular pacing; LBBP, left bundle branch pacing; LOT-CRT, left bundle branch-optimized cardiac resyn­
chronization therapy.

Upgrade to conduction system

Advice: HOT/LOT-CRT Strength of
pacing
evidence Device upgrade can be considered in patients with a cardiac implantable
.................................................................. electronic device (CIED) in whom worsening of ventricular function oc­
May be appropriate TO DO curs, either due to disease progression or secondary to PICM, defined
It may be appropriate to propose HOT/LOT-CRT at as a decline in LVEF (with variable cut-offs in different studies, usually to
implantation in case of suboptimal <40–50% or decline by ≥10% from baseline229) secondary to chronic
electrocardiographic results of CSP or BiVP, taking ventricular pacing. Upgrade to BiVP in these patients has been shown to
into account operator experience and patient risk. improve LVEF in randomized controlled trials.230–232 A meta-analysis of
six RCTs (including 161 patients, baseline LVEF 35 ± 10%) and 47 ob­
It may be appropriate to propose HOT/LOT-CRT as
servational studies (including 2644 patients, baseline LVEF 26 ± 8%)
an upgrade procedure in selected CRT candidates
showed improvement in LVEF, NYHA class, QoL, and brain natriuretic
in case of suboptimal clinical and peptide (BNP) levels.230 The more recent BUDAPEST CRT trial rando­
electrocardiographic result with CSP-CRT or mized 360 pacemaker patients with LVEF ≤35% (mean 25%) who had
BiV-CRT, especially in the setting of non-specific >20% RVP with paced QRS >150 ms to an upgrade with either an im­
intra-ventricular conduction delay or mixed plantable cardioverter–defibrillator (ICD) or CRT-D. The primary out­
conduction disease,a,99,212,213,221,222,226,227 taking come was the composite of all-cause mortality, HFH, or <15%
into account operator experience and patient risk. reduction of LV end-systolic volume assessed at 12 months, with a
odds ratio of 0.11 (95% CI 0.06–0.19) in the CRT-D arm.232
a
Mixed conduction disease refers to association of bundle branch/fascicular conduction Conduction system pacing has been shown to achieve greater im­
delay with peripheral conduction disease and/or intra-myocardial propagation delay, provement in LVEF and reduction in QRS duration in small short-term
which cannot be corrected by CSP alone. RCTs68,122,177,209 and has been associated with improved clinical out­
comes in observational studies, compared with BiVP.132,134
ESC/EHRA clinical consensus statement 21

Conduction system pacing therefore might be expected to be a suitable Currently, most transvenous defibrillators use the DF-4 standard, in
alternative to BiVP in patients requiring device upgrade for PICM. which both the high- and low-voltage (i.e. pacing) connections are in a
Several small observational studies have already shown this with a sig­ single pin, thus reducing the need for bulky device headers and facilitat­
nificant LVEF increase in patients undergoing CSP, as well as reductions ing connection during implant. Although this advantage has led to wide­
in LV end-systolic volume, improvement in functional capacity, and QRS spread adoption of this type of connection, patients in whom device
duration, with similar improvements observed with both HBP and downgrade is required (i.e. from a defibrillator to a pacemaker) will re­
LBBAP.129,230,233–239 These observational studies show scope for im­ quire either the utilization of a DF-4 ICD with deactivation of the high
provement in those patients with mild–moderate LV impairment as energy capabilities or insertion of an additional IS-1 lead to facilitate the
well as those with severe LV dysfunction (see Supplementary use of a standard pacemaker.241 Moreover, patients who have a defib­
material online, Table S7). In a meta-analysis of eight observational stud­ rillator implanted may, during their lifetime, require upgrading to a de­
ies including 217 patients (mean baseline LVEF 38.4%± 8.8), LVEF, vice capable of CRT. In this scenario, the use of a DF-1 device may
NYHA, and QoL were significantly improved by upgrade to CSP.230 facilitate LBBAP and even avoid having to change the generator if the
Predictors of PICM or HF development after RVP include a lower residual longevity is considered to be adequate (see Supplementary
baseline LVEF, a larger LV end-diastolic diameter, a longer paced material online, Figure S2 and Table S8). When using a DF-1 device,

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QRS duration, and a higher RVP percentage.233 Importantly, although the CSP lead (usually LBBAP, as HBP provides suboptimal sensing para­
upgrading to CSP may improve echocardiographic parameters in pa­ meters) is connected to the IS-1 port in the defibrillator block, and the
tients with PICM, the mechanism of improvement is unclear and the IS-1 connector pin from the DF-1 lead is capped and abandoned. Thus,
mechanistic contribution of factors including change in activation pat­ CRT can be achieved with a less expensive device and without the need
tern (broad QRS to narrower QRS) and reverse remodelling is un­ for a new generator.242 As sensing parameters are favourable in the left
known. That said, in observational studies with up to 12-month bundle branch area, it is anticipated that arrhythmia detection using a
follow-up, the improvements in LVEF and LV end-diastolic dimension LBBAP lead will be similar to that of a lead located in the RV apex. A
do not appear to return to the levels seen in individual patients prior small study showed no significant differences in the detection duration
to RVP.128,129,234 Thus, identifying patients at a higher risk of developing of an induced ventricular fibrillation episode between left bundle
PICM prior to initial device implant may be important when selecting branch area and RV lead locations.243 Alternative approaches here in­
between RVP and CSP, as CSP has been seen to be associated with a clude utilization of a new generator with a DF-4 connector and IS-1
lower risk of adverse outcomes associated with PICM and subsequent connector for the upgraded lead. This has the advantage of no aban­
HF-related hospitalization.26,107 doned lead component.
Device upgrade to BiV-CRT may be considered in patients with A concept that is emerging is the use of ICD leads for delivering
PICM and LVEF ≤35% according to the 2021 ESC guidelines on cardiac CSP.244,245 However, the long-term safety and efficacy of this approach
pacing and resynchronization therapy, acknowledging the possibility of needs to be evaluated.
increased risk of procedure-related complications,1 including infection,
pneumo/hemothorax, and lead-related complications. Although the
benefits of upgrading may exceed the risks, interventions aimed at re­
ducing these risks must be undertaken.240
Clinicians need to have an appropriate care pathway in place to en­
Advice: upgrade to CSP Strength of evidence
able the screening of CIED patients to identify patients who might ..................................................................
benefit from a device upgrade. Pacing burden and patient symptom as­
Advice TO DO
sessment are likely to form the cornerstone of this evaluation and be
complemented by measurement of BNP levels and echocardiographic It is advised that patients should be
assessment where indicated. Assessment should be performed in ad­ assessed regularly and particularly prior
vance of all planned generator replacements and considered at any to elective generator replacement for
point in a patient’s follow-up if symptoms change or pacing percent­ need for device upgrade. Considerations
age increases. Suitability criteria and threshold for an upgrade might include: pacing percentage, symptoms,
>90% agree
be different contingent on the patient frailty, as well as whether a pa­
LVEF, BNP, risk of infection, and patient
tient is at the elective replacement indicator vs. other earlier time
frailty230,231
points. A multidisciplinary team opinion should be sought for border­
line cases. May be appropriate TO DO
Current ESC guidelines for upgrade to BiV-CRT suggest waiting In patients with PICM, it may be
until LV dysfunction has become severe (≤ 35%) as evidence is appropriate to upgrade to CSP to
strongest in this patient population. However, for de novo device improve HF symptoms and
implantation, the ESC guidelines recommend CRT for patients
LVEF129,230,233–239 particularly in
with AV block and EF < 40% or even milder LV dysfunction after
AVNA.1 The 2023 HRS/APHRS/LAHRS guidelines on physiological patients with an intact His–Purkinje
pacing recommend the use of CSP approaches for patients with systema (where CSP is likely to deliver
even mild LV dysfunction (LVEF < 50%).12 Therefore, the indication synchronous activation).129,230,233–239
of device upgrade requires further attention. The PROTECT UP When upgrading to CSP, it may be
clinical trial (NCT06052475) is currently recruiting and aims to as­ appropriate to incorporate all pacing
sess the benefit of device upgrade on QoL in 155 patients with
leads into the pacing system rather than
mild-to-moderate LV impairment only.
abandoning the existing ventricular lead,
Depending on the existing device, several strategies can be used dur­ >90% agree
ing device upgrade, including use of the same device (abandoning the as it enables backup pacing and facilitates
existing ventricular lead), implanting a new generator with an additional MRI-conditionality
port to connect the CSP lead and avoid abandoning the existing ven­
a
tricular lead or performing HOT/LOT-CRT (see Supplementary Patients with narrow QRS or nodal AV block.
material online, Figures S1–S3).
22 M. Glikson et al.

Patient education and shared

decision-making Advice: shared decision-making Strength of evidence
Patients face a broad range of treatment options when in need of pa­ ..................................................................
cing. Not only are they confronted with single, dual- or biventricular de­ Advice TO DO
vices, but there is also transvenous vs. leadless pacing. The emergence It is advised that CSP is part of shared
of CSP in the form of HBP and LBBAP adds even more choices to the decision-making, emphasizing the
decision-making process, making it more complex. novelty of the procedure, lack of large
This document therefore reinforces the importance of patient-centred
RCTs and of long-term follow-up, as
care and shared decision-making between patients and clinicians.1,246 >90% agree
When implanting a pacemaker or CRT, the patient’s preferences, values, well as the existing alternatives
and goals of care must be considered and carefully balanced with the best
available evidence and the individual risks and benefits.

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It is the healthcare provider’s responsibility to encourage shared
decision-making. As part of such a process, all treatment options,
their risks, and benefits must be explained in a way the patient and
Future perspectives
their caregivers can understand. The physician should explore to­ As CSP continues to gain traction, several ongoing RCTs are underway
gether with the patient which of the alternatives best fits their medical (see Figure 11 and Supplementary material online, Table S9). Several
needs and personal preferences and goals. It is important to recognize small-/mid-sized studies are expected to be completed soon, while lar­
that while shared decision-making should be encouraged, it cannot be ger studies with hard primary endpoints are anticipated to conclude by
imposed; some patients may decide to not engage in the process for the end of the decade. The outcomes of these RCTs have the potential
various reasons which must be respected. If CSP is considered in the to significantly influence the future pacing guidelines directing the
setting of device revision or replacement, it is important to keep in broader implementation of CSP in clinical practice across various pa­
mind that a patient’s personal preferences and expectations may tient groups. Cost-effectiveness analyses of these RCTs will clarify pos­
have changed as compared to when the device was first implanted. sible long-term economic benefits of CSP, potentially influencing
Therefore, they must be assessed again as part of the shared decision- reimbursement models. Additionally, there are trials studying treat­
making process. ment strategies involving CSP such as a pace-and-ablate strategy com­
Whenever new technologies or approaches for treatment are avail­ pared with AF ablation as well as studies evaluating different types of
able, shared decision-making including the communication of evidence leads used for CSP.
becomes even more important because there are not only potential Although CSP is gaining increasing adoption, many aspects of CSP
benefits associated with them but there typically is less evidence and implantation are likely to be improved in the near future. The pacing
there is uncertainty regarding mid- and long-term outcomes and risks. leads currently used for CSP were initially designed for conventional
Hence, as CSP is still lacking evidence from large, randomized trials, it is endocardial pacing sites, and concerns remain regarding their long-
of outmost importance to be transparent about what is known and not term performance.10 In particular with LBBAP, the lead is screwed
yet known about this recent pacing modality. Patients should be able to deeply into the septum, creating novel forms of mechanical stress
not only understand the potential benefits it may offer compared with on these leads. Despite several pacing leads being approved for CSP
more well-established pacing techniques, but also be aware of the lack by regulatory boards, data on the impact of these new use conditions
of evidence that exists regarding aspects such as lead longevity, impact on long-term lead performance are scarce. Early conductor fractures,
on the device’s battery, experiences with lead removal and the possibil­ especially with LBBAP, have been reported in case studies or as single-
ity of yet unknown long-term risks of CSP. Furthermore, they must be centre experiences.247–251 The recent LIFE-LBBAP study,252 a large
aware of risks associated with the implanter’s experience in CSP; many international multicentre registry, showed a lead survival probability
patients are being treated by physicians who are new to this pacing mo­ of 99.7% at mid-term follow-up, with lead fracture rates varying be­
dality and so the operator’s learning curve is another aspect that should tween 0.04 and 0.4%, depending on the lead design. Some of these
not be neglected. early conductor fractures with LBBAP have been attributed to
An important aspect of patient’s education should take place follow­ implant-related conditions, such as kinking of the lead during septal
ing CSP implantation. This is especially relevant in an emergency setting, deployment or excessive angulation within the septum, while others
in particular, when the patient is in a medical centre that is not familiar might result from fatigue due to repeated bending over time.248,251
with new CSP technologies. Such efforts can include supplying the pa­ Identifying these mechanisms can guide future developments in
tient with a card and / or digital records of the new pacing hardware and CSP-specific lead designs. Prototypes of new dedicated CSP lead de­
programming, as well as establishing a central medical entity that can be signs are in the pipeline, and the feasibility of using ICD leads for LBBP
approached by patients, as well medical staff in need for specific instruc­ (HV-LBBAP)244,245,253 and leadless CSP systems are being ex­
tions. Finally, establishing in-person and online medical education ap­ plored.254,255 Until dedicated CSP leads become available, proper
proaches to transfer the knowledge on the new pacing technologies lead handling and awareness of the potential higher risk of lead failure
to a broad spectrum of medical personnel could improve patients’ are advised. Further data on long-term lead performance are needed
care and long-term safety. to implement CSP in future guidelines.
ESC/EHRA clinical consensus statement 23

Atrioventricular block Heart failure

LVEF <40% LVEF 40–49% LVEF >
– 50%
LVEF >
– 50% LVEF 40–49% LVEF <40%
HFrEF HFmrEF HFpEF

ABACUS. CSP+AVNA vs. AF ablation n = 220

CSP-SYNC. CSP vs. BiVP n = 62

PhysioVP-AF. CSP vs. RVP n = 400 NCT06342492. CSP vs. surgical
epicardial LV lead n = 100
PHYSPAVB. CSP vs. RVP n = 200 PROTECT UP. Upgrade to CSP vs. RVP n ~155 HIS-alt_2. CSP vs. BiVP n = 125
HIS alternative II.
PHYS-TAVI I/II. CSP vs. RVP n = 24 CSP vs. BiVP n = 40
and 48 CONSYST-CRT.
PROTECT HF. CSP vs. RVP n = 2600 CSP vs. BiV CRT n = 130
PhysioSync-HF
HIS-PrEF. HBP vs. RVP n = 40 CSP vs. BiVP n = 304
CONSYST-CRT II.
CSP CSP vs. BiV CRT n = 320

LEFT vs. LEFT RCT. CSP vs. BiV CRT n = 2136

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CSP-UPGRADE. CSP vs. BiVP n = 66

CONDUCT-AF. CSP+AVNA vs. BiVP+AVNA n = 82

HIS-CRT. CSP vs. BiVP n = 120

ESCPAND. CSP vs. RVP n = 75
LIT-HF. CSP vs. OMT n = 120 PACE-FIB. CSP+AVNA vs. OMT n = 334

RAFT-Preserved. CSP vs. BiVP vs. OMT n = 370

EARLY-RESYNC. LBBP vs. OMT n = 60

Protect-Sync. LBBAP vs. RVP n = 450

BOSTON PACE. LBBAP vs. RVP

n = 100 LBBP Noninferior CRT. LBBP vs. BiVP n = 160

PLANET. LBBAP vs. RVP n = 30

OptimPacing. LBBAP vs. RVP n = 683 LEFT-BUNDLE-CRT Trial.

LBBAP vs. BiVP n = 176
STAY. LBBAP vs. RVP n = 75

LBBAP LEFT-HF. LBBAP vs. RVP n = 1300 LBBAP-AFHF. LBBAP vs. BiVP n = 60

STYLE-LBBP. LBBAP SDL vs. LLL

n = 120
LBBP in TAVI. LBBP vs. RVP n = 50 RAFT-P&A. CSP+AVNA vs. OMT n = 600
Left Bundle BRAVE. LBBP vs. RVP
n = 46
LeCaRT. LBBAP vs. CRT n = 170
LEAP-CAR. LBBP vs. RVP n = 130

LEAP-Block. LBBAP vs. RVP n = 458

RECOVER-HF. LBBP vs. BiVP n = 60
LEAP-pilot, LEAP. LBBAP vs. RVP n = 470

BATTLE. LOT-CRT vs. BiVP, n = 86

LOT-CRT RESCUE. LOT-CRT vs. LBBAP vs.
BiVP n = 30

Figure 11 Summary of ongoing RCTs on conduction system pacing. The background colours of the study names represent different types of study
endpoints: light grey indicates soft endpoints, dark grey indicates hard endpoints, and medium grey indicates a combination of soft and hard endpoints.
AF, atrial fibrillation; AVNA, atrioventricular node ablation; BiVP, biventricular pacing; CRT, cardiac resynchronization therapy; CSP, conduction system
pacing; HBP, His bundle pacing; HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; HFprEF,
heart failure with preserved ejection fraction; LBBAP, left bundle branch area pacing; LBBP, left bundle branch pacing; LOT-CRT, left bundle
branch-optimized cardiac resynchronization therapy; LV, left ventricle; LVEF, left ventricular ejection fraction; OMT, optimal medical therapy; RVP, right
ventricular pacing.

Implantation will also be facilitated by accessories such as pin connectors and significant arrhythmias through automated alerts. For patients with
which allow continuous pacing during lumenless lead deployment, and de­ CIEDs, remote monitoring is part of standard of care.1,256 More data
livery catheters with a range of shapes to better suit variable anatomies. are needed on the usability of remote monitoring specifically in CSP.
For implanting centres lacking a dedicated electrophysiology record­ Data on the safety of extracting CSP leads are limited, and data on
ing system, affordable laptop/programmer/tablet-based solutions cap­ extraction of CSP leads with long lead dwell times are needed. In the
able of continuously recording multilead ECGs and electrograms recent international TECSPAM study, the success and safety of extract­
(both filtered and unfiltered), delivering pacing and equipped with digital ing HBP and LBBAP leads were high, although the average lead dwell
callipers for precise measuring of time intervals (V6RWPT, V6–V1 inter­ time was only 2 years. Retained distal fragments might pose a risk during
peak intervals, QRS duration, etc.) and current of injury amplitude, the extraction of fractured lead segments, indicating the need for ex­
would greatly facilitate implantation. Ideally, these systems may auto­ pertise with femoral extraction tools in CSP lead extraction.257
matically perform these measurements on a beat-to-beat basis during Additionally, specific extraction tools may be needed in the future to
lead deployment, which would standardize them, streamline the pro­ extract CSP leads with longer dwell times.
cedure, and reduce the need for specialized personnel. Eventually, arti­ There are scant data regarding CSP in populations such as children,
ficial intelligence might help to identify conduction system capture or patients with complex congenital heart disease, or specific conditions
physiological pacing at implantation and follow-up. such as genetic conditions or sarcoidosis. There is a need for more
Dedicated pulse generators designed for CSP are being developed and data collection in these populations in the future.
might further facilitate CSP programming and follow-up. These generators
might include algorithms that offer automated capture management to
ensure conduction system capture, automated fusion of CSP, and intrinsic
right ventricular activation during LBBAP or HOT/LOT-CRT. Remote
Conclusions
monitoring of CIEDs offers several advantages over traditional in-office The field of CSP is rapidly moving forward. We are continuing to gain a
visits, including the early detection of lead failures, device malfunctions, better understanding of its physiological principles and basic
24 M. Glikson et al.

mechanisms (for which there is yet much to learn). Following the cur­ 10. Burri H, Jastrzebski M, Cano O, Curila K, de Pooter J, Huang W et al. EHRA clinical con­
rently available data from observational studies and small short-term sensus statement on conduction system pacing implantation: endorsed by the Asia
Pacific Heart Rhythm Society (APHRS), Canadian Heart Rhythm Society (CHRS), and
RCTs which report encouraging results for this pacing modality, the
Latin American Heart Rhythm Society (LAHRS). Europace 2023;25:1208–36.
foundations to provide solid evidence have been laid for large ongoing 11. Trines SA, Moore P, Burri H, Goncalves Nunes S, Massoullie G, Merino JL et al. 2024
RCTs which will serve to strengthen recommendations in future guide­ updated EHRA core curriculum for physicians and allied professionals. A statement of
lines. In the meantime, our Clinical Consensus Statement aims to pro­ the European heart rhythm association (EHRA) of the ESC. Europace 2024;26:
vide guidance for patient indications in daily clinical practice, bearing in euae243.
mind that knowledge in this field is rapidly evolving. 12. Chung MK, Patton KK, Lau CP, Dal Forno ARJ, Al-Khatib SM, Arora V et al. 2023 HRS/
APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitiga­
tion of heart failure. Heart Rhythm 2023;20:e17–91.
Supplementary material 13. Wiggers CJ. The muscular reactions of the mammalian ventricles to artificial surface
stimuli. Am J Physiol 1925;73:346–78.
Supplementary material is available at Europace online. 14. Vernooy K, Verbeek XA, Peschar M, Prinzen FW. Relation between abnormal ven­
tricular impulse conduction and heart failure. J Interv Cardiol 2003;16:557–62.
15. Sweeney MO, Prinzen FW. A new paradigm for physiologic ventricular pacing. J Am Coll
Funding

Downloaded from https://academic.oup.com/europace/article/27/4/euaf050/8100402 by guest on 01 April 2025

Cardiol 2006;47:282–8.
None declared. 16. Mafi-Rad M, Luermans JG, Blaauw Y, Janssen M, Crijns HJ, Prinzen FW et al. Feasibility
and acute hemodynamic effect of left ventricular septal pacing by transvenous approach
Conflict of interest: A.A. declares speaker’s honoraria from Boston
through the interventricular septum. Circ Arrhythm Electrophysiol 2016;9:e003344.
Scientific and Bayer and speaker honoraria from Medtronic, Abbott,
17. Tops LF, Schalij MJ, Holman ER, van Erven L, van der Wall EE, Bax JJ. Right ventricular
and Biotronik. C.W.I. reports the following—advisory board:
pacing can induce ventricular dyssynchrony in patients with atrial fibrillation after atrio­
Impulse-Dynamics, Medtronic, Zoll, honoraria for presentations, re­
ventricular node ablation. J Am Coll Cardiol 2006;48:1642–8.
imbursement for travel/congress costs: Abbott, Biotronik, Boston
18. Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL et al.
Scientific, Impulse-Dynamics, Medtronic, Microport, and Zoll. D.K. re­ Adverse effect of ventricular pacing on heart failure and atrial fibrillation among pa­
ceives Honoraria and Research Support Medtronic and Abbott. H.B. tients with normal baseline QRS duration in a clinical trial of pacemaker therapy for
reports institutional fellowship and research support, speaker’s bur­ sinus node dysfunction. Circulation 2003;107:2932–7.
eau, and advisory boards from Abbott, Biotronik, Boston Scientific, 19. Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R et al. Ventricular pacing
Medtronic, and Microport. J.C.D. reports speaker and proctoring hon­ or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002;346:1854–62.
oraria for Medtronic, Boston Scientific, and Biotronik. M.G. has parti­ 20. Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H et al.
cipated in Medtronic advisory boards, for which he has received minor Dual-chamber pacing or ventricular backup pacing in patients with an implantable de­
compensation. J.K. declares speaker honoraria and/or consultancy fibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) trial. JAMA
fees from Abbott, Biotronik, Boston Scientific, and Medtronic and ad­ 2002;288:3115–23.
visory board (Medtronic). J.D.P. reports speaker fees and honoraria 21. Kiehl EL, Makki T, Kumar R, Gumber D, Kwon DH, Rickard JW et al. Incidence and
from Medtronic, Boston Scientific, Abbott, and Biotronik. K.C. reports predictors of right ventricular pacing-induced cardiomyopathy in patients with com­
advisory boards with Medtronic and Abbott and shares with VDI plete atrioventricular block and preserved left ventricular systolic function. Heart
Technologies Inc. M.P.-L. has received speaker honoraria from Rhythm 2016;13:2272–8.
Medtronic. Y.M. is a consultant for Edwards Lifesciences (Irvine, 22. Khurshid S, Epstein AE, Verdino RJ, Lin D, Goldberg LR, Marchlinski FE et al. Incidence
California). All remaining authors have declared no conflicts of and predictors of right ventricular pacing-induced cardiomyopathy. Heart Rhythm
interest. 2014;11:1619–25.
23. Zhang XH, Chen H, Siu CW, Yiu KH, Chan WS, Lee KL et al. New-onset heart failure
after permanent right ventricular apical pacing in patients with acquired high-grade
Data availability atrioventricular block and normal left ventricular function. J Cardiovasc Electrophysiol
Data availability does not apply since no patient data are involved. 2008;19:136–41.
24. Kaye GC, Linker NJ, Marwick TH, Pollock L, Graham L, Pouliot E et al. Effect of right
ventricular pacing lead site on left ventricular function in patients with high-grade atrio­
References ventricular block: results of the Protect-Pace study. Eur Heart J 2015;36:856–62.
1. Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM et al. 2021 25. Beer D, Sharma PS, Subzposh FA, Naperkowski A, Pietrasik GM, Durr B et al. Clinical
ESC guidelines on cardiac pacing and cardiac resynchronization therapy. Europace outcomes of selective versus nonselective His bundle pacing. JACC Clin Electrophysiol
2022;24:71–164.
2019;5:766–74.
2. Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS et al.
26. Abdelrahman M, Subzposh FA, Beer D, Durr B, Naperkowski A, Sun H et al. Clinical
On-treatment comparison between corrective His bundle pacing and biventricular pa­
outcomes of His bundle pacing compared to right ventricular pacing. J Am Coll Cardiol
cing for cardiac resynchronization: a secondary analysis of the His-SYNC pilot trial.
2018;71:2319–30.
Heart Rhythm 2019;16:1797–807.
27. Su L, Wang S, Wu S, Xu L, Huang Z, Chen X et al. Long-term safety and feasibility of left
3. Lustgarten DL, Crespo EM, Arkhipova-Jenkins I, Lobel R, Winget J, Koehler J et al.
bundle branch pacing in a large single-center study. Circ Arrhythm Electrophysiol 2021;
His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy pa­
14:e009261.
tients: a crossover design comparison. Heart Rhythm 2015;12:1548–57.
28. Curila K, Jurak P, Halamek J, Prinzen F, Waldauf P, Karch J et al. Ventricular activation
4. Kronborg MB, Mortensen PT, Poulsen SH, Gerdes JC, Jensen HK, Nielsen JC. His or
pattern assessment during right ventricular pacing: ultra-high-frequency ECG study.
para-His pacing preserves left ventricular function in atrioventricular block: a double-
blind, randomized, crossover study. Europace 2014;16:1189–96. J Cardiovasc Electrophysiol 2021;32:1385–94.
5. Occhetta E, Bortnik M, Magnani A, Francalacci G, Piccinino C, Plebani L et al. 29. Jastrzebski M, Kielbasa G, Moskal P, Bednarek A, Rajzer M, Curila K et al. Right bundle
Prevention of ventricular desynchronization by permanent para-Hisian pacing after branch pacing: criteria, characteristics, and outcomes. Heart Rhythm 2023;20:
atrioventricular node ablation in chronic atrial fibrillation: a crossover, blinded, rando­ 492–500.
mized study versus apical right ventricular pacing. J Am Coll Cardiol 2006;47:1938–45. 30. Curila K, Prochazkova R, Jurak P, Jastrzebski M, Halamek J, Moskal P et al. Both selective
6. Kron J, Bernabei M, Kaiser D, Nanda S, Subzposh FA, Zimmerman P et al. Real-world and nonselective His bundle, but not myocardial, pacing preserve ventricular electrical
performance of conduction system pacing compared with traditional pacing. Circ synchrony assessed by ultra-high-frequency ECG. Heart Rhythm 2020;17:607–14.
Arrhythm Electrophysiol 2023;16:411–2. 31. Arnold AD, Shun-Shin MJ, Ali N, Keene D, Howard JP, Chow JJ et al. Left ventricular
7. Keene D, Anselme F, Burri H, Perez OC, Curila K, Derndorfer M et al. Conduction activation time and pattern are preserved with both selective and nonselective His
system pacing, a European survey: insights from clinical practice. Europace 2023;25: bundle pacing. Heart Rhythm O2 2021;2:439–45.
euad019. 32. Zhang J, Guo J, Hou X, Wang Y, Qian Z, Li K et al. Comparison of the effects of se­
8. Kircanski B, Boveda S, Prinzen F, Sorgente A, Anic A, Conte G et al. Conduction system lective and non-selective His bundle pacing on cardiac electrical and mechanical syn­
pacing in everyday clinical practice: EHRA physician survey. Europace 2023;25:682–7. chrony. Europace 2018;20:1010–7.
9. Jastrzebski M, Kielbasa G, Cano O, Curila K, Heckman L, De Pooter J et al. Left bundle 33. Bednarek A, Ionita O, Moskal P, Linkova H, Kielbasa G, Prochazkova R et al.
branch area pacing outcomes: the multicentre European MELOS study. Eur Heart J Nonselective versus selective His bundle pacing: an acute intrapatient speckle-tracking
2022;43:4161–73. strain echocardiographic study. J Cardiovasc Electrophysiol 2021;32:117–25.
ESC/EHRA clinical consensus statement 25

34. Curila K, Poviser L, Stros P, Jurak P, Whinnett Z, Jastrzebski M et al. LVSP and LBBP strategy: systematic review and meta-analysis. Pacing Clin Electrophysiol 2023;46:
result in similar or improved LV synchrony and hemodynamics compared to BVP. 1315–24.
JACC Clin Electrophysiol 2024;10:1722–32. 58. Vazquez PM, Mohamed U, Zanon F, Lustgarten DL, Atwater B, Whinnett ZI et al.
35. Heckman LIB, Luermans J, Curila K, Van Stipdonk AMW, Westra S, Smisek R et al. Result of the physiologic pacing registry, an international multicenter prospective ob­
Comparing ventricular synchrony in left bundle branch and left ventricular septal pa­ servational study of conduction system pacing. Heart Rhythm 2023;20:1617–25.
cing in pacemaker patients. J Clin Med 2021;10:822. 59. Ye Y, Gao B, Lv Y, Xu TT, Zhang SS, Lu XL et al. His bundle pacing versus left bundle
36. Curila K, Jurak P, Jastrzebski M, Prinzen F, Waldauf P, Halamek J et al. Left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a
branch pacing compared to left ventricular septal myocardial pacing increases inter­ prospective crossover comparison. J Geriatr Cardiol 2023;20:51–60.
ventricular dyssynchrony but accelerates left ventricular lateral wall depolarization. 60. Marinaccio L, Vetta F, Ginocchio G, Maria Marchese G, Marchese D.
Heart Rhythm 2021;18:1281–9. Electrocardiographic diagnosis of acute myocardial ischemia during His bundle pacing.
37. Rijks JHJ, Heckman L, Westra S, Cornelussen R, Ghosh S, Curila K et al. Assessment of Anatol J Cardiol 2022;26:328–30.
ventricular electrical heterogeneity in left bundle branch pacing and left ventricular sep­ 61. Curila K, Stros P, Herman D, Vesela J, Prochazkova R, Osmancik P et al.
tal pacing by using various electrophysiological methods. J Cardiovasc Electrophysiol 2024; Electrocardiogram changes due to myocardial infarction in a patient with selective
35:2282–92. His bundle pacing. Kardiol Pol 2019;77:237.
38. Meiburg R, Rijks JHJ, Beela AS, Bressi E, Grieco D, Delhaas T et al. Comparison of novel 62. Deluca F, Marcantoni L, Pastore G, Valenza S, Porcelli G, Zanon F. Acute myocardial
ventricular pacing strategies using an electro-mechanical simulation platform. Europace infarction in a patient with permanent left bundle branch pacing. J Electrocardiol 2024;

Downloaded from https://academic.oup.com/europace/article/27/4/euaf050/8100402 by guest on 01 April 2025

2023;25:euad144. 87:153804.
39. Zhu H, Qin C, Du A, Wang Q, He C, Zou F et al. Comparisons of long-term clinical 63. Zaidi SMJ, Sohail H, Satti DI, Sami A, Anwar M, Malik J et al. Tricuspid regurgitation in
outcomes with left bundle branch pacing, left ventricular septal pacing, and biventricu­ His bundle pacing: a systematic review. Ann Noninvasive Electrocardiol 2022;27:
lar pacing for cardiac resynchronization therapy. Heart Rhythm 2024;21:1342–53. e12986.
40. Diaz JC, Tedrow UB, Duque M, Aristizabal J, Braunstein ED, Marin J et al. Left bundle 64. Hu Q, You H, Chen K, Dai Y, Lu W, Li Y et al. Distance between the lead-implanted
branch pacing vs left ventricular septal pacing vs biventricular pacing for cardiac resyn­ site and tricuspid valve annulus in patients with left bundle branch pacing: effects on
chronization therapy. JACC Clin Electrophysiol 2024;10:295–305. postoperative tricuspid regurgitation deterioration. Heart Rhythm 2023;20:217–23.
41. Liu W, Fulati Z, Tian F, Xu N, Cheng Y, Zhao Y et al. Relationship of different left bun­ 65. Burri H, Jastrzebski M, Vijayaraman P. Electrocardiographic analysis for His bundle pa­
dle branch pacing sites and clinical outcomes in patients with heart failure. Heart cing at implantation and follow-up. JACC Clin Electrophysiol 2020;6:883–900.
Rhythm 2025 (EPUB ahead of print). 66. Sharma PS, Naperkowski A, Bauch TD, Chan JYS, Arnold AD, Whinnett ZI et al.
42. Ali N, Arnold AD, Miyazawa AA, Keene D, Chow JJ, Little I et al. Comparison of meth­ Permanent His bundle pacing for cardiac resynchronization therapy in patients with
ods for delivering cardiac resynchronization therapy: an acute electrical and haemo­ heart failure and right bundle branch block. Circ Arrhythm Electrophysiol 2018;11:
dynamic within-patient comparison of left bundle branch area, His bundle, and e006613.
biventricular pacing. Europace 2023;25:1060–7. 67. Vijayaraman P, Cano O, Ponnusamy SS, Molina-Lerma M, Chan JYS, Padala SK et al.
43. Arnold AD, Shun-Shin MJ, Keene D, Howard JP, Sohaib SMA, Wright IJ et al. His re­ Left bundle branch area pacing in patients with heart failure and right bundle branch
synchronization versus biventricular pacing in patients with heart failure and left bundle block: results from international LBBAP collaborative-study group. Heart Rhythm O2
branch block. J Am Coll Cardiol 2018;72:3112–22. 2022;3:358–67.
44. Salden F, Luermans J, Westra SW, Weijs B, Engels EB, Heckman LIB et al. Short-term 68. Vinther M, Risum N, Svendsen JH, Mogelvang R, Philbert BT. A randomized trial of His
hemodynamic and electrophysiological effects of cardiac resynchronization by left ven­ pacing versus biventricular pacing in symptomatic HF patients with left bundle branch
tricular septal pacing. J Am Coll Cardiol 2020;75:347–59. block (His-alternative). JACC Clin Electrophysiol 2021;7:1422–32.
45. Vijayaraman P, Hughes G, Manganiello M, Johns A, Ghosh S. Non-invasive assessment 69. Vijayaraman P, Ponnusamy S, Cano O, Sharma PS, Naperkowski A, Subsposh FA et al.
of ventricular electrical heterogeneity to optimize left bundle branch area pacing. Left bundle branch area pacing for cardiac resynchronization therapy: results from the
J Interv Card Electrophysiol 2023;66:1103–12. international LBBAP collaborative study group. JACC Clin Electrophysiol 2021;7:135–47.
46. Azzolini G, Bianchi N, Vitali F, Malagù M, Balla C, De Raffele M et al. A comparative 70. Keene D, Arnold AD, Jastrzebski M, Burri H, Zweibel S, Crespo E et al. His bundle pa­
assessment of myocardial work performance during spontaneous rhythm, His bundle cing, learning curve, procedure characteristics, safety, and feasibility: insights from a
pacing, and left bundle branch area pacing: insights from the EMPATHY study. large international observational study. J Cardiovasc Electrophysiol 2019;30:1984–93.
J Cardiovasc Dev Dis 2023;10:444. 71. Teigeler T, Kolominsky J, Vo C, Shepard RK, Kalahasty G, Kron J et al.
47. Vijayaraman P, Rajakumar C, Naperkowski AM, Subzposh FA. Clinical outcomes of left Intermediate-term performance and safety of His-bundle pacing leads: a single-center
bundle branch area pacing compared to His bundle pacing. J Cardiovasc Electrophysiol experience. Heart Rhythm 2021;18:743–9.
2022;33:1234–43. 72. Vijayaraman P, Dandamudi G, Worsnick S, Ellenbogen KA. Acute His-bundle injury
48. Tan ESJ, Soh R, Boey E, Lee JY, de Leon J, Chan SP et al. Comparison of pacing perform­ current during permanent His-bundle pacing predicts excellent pacing outcomes.
ance and clinical outcomes between left bundle branch and His bundle pacing. JACC Clin Pacing Clin Electrophysiol 2015;38:540–6.
Electrophysiol 2023;9:1393–403. 73. Vijayaraman P, Dandamudi G, Zanon F, Sharma PS, Tung R, Huang W et al. Permanent
49. Wu S, Su L, Vijayaraman P, Zheng R, Cai M, Xu L et al. Left bundle branch pacing for His bundle pacing: recommendations from a multicenter His bundle pacing collabora­
cardiac resynchronization therapy: nonrandomized on-treatment comparison with tive working group for standardization of definitions, implant measurements, and
His bundle pacing and biventricular pacing. Can J Cardiol 2021;37:319–28. follow-up. Heart Rhythm 2018;15:460–8.
50. Hua W, Fan X, Li X, Niu H, Gu M, Ning X et al. Comparison of left bundle branch and 74. Vijayaraman P, Naperkowski A, Subzposh FA, Abdelrahman M, Sharma PS, Oren JW
His bundle pacing in bradycardia patients. JACC Clin Electrophysiol 2020;6:1291–9. et al. Permanent His-bundle pacing: long-term lead performance and clinical outcomes.
51. Vijayaraman P, Longacre C, Kron J, Subzposh F, Zimmerman P, Butler K et al. Heart Rhythm 2018;15:696–702.
Conduction system pacing associated with reduced heart failure hospitalizations and 75. Su L, Wu S, Wang S, Wang Z, Xiao F, Shan P et al. Pacing parameters and success rates
all-cause mortality compared with traditional right ventricular pacing in the of permanent His-bundle pacing in patients with narrow QRS: a single-centre experi­
Medicare population. Heart Rhythm 2025;22:735–43. ence. Europace 2019;21:763–70.
52. Cai M, Wu S, Wang S, Zheng R, Jiang L, Lian L et al. Left bundle branch pacing post­ 76. Vijayaraman P, Subzposh FA, Naperkowski A. Atrioventricular node ablation and His
atrioventricular junction ablation for atrial fibrillation: propensity score matching bundle pacing. Europace 2017;19:iv10–6.
with His bundle pacing. Circ Arrhythm Electrophysiol 2022;15:e010926. 77. De Leon J, Seow SC, Boey E, Soh R, Tan E, Gan HH et al. Adopting permanent His
53. Pillai A, Kolominsky J, Koneru JN, Kron J, Shepard RK, Kalahasty G et al. bundle pacing: learning curves and medium-term outcomes. Europace 2022;24:
Atrioventricular junction ablation in patients with conduction system pacing leads: a 606–13.
comparison of His-bundle vs left bundle branch area pacing leads. Heart Rhythm 78. Sritharan A, Kozhuharov N, Masson N, Bakelants E, Valiton V, Burri H. Procedural out­
2022;19:1116–23. come and follow-up of stylet-driven leads compared with lumenless leads for left bun­
54. Yuan Z, Cheng L, Wu Y. Meta-analysis comparing safety and efficacy of left bundle dle branch area pacing. Europace 2023;25:euad295.
branch area pacing versus His bundle pacing. Am J Cardiol 2022;164:64–72. 79. Li X, Zhu H, Fan X, Wang Q, Wang Z, Li H et al. Tricuspid regurgitation outcomes in
55. Zhuo W, Zhong X, Liu H, Yu J, Chen Q, Hu J et al. Pacing characteristics of His bundle left bundle branch area pacing and comparison with right ventricular septal pacing.
pacing vs. Left bundle branch pacing: a systematic review and meta-analysis. Front Heart Rhythm 2022;19:1202–3.
Cardiovasc Med 2022;9:849143. 80. Vijayaraman P, Naperkowski A, Ellenbogen KA, Dandamudi G. Electrophysiologic in­
56. Vijayaraman P, West M, Dresing T, Oren J, Abbey S, Zimmerman P et al. Safety and sights into site of atrioventricular block: lessons from permanent His bundle pacing.
performance of conduction system pacing: real-world experience from a product sur­ JACC Clin Electrophysiol 2015;1:571–81.
veillance registry. Heart Rhythm 2025;22:318–24. 81. Ponnusamy SS, Murugan M, Ganesan V, Vijayaraman P. Predictors of procedural failure
57. Abdin A, Werner C, Burri H, Merino JL, Vukadinovic D, Sawan N et al. Outcomes of of left bundle branch pacing in scarred left ventricle. J Cardiovasc Electrophysiol 2023;34:
left bundle branch area pacing compared to His bundle pacing as a primary pacing 760–4.
26 M. Glikson et al.

82. Bhatt AG, Musat DL, Milstein N, Pimienta J, Flynn L, Sichrovsky T et al. The efficacy of 107. Sharma PS, Patel NR, Ravi V, Zalavadia DV, Dommaraju S, Garg V et al. Clinical out­
His bundle pacing: lessons learned from implementation for the first time at an experi­ comes of left bundle branch area pacing compared to right ventricular pacing: results
enced electrophysiology center. JACC Clin Electrophysiol 2018;4:1397–406. from the Geisinger-Rush conduction system pacing registry. Heart Rhythm 2022;19:
83. Vijayaraman P, Cano O, Koruth JS, Subzposh FA, Nanda S, Pugliese J et al. His-Purkinje 3–11.
conduction system pacing following transcatheter aortic valve replacement: feasibility 108. Tan ESJ, Soh R, Lee J-Y, Boey E, Ho K-H, Aguirre S et al. Clinical outcomes in conduc­
and safety. JACC Clin Electrophysiol 2020;6:649–57. tion system pacing compared to right ventricular pacing in bradycardia. JACC Clin
84. Sharma PS, Subzposh FA, Ellenbogen KA, Vijayaraman P. Permanent His-bundle pacing Electrophysiol 2023;9:992–1001.
in patients with prosthetic cardiac valves. Heart Rhythm 2017;14:59–64. 109. Li X, Zhang J, Qiu C, Wang Z, Li H, Pang K et al. Clinical outcomes in patients with left
85. Bednarek A, Kiełbasa G, Moskal P, Ostrowska A, Bednarski A, Sondej T et al. Left bun­ bundle branch area pacing vs. right ventricular pacing for atrioventricular block. Front
dle branch area pacing improves right ventricular function and synchrony. Heart Cardiovasc Med 2021;8:685253.
Rhythm 2024;21:2234–41. 110. Okubo Y, Sakai T, Miyamoto S, Uotani Y, Oguri N, Furutani M et al. Mid-term clinical
86. Nagarajan VD, Ho SY, Ernst S. Anatomical considerations for His bundle pacing. Circ outcomes of left bundle branch area pacing compared to accurate right ventricular
Arrhythm Electrophysiol 2019;12:e006897. septal pacing. J Interv Card Electrophysiol 2025;68:55–63.
87. Andreas M, Burri H, Praz F, Soliman O, Badano L, Barreiro M et al. Tricuspid valve dis­ 111. Niu HX, Liu X, Gu M, Chen X, Cai C, Cai M et al. Conduction system pacing for post
ease and cardiac implantable electronic devices. Eur Heart J 2024;45:346–65. transcatheter aortic valve replacement patients: comparison with right ventricular pa­
88. Jastrzebski M, Moskal P, Bednarek A, Kielbasa G, Vijayaraman P, Czarnecka D. cing. Front Cardiovasc Med 2021;8:772548.

Downloaded from https://academic.oup.com/europace/article/27/4/euaf050/8100402 by guest on 01 April 2025

Programmed His bundle pacing: a novel maneuver for the diagnosis of His bundle cap­ 112. Dell’Era G, Baroni M, Frontera A, Ghiglieno C, Carbonaro M, Penela D et al. Left bun­
ture. Circ Arrhythm Electrophysiol 2019;12:e007052. dle branch area versus conventional pacing after transcatheter valve implant for aortic
89. Liang Y, Yu H, Wang N, Liang Z, Xu B, Gao Y et al. Cycle length criteria for His-bundle stenosis: the LATVIA study. J Cardiovasc Med (Hagerstown) 2024;25:450–6.
capture are capable of determining pacing types misclassified by output criteria. Heart 113. Okubo Y, Miyamoto S, Uotani Y, Ikeuchi Y, Miyauchi S, Okamura S et al. Clinical impact
Rhythm 2019;16:1629–35. of left bundle branch area pacing in heart failure with preserved ejection fraction and
90. Jastrzebski M, Moskal P, Curila K, Fijorek K, Kukla P, Bednarek A et al. mid-range ejection fraction. Pacing Clin Electrophysiol 2022;45:499–508.
Electrocardiographic characterization of non-selective His-bundle pacing: validation 114. Qu Q, Sun JY, Zhang ZY, Kan JY, Wu LD, Li F et al. His-Purkinje conduction system
of novel diagnostic criteria. Europace 2019;21:1857–64. pacing: a systematic review and network meta-analysis in bradycardia and conduction
91. Curila K, Jurak P, Vernooy K, Jastrzebski M, Waldauf P, Prinzen F et al. Left ventricular disorders. J Cardiovasc Electrophysiol 2021;32:3245–58.
myocardial septal pacing in close proximity to LBB does not prolong the duration of 115. Abdin A, Aktaa S, Vukadinovic D, Arbelo E, Burri H, Glikson M et al. Outcomes of con­
the left ventricular lateral wall depolarization compared to LBB pacing. Front duction system pacing compared to right ventricular pacing as a primary strategy for
Cardiovasc Med 2021;8:787414. treating bradyarrhythmia: systematic review and meta-analysis. Clin Res Cardiol 2022;
92. Ali N, Saqi K, Arnold AD, Miyazawa AA, Keene D, Chow JJ et al. Left bundle branch 111:1198–209.
pacing with and without anodal capture: impact on ventricular activation pattern 116. Liu X, Li W, Wang L, Tian S, Zhou X, Wu M. Safety and efficacy of left bundle branch
and acute haemodynamics. Europace 2023;25:euad264. pacing in comparison with conventional right ventricular pacing: a systematic review
93. Sato T, Togashi I, Ikewaki H, Mohri T, Katsume Y, Tashiro M et al. Diverse QRS morph­ and meta-analysis. Medicine (Baltimore) 2021;100:e26560.
ology reflecting variations in lead placement for left bundle branch area pacing. 117. Herbert J, Kovacsovics A, Brito R, Masson N, Burri H. Mid-term performance of His
Europace 2023;25:euad241. bundle pacing and usefulness of backup leads. Europace 2024;26:euae168.
94. Upadhyay GA. QRS morphologies in V1 and V6 during left bundle branch area pacing: 118. Vijayaraman P, Patel N, Colburn S, Beer D, Naperkowski A, Subzposh FA. His-Purkinje
assessing the patterns. Europace 2023;25:euad284. conduction system pacing in atrioventricular block: new insights into site of conduction
95. Burri H, Kozhuharov N, Jastrzebski M. Proximal and distal right bundle branch pacing: block. JACC Clin Electrophysiol 2022;8:73–85.
insights into conduction system physiology. HeartRhythm Case Rep 2023;9:372–5. 119. Curtis AB, Worley SJ, Adamson PB, Chung ES, Niazi I, Sherfesee L et al. Biventricular pa­
96. Parlavecchio A, Vetta G, Coluccia G, Pistelli L, Caminiti R, Crea P et al. Success and cing for atrioventricular block and systolic dysfunction. N Engl J Med 2013;368:1585–93.
complication rates of conduction system pacing: a meta-analytical observational com­ 120. Kindermann M, Hennen B, Jung J, Geisel J, Bohm M, Frohlig G. Biventricular versus con­
parison of left bundle branch area pacing and His bundle pacing. J Interv Card ventional right ventricular stimulation for patients with standard pacing indication and
Electrophysiol 2024;67:719–29. left ventricular dysfunction: the Homburg biventricular pacing evaluation
97. Albertsen AE, Mortensen PT, Jensen HK, Poulsen SH, Egeblad H, Nielsen JC. Adverse (HOBIPACE). J Am Coll Cardiol 2006;47:1927–37.
effect of right ventricular pacing prevented by biventricular pacing during long-term 121. Filho MM, de Siqueira SF, Costa R, Greco OT, Moreira LF, D’Avila A et al. Conventional
follow-up: a randomized comparison. Eur J Echocardiogr 2011;12:767–72. versus biventricular pacing in heart failure and bradyarrhythmia: the COMBAT study.
98. Yu CM, Chan JY, Zhang Q, Omar R, Yip GW, Hussin A et al. Biventricular pacing in J Card Fail 2010;16:293–300.
patients with bradycardia and normal ejection fraction. N Engl J Med 2009;361: 122. Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS et al.
2123–34. His corrective pacing or biventricular pacing for cardiac resynchronization in heart fail­
99. Zweerink A, Zubarev S, Bakelants E, Potyagaylo D, Stettler C, Chmelevsky M ure. J Am Coll Cardiol 2019;74:157–9.
et al. His-optimized cardiac resynchronization therapy with ventricular fusion pa­ 123. Pujol-Lopez M, Jimenez-Arjona R, Garre P, Guasch E, Borras R, Doltra A et al.
cing for electrical resynchronization in heart failure. JACC Clin Electrophysiol 2021; Conduction system pacing vs biventricular pacing in heart failure and wide QRS pa­
7:881–92. tients: LEVEL-AT trial. JACC Clin Electrophysiol 2022;8:1431–45.
100. Kirkfeldt RE, Johansen JB, Nohr EA, Moller M, Arnsbo P, Nielsen JC. Risk factors for 124. Vijayaraman P, Pokharel P, Subzposh FA, Oren JW, Storm RH, Batul SA et al. His-Purkinje
lead complications in cardiac pacing: a population-based cohort study of 28,860 conduction system pacing optimized trial of cardiac resynchronization therapy vs biven­
Danish patients. Heart Rhythm 2011;8:1622–8. tricular pacing: HOT-CRT clinical trial. JACC Clin Electrophysiol 2023;9:2628–38.
101. Mei DA, Imberti JF, Vitolo M, Bonini N, Serafini K, Mantovani M et al. Systematic review 125. Ajijola OA, Upadhyay GA, Macias C, Shivkumar K, Tung R. Permanent His-bundle pa­
and meta-analysis on the impact on outcomes of device algorithms for minimizing right cing for cardiac resynchronization therapy: initial feasibility study in lieu of left ventricu­
ventricular pacing. Europace 2024;26:euae212. lar lead. Heart Rhythm 2017;14:1353–61.
102. Mizner J, Waldauf P, Grieco D, Linkova H, Ionita O, Vijayaraman P et al. A randomized 126. Sharma PS, Dandamudi G, Herweg B, Wilson D, Singh R, Naperkowski A et al.
comparison of HBP versus RVP: effect on left ventricular function and biomarkers of Permanent His-bundle pacing as an alternative to biventricular pacing for cardiac re­
collagen metabolism. Kardiol Pol 2023;81:472–81. synchronization therapy: a multicenter experience. Heart Rhythm 2018;15:413–20.
103. Wang J, Liang Y, Wang W, Chen X, Bai J, Chen H et al. Left bundle branch area pacing is 127. Li Y, Yan L, Dai Y, Zhou Y, Sun Q, Chen R et al. Feasibility and efficacy of left bundle
superior to right ventricular septum pacing concerning depolarization-repolarization branch area pacing in patients indicated for cardiac resynchronization therapy.
reserve. J Cardiovasc Electrophysiol 2020;31:313–22. Europace 2020;22:ii54–60.
104. Zhang J, Wang Z, Cheng L, Zu L, Liang Z, Hang F et al. Immediate clinical outcomes of 128. Qian Z, Wang Y, Hou X, Qiu Y, Wu H, Zhou W et al. Efficacy of upgrading to left bun­
left bundle branch area pacing vs conventional right ventricular pacing. Clin Cardiol dle branch pacing in patients with heart failure after right ventricular pacing. Pacing Clin
2019;42:768–73. Electrophysiol 2021;44:472–80.
105. Yao L, Qi Y, Xiao S, Liu R, Wo J. Effect of left bundle branch pacing on left ventricular 129. Rademakers LM, Bouwmeester S, Mast TP, Dekker L, Houthuizen P, Bracke FA.
systolic function and synchronization in patients with third-degree atrioventricular Feasibility, safety and outcomes of upgrading to left bundle branch pacing in patients
block, assessment by 3- dimensional speckle tracking echocardiography. with right ventricular pacing induced cardiomyopathy. Pacing Clin Electrophysiol 2022;
J Electrocardiol 2022;72:61–5. 45:726–32.
106. Gonzalez-Matos CE, Rodriguez-Queralto O, Zaraket F, Jimenez J, Casteigt B, Valles E. 130. Pujol-Lopez M, Jimenez Arjona R, Guasch E, Borras R, Doltra A, Vazquez-Calvo S et al.
Conduction system stimulation to avoid left ventricle dysfunction. Circ Arrhythm Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunc­
Electrophysiol 2024;17:e012473. tion and AV block. Pacing Clin Electrophysiol 2022;45:1115–23.
ESC/EHRA clinical consensus statement 27

131. Vijayaraman P, Zalavadia D, Haseeb A, Dye C, Madan N, Skeete JR et al. Clinical out­ 155. Buys EM, van Hemel NM, Kelder JC, Ascoop CA, van Dessel PF, Bakema L et al.
comes of conduction system pacing compared to biventricular pacing in patients re­ Exercise capacity after His bundle ablation and rate response ventricular pacing for
quiring cardiac resynchronization therapy. Heart Rhythm 2022;19:1263–71. drug refractory chronic atrial fibrillation. Heart 1997;77:238–41.
132. Diaz JC, Sauer WH, Duque M, Koplan BA, Braunstein ED, Marin JE et al. Left bundle 156. Twidale N, McDonald T, Nave K, Seal A. Comparison of the effects of AV nodal ab­
branch area pacing versus biventricular pacing as initial strategy for cardiac resynchro­ lation versus AV nodal modification in patients with congestive heart failure and un­
nization. JACC Clin Electrophysiol 2023;9:1568–81. controlled atrial fibrillation. Pacing Clin Electrophysiol 1998;21:641–51.
133. Ezzeddine FM, Pistiolis SM, Pujol-Lopez M, Lavelle M, Wan EY, Patton KK et al. 157. Lee SH, Chen SA, Tai CT, Chiang CE, Wen ZC, Cheng JJ et al. Comparisons of quality
Outcomes of conduction system pacing for cardiac resynchronization therapy in pa­ of life and cardiac performance after complete atrioventricular junction ablation and
tients with heart failure: a multicenter experience. Heart Rhythm 2023;20:863–71. atrioventricular junction modification in patients with medically refractory atrial fibril­
134. Vijayaraman P, Sharma PS, Cano O, Ponnusamy SS, Herweg B, Zanon F et al. lation. J Am Coll Cardiol 1998;31:637–44.
Comparison of left bundle branch area pacing and biventricular pacing in candidates 158. Kay GN, Ellenbogen KA, Giudici M, Redfield MM, Jenkins LS, Mianulli M et al. The ablate
for resynchronization therapy. J Am Coll Cardiol 2023;82:228–41. and pace trial: a prospective study of catheter ablation of the AV conduction system
135. Liang Y, Xiao Z, Liu X, Wang J, Yu Z, Gong X et al. Left bundle branch area pacing ver­ and permanent pacemaker implantation for treatment of atrial fibrillation. APT inves­
sus biventricular pacing for cardiac resynchronization therapy on morbidity and mor­ tigators. J Interv Card Electrophysiol 1998;2:121–35.
tality. Cardiovasc Drugs Ther 2024;38:471–81. 159. Marshall HJ, Harris ZI, Griffith MJ, Gammage MD. Prospective, randomized study of
136. Graterol FR, Pujol-Lopez M, Borras R, Ayala B, Uribe L, Guasch E et al. Predictors of atrioventricular node ablation and mode-switching, dual chamber pacemaker implant­

Downloaded from https://academic.oup.com/europace/article/27/4/euaf050/8100402 by guest on 01 April 2025

failed left bundle branch pacing implant in heart failure with reduced ejection fraction: ation using two different algorithms in patients with paroxysmal atrial fibrillation.
importance of left ventricular diameter and QRS morphology. Heart Rhythm 2024;21: Europace 1999;1:20–1.
2571–8. 160. Weerasooriya R, Davis M, Powell A, Szili-Torok T, Shah C, Whalley D et al. The
137. Glikson M, Jastrzebski M, Gold MR, Ellenbogen K, Burri H. Conventional biventricular Australian intervention randomized control of rate in atrial fibrillation trial
pacing is still preferred to conduction system pacing for atrioventricular block in pa­ (AIRCRAFT). J Am Coll Cardiol 2003;41:1697–702.
tients with reduced ejection fraction and narrow QRS. Europace 2023;26:euad337. 161. Leon AR, Greenberg JM, Kanuru N, Baker CM, Mera FV, Smith AL et al. Cardiac resyn­
138. Pujol-Lopez M, Jimenez-Arjona R, Garcia-Ribas C, Borras R, Guasch E, Regany-Closa chronization in patients with congestive heart failure and chronic atrial fibrillation: ef­
M et al. Longitudinal comparison of dyssynchrony correction and ‘strain’ improvement fect of upgrading to biventricular pacing after chronic right ventricular pacing. J Am Coll
by conduction system pacing: LEVEL-AT trial secondary findings. Eur Heart J Cardiovasc Cardiol 2002;39:1258–63.
Imaging 2024;25:1394–404. 162. Linde C, Leclercq C, Rex S, Garrigue S, Lavergne T, Cazeau S et al. Long-term benefits
139. Vijayaraman P, Herweg B, Verma A, Sharma PS, Batul SA, Ponnusamy SS et al. Rescue
of biventricular pacing in congestive heart failure: results from the MUltisite
left bundle branch area pacing in coronary venous lead failure or nonresponse to bi­
STimulation in cardiomyopathy (MUSTIC) study. J Am Coll Cardiol 2002;40:111–8.
ventricular pacing: results from international LBBAP collaborative study group.
163. Puggioni E, Brignole M, Gammage M, Soldati E, Bongiorni MG, Simantirakis EN et al.
Heart Rhythm 2022;19:1272–80.
Acute comparative effect of right and left ventricular pacing in patients with permanent
140. Joza JBH, Andrade JG, Linz D, Ellenbogen KA, Vernooy K. Pacemaker implantation and
atrial fibrillation. J Am Coll Cardiol 2004;43:234–8.
atrioventricular node ablation for the treatment of atrial fibrillation in the era of con­
164. Simantirakis EN, Vardakis KE, Kochiadakis GE, Manios EG, Igoumenidis NE, Brignole M
duction system pacing. Eur Heart J 2024;45:4887–901.
et al. Left ventricular mechanics during right ventricular apical or left ventricular-based
141. Tan ES, Rienstra M, Wiesfeld AC, Schoonderwoerd BA, Hobbel HH, Van Gelder IC.
pacing in patients with chronic atrial fibrillation after atrioventricular junction ablation.
Long-term outcome of the atrioventricular node ablation and pacemaker implantation
J Am Coll Cardiol 2004;43:1013–8.
for symptomatic refractory atrial fibrillation. Europace 2008;10:412–8.
165. Doshi RN, Daoud EG, Fellows C, Turk K, Duran A, Hamdan MH et al. Left ventricular-
142. Wood MA, Kay GN, Ellenbogen KA. The North American experience with the ablate
based cardiac stimulation post AV nodal ablation evaluation (the PAVE study).
and pace trial (APT) for medically refractory atrial fibrillation. Europace 1999;1:22–5.
J Cardiovasc Electrophysiol 2005;16:1160–5.
143. Kirkutis A, Poviliŭnas A, Griciene P, Polena S, Yang S, Yalamanchi G et al. Cardiac rate
166. Brignole M, Gammage M, Puggioni E, Alboni P, Raviele A, Sutton R et al. Comparative
normalization in chronic atrial fibrillation: comparison of long-term efficacy of treat­
assessment of right, left, and biventricular pacing in patients with permanent atrial fib­
ment with amiodarone versus AV node ablation and permanent His-bundle pacing.
rillation. Eur Heart J 2005;26:712–22.
Proc West Pharmacol Soc 2004;47:69–70.
167. Orlov MV, Gardin JM, Slawsky M, Bess RL, Cohen G, Bailey W et al. Biventricular pacing
144. Wang T, Fang T, Cheng Z. Comparison of the efficacy and safety endpoints of five ther­
improves cardiac function and prevents further left atrial remodeling in patients with
apies for atrial fibrillation: a network meta-analysis. Front Cardiovasc Med 2022;9:853149.
145. Geelen P, Goethals M, de Bruyne B, Brugada P. A prospective hemodynamic evaluation symptomatic atrial fibrillation after atrioventricular node ablation. Am Heart J 2010;
of patients with chronic atrial fibrillation undergoing radiofrequency catheter ablation 159:264–70.
of the atrioventricular junction. Am J Cardiol 1997;80:1606–9. 168. Brignole M, Botto G, Mont L, Iacopino S, De Marchi G, Oddone D et al. Cardiac re­
146. Morady F, Calkins H, Langberg JJ, Armstrong WF, de Buitleir M, el-Atassi R et al. A pro­ synchronization therapy in patients undergoing atrioventricular junction ablation for
spective randomized comparison of direct current and radiofrequency ablation of the permanent atrial fibrillation: a randomized trial. Eur Heart J 2011;32:2420–9.
atrioventricular junction. J Am Coll Cardiol 1993;21:102–9. 169. Brignole M, Pentimalli F, Palmisano P, Landolina M, Quartieri F, Occhetta E et al. AV
147. Olgin JE, Scheinman MM. Comparison of high energy direct current and radiofrequency junction ablation and cardiac resynchronization for patients with permanent atrial fib­
catheter ablation of the atrioventricular junction. J Am Coll Cardiol 1993;21:557–64. rillation and narrow QRS: the APAF-CRT mortality trial. Eur Heart J 2021;42:4731–9.
148. Brignole M, Gianfranchi L, Menozzi C, Bottoni N, Bollini R, Lolli G et al. Influence of 170. Deshmukh P, Casavant DA, Romanyshyn M, Anderson K. Permanent, direct
atrioventricular junction radiofrequency ablation in patients with chronic atrial fibrilla­ His-bundle pacing: a novel approach to cardiac pacing in patients with normal
tion and flutter on quality of life and cardiac performance. Am J Cardiol 1994;74:242–6. His-Purkinje activation. Circulation 2000;101:869–77.
149. Jensen SM, Bergfeldt L, Rosenqvist M. Long-term follow-up of patients treated by 171. Deshmukh PM, Romanyshyn M. Direct His-bundle pacing: present and future. Pacing
radiofrequency ablation of the atrioventricular junction. Pacing Clin Electrophysiol Clin Electrophysiol 2004;27:862–70.
1995;18:1609–14. 172. Occhetta E, Bortnik M, Marino P. Permanent parahisian pacing. Indian Pacing
150. Edner M, Caidahl K, Bergfeldt L, Darpo B, Edvardsson N, Rosenqvist M. Prospective Electrophysiol J 2007;7:110–25.
study of left ventricular function after radiofrequency ablation of atrioventricular junc­ 173. Huang W, Su L, Wu S, Xu L, Xiao F, Zhou X et al. Benefits of permanent His bundle
tion in patients with atrial fibrillation. Br Heart J 1995;74:261–7. pacing combined with atrioventricular node ablation in atrial fibrillation patients with
151. Fitzpatrick AP, Kourouyan HD, Siu A, Lee RJ, Lesh MD, Epstein LM et al. Quality of life heart failure with both preserved and reduced left ventricular ejection fraction. J Am
and outcomes after radiofrequency His-bundle catheter ablation and permanent pace­ Heart Assoc 2017;6:e005309.
maker implantation: impact of treatment in paroxysmal and established atrial fibrilla­ 174. Wang S, Wu S, Xu L, Xiao F, Whinnett ZI, Vijayaraman P et al. Feasibility and efficacy of
tion. Am Heart J 1996;131:499–507. His bundle pacing or left bundle pacing combined with atrioventricular node ablation in
152. Bubien RS, Knotts-Dolson SM, Plumb VJ, Kay GN. Effect of radiofrequency catheter patients with persistent atrial fibrillation and implantable cardioverter-defibrillator
ablation on health-related quality of life and activities of daily living in patients with re­ therapy. J Am Heart Assoc 2019;8:e014253.
current arrhythmias. Circulation 1996;94:1585–91. 175. Su L, Cai M, Wu S, Wang S, Xu T, Vijayaraman P et al. Long-term performance and risk
153. Darpo B, Walfridsson H, Aunes M, Bergfeldt L, Edvardsson N, Linde C et al. Incidence factors analysis after permanent His-bundle pacing and atrioventricular node ablation
of sudden death after radiofrequency ablation of the atrioventricular junction for atrial in patients with atrial fibrillation and heart failure. Europace 2020;22:ii19–26.
fibrillation. Am J Cardiol 1997;80:1174–7. 176. Senes J, Mascia G, Bottoni N, Oddone D, Donateo P, Grimaldi T et al. Is His-optimized
154. Brignole M, Gianfranchi L, Menozzi C, Alboni P, Musso G, Bongiorni MG et al. superior to conventional cardiac resynchronization therapy in improving heart failure?
Assessment of atrioventricular junction ablation and DDDR mode-switching pace­ Results from a propensity-matched study. Pacing Clin Electrophysiol 2021;44:1532–9.
maker versus pharmacological treatment in patients with severely symptomatic parox­ 177. Huang W, Wang S, Su L, Fu G, Su Y, Chen K et al. His-bundle pacing vs biventricular
ysmal atrial fibrillation: a randomized controlled study. Circulation 1997;96:2617–24. pacing following atrioventricular nodal ablation in patients with atrial fibrillation and
28 M. Glikson et al.

reduced ejection fraction: a multicenter, randomized, crossover study-the with complete left bundle branch block and the relation between native QRS axis, dur­
ALTERNATIVE-AF trial. Heart Rhythm 2022;19:1948–55. ation, and normalization. Am J Cardiol 2016;118:527–34.
178. Ivanovski M, Mrak M, Meznar AZ, Zizek D. Biventricular versus conduction system pa­ 199. Sharma PS, Ellison K, Patel HN, Trohman RG. Overcoming left bundle branch block by
cing after atrioventricular node ablation in heart failure patients with atrial fibrillation. permanent His bundle pacing: evidence of longitudinal dissociation in the His via re­
J Cardiovasc Dev Dis 2022;9:209. cordings from a permanent pacing lead. HeartRhythm Case Rep 2017;3:499–502.
179. Vijayaraman P, Mathew AJ, Naperkowski A, Young W, Pokharel P, Batul SA et al. 200. Moustafa AT, Tang AS, Khan HR. Conduction system pacing on track to replace CRT?
Conduction system pacing versus conventional pacing in patients undergoing atrioven­ Review of current evidence and prospects of conduction system pacing. Front
tricular node ablation: nonrandomized, on-treatment comparison. Heart Rhythm O2 Cardiovasc Med 2023;10:1220709.
2022;3:368–76. 201. Barba-Pichardo R, Manovel Sanchez A, Fernandez-Gomez JM, Morina-Vazquez P,
180. Qi P, An H, Lv Y, Geng Y, Chen S, Li S et al. His-Purkinje conduction system pacing and Venegas-Gamero J, Herrera-Carranza M. Ventricular resynchronization therapy by direct
atrioventricular node ablation in treatment of persistent atrial fibrillation refractory to His-bundle pacing using an internal cardioverter defibrillator. Europace 2013;15:83–8.
multiple ablation procedures: a case report. SAGE Open Med Case Rep 2023;11: 202. Zanon F, Abdelrahman M, Marcantoni L, Naperkowski A, Subzposh FA, Pastore G
2050313X231172873. et al. Long term performance and safety of His bundle pacing: a multicenter experi­
181. Palmisano P, Ziacchi M, Dell’Era G, Donateo P, Ammendola E, Aspromonte V et al. ence. J Cardiovasc Electrophysiol 2019;30:1594–601.
Ablate and pace: comparison of outcomes between conduction system pacing and bi­ 203. Upadhyay GA, Cherian T, Shatz DY, Beaser AD, Aziz Z, Ozcan C et al. Intracardiac
ventricular pacing. Pacing Clin Electrophysiol 2023;46:1258–68. delineation of septal conduction in left bundle-branch block patterns. Circulation

Downloaded from https://academic.oup.com/europace/article/27/4/euaf050/8100402 by guest on 01 April 2025

182. Chaumont C, Azincot M, Savoure A, Auquier N, Hamoud RA, Popescu E et al. His bun­ 2019;139:1876–88.
dle pacing versus left bundle branch area pacing in patients undergoing atrioventricular 204. Whinnett ZI, Shun-Shin MJ, Tanner M, Foley P, Chandrasekaran B, Moore P et al. Effects
node ablation: a prospective and comparative study. Arch Cardiovasc Dis 2024;117: of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure
505–13. symptoms and exercise capacity: the His optimized pacing evaluated for heart failure
183. Jacobs M, Bodin A, Spiesser P, Babuty D, Clementy N, Bisson A. Single-center experi­ (HOPE-HF) randomized, double-blind, cross-over trial. Eur J Heart Fail 2023;25:274–83.
ence of efficacy and safety of atrioventricular node ablation after left bundle branch 205. Li Y, Chen K, Dai Y, Li C, Sun Q, Chen R et al. Left bundle branch pacing for symptom­
area pacing for the management of atrial fibrillation. J Interv Card Electrophysiol 2024; atic bradycardia: implant success rate, safety, and pacing characteristics. Heart Rhythm
67:1865–76. 2019;16:1758–65.
184. Zweerink A, Bakelants E, Stettler C, Burri H. Cryoablation vs. radiofrequency ablation of 206. Wu S, Sharma PS, Huang W. Novel left ventricular cardiac synchronization: left ven­
the atrioventricular node in patients with His-bundle pacing. Europace 2021;23:421–30. tricular septal pacing or left bundle branch pacing? Europace 2020;22:ii10–8.
185. Mahajan A, Trivedi R, Subzposh FA, Vijayaraman P. Feasibility of His bundle pacing and 207. Chen J, Ezzeddine FM, Liu X, Vaidya V, McLeod CJ, Valverde AM et al. Left bundle
atrioventricular junction ablation with left bundle branch area pacing as backup. Heart branch pacing vs ventricular septal pacing for cardiac resynchronization therapy.
Rhythm 2024;21:1180–1. Heart Rhythm O2 2024;5:150–7.
186. Rodríguez Muñoz D, Crespo-Leiro MG, Fernández Lozano I, Zamorano Gómez JL, 208. Mirolo A, Chaumont C, Auquier N, Savoure A, Godin B, Vandevelde F et al. Left bun­
Peinado Peinado R, Manzano Espinosa L et al. Conduction system pacing and atrioven­ dle branch area pacing in patients with baseline narrow, left, or right bundle branch
tricular node ablation in heart failure: the PACE-FIB study design. ESC Heart Fail 2023;
block QRS patterns: insights into electrocardiographic and echocardiographic features.
10:3700–9.
Europace 2023;25:526–35.
187. Sweeney MO, Bank AJ, Nsah E, Koullick M, Zeng QC, Hettrick D et al. Minimizing ven­
209. Wang Y, Zhu H, Hou X, Wang Z, Zou F, Qian Z et al. Randomized trial of left bundle
tricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med 2007;357:
branch vs biventricular pacing for cardiac resynchronization therapy. J Am Coll Cardiol
1000–8.
2022;80:1205–16.
188. Salden F, Huntjens PR, Schreurs R, Willemen E, Kuiper M, Wouters P et al. Pacing therapy
210. Ferreira Felix I, Collini M, Fonseca R, Guida C, Armaganijan L, Healey JS et al.
for atrioventricular dromotropathy: a combined computational-experimental-clinical
Conduction system pacing versus biventricular pacing in heart failure with reduced
study. Europace 2022;24:784–95.
ejection fraction: a systematic review and meta-analysis of randomized controlled
189. Salden F, Kutyifa V, Stockburger M, Prinzen FW, Vernooy K. Atrioventricular dromo­
trials. Heart Rhythm 2024;21:881–9.
tropathy: evidence for a distinctive entity in heart failure with prolonged PR interval?
211. Friedman DJ, Al-Khatib SM, Dalgaard F, Fudim M, Abraham WT, Cleland JGF et al.
Europace 2018;20:1067–77.
Cardiac resynchronization therapy improves outcomes in patients with intraventricu­
190. Boriani G, Tukkie R, Manolis AS, Mont L, Purerfellner H, Santini M et al. Atrial antita­
lar conduction delay but not right bundle branch block: a patient-level meta-analysis of
chycardia pacing and managed ventricular pacing in bradycardia patients with paroxys­
randomized controlled trials. Circulation 2023;147:812–23.
mal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre
212. Chen X, Li X, Bai Y, Wang J, Qin S, Bai J et al. Electrical resynchronization and clinical
international trial. Eur Heart J 2014;35:2352–62.
outcomes during long-term follow-up in intraventricular conduction delay patients ap­
191. John RM, Kumar S. Sinus node and atrial arrhythmias. Circulation 2016;133:1892–900.
192. Auricchio A, Prinzen FW. Update on the pathophysiological basics of cardiac resyn­ plied left bundle branch pacing-optimized cardiac resynchronization therapy. Circ
chronization therapy. Europace 2008;10:797–800. Arrhythm Electrophysiol 2023;16:e011761.
193. Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S et al. 213. Jastrzębski M, Foley P, Chandrasekaran B, Whinnett Z, Vijayaraman P, Upadhyay GA
Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med et al. Multicenter hemodynamic assessment of the LOT-CRT strategy: when does
2010;363:2385–95. combining left bundle branch pacing and coronary venous pacing enhance resynchro­
194. Zareba W, Klein H, Cygankiewicz I, Hall WJ, McNitt S, Brown M et al. Effectiveness of nization? Primary results of the CSPOT-study. Circ ArrhythmElectrophysiol 2024;17:
cardiac resynchronization therapy by QRS morphology in the multicenter automatic e013059.
defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT). 214. Chung ES, Katra RP, Ghio S, Bax J, Gerritse B, Hilpisch K et al. Cardiac resynchroniza­
Circulation 2011;123:1061–72. tion therapy may benefit patients with left ventricular ejection fraction >35%: a
195. Giraldi F, Cattadori G, Roberto M, Carbucicchio C, Pepi M, Ballerini G et al. Long-term PROSPECT trial substudy. Eur J Heart Fail 2010;12:581–7.
effectiveness of cardiac resynchronization therapy in heart failure patients with un­ 215. Cha YM, Lee HC, Mulpuru SK, Deshmukh AJ, Friedman PA, Asirvatham SJ et al.
favorable cardiac veins anatomy comparison of surgical versus hemodynamic proced­ Cardiac resynchronization therapy for patients with mild to moderately reduced ejec­
ure. J Am Coll Cardiol 2011;58:483–90. tion fraction and left bundle branch block. Heart Rhythm 2024;21:2250–9.
196. Daubert J-C, Saxon L, Adamson PB, Auricchio A, Berger RD, Beshai JF et al. 2012 216. Yu GI, Kim TH, Cho YH, Bae JS, Ahn JH, Jang JY et al. Left bundle branch area pacing in
EHRA/HRS expert consensus statement on cardiac resynchronization therapy in heart mildly reduced heart failure: a systematic literature review and meta-analysis. Clin
failure: implant and follow-up recommendations and management: a registered branch Cardiol 2023;46:713–20.
of the European Society of Cardiology (ESC), and the Heart Rhythm Society; and in 217. Ye Y, Chen X, He L, Wu S, Su L, He J et al. Left bundle branch pacing for heart failure
collaboration with the Heart Failure Society of America (HFSA), the American and left bundle branch block patients with mildly reduced and preserved left ventricu­
Society of Echocardiography (ASE), the American Heart Association (AHA), the lar ejection fraction. Can J Cardiol 2023;39:1598–607.
European Association of Echocardiography (EAE) of the ESC and the Heart Failure 218. Zeng J, He C, Zou F, Qin C, Xue S, Zhu H et al. Early left bundle branch pacing in heart
Association of the ESC (HFA). Endorsed by the governing bodies of AHA, ASE, failure with mildly reduced ejection fraction and left bundle branch block. Heart Rhythm
EAE, HFSA, HFA, EHRA, and HRS. Europace 2012;14:1236–86. 2023;20:1436–44.
197. Leclercq C, Burri H, Delnoy PP, Rinaldi CA, Sperzel J, Calò L et al. Cardiac resynchro­ 219. Vijayaraman P, Zanon F, Ponnusamy SS, Herweg B, Sharma P, Molina-Lerma M et al.
nization therapy non-responder to responder conversion rate in the MORE-CRT MPP Conduction system pacing compared with biventricular pacing for cardiac resynchro­
trial. Europace 2023;25:euad294. nization therapy in patients with heart failure and mildly reduced left ventricular ejec­
198. Teng AE, Lustgarten DL, Vijayaraman P, Tung R, Shivkumar K, Wagner GS et al. tion fraction: results from international collaborative LBBAP study (I-CLAS) group.
Usefulness of His bundle pacing to achieve electrical resynchronization in patients Heart Rhythm 2025. (EPUB ahead of print)
ESC/EHRA clinical consensus statement 29

220. Chen X, Jin Q, Qiu Z, Qian C, Liang Y, Wang J et al. Outcomes of upgrading to LBBP in 239. Vijayaraman P, Herweg B, Dandamudi G, Mittal S, Bhatt AG, Marcantoni L et al.
CRT nonresponders: a prospective, multicenter, nonrandomized, case-control study. Outcomes of His-bundle pacing upgrade after long-term right ventricular pacing
JACC Clin Electrophysiol 2024;10:108–20. and/or pacing-induced cardiomyopathy: insights into disease progression. Heart
221. Vijayaraman P, Herweg B, Ellenbogen KA, Gajek J. His-optimized cardiac resynchroni­ Rhythm 2019;16:1554–61.
zation therapy to maximize electrical resynchronization: a feasibility study. Circ 240. Burri H, Starck C, Auricchio A, Biffi M, Burri M, D’Avila A et al. EHRA expert consensus
Arrhythm Electrophysiol 2019;12:e006934. statement and practical guide on optimal implantation technique for conventional pa­
222. Jastrzebski M, Moskal P, Huybrechts W, Curila K, Sreekumar P, Rademakers LM et al. cemakers and implantable cardioverter-defibrillators: endorsed by the Heart Rhythm
Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT): results Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the
from an international LBBAP collaborative study group. Heart Rhythm 2022;19:13–21. Latin-American Heart Rhythm Society (LAHRS). Europace 2021;23:983–1008.
223. Jastrzebski M, Kielbasa G, Curila K, Moskal P, Bednarek A, Rajzer M et al. 241. Sticherling C, Ellenbogen KA, Burri H. Stepping back for good reasons: a reappraisal of
Physiology-based electrocardiographic criteria for left bundle branch capture. Heart the DF-1 connector for defibrillator leads. Europace 2024;26:euae057.
Rhythm 2021;18:935–43. 242. Ponnusamy SS, Ramalingam V, Ganesan V, Syed T, Kumar M, Mariappan S et al.
224. Jastrzebski M, Baranchuk A, Fijorek K, Kisiel R, Kukla P, Sondej T et al. Cardiac resyn­ Left bundle branch pacing-optimized implantable cardioverter-defibrillator
chronization therapy-induced acute shortening of QRS duration predicts long-term (LOT-ICD) for cardiac resynchronization therapy: a pilot study. Heart Rhythm O2
mortality only in patients with left bundle branch block. Europace 2019;21:281–9. 2022;3:723–7.
225. Zweerink A, Burri H. His-optimized and left bundle branch-optimized cardiac resynchro­ 243. Clementy N, Bodin A, Ah-Fat V, Babuty D, Bisson A. Dual-chamber ICD for left bundle

Downloaded from https://academic.oup.com/europace/article/27/4/euaf050/8100402 by guest on 01 April 2025

nization therapy: in control of fusion pacing. Card Electrophysiol Clin 2022;14:311–21. branch area pacing: the cardiac resynchronization and arrhythmia sensing via the left
226. Deshmukh A, Sattur S, Bechtol T, Heckman LIB, Prinzen FW, Deshmukh P. Sequential bundle (cross-left) pilot study. J Interv Card Electrophysiol 2023;66:905–12.
His bundle and left ventricular pacing for cardiac resynchronization. J Cardiovasc 244. Imnadze G, Fink T, Eitz T, Bocchini Y, Antonyan L, Harutyunyan K et al. Standard de­
Electrophysiol 2020;31:2448–54. fibrillator leads for left bundle branch area pacing: first-in-man experience and short-
227. Parale C, Bootla D, Jain A, Satheesh S, Anantharaj A, Ahmed AS et al. Comparison of term follow-up. JACC Clin Electrophysiol 2024;10:2263–8.
electrocardiographic parameters between left bundle optimized cardiac resynchroni­ 245. Ponnusamy SS, Ganesan V, Vijayaraman P. Feasibility, safety, and short-term follow-up
zation therapy (LOT-CRT) and left bundle branch pacing-cardiac resynchronization
of defibrillator lead at left bundle branch area pacing location: a pilot study. Heart
therapy (LBBP-CRT). Pacing Clin Electrophysiol 2023;46:840–7.
Rhythm 2024;21:1900–6.
228. Burri H, Prinzen FW, Gasparini M, Leclercq C. Left univentricular pacing for cardiac
246. Chung MK, Fagerlin A, Wang PJ, Ajayi TB, Allen LA, Baykaner T et al. Shared decision
resynchronization therapy. Europace 2017;19:912–9.
making in cardiac electrophysiology procedures and arrhythmia management. Circ
229. Somma V, Ha FJ, Palmer S, Mohamed U, Agarwal S. Pacing-induced cardiomyopathy: a
Arrhythm Electrophysiol 2021;14:e007958.
systematic review and meta-analysis of definition, prevalence, risk factors, and manage­
247. Mahajan A, Pokharel P, Vijayaraman P. Lead-to-lead interaction leading to left bundle
ment. Heart Rhythm 2023;20:282–90.
branch area pacing lead failure. HeartRhythm Case Rep 2023;9:72–5.
230. Kaza N, Htun V, Miyazawa A, Simader F, Porter B, Howard JP et al. Upgrading right
248. Ozpak E, Van Heuverswyn F, Timmermans F, De Pooter J. Lead performance of stylet-
ventricular pacemakers to biventricular pacing or conduction system pacing: a system­
driven leads in left bundle branch area pacing: results from a large single-center cohort
atic review and meta-analysis. Europace 2023;25:1077–86.
and insights from in vitro bench testing. Heart Rhythm 2024;21:865–73.
231. Merkely B, Hatala R, Merkel E, Szigeti M, Veres B, Fabian A et al. Benefits of upgrading
249. Rangaswamy VV, Ponnusamy SS. Late distal conductor fracture of the lumenless pacing
right ventricular to biventricular pacing in heart failure patients with atrial fibrillation.
lead after left bundle branch area pacing. Heart Rhythm 2024;21:490–1.
Europace 2024;26:euae179.
250. Thaler R, Sinner MF, Joghetaei N, Fichtner S. Early sudden distal conductor fracture of a
232. Merkely B, Hatala R, Wranicz JK, Duray G, Foldesi C, Som Z et al. Upgrade of right
ventricular pacing to cardiac resynchronization therapy in heart failure: a randomized stylet-driven lead implanted for left bundle branch area pacing. HeartRhythm Case Rep
trial. Eur Heart J 2023;44:4259–69. 2023;9:28–30.
233. Wang N, Ma PP, Jing ZM, Chen Y, Jia JJ, Zhao FL et al. Predictors of pacing-induced 251. Zou J, Chen K, Liu X, Xu Y, Jiang L, Dai Y et al. Clinical use conditions of lead deploy­
cardiomyopathy detection and outcomes demonstration after conduction system pa­ ment and simulated lead fracture rate in left bundle branch area pacing. J Cardiovasc
cing upgrade on patients with long-term persistent atrial fibrillation. Pacing Clin Electrophysiol 2023;34:718–25.
Electrophysiol 2023;46:684–92. 252. De Pooter J, Breitenstein A, Özpak E, Haeberlin A, Hofer D, Le Polain de Waroux JB
234. Shan Y, Lin M, Sun Y, Zhang J, Jiang H, Fu G et al. The specific value of upgrading to left et al. Lead integrity and failure evaluation in left bundle branch area pacing (LIFE-LBBAP
bundle branch area pacing in patients with pacing-induced cardiomyopathy or study). JACC Clin Electrophysiol 2025;11:158–70.
non-pacing-induced cardiomyopathy related upgrade status: a retrospective study. 253. Huybrechts WLH, Bergonti M, Saenen JB, Miljoen H, Van Leuven O, Van Assche L et al.
Pacing Clin Electrophysiol 2023;46:761–70. Left bundle branch area defibrillator (LBBAD): a first-in-human feasibility study. JACC
235. Gardas R, Golba KS, Soral T, Biernat J, Kulesza P, Sajdok M et al. The effects of His bun­ Clin Electrophysiol 2023;9:620–7.
dle pacing compared to classic resynchronization therapy in patients with 254. Elliott MK, Jacon P, Sidhu BS, Smith LJ, Mehta VS, Gould J et al. Technical feasibility of
pacing-induced cardiomyopathy. J Clin Med 2022;11:5723. leadless left bundle branch area pacing for cardiac resynchronization: a case series. Eur
236. Zheng R, Yao H, Lian L. His-Purkinje conduction system pacing for pacing-induced car­ Heart J Case Rep 2021;5:ytab379.
diomyopathy: a systematic literature review and meta-analysis. J Interv Card 255. Wijesuriya N, Elliott MK, Mehta V, Sidhu BS, Strocchi M, Behar JM et al. Leadless left
Electrophysiol 2023;66:1005–13. bundle branch area pacing in cardiac resynchronisation therapy: advances, challenges
237. Yang YH, Wang KX, Ma PP, Zhang RF, Waleed KB, Yin X et al. His-purkinje system and future directions . Front Physiol 2022;13:898866.
pacing upgrade improve the heart performances in patients suffering from 256. Ferrick AM, Raj SR, Deneke T, Kojodjojo P, Lopez-Cabanillas N, Abe H et al. 2023
pacing-induced cardiomyopathy with or without permanent atrial fibrillation. Int J HRS/EHRA/APHRS/LAHRS expert consensus statement on practical management
Cardiol 2021;335:47–51. of the remote device clinic. Europace 2023;25:euad123.
238. Ye Y, Wu S, Su L, Sheng X, Zhang J, Wang B et al. Feasibility and outcomes of upgrading 257. Vijayaraman P, Trivedi RS, Koneru JN, Sharma PS, De Pooter J, Schaller RD et al.
to left bundle branch pacing in patients with pacing-induced cardiomyopathy and infra­ Transvenous extraction of conduction system pacing leads: an international multicen­
nodal atrioventricular block. Front Cardiovasc Med 2021;8:674452. ter (TECSPAM) study. Heart Rhythm 2024;21:1953–61.