2025 ESC／EHRA关于传导系统起搏适应证的临床共识声明

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

Table of contents

Preamble............................................................................................................................ 3 Definition of categories of advice and areas of uncertainty........................ 3 Scientific background—an update .......................................................................... 4 Differences between conduction system pacing methods .......................... 4 His bundle pacing vs. left bundle branch area pacing..................................... 5 Criteria for His bundle capture .......................................................................... 8 Criteria for left bundle branch area pacing.................................................... 8 Success rates, procedural outcomes, and complications of His bundle pacing and left bundle branch area pacing...................................... 9 Conduction system pacing for atrioventricular block with left ventricular ejection fraction $>40\%$ ........................................................................ 9 Conduction system pacing for atrioventricular block in reduced left ventricular ejection fraction $(\leq\!40\%)$ ................................................................... 11 Conduction system pacing in atrioventricular node ablation ................... 12 Conduction system pacing in sinus node dysfunction ................................. 15 Conduction system pacing for heart failure without bradycardia pacing indication ........................................................................................................... 15 His bundle pacing.................................................................................................... 15 Left bundle branch area pacing......................................................................... 16 Conduction system pacing in non-left bundle branch pacing patients........................................................................................................................ 16 Conduction system pacing in patients with left ventricular ejection fraction $36–50\%$ ....................................................................................................... 16 Conduction system pacing cardiac resynchronization therapy in non-responders to biventricular cardiac resynchronization therapy......................................................................................................................... 17 Clinical implications................................................................................................ 17

His-optimized and left bundle branch pacing-optimized cardiac resynchronization therapy........................................................................................ 18 Delineation and rationale .................................................................................... 18 Published data and practical considerations................................................ 18 Upgrade to conduction system pacing............................................................... 20 Patient education and shared decision-making ............................................... 22 Future perspectives..................................................................................................... 22 Conclusions .................................................................................................................... 23 Supplementary material............................................................................................. 24 Funding.............................................................................................................................. 24 Data availability.............................................................................................................. 24 References ..................................................................................................................... 24

Abbreviations

AF APHRS AV AVN AVNA BiV-CRT BiVP BNP CHRS CI CSP CSP-CRT atrial fibrillation Asian Pacific Heart Rhythm Association atrioventricular atrioventricular node atrioventricular node ablation biventricular cardiac resynchronization therapy biventricular pacing brain natriuretic peptide Canadian Heart Rhythm Society confidence interval conduction system pacing conduction system pacing cardiac resynchronization therapy cardiac resynchronization therapy defibrillator European Heart Rhythm Association

EHRA

ESC/EHRA clinical consensus statement

ESC European Society of Cardiology HBP His bundle pacing HF heart failure HFH heart failure hospitalization HFmrEF heart failure and mildly reduced ejection fraction HFpEF heart failure with preserved ejection fraction HFrEF heart failure with reduced ejection fraction HOT-CRT His-optimized cardiac resynchronization therapy HR hazard ratio HRS Heart Rhythm Society ICD implantable cardioverter–defibrillator LAHRS Latin America Heart Rhythm Society LBBAP left bundle branch area pacing LBBB left bundle branch block LBBP left bundle branch pacing LFP left fascicular pacing LOT-CRT left bundle branch optimized CRT LV left ventricular LVEF left ventricular ejection fraction LVSP left ventricular septal pacing ms millisecond NIVCD non-specific intra-ventricular conduction delay nsHBP non-selective His bundle pacing NYHA New York Heart Association PICM pacing-induced cardiomyopathy QoL quality of life QRSd QRS duration RCT randomized clinical trials RBBB right bundle branch block RBBP right bundle branch pacing RV right ventricular RVP right ventricular pacing RWPT R-wave peak time sHBP selective His bundle pacing SND sinus node dysfunction TAVI transcatheter aortic valve implantation TR tricuspid valve regurgitation V volt

Preamble

Conduction system pacing (CSP) is an overarching term including His bundle pacing (HBP) as well as left bundle branch area pacing (LBBAP). This is a relatively new area of pacing that is continuing to gain popularity among pacing specialists as being more physiological than the traditional form of right ventricular pacing (RVP), as well as emerging as an alterna tive to biventricular cardiac resynchronization therapy (BiV-CRT) in cases of heart failure (HF) with conduction system disease.

When the 2021 European Society of Cardiology (ESC) guidelines on pacing 1 were being formulated, CSP had already been investigated for 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 stitute for BiV-CRT in selected patients. At that point, most of the in formation on HBP was observational with short-term follow-up, and there were only two small randomized controlled pilot trials that in cluded more than one centre. 2 – 5 A conservative approach towards HBP was therefore taken, and no recommendations regarding LBBAP were formulated due to limited available data at that time.

Ever since the publication of the 2021 guidelines, the use of CSP has greatly evolved, mainly with LBBAP, 6 due to perceived greater ease of implantation and superior electrical parameters compared with HBP. Recent European surveys 7 , 8 and the recent MELOS registry 9 are

examples of the extensive use of CSP. The European Heart Rhythm Association (EHRA) published a consensus document on CSP implant ation to standardize the technique. 10 The 2024 updated EHRA core curriculum now includes CSP in its syllabus. 11 This emphasizes the im portance of proper training and patient selection for CSP.

Recently, the Heart Rhythm Society (HRS) guidelines on physiologic al pacing have expanded the indications for CSP. 12 Given the increasing published evidence and consensus among European experts on the likely benefits of CSP and to reconcile the European recommendations on pacing and cardiac resynchronization with current practice, we decided to update advice on indications for CSP.

This document represents a collaborative effort of the ESC and EHRA, as well as EHRA’s sister societies: the Asia Pacific Heart Rhythm Society (APHRS), Canadian Heart Rhythm Society (CHRS), HRS, and Latin American Heart Rhythm Society (LAHRS). It follows the principles of the ESC and EHRA scientific document committees in terms of evaluating evidence and providing advice. All advice was submitted to anonymous voting and had to be approved by ${>}70\%$ of the writing group to be imple mented (the patient representative did not vote, due to the technical na ture of the advices). The authors include early CSP adopters (all of whom have extensive experience with BiV-CRT), experts in CRT who primarily perform biventricular pacing (BiVP), non-implanting HF specialists, and a patient representative (I.D.). We thus aim to provide a balanced and con sensual view, from multiple perspectives.

## Definition of categories of advice and areas of uncertainty

|Definition|Categories of advice|Icons| |---|---|---| | Evidence or general agreement that a given measure is clinically useful and appropriate |AdviceTODO|| | Evidence or general agreement that a given measure may be clinically useful and appropriate | May be appropriate TODO || | Evidence or general agreement that a given measure is not appropriate or harmful |AdviceNOT TO DO|| | No advice can be given because of lack of data or inconsistency of data. The topic is important to be addressed |Areas of uncertainty||

|Type of supporting evidence| Strength of evidence|Icons| |---|---|---| |Published datas| >1 high quality RCT Meta-analysis of high quality RCT || |Published datas| High quality RCT >1 moderate quality RCT Meta-analysis of moderate quality RCT || |Published datas|High quality,large observational studies|| |Expert opinion*#| Strong consensus >90% of writing group supports advice |>90% agree| |Expert opinion*#| Consensus >70% of writing group supports advice |>70%agree|

\$ The reference for the published data that fulfil the criteria is indicated in the table of advice, if applicable \*Expert opinion also takes into account randomized, nonrandomized, observational or registry studies with limitations of design or execution, case series, meta -analyses of such studies, physiological or mechanistic studies in human subjects # For areas of uncertainty:strong consensus that the topic is relevant and important to be addressed by future trials

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![Advice: CSP implantation and Advice: CSP implantation and Strength of evidence Strength of evidence training training .................................................................. Advice TO DO Advice TO DO Conduction system pacing implantation Conduction system pacing implantation should be performed by physicians who should be performed by physicians who have undergone adequate training and have undergone adequate training and who have acquired the necessary skills who have acquired the necessary skills to perform the procedure safely and to perform the procedure safely and >90% agree >90%agree effectively, with systematic evaluation of effectively, with systematic evaluation of type of pacing that is achieved [e.g. type of pacing that is achieved [e.g. selective vs. non-selective HBP (nsHBP), selective vs. non-selective HBP (nsHBP), LBBP, left fascicular pacing (LFP), left LBBP, left fascicular pacing (LFP), left ventricular septal pacing (LVSP), etc.] ventricular septal pacing (LVSP), etc.] ](https://venus-llm-1258344701.cos-internal.ap-guangzhou.tencentcos.cn/userUpload/is-62e36cd9/2025-04-08/430da18f-e70e-4060-9242-648f61f22ef5/430da18f-e70e-4060-9242-648f61f22ef5.jpg?q-sign-algorithm=sha1&q-ak=AKID61g5D5fy1TjiRv84nEOHtFJ8gyzjCPL0&q-sign-time=1744125596%3B1744129196&q-key-time=1744125596%3B1744129196&q-header-list=host&q-url-param-list=&q-signature=a4d43240df45b5b03fa96d25c7d3e0f48db47738)

Scientific background—an update

In 1925, Wiggers first highlighted the potential detrimental effects of RVP due to the asynchronous activation of the ventricles. 13 Following the advent of cardiac pacing in the late 1950s, numerous observations have since underscored the progressive sequence of harm. This process begins at the molecular level and extends to macroscopic changes, such as asynchronous hypertrophy, leading to a progressive decline in left ventricular (LV) function ( Figure 1 ). This decline is associated with in creased episodes of HF and, consequently, higher mortality. 15

Evidence suggests that pacing at any myocardial site within the right ventricle (RV), not just the apex, is associated with detrimental haemo dynamic effects. 16 The slow electrical propagation through the myocar dium can lead to ventricular mechanical dyssynchrony, 17 LV dysfunction, and HF, particularly in patients who require a high percent age of pacing. 18

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 diomyopathy (PICM) was introduced over the following years, which af fects $10{-}20\%$ of patients who receive RVP. 21 , 22 It is difficult to ascertain which patients will develop PICM, despite some predictors having been described [e.g. paced QRS duration $(\dot{Q}{\sf R S d})^{23}]$ . In addition, there is no evidence of clinical benefit of alternative pacing sites such as RV septal pa cing over RV apical pacing. 24 For these reasons, pacing strategies such as BiVP or CSP have been developed to avoid or to attenuate PICM.

Differences between conduction system pacing methods

Capture of the conduction system is present with HBP, proximal right 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 system, 10 for the purposes of this document we also included LVSP as being part of CSP.

Left bundle branch area pacing includes LBBP, LFP, and LVSP. 10 Capture of the conduction system may be either selective (with exclu sive capture of conduction tissue) or non-selective (with concurrent capture of conductive tissue and local myocardium). With HBP, ap proximately two-thirds of patients have nsHBP at programmed out put, 25 , 26 while LBBP, LFP, and RBBP are almost always non-selective due to more surrounding myocardial tissue. 27 – 29 Previous studies showed that despite the differences in QRSd, ventricular synchrony during nsHBP is similar to selective HBP (sHBP) and much more physio logical than RV septal pacing. 30 – 33 Also, no difference in clinical out comes between nsHBP and sHBP has been observed. 25

During LVSP, the conduction tissue is not captured; however, capturing myocytes close to the left septal endocardium leads to more synchronous ventricular activation than during RVP. 16 , 34 , 35 Both LBBP and LVSP have

 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

 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 tricular activation patterns. 37 Whereas LVSP produces less interventricu lar dyssynchrony than LBBP (due to delayed LV activation, which nevertheless occurs before RV activation), the latter is associated with bet ter LV synchrony (due to more rapid and homogenous LV activation) (see Figures 2 and 3 ). 36 It is still a matter of debate whether capture of the left-sided conduction system impacts clinical outcomes. Most probably, this makes little difference in patients without documented structural heart disease, 36 but some observational studies have reported worse outcomes for patients with HF with LVSP compared with LBBP. 39 , 40 Another open question is whether LBBP is superior to LFP, as suggested by a small ob servational study in patients with HF. 41

His bundle pacing vs. left bundle branch area pacing

Conduction system pacing utilizing HBP and LBBAP has been utilized for the management of both bradycardia and HF indications. While HBP provides ex cellent synchronous biventricular activation, LBBAP preserves or restores intra-ventricular LV synchrony, with both modalities providing comparable mechanical performance of the heart. 30 , 31 , 34 , 36 , 38 , 42 – 46 The clinical impact of RV dyssynchrony or delayed activation induced by LBBAP is currently unclear.

While there are no high-quality long-term randomized comparisons between HBP and LBBAP, 42 , 47 – 55 observational data comparing HBP

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 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 amplitude, and lead complication rates are more favourable with LBBAP, while acute haemodynamic improvement and clinical outcomes including LVEF, HF, and mortality outcomes appear overall compar able. 46 , 47 , 51 , 56 – 58 The only randomized trial comparing HBP and LBBAP was a small crossover study in 23 patients who underwent AVN ablation followed by 6 months of pacing in each modality, without any significant differences in LVEF. 59

The more favourable electrical parameters and perceived ease of im plantation have led to preferential adoption of LBBAP over HBP in clin ical practice over the past years. 6 – 8 , 51 , 56 There are nevertheless inherent advantages and disadvantages with both CSP techniques (see Table 1 ), which makes it worthwhile to encourage acquiring profi ciency with HBP as well as LBBAP.

Despite certain challenges associated with HBP (achieving favourable electrical parameters, difficulty in correcting distal conduction dis ease), 25 , 56 , 58 , 70 – 74 employment of the implant technique outlined in the EHRA CSP consensus document (e.g. ensuring torque buildup, cur rent of injury of the His potential, stability testing, etc.) and application of strict implant criteria (e.g. capture threshold of ${\leq}1.5\ \lor/0.5$ ms and sensing ${>}2\ \mathsf{m V}$ ) may allow stable and effective HBP delivery. Implantation at the distal His bundle offers several advantages com pared with the proximal His bundle: lower thresholds, larger R-wave sensing, less P -wave oversensing, nsHBP with septal myocardial capture as backup in case of loss of HB capture, and less interference with sub sequent AV node ablation (AVNA). 75 , 76

The learning curve for HBP implantation is sometimes perceived to be unduly prolonged. However, in a multicentre report, a success rate

ESC/EHRA clinical consensus statement

Table 1 Comparison of HBP vs. LBBAP

||HBP|LBBAP| |---|---|---| | Pacing threshold and||| |energy consumption| May be high (ideally accept only if pacing threshold ≤1.5V/ 0.5ms) |Low (usually ≤1.5V/0.5 ms)| |Sensing| Usuallysmaller R waves, P wave far-field oversensing (accept only if R waves >2 mV with far-field P waves ||

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.

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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| |---|---|---| ||Scheduled AVN ablation53|Heart failure indication| ||Infra-nodal AV block80 |Nodal AV block| |Bailout in case of unsuccessful/unsatisfactory LBBAP| Previous or scheduled TAVl 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 $\mathbf{\xi},\equiv$ 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.

of $87\%$ was achieved after 40 cases. 70 In another report from three cen tres, the success rate flattened after ∼ 30–40 cases. 77 However, HBP success was defined as a threshold of ≤ 3.5V/1ms, and required num bers are likely to be higher to achieve lower capture thresholds. Conversely, LBBAP may seem to be relatively easy and with a high suc cess rate, even for beginners. However, many implantations in inexperi enced hands represent only deep septal pacing rather than true LBBAP. Even in experienced centres, success may be met in only $92\%$ of patients with bradycardia and is even lower in patients with HF $(82\%)$ , although these figures included the learning curves of the operators. 9 The learning curve for successful LBBAP implantation has been reported to flatten after 50–100 patients in a single-centre report with one main oper ator. 78 In another single-centre study with three operators, LBBAP im plantation success was evaluated for the first 126 cases and was $79\%$ for the first 42 patients and increased to $90\%$ for the following 42 cases and to $95\%$ for the last tertile. In the multicentre MELOS registry, 9 success rate continued to increase over the first 270 cases, with fluoroscopy time and V 6 RWPT reaching a plateau after approximately 110 cases. Therefore, the learning curve for LBBAP may not be shorter than for HBP, and each technique presents its own set of challenges.

There may be instances where one pacing modality is preferred ( Table 2 ).

The capture thresholds are higher and success rates of HBP are low 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 eter aortic valve implantation (TAVI) or aortic valve surgery may com promise HBP lead function. As discussed in the following sections, patients with infra-nodal AV block or those requiring AV nodal ablation are better served with LBBAP than with HBP.

A final consideration is the potential worsening of tricuspid valve regur gitation (TR), observed in up to one-third of patients undergoing LBBAP, particularly in a basal position. 64 , 79 , 85 However, this finding requires valid ation in large studies. Notably, this issue does not appear to be as prevalent with HBP, although sheath and lead manipulation at the level of the valve may risk entanglement in the subvalvular apparatus. 63 The His bundle may be paced from the atrial aspect of the tricuspid valve (thereby avoiding the valve altogether) or from the ventricular aspect as it courses in proximity to the commissure between the septal and anterosuperior leaflets. 86 In in stances where the tricuspid valve needs to be spared, such as patients with a history of tricuspid valve surgery or transcatheter repair, HBP is prefer rable. 87 Long-term evolution of TR with CSP needs to be further studied.

In general, implanters may use the CSP modality that best suits them. However, CSP implanting centres should ideally be able to perform both HBP and LBBAP and should also be able to perform BiVP implant ation (as CSP is not always successful). Being proficient with all techni ques offers the operator an alternative for a bailout solution in case the initial technique is unsuccessful or suboptimal.

Criteria for His bundle capture

Confirming HB capture during the implantation procedure is clinically important since myocardial pacing in the para-Hisian area actually cor responds to right ventricular septal pacing (RVSP) and leads to dyssyn chronous ventricular activation (unlike nsHBP, where conduction system capture is achieved in addition to myocardial capture). 30 , 32 Confirmation of HBP in patients with narrow QRS is straightforward because QRS complex morphology and duration are the same as spon taneous complexes during sHBP with an isoelectric interval corre sponding to the HV interval, or only slightly different with a pseudo-delta wave during nsHBP. 65 , 73 It is more complex in case of nsHBP with uncorrected bundle branch block, where the QRS com plexes may be even wider than with intrinsic rhythm. 65

The gold standard for confirming HB capture is to demonstrate tran sitions in QRS morphology with decrementing output (from nsHBP to either sHBP or to myocardial capture, or loss of correction of bundle branch block) . 65 , 73 Transitions are absent in $5{-}10\%$ of patients (e.g. due to near-identical thresholds between the HB and myocytes), and in those cases, other methods of confirmation have to be used (such as programmed stimulation, which leverages differences in refractory periods between tissues). 65 , 88 – 90 QRS morphology criteria have also been described and are detailed in the recent EHRA consensus docu ment on CSP implantation. 10

Criteria for left bundle branch area pacing

Left bundle branch area pacing consists of LBBP and LVSP with both being associated with better ventricular synchrony and LV haemodynamics than RVP. 16 , 33 – 35 , 37 , 91 For evaluation of LBBAP, correct positioning of the V1 chest electrode is essential as the terminal $r^{\prime}/R^{\prime}$ deflection may be missed if the electrode is placed too high. In some cases, LBBAP without a termin al r ′/ R ′-wave in V1 can be observed, 10 presumably due to rapid transseptal activation, or right ventricular activation occurring via rapid retrograde conduction to the HB and down the RBB, or slow propagation via dis eased LBB, resulting in simultaneous biventricular activation, which is probably the dominant mechanism in patients with HF. Other causes for absence of a terminal r ′/ R ′ in V1 are anodal capture with bipolar pa cing, 92 or fusion with intrinsic conduction.

A number of criteria have been described in the EHRA consensus document on CSP implantation to confirm conduction system capture in LBBP, the gold standard of which is transitions in QRS morphology during decremental output with unipolar pacing (i.e. with transitions from non-selective LBBP to LVSP or to selective LBBP). 10 The accuracy of R-wave peak time (RWPT) criteria is uncertain, especially in patients with low septal and/or apical lead placements, 93 , 94 as these pacing loca tions can produce $\mathsf{V}_{6}\mathsf{R W P T}$ shortening and $\mathsf{V}_{6}\mathrm{-}\mathsf{V}_{1}$ interpeak interval prolongation without conduction system capture and can cause mis classification of LVSP as LBBP. In addition to pacing site, the

ESC/EHRA clinical consensus statement

$\mathsf{V}_{6}\mathsf{R W P T}$ depends upon heart size and conduction velocity (e.g. with misclassification of LBBP as LVSP due to long $\mathsf{V}_{6}\mathsf{R W P T}$ in patients with slow conduction or dilated hearts). It is therefore important to realize that none of the $\mathsf{V}_{6}\mathsf{R W P T}$ cut-offs (or for the $\mathsf{V}_{6}\mathrm{-}\mathsf{V}_{1}$ interpeak interval) are $100\%$ accurate for diagnosing conduction system capture and there is little information on the optimal cut-offs in patients with HF. Also, a terminal r / R wave in V1 may occasionally be visible when pace mapping from the RV septum and is therefore per se not diagnos tic of LBBAP. 95

The criteria for LVSP are as follows: (i) deep septal deployment of the pacing lead together with (ii) terminal $r^{\prime}/R^{\prime}$ -wave in lead V1, without criteria for conduction system capture. 10

Success rates, procedural outcomes, and complications of His bundle pacing and left bundle branch area pacing

A meta-analysis of 15 observational studies involving 2491 patients found that LBBAP had significantly higher success rates compared with HBP (91.1 vs. $80.9\%$ ; $P<0.001\big>$ ), along with significantly lower lead-related complications over follow-up, which included lead failure, inactivation for elevated thresholds and dislodgment (1.1 vs. $4.3\%$ ; $P\,{=}\,0.003,$ ). 96 The meta-analysis also found no significant difference in lead dislodgement rates between CSP and traditional RVP. 96

In a multicentre study involving 870 subjects, of whom 849 were fol lowed for 6 months, CSP lead implantation was successful in 768 patients $(90\%)$ , with a success rate of $95\%$ for LBBAP and $88\%$ for HBP ( $P\!=$ 0.002). 58 The two pacing modalities had no significant differences in pro cedural or fluoroscopy duration. However, the threshold at implantation was higher for HBP ( $\uparrow.44\pm1.03\;\lor$ at $0.71\pm0.33\;{\sf m s})$ ) than for LBBAP $(0.69\pm0.39\ \lor$ at $0.46\pm0.15~\mathrm{ms}$ , $P<0.001]$ ). At 6-month follow-up, HBP continued to have a higher threshold than LBBAP ( $1.59\pm0.97~\forall$ at $0.67\pm0.31$ ms vs. $0.79\pm0.33\lor$ at $0.44\pm0.13$ ms; $P<0.001$ ). An in crease in the pacing threshold of more than 1 V at 6 months was ob served in 3 of 208 patients $(1.4\%)$ with LBBAP and 55 of 418 patients $(13.2\%)$ with HBP $\left.\begin{array}{r l}\end{array}\right.$ ). Serious adverse events related to the im plantation procedure or the CSP lead occurred in 5 of 251 patients $(2.0\%)$ with LBBAP and 25 of 598 patients $(4.2\%)$ with HBP $(P\,{=}\,0.11)$ ).


Conduction system pacing for atrioventricular block with left ventricular ejection fraction $>40\%$

In patients with high-grade AV block and normal systolic function, BiVP has been shown to preserve LVEF during follow-up compared with a significant decline in patients who had been randomized to RVP (with out, however, any differences in clinical outcome). 97 , 98 Biventricular pa cing nevertheless bypasses the His–Purkinje system, inevitably resulting in ventricular dyssynchrony 38 , 43 , 99 (see Figures 2 and 4 ). As BiVP re 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 2021 ESC pacing guidelines. 1 According to these guidelines, HBP may be considered for treating these patients, who were anticipated to have ${>}20\%$ ventricular pacing, without giving any recommendation for LBBAP due to the limited amount of data available at that time. More recently, the 2023 HRS/APHRS/LAHRS guidelines on physio logical pacing stated that LBBAP may be useful (along with CRT) in AV block patients with LVEF $36–50\%$ and that it may be considered in those with LVEF ${>}50\%$ . 12

In patients with AV block in whom ventricular pacing is anticipated to be infrequent $(<\!20\%)$ , strategies that minimize ventricular pacing are appropriate, similar to what is outlined in the 2021 ESC pacing guide lines. 1 , 101 However, as the course of evolution of the conduction disor ders in these patients may be unforeseeable, CSP may be an option in proficient centres to provide a physiological means of delivering pacing therapy in case ventricular pacing burden increases.

Over the past years, various studies have compared either HBP and/or LBBAP with RVP in patients with AV block (most of whom had mildly reduced to normal LVEF) and showed that this emerging pacing strategy seems very promising. Unfortunately, so far only a few small randomized clinical trials (RCTs) have compared CSP with RVP in patients with bradycardia and near-normal LVEF, none of which have long-term follow-up. One early trial showed in 38 pa tients that HBP preserved LVEF and mechanical synchrony as com pared to RVP after 12 months. 4 A recent RCT in 92 patients also showed superiority of HBP over RVP, with a higher LVEF and lower levels of TGF β 1 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 bal longitudinal strain, QRS duration, as well as echocardiographic mea surements of dyssynchrony were significantly better during LBBP as compared to RVP. In the single-centre STAY study, 70 patients with AV block, $\mathsf{L V E F}\,{>}\,40\%$ (mean ${\sim}60\%$ ), and an expected high ventricular pacing burden (mean ${\sim}91\%$ were randomized to either RVP or CSP (9 HBP, 17 LBBP, and 10 LVSP). 106 Over a 6-month follow-up, RVP was associated with a significant decrease in LVEF {mean difference, $-5.8\%$ [ $\cdot95\%$ 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, 0.1–6.2); $P\!=\!0.04]$ . In addition, HF-related admissions were higher in the RVP group (22.6 vs. $5.1\%$ ; $P\!=\!0.03$ ).

Besides the few small short-term RCTs that show superiority of CSP over RVP in patients with AV block, larger observational studies have been performed (for which data should be interpreted with caution due to the inherent caveats of non-randomized studies). In a compari 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 with HBP (all-cause mortality, HF hospitalizations (HFH), or need for upgrade to BiVP) was found after a mean follow-up of ${\sim}2$ years (with a requirement for lead revision in $4.2\%$ of patients with HBP

10

 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 come of the same primary endpoint in 321 patients with LBBAP com pared with 382 patients with RVP after a mean follow-up of 1.6 years. 107 Among patients with ventricular pacing ${>}20\%$ , LBBAP was as sociated with a significant reduction in mortality [7.8 vs. $15\%$ ; hazard ra tio (HR) 0.59; $P\,{=}\,0.03]$ ] and HFH (3.7 vs. $10.5\%$ ; HR 0.38; P = 0.004) as compared to RVP. Another series reported similar results in 628 pa tients who received RVP compared with 231 patients received CSP (95 HBP and 136 LBBAP), with a reduction in HFH in patients with ${>}20\%$ ventricular pacing in a multivariable-adjusted model, with a HR of 0.40 $95\%$ CI, 0.17–0.95). 108 These studies did not specifically target a population with AV block and LVEF ${>}40\%$ , but ${\sim}50{-}65\%$ of patients had AV block and the mean LVEF was ${>}50\%$ . Reduced mortality was also reported in a large population-based study in patients with dual-chamber pacemakers using data from Medicare claims in 6197 patients with CSP (4738 LBBAP and 1459 HBP) compared with 16 989 patients with RVP, roughly half of whom had an AV block indication for pacing

(LVEF was not reported but was presumably preserved overall). 51 All-cause mortality at 6 months was lower in the CSP group (HR 0.66; $P<0.0001$ ) as was HFH (HR 0.70; P = 0.02). Other observational studies showed that the incidence of HFH and need for an upgrade to BiVP was significantly lower in patients undergoing LBBP as compared to those receiving RVP. 109 , 110 Also, for other populations such as AV block after TAVI 111 , 112 and for patients with AV block and HF with pre served ejection fraction, 113 LBBP seems to be a better alternative com pared with RVP.

Meta-analyses of the few randomized trials and larger observational co horts comparing CSP with RVP in patients with AV block showed that CSP was significantly superior in preserving LVEF, shortening paced QRS duration, and reducing rates of HFH. 114 – 116 On the contrary, RVP was associated with higher implantation success rate and shorter proced ure/fluoroscopy duration and had fewer lead complications.

While awaiting the results of the ongoing larger RCTs in patients with AV block and mildly reduced to normal LVEF $(>40\%)$ requiring

ESC/EHRA clinical consensus statement

frequent $(>\!20\%)$ ventricular pacing, both HBP and LBBP might be con sidered as alternatives to RVP in these patients. It has nevertheless been shown that HBP implantation is less successful in infra-nodal block com pared with nodal block (76 vs. $93\%$ , $P<0.05$ ). 80 A backup lead may be useful to avoid asystole in HBP patients with AV block, particularly if the block is infra-nodal or in case of sensing issues. 1 , 10 , 117 Left bundle branch area pacing may be a more effective and reliable form of pacing in these instances and has been shown to require fewer lead revisions, yield low er pacing thresholds, greater R-wave amplitudes, and similar paced QRS duration compared with HBP in patients with AV block. 47 , 118

Conduction system pacing for atrioventricular block in reduced left ventricular ejection fraction $(\leq\!40\%)$

Current ESC pacing guidelines state, based on several RCTs, 119 – 121 that BiV-CRT rather than RVP is recommended for patients with HF with re duced EF (HFrEF, LVEF ${\leq}40\%$ ) who have AV block and an indication for ventricular pacing, regardless of New York Heart Association (NYHA) class and QRS duration, in order to reduce morbidity; this includes pa tients with AF. 1 The largest relevant trial is BLOCK HF, 119 which included 208 patients who had LVEF $<35\%$ ( $30\%$ of the total cohort of the trial). HOBIPACE 120 and COMBAT 121 (which both only included patients with LVEF $<40\%$ ) totalled 90 patients together. Therefore, the evidence for the efficacy of BiVP in the context of AV block is relatively scarce com pared with that of BiV-CRT for treating HF.

The 2023 HRS/APHRS/LAHRS guidelines on physiological pacing do not give any specific recommendations for pacing in patients with AV

block and $\mathsf{L V E F}<35\%$ , and refer the reader to the recommendations for treating HF. 12

There is a paucity of evidence regarding CSP in AV block patients with LVEF $<40\%$ . Randomized trials comparing conduction system pa cing cardiac resynchronization therapy (CSP-CRT) to BiV-CRT typically do not indicate the percentages of patients with AV block, but these presumably are low 3 , 68 , 122 – 124 (see Supplementary material online, Table S1 ). Randomized trials involving CSP as a treatment modality focus ing on patients with AV block and LVEF $<\!40\%$ have not been performed 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 $\mathsf{L V E F}<40\%$ . They mostly included patients with LVEF < $50\%$ and a mix of indications for CRT, AVNA, or device upgrade and a minority of patients with AV block, without separate reporting of results in these subgroups 9 , 40 , 49 , 69 , 125 – 135 (see Supplementary material online, Table S1 ). Patients included in observational studies dedicated to CSP in AV block had an average LVEF of ${>}50\%$ . 80 , 118

A small $(n=50)$ ) observational case–control matched study evalu ated the benefits of CSP in patients with LVEF ${\leq}45\%$ who were candi dates for CRT due to either AV block or an upgrade from RVP. 130 Conduction system pacing (with either HBP or LBBP) and BiVP re sulted in similar echocardiographic response and LVEF improvement at 6-month follow-up; decreased mitral regurgitation and improved functional class were observed with CSP.

In patients with HF, CSP implant success rate is lower compared with bradycardia indication. 9 In the specific population with complete AV block and LVEF ${\leq}40\%$ $(n\,{=}\,77)$ , an $88.3\%$ implant success rate has been reported. 136 Owing to the pros and cons of CSP and of BiVP for treating AV block in patients with LVEF < 40%, it is a matter of de bate whether one or the other pacing modality should be preferred. This is particularly the case in patients with a narrow QRS, 137 where

 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

BiVP circumvents the His–Purkinje system and delivers myocardial pa cing. Conduction system pacing may provide a more physiological form of pacing with similar dyssynchrony and strain correction over time. 138 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 intra-Hisian level, and is therefore amenable to correction with CSP (which was successful in $97\%$ of patients). 118

Trials studying CSP in AV block and LVEF ${\tt<}40\%$ are ongoing and vary in the patient population recruited, and usually also include a CRT indication (e.g. Left vs. Left, CONSYST-CRT 2, etc.). The LVEF cut-off differs but generally includes patients with LVEF ${\tt<}40\%$ as a subset. The interventions broadly compare CSP with RVP or BiVP depending on the patient cohort (c.f. Figure 11 and supplementary material online, Table S9 ).

A summary for CSP indications in AV block, as opposed to BiVP and to RVP, is shown in Figure 5 (for HOT/LOT-CRT, see relevant section).

 It is advised to avoid RV pacing inpatients with AV block, LVEF , and frequent $(>\!20\%)$ anticipated ventricular pacing 119 – 121

 a The decision for implanting HBP vs. LBBAP can be based on the relevant advice Table and Table 2 . In patients undergoing HBP, a backup lead may be useful, particularly if the block is infra-nodal or in case of sensing issues.

Conduction system pacing in atrioventricular node ablation

In patients with rapidly conducted and symptomatic atrial tachyarrhyth mias refractory to medical or ablative therapy, AVNA is an established therapeutic strategy. In patients with atrial fibrillation (AF), the combined effects of loss of AV synchrony, beat-to-beat irregularity, and rapid ven tricular rates can lead to a reduction in cardiac output with adverse car diac remodelling, and HF symptoms. These patients may benefit from a ‘pace-and-ablate’ strategy ( Figure 6 ). 140 – 143 In a recent network meta-analysis comparing AF therapies including pharmacological treat ment and different AF ablation modalities (radiofrequency, cryoballoon, and surgical ablation), the ‘pace-and-ablate’ strategy showed a consistent 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 LVEF were significantly improved with AVNA + RVP in observational and randomized studies in comparison with pharmacological rate con trol (see Supplementary material online, Table S2 ). 145 – 160 However, concerns about the potential deleterious effects of RVP have led to the emergence of BiVP as an alternative modality for patients undergo ing AVNA. Multiple studies including RCTs comparing BiVP with RVP have shown variable benefits of BiVP in terms of QoL, 6-min walking dis tance, and/or LVEF in patients undergoing AVNA (see Supplementary material online, Table S3 ). 161 – 169 In the APAF-CRT mortality trial, 169 133 elderly patients with severely symptomatic permanent AF, narrow QRS $(\leq\!110\,\mathsf{m s})$ ), and at least one HFH during the previous year were ran domly assigned to AVNA + BiVP vs. pharmacological rate control. A sig nificant absolute mortality reduction of $18\%$ was obtained with AVNA + BiVP at 4-year follow-up $[11\%$ mortality in the AVNA $^+$ BiVP group vs. $29\%$ in the pharmacological rate control group (HR 0.26, $95\%$ CI 0.10–0.65)].

The different available pacing modalities for combination with AVNA are outlined in Table 3 . Conduction system pacing appears to be an ef fective method for pace-and-ablate therapy due to its ability to maintain normal ventricular activation in this pacing-dependent group who are at risk of developing PICM, particularly if the baseline QRS is narrow. This approach is further supported by previously reported positive out comes of BiVP in this setting.

The 2021 ESC guidelines on cardiac pacing and cardiac resynchroni zation therapy (CRT) stated that the ‘pace-and-ablate’ strategy using HBP with an additional RV backup lead may be considered. 1 Since its publication, new data exploring the ‘pace-and-ablate’ strategy using both HBP and LBBAP have become available. Most of the currently published studies have an observational and retrospective design, with limited prospective and randomized data, and have included most ly patients with baseline impaired LVEF and HF. 5 , 76 , 170 – 184 Overall, CSP was associated with a similar improvement in LVEF, NYHA, and QoL parameters when compared with BiVP but was superior to RVP (see Supplementary material online, Table S4 ). A single-centre retrospective study included 223 patients who underwent AVNA and who received either CSP ( $\dot{n}=110$ , HBP 84, LBBAP 46) or RVP ( $(n=113)$ ). 179 After a mean follow-up of $27\pm19$ months, LVEF significantly increased in both groups but the combined primary outcome of time to death or HFH was significantly reduced with CSP ( $48\%$ for CSP vs. $62\%$ for RV myo cardial pacing, HR 0.61, 95% CI 0.42–0.89, $P<0.01$ ), although patients in the RVP group were sicker with significantly lower baseline LVEF and wider baseline QRS duration. In the ALTERNATIVE-AF trial, 177 50 pa tients with persistent AF and LVEF ${\leq}40\%$ with $\mathsf{Q R S<120m s}$ or RBBB underwent AVNA and sequentially received 9 months of treatment with both HBP and BiVP in a randomized, crossover trial. Improvement in LVEF was significantly greater with HBP compared

ESC/EHRA clinical consensus statement

 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|| | LV synchrony|Impaired|||May be complex| |LVEF|Impaired| Preserved/restored Preserved/restored | Preserved/restored|Preserved/restored| | Pacing threshold|LOW|| Preserved/restored High |Preserved/restored| |Lead-related complications|LOW| High Intermediate ||LOW>| |Battery longevity|┌ong|Shorter|High|LOW| |AVN ablation||| Shorter|rong| | Risk of rise in capture threshold due to AVN ablation| Easy ¥70 | Easy ¥70號 | Challenging Yes |Easy| | Risk of recurrence of AV conduction at follow-up|LO|LOW||¥70| |Backup lead advised|¥70|¥70號| Intermediate Yes |LOW| |||||¥70|

with BiVP, with similar improvement in NYHA class, LV end-diastolic diameter, and B-type natriuretic peptide levels. In a retrospective study, the outcomes of 68 patients with permanent AF and uncontrolled heart rate undergoing AVNA and LBBAP were compared with a con trol group including both RVP $(n\,{=}\,44)$ and BiVP ( $(n=24)$ using propen sity matching. 183 Patients with LBBAP had a higher LVEF improvement and a lower 1-year rate of the composite score of HFH or mortality, whereas AVNA procedure data and complications were comparable.

Notably, CSP allows the use of a more straightforward device with less hardware in the venous system and usually a relatively simple pro cedure in experienced hands. As a result, in the presence of specific pa tient populations where a simpler device or procedure is desirable (e.g. older and frail patients or those requiring a smaller device), CSP could be chosen over BiV-CRT.

Direct comparisons between HBP and LBBAP in patients undergoing AVNA are scarce. Improvement in LVEF was similar between the two

14

pacing modalities in a series of 162 patients with propensity-matched groups 52 and in a small randomized crossover study with 23 pa tients. 59 A prospective, multicentre study reported the incidence of device-related complications in patients undergoing AVNA and implantation of either BiVP $(n=263)$ ) or CSP (HBP $n=68$ , LBBAP $n\,{=}\,42$ ). 181 At 12-month follow-up, the risk of device-related compli cations was comparable ( $5.7\%$ for BiVP, $4.4\%$ for HBP, and $2.4\%$ for LBBAP, $P=0.65$ ) as was the risk of HFH (2.7, 1.5, and $2.4\%$ , respect ively, $P=0.85$ ). However, compared with BiVP and HBP, LBBAP was associated with shorter procedural and fluoroscopy times, lower pa cing thresholds, and longer estimated residual battery longevity. Similar findings were reported in 164 patients who underwent either HBP $\mathit{(n=68)}$ ) or LBBAP ( $(n=96)$ ) and AVNA, with shorter mean pace maker implantation and AVNA times for LBBAP. 182 Higher acute and 12-month follow-up complete AV block rates were also obtained with LBBAP in comparison with HBP with a comparable improve ment in NYHA class and LVEF. A significant rise in the pacing thresh old > 1V occurred in $11\%$ of HBP patients (with one patient undergoing lead revision) with no such cases among LBBAP patients. The relatively short follow-up in these two studies should be noted when commenting on long-term safety. In a multicentre series of 98 AVNA patients with CSP (48 HBP, 50 LBBAP), $a>1\lor$ rise in cap ture threshold was noted in $14.5\%$ patients with HBP, without any lead issues in the LBBAP patients. 53

The risk of threshold rise due to AVNA rises exponentially when the ablation site is < 6mm from the HBP lead tip and is not mitigated by cryoablation. 184 Due to the risk of threshold rise and loss of capture, the 2021 ESC pacing guidelines stated that a backup lead should be con sidered in HBP patients who are planned for AVNA 1 (a backup LBBAP lead is an option 185 ). Notably, a backup lead may be considered accord ing to the HRS document on physiological pacing. 12 Experienced opera tors who perform HBP implantation and AVNA in the same session may opt to not implant a backup lead. However, a backup lead may otherwise be useful in the interest of patient safety.

Due to the potential issues with HBP in the setting of AVNA (difficult ablation with risk of rise in capture thresholds and recurrence of AV conduction, requirement for a backup lead, etc.), LBBAP is the pre ferred CSP option.

Ongoing large, multicentre, RCTs are currently evaluating the role of CSP in patients undergoing AVNA in comparison with RVP (included in the patient population of PROTECT-HF, NCT05815745), pharmaco logical treatment (PACE-FIB, 186 NCT05029570 and RAFT P &A study, NCT06299514) or AF ablation (ABACUS, NCT06207383). They will provide the definite answers as to superiority of one treatment modality over another.

A summary of indications for CSP in the setting of AVNA, as op posed to BiVP and RVP, is shown in Figure 7 (for HOT/LOT-CRT, see relevant section).

 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

 Advice: CSP for AVNA .................................................................. Advice TO DO It is advised that CSP is implanted as a rescue strategy if coronary sinus lead implantation fails May be appropriate TO DO It may be appropriate that patients undergoing HBP as a primary strategy for ‘ablate-and-pace’ therapy receive a ‘backup’ ventricular lead in the interest of safety, taking into account operator experience and whether the procedures are performed concomitantly or in a staged manner 1 , 117 In patients scheduled for AVNA, it may be appropriate that LBBAP is preferred over HBP to simplify the ablation, avoid increase in capture thresholds and recurrence of AV conduction, and avoid requirement for a backup lead In patients with an LVEF ${>}40\%$ undergoing AVNA, it may be appropriate to implant CSP in lieu of RVP or BiVP in order to preserve LV function and improve HF symptoms. 5 , 76 , 172 , 173 , 175 , 179 – 181 , 183 In patients with an LVEF $\leq40\%$ undergoing AVNA, it may be appropriate to implant CSP in lieu of BiVP in order to improve LV function and HF symptoms 170 , 171 , 174 , 176 , 178 In the presence of specific patient populations where a simpler device is desired (e.g. frail patients, patients with limited life expectancy, or those requiring a smaller device), it may be appropriate to choose CSP instead of BiVP as a primary strategy, taking into account operator experience

Conduction system pacing in sinus node dysfunction

There is good evidence that in patients with sinus node dysfunction (SND), unnecessary RVP should be minimized to avoid AF and HF, par ticularly if systolic function is impaired or borderline. 20 , 187 This may be achieved by programming long AV intervals or specific algorithms, which may, however, lead to long PR intervals with AV dyssyn chrony. 101 , 188 , 189 Atrial pacing significantly lengthens PR intervals 190 and may even result in AV block due to decremental conduction during rate-adaptive pacing. Implanting the atrial lead first in these patients al lows for evaluation of AV conduction to help decide whether CSP may

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.

Sinus node dysfunction and AF often coexist with $40–70\%$ of patients 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 stance, having a CSP lead from the onset may be desirable. In a recent analysis using Medicare data in patients with dual-chamber pace makers, as many as $37\%$ of patients implanted with CSP had SND as the indication for pacing. 51

Due to the paucity of data, it was decided not to formulate advice on this topic for the time being.

Conduction system pacing for heart failure without bradycardia pacing indication

Left bundle branch block causes interventricular dyssynchrony and de layed activation of the LV, which negatively impacts cardiac function, es pecially in patients with HFrEF. 192 Landmark clinical trials have clearly demonstrated that BiV-CRT enhances QoL, reduces LV remodelling, and decreases cardiovascular events such as hospitalizations and mor tality in patients with impaired LV function and LBBB, and this effect is less pronounced in patients with a less wide QRS and non-LBBB. 193 , 194 The efficacy of BiV-CRT stems from correcting the delayed LV electric al activation through pacing, which involves leads placed in the RV and an appropriate branch of the coronary sinus to deliver epicardial LV stimulation. However, despite significant advancements in delivery tools and leads, BiVP is not always feasible. 195 Challenges in coronary sinus cannulation, a lack of suitable coronary sinus tributaries, high pa cing threshold, or phrenic nerve capture hinder successful implantation in ${\sim}5{-}10\%$ of cases. 73 , 195 Additionally, one-third of patients do not re spond to BiV-CRT, with the rate of non-responders remaining consist ent over time, particularly among patients with non-LBBB or QRS complexes $<150~\mathrm{ms}$ . 66 , 196 , 197 Given these challenges, alternative pacing modalities to deliver CRT have been explored. In recent years, CSP has gained attention as a potential alternative to BiVP by restoring resynchro nized ventricular activation. 3 , 123 , 198 – 200 Cardiac resynchronization therapy with CSP has been employed either as the initial therapy for CRT, 12 in cases when BiVP is not possible and as a rescue approach. 1 , 12 , 201

His bundle pacing

His bundle pacing and LBBAP restore LV synchrony to a greater extent, with superior acute haemodynamic response, compared with BiVP. 42 Permanent HBP was first reported as an alternative to BiVP for CRT in 2013. 201 In a randomized crossover study of 29 patients referred 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 ive, randomized controlled trial aiming to assess the feasibility and efficacy of HBP as a first-line strategy compared with BiV-CRT. 2 Among the 41 patients enrolled, HBP demonstrated superior QRS narrowing with a trend to greater improvement in LVEF compared with BiV-CRT. However, the study was limited by high crossover rates towards the BiV-CRT group, mainly due to the inability to correct the QRS complex because of non-specific intra-ventricular conduction delays.

The Direct His pacing as an Alternative to BiVP in Symptomatic HFrEF Patients with True LBBB (His-Alternative) trial randomized 50 patients to HBP vs. BiV-CRT. 68 In the HBP group, $72\%$ achieved suc cessful LBBB correction, and HBP provided comparable clinical and echocardiographic improvements, though with higher pacing

16

thresholds. When LBBB correction can be achieved with HBP, it is a reasonable alternative to BiV-CRT, especially when effective CRT can not be achieved with an LV/coronary sinus lead (see Supplementary material online, Table S5 ).

Despite these encouraging preliminary results, technical difficulties in achieving the target pacing site, unsatisfactory electrical lead para meters, especially regarding increases in pacing thresholds over time, and the inability to correct infra-Hisian or more distal conduction dis ease limit the adoption of HBP as a standard alternative to conventional BiV-CRT. 71 , 202 , 203

In patients with HFrEF, impaired LV filling due to AV dyssynchrony resulting from prolonged PR intervals may contribute to pump fail ure. 188 The HOPE-HF study 204 was a randomized double-blind cross over study in 167 patients with HFrEF, $\mathsf{P R}>200$ ms (average 249 ms) and either QRS < 140 ms or RBBB and found no meaningful benefit of HBP over backup ventricular pacing. Therefore, there is currently insuf ficient evidence that CSP-CRT is indicated solely for the purpose of correcting slight PR prolongation in patients with HF.

Left bundle branch area pacing

With the above-mentioned limitations of HBP, LBBAP might address these issues by capturing the conduction system more distally, with more stable pacing parameters. Following the encouraging results in bradycardia indications, 115 , 205 LBBP was investigated in patients with HF and CRT indications. 206 Observational data suggest than conduction system capture with LBBP (rather than LVSP) impacts clinical outcome in patients with CRT indications, 39 , 40 but this deserves further study as results are heterogenous. 207

In a cohort of 325 patients with $\mathsf{L V E F}<50\%$ and an indication for CRT, LBBP was successfully achieved in $85\%$ of patients. 69 This was asso ciated with a significant reduction in QRS duration (from $152\pm32$ to $137\pm22\,\mathsf{m s},P<0.01)$ ) and an improvement in LVEF at 6-month follow-up (from $33\pm10$ to $44\pm11\%$ , $P<0.01$ ). Additionally, data suggest that patients with RBBB may benefit from LBBP, with QRS narrowing, a re duction in interventricular mechanical delay, 208 and an increase in LVEF. 67

In a large retrospective study of 1778 CRT patients, LBBP was com pared to BiVP. 134 After a mean follow-up of $33\pm16$ months, time to death or HFH was superior in the LBBP group (HR 1.5, $95\%$ CI 1.2– 1.8, $P<0.001$ ) with significantly reduced HFH and a trend in improved survival. At follow-up, NYHA and LVEF were also significantly superior with LBBAP. The results were consistent in patients with LBBB (a sub group which is most likely to respond to BiVP).

The MELOS study, a large observational registry on LBBP outcomes, reported a lead implantation success rate of $82.2\%$ for HF indications and an overall complication rate of $11.7\%$ , including both acute and late complications. 9 This rate is comparable to previously reported data for BiVP implantations. Specifically, $8.3\%$ of the complications were related to the LBBP lead, including $3.7\%$ of acute LV perforations, which were managed by lead repositioning and were not associated with adverse clinical consequences.

There are currently three published modest size randomized con trolled trials with limited follow-up duration comparing LBBAP and BiV-CRT. The LEVEL-AT study included 70 patients with HF with LVEF $<35\%$ , LBBB ${>}130$ ms, or non-LBBB $\stackrel{\cdot}{>}150\,\mathrm{\mus}$ . 123 Patients were randomized 1:1 to CSP (4 HBP, 31 LBBAP) or to BiVP. Conduction system pacing was non-inferior in terms of reduction of LV activation time (LVAT) measured by ECG imaging (the primary end point), HFH or mortality (combined endpoint), LV remodelling (LV end-systolic volume), improvement in NYHA, and QRS shortening. The LBBP-RESYNC trial included 40 patients in sinus rhythm with non-ischaemic cardiomyopathy and LBBB (i.e. at high likelihood of respond ing to BiV-CRT), randomized to either LBBP or BiVP. 209 At 6-month follow-up, LBBP was associated with a significantly greater improve ment in LVEF compared with BiVP (mean difference: $5.6\%$ ; $95\%$ CI:

0.3–10.9; $P\,{=}\,0.039)$ ). The HOT-CRT trial 124 included 100 patients with LVEF $<50\%$ and an indication for CRT and randomized patients to either CSP-CRT (39 LBBAP, 5 LBBAP $^+$ coronary sinus pacing, 4 HBP, and 2 crossover) or BiV-CRT (41 BiVP and 9 crossover). The pri mary endpoint was improvement in LVEF at 6 months, which was greater with CSP-CRT compared with BiV-CRT ( $12.4\pm7.3$ vs. $8.0\,\pm$ $10.1\%$ , $P\,{=}\,0.02$ ). Complications were more frequent in the BiV-CRT group, mainly driven by rises in coronary sinus lead pacing threshold and phrenic nerve capture (see Supplementary material online, Table S5 ).

In a meta-analysis of seven randomized controlled trials comparing 200 CSP-CRT patients with 208 BiV-CRT patients, CSP-CRT was su perior in terms of improvement in NYHA class and LVEF, with no sig nificant differences in HF hospizalization and mortality over limited follow-up time. 210

Conduction system pacing in non-left bundle branch pacing patients

Patients with HF and non-LBBB present a significant challenge in clinical practice, as data from large BiV-CRT clinical trials do not indicate fa vourable outcomes for these patients. 211 According to the 2021 ESC guidelines, BiVP should be considered for patients with non-LBBB and a QRS duration ${>}150$ ms, and a Class IIb recommendation for those with a QRS duration of 130–150 ms, without any indication for CSP. 1 The 2023 HRS/APHRS/LAHRS guidelines attribute a Class 2b indication for CSP in patients with non-LBBB with NYHA III–IV + QRS 120–149 ms, as well as NYHA $||+\mathsf{Q R S}\ge\!150~|$ ms. 12

His bundle pacing has been shown to achieve electrical resynchroniza tion and improve clinical outcomes in a small multicentre observational study with 37 patients with right bundle branch block (RBBB) and re duced LVEF. 66 Similarly, data from some observational studies indicate that LBBAP is a feasible alternative for delivering CRT or physiological ventricular pacing in patients with RBBB, HF, and LV dysfunction. 67 , 208 The number of patients with non-specific intra-ventricular conduction delay (NIVCD) who have been studied with LBBAP is very small, and treatment efficacy in this patient subgroup has not been reported separ ately. 69 No randomized trial has yet assessed the benefit of CSP-CRT compared with BiV-CRT in this population, and further studies are needed to establish its advantages. Observational data on LBBAP com bined with coronary sinus pacing, known as left bundle branch-optimized CRT (LOT-CRT), have shown encouraging results in patients with NIVCD and are discussed later. 212 , 213

Conduction system pacing in patients with left ventricular ejection fraction 36–50%

Indications for BiV-CRT in patients with an LVEF ${\leq}35\%$ are well estab lished. However, the criteria for patients with HF with an LVEF of 36 $-50\%$ are less clear. In a substudy of the multicentre PROSPECT study, patients with NYHA functional Class III − IV status and a QRS duration ${>}130$ ms who had an LVEF ${>}35\%$ and underwent BiV-CRT, experi enced significant clinical benefits, as well as structural improvements compared with baseline. 214 A recent randomized crossover trial in 76 patients with LVEF $35{-}50\%$ and LBBB showed significant improve ment in LVEF and ventricular remodelling after 6 months of CRT. 215

There is also scant evidence of CSP efficacy in HF patients with LVEF $>35\%$ , who do not have an indication for pacing. Most studies on CSP in patients with HF and mildly reduced ejection fraction (HFmrEF) also included a mix of patients with AV block or PICM. A meta-analysis 216 and some additional series 217 – 219 reported together $<\!300$ HFmrEF pa tients without a pacing indication, the largest of these being I-CLAS 219 which included 168 such patients. Although the results were not re ported separately for this specific subgroup of patients with HFmrEF and LBBB, 260 patients with CSP had significantly lower composite

ESC/EHRA clinical consensus statement

outcome of death or HFH compared with 75 patients who had re ceived BiVP (HR 0.49, $P\,{=}\,0.006$ ). However, randomized, large pro spective studies are needed to evaluate the effects of CSP-CRT on patients with HF and an LVEF ${>}35\%$ .

Conduction system pacing cardiac resynchronization therapy in non-responders to biventricular cardiac resynchronization therapy

A substantial number of patients do not respond to CRT (in terms of symptoms and/or ventricular remodelling). Among the different causes, a suboptimal resynchronization with BiVP can be responsible for non-response, especially in patients with remaining QRS prolongation des pite BiVP. To optimize the quality of cardiac resynchronization, CSP has emerged as a potential solution. A multicentre international observa tional study tested the hypothesis of whether LBBAP could be a viable alternative in 44 BiV-CRT non-responders with a mean QRS duration of $150\pm22$ ms with BiVP, at a median of 5.1 years after the original im plant. This strategy was associated with a significant shortening of QRS duration, improvements in NYHA functional class, and improved echo cardiographic parameters (LVEF and LV end-systolic and end-diastolic volumes). However, death or hospitalization due to HF occurred in $30\%$ of patients at 1-year follow-up. 139

Another non-randomized, prospective, multicentre, case–control study evaluated the feasibility, clinical efficacy, and outcomes of upgrad ing to LBBAP in 48 BiV-CRT non-responders. The results indicated that

upgrading to LBBAP is both feasible and effective, with significant clinical improvements being observed. 220 This makes LBBAP a potential pacing strategy, albeit with limited evidence at this point, for patients who do 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.

Clinical implications

Conduction system pacing cardiac resynchronization therapy , particu larly with LBBP, has increasingly gained support as an alternative to con ventional BiV-CRT due to encouraging initial results (even compared with patients with the highest likelihood of responding favourably to BiV-CRT), simpler (and more economical) pacing systems, and enthu siasm generated by new pacing techniques. However, the lack of data from large randomized studies refrains routine adoption of this ap proach over BiV-CRT in daily clinical practice. While awaiting results from ongoing large randomized controlled trials assessing the role of CSP in patients with HF (see section below), CSP-CRT may be used as an alternative to BiV-CRT in selected patients. This is particularly ap plicable as rescue therapy when effective CRT cannot be achieved due to the inability to place a coronary sinus lead in a suitable, stable loca tion, or in non-responders to BiV-CRT. 139 Another option is combining CSP and coronary sinus-based CRT, which is covered below.

A summary of indication for CSP-CRT, as opposed to BiV-CRT, is shown in Figure 8 (for PICM and HOT/LOT-CRT, see later correspond ing sections).

 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


His-optimized and left bundle branch pacing-optimized cardiac resynchronization therapy

Delineation and rationale

Two hybrid pacing modalities combining CSP and coronary sinus pacing were recently introduced: His bundle-optimized CRT (HOT-CRT) 221 and left bundle branch-optimized CRT (LOT-CRT). 222 In the setting of sHBP without correction of RBBB, RVP may be used to correct RV electrical dyssynchrony and potentially also qualify as HOT-CRT. 99 The rationale for adding a coronary sinus lead to a CSP lead (or vice versa, depending on the initial CRT strategy) stems from the limitations of CSP-CRT, and BiV-CRT and the not infrequently ob served suboptimal electrical, echocardiographic, and clinical outcomes with each of these CRT modalities. Delayed activation of the LV lateral

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, electrical uncoupling, myocardial scar, and functional conduction block. In patients with wider QRS, non-typical LBBB and more advanced HF, both mechanisms (focal proximal lesion and distal delay) often coexist. Analysis of V 6 RWPT—an electrocardiographic marker of LV lateral wall activation time, indicates that such conduction delay cannot be cor rected by CSP alone. 223 In patients with narrow QRS complexes or iso lated RBBB, the V 6 RWPT during LBBP closely follows the intrinsic native activation times and remains within the norm for the V6 intrinsic deflection time (i.e. 50–60 ms). This value plus the left bundle branch latency of 20–30 ms yields physiologically paced $\mathsf{V}_{6}\mathsf{R W P T}$ values of 70–90 ms. However, in patients with wide baseline QRS complexes due to LBBB or NIVCD, V 6 RWPT values during confirmed left bundle branch capture are often non-physiological $(\mathord{>}90~\mathsf{m s})$ , suggesting that despite proximal LBB capture, additional LV conduction delay remained and coronary sinus pacing may be required to correct this. 223 Furthermore, in a significant percentage of patients in whom LBBP is attempted, only LVSP is achieved, 9 resulting in a potentially important additional delay in LV lateral wall activation.

On the contrary, conventional BiV-CRT is also limited in its ability to fully restore physiological LV activation. This is due to several factors: potentially desynchronizing effects of myocardial pacing with the RV lead, localized non-physiological epicardial LV pacing, latency, and sub optimal LV lead position (paraseptal/apical) due to unfavourable cardiac venous anatomy and/or LV scar. Failure of BiV-CRT to restore physio logic activation may manifest as QRS prolongation rather than narrow ing. This is observed in one-third of BiV-CRT patients and is associated with a poor prognosis compared with patients with narrowing of QRS after BiV-CRT. 224

The combination of CSP and coronary sinus pacing/RVP ( Figure 9 ) may address some of the limitations of both techniques, providing more physiological LV activation and thus a narrower QRS and a more efficient form of CRT. Although more data from long-term RCTs are needed, this approach may be pursued in difficult cases with suboptimal electrocar diographic results of CSP or coronary sinus pacing-based CRT at im plantation. Furthermore, His-optimized and left bundle branch pacing-optimized cardiac resynchronization therapy (HOT/LOT-CRT) is an option in patients who do not respond clinically to BiV-CRT or to CSP-CRT and in whom the paced QRS is considered suboptimal.

Published data and practical 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 tients with a mean LVEF ${<}30\%$ and compared HOT/LOT-CRT with BiVP, LBBAP, or HBP. The principal outcomes and conclusions of these studies are presented in more detail in Supplementary material online, Table S6 . All studies showed superior electrical resynchronization (QRS narrowing or LVAT reduction) and some also superior echocardio graphic or haemodynamic outcomes when LOT-CRT was compared to BiVP and/or CSP alone. The absence of studies examining mortality with long-term follow-up and randomized trials represents a significant limitation to the current understanding of the benefits and risks of hy brid pacing approach for CRT. A further significant practical limitation is the lack of uniform criteria for the addition of a coronary sinus lead to a CSP-based CRT system and the increased complexity of the proced ure. The prevailing expert opinion is that there is no necessity to add a coronary sinus lead to a CSP-based CRT system if the obtained paced QRS already indicates a physiological, i.e. fast and synchronous LV acti vation. If the paced QRS is not deemed satisfactory (based on criteria

ESC/EHRA clinical consensus statement

 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.

LBBAP, left bundle branch area pacing; RWPT, R-wave peak time.

Table 4

Criteria used to determine whether HOT/LOT-CRT may be required after having implanted a CSP lead

Paced QRS width

Presence of conduction system capture

or aVL RWPT interpeak interval

Paced QRS notching

QRS axis (normal vs. axis deviation)

Anatomical position of LBBAP lead (basal, mid, or apical)

Absence or minimal acute haemodynamic response to pacing

outlined in Table 4 ), there may be benefit from the HOT/LOT-CRT ap proach ( Figure 10 ).

A recent randomized study investigating CSP-based vs. BiVP-based CRT strategies used that criterion and determined that LOT-CRT was necessary for $10\%$ of CRT candidates in the CSP-CRT arm. 124 The multicentre CSPOT study, which specifically addresses this ques tion, found that the haemodynamic benefit of LOT-CRT over LBBAP was present when there was distal conduction disease, as indicated by a longer QRS duration $(>\!171$ ms, which was the mean value for the group) or when the obtained QRS was suboptimal (lacking a ter minal r wave in lead V1). When both these conditions were met, the benefit of LOT-CRT was most pronounced, with a $14.5\%$ greater im provement in LV dP/dtmax and a 20.8 ms shorter QRS duration than during LBBAP. 213

The selection of LOT-CRT over HOT-CRT or vice versa is currently based on the operator’s preference, experience, and ability to imple ment HBP and LBBP, as well as on case-dependent anatomical and physiological factors that influence the feasibility of HBP and LBBAP. It is important to note, however, that LOT-CRT usually offers superior pacing parameters and normal sensing without compromising arrhyth mia detection in cardiac resynchronization therapy defibrillator (CRT-D) systems, while HOT-CRT may provide superior QRS nar rowing due to the direct recruitment of the right bundle branch in the setting of LBBB.

Patients with permanent AF cannot benefit from algorithms which adjust AV delays to promote fusion between intrinsic conduction and ventricular pacing, used in BiV-CRT. 228 In these patients, HOT-CRT with HBP (usually using the off-label configuration of connecting the lead to the unused atrial channel of the generator) combined with cor 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/ LOT-CRT, it is pertinent to note that, unlike CSP-CRT, these pacing modalities do not deviate too much from conventional BiV-CRT as they also include a coronary sinus lead (which is considered the dom inant factor in conventional resynchronization) and a septal pacing lead (due to non-selective septal capture during HBP or LBBAP). In con trast to CSP-CRT, the HOT/LOT-CRT approach does not replace key BiV-CRT components, but builds on them. Therefore, it is anticipated that favourable major endpoint results from CRT trials will be main tained with HOT/LOT-CRT. Nevertheless, operator experience and patient risk need to be carefully taken into account, particularly when evaluating upgrade procedures. Randomized clinical trials are still needed to determine the safety of a more complex procedure and whether the superior electrical resynchronization translates into hard outcomes such as mortality and hospitalization for HF.

20

 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.

Advice: HOT/LOT-CRT

Strength of

evidence

..................................................................

May be appropriate TO DO

 It may be appropriate to propose HOT/LOT-CRT at implantation in case of suboptimal electrocardiographic results of CSP or BiVP, taking into account operator experience and patient risk. It may be appropriate to propose HOT/LOT-CRT as an upgrade procedure in selected CRT candidates in case of suboptimal clinical and electrocardiographic result with CSP-CRT or BiV-CRT, especially in the setting of non-specific intra-ventricular conduction delay or mixed conduction disease, a, 99 , 212 , 213 , 221 , 222 , 226 , 227 taking into account operator experience and patient risk.

 a Mixed conduction disease refers to association of bundle branch/fascicular conduction delay with peripheral conduction disease and/or intra-myocardial propagation delay, which cannot be corrected by CSP alone.

Upgrade to conduction system pacing

Device upgrade can be considered in patients with a cardiac implantable electronic device (CIED) in whom worsening of ventricular function oc curs, either due to disease progression or secondary to PICM, defined as a decline in LVEF (with variable cut-offs in different studies, usually to ${<}40–50\%$ or decline by ${\geq}10\%$ from baseline 229 ) secondary to chronic ventricular pacing. Upgrade to BiVP in these patients has been shown to improve LVEF in randomized controlled trials. 230 – 232 A meta-analysis of six RCTs (including 161 patients, baseline LVEF $35\pm10\%)$ and 47 ob servational studies (including 2644 patients, baseline LVEF $26\pm8\%)$ showed improvement in LVEF, NYHA class, QoL, and brain natriuretic peptide (BNP) levels. 230 The more recent BUDAPEST CRT trial rando mized 360 pacemaker patients with LVEF ${\leq}35\%$ (mean $25\%$ ) who had ${>}20\%$ RVP with paced $\mathtt{Q R S}\!>\!150$ ms to an upgrade with either an im plantable cardioverter–defibrillator (ICD) or CRT-D. The primary out come was the composite of all-cause mortality, HFH, or ${<}15\%$ reduction of LV end-systolic volume assessed at 12 months, with a odds ratio of 0.11 $(95\%\subset|\:0.06–0.19)$ in the CRT-D arm. 232

Conduction system pacing has been shown to achieve greater im provement in LVEF and reduction in QRS duration in small short-term RCTs 68 , 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

Conduction system pacing therefore might be expected to be a suitable alternative to BiVP in patients requiring device upgrade for PICM. Several small observational studies have already shown this with a sig nificant LVEF increase in patients undergoing CSP, as well as reductions in LV end-systolic volume, improvement in functional capacity, and QRS duration, with similar improvements observed with both HBP and LBBAP. 129 , 230 , 233 – 239 These observational studies show scope for im provement in those patients with mild–moderate LV impairment as well as those with severe LV dysfunction (see Supplementary material online, Table S7 ). In a meta-analysis of eight observational stud ies including 217 patients (mean baseline LVEF $38.4\%\pm\:8.8$ ), LVEF, NYHA, and QoL were significantly improved by upgrade to CSP. 230

Predictors of PICM or HF development after RVP include a lower baseline LVEF, a larger LV end-diastolic diameter, a longer paced QRS duration, and a higher RVP percentage. 233 Importantly, although upgrading to CSP may improve echocardiographic parameters in pa tients with PICM, the mechanism of improvement is unclear and the mechanistic contribution of factors including change in activation pat tern (broad QRS to narrower QRS) and reverse remodelling is un known. That said, in observational studies with up to 12-month follow-up, the improvements in LVEF and LV end-diastolic dimension do not appear to return to the levels seen in individual patients prior to RVP. 128 , 129 , 234 Thus, identifying patients at a higher risk of developing PICM prior to initial device implant may be important when selecting between RVP and CSP, as CSP has been seen to be associated with a lower risk of adverse outcomes associated with PICM and subsequent HF-related hospitalization. 26 , 107

Device upgrade to BiV-CRT may be considered in patients with PICM and LVEF ${\leq}35\%$ according to the 2021 ESC guidelines on cardiac pacing and resynchronization therapy, acknowledging the possibility of 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 able the screening of CIED patients to identify patients who might benefit from a device upgrade. Pacing burden and patient symptom as sessment are likely to form the cornerstone of this evaluation and be complemented by measurement of BNP levels and echocardiographic assessment where indicated. Assessment should be performed in ad vance of all planned generator replacements and considered at any point in a patient’s follow-up if symptoms change or pacing percent age increases. Suitability criteria and threshold for an upgrade might be different contingent on the patient frailty, as well as whether a pa tient is at the elective replacement indicator vs. other earlier time points. A multidisciplinary team opinion should be sought for border line cases.

Current ESC guidelines for upgrade to BiV-CRT suggest waiting until LV dysfunction has become severe $(\leq\,35\%)$ as evidence is strongest in this patient population. However, for de novo device implantation, the ESC guidelines recommend CRT for patients with AV block and $\mathsf{E F<40\%}$ or even milder LV dysfunction after AVNA. 1 The 2023 HRS/APHRS/LAHRS guidelines on physiological pacing recommend the use of CSP approaches for patients with even mild LV dysfunction $(\mathsf{L}\mathsf{V E F}<50\%)$ ). 12 Therefore, the indication of device upgrade requires further attention. The PROTECT UP clinical trial (NCT06052475) is currently recruiting and aims to as sess the benefit of device upgrade on QoL in 155 patients with mild-to-moderate LV impairment only.

Depending on the existing device, several strategies can be used dur ing device upgrade, including use of the same device (abandoning the existing ventricular lead), implanting a new generator with an additional port to connect the CSP lead and avoid abandoning the existing ven tricular lead or performing HOT/LOT-CRT (see Supplementary material online, Figures S1 – S 3) .

Currently, most transvenous defibrillators use the DF-4 standard, in which both the high- and low-voltage (i.e. pacing) connections are in a single pin, thus reducing the need for bulky device headers and facilitat ing connection during implant. Although this advantage has led to wide spread adoption of this type of connection, patients in whom device downgrade is required (i.e. from a defibrillator to a pacemaker) will re quire either the utilization of a DF-4 ICD with deactivation of the high energy capabilities or insertion of an additional IS-1 lead to facilitate the use of a standard pacemaker. 241 Moreover, patients who have a defib rillator implanted may, during their lifetime, require upgrading to a de vice capable of CRT. In this scenario, the use of a DF-1 device may facilitate LBBAP and even avoid having to change the generator if the residual longevity is considered to be adequate (see Supplementary material online, Figure S2 and Table S8 ). When using a DF-1 device, the CSP lead (usually LBBAP, as HBP provides suboptimal sensing para meters) is connected to the IS-1 port in the defibrillator block, and the IS-1 connector pin from the DF-1 lead is capped and abandoned. Thus, CRT can be achieved with a less expensive device and without the need for a new generator. 242 As sensing parameters are favourable in the left bundle branch area, it is anticipated that arrhythmia detection using a LBBAP lead will be similar to that of a lead located in the RV apex. A small study showed no significant differences in the detection duration of an induced ventricular fibrillation episode between left bundle branch area and RV lead locations. 243 Alternative approaches here in clude utilization of a new generator with a DF-4 connector and IS-1 connector for the upgraded lead. This has the advantage of no aban doned lead component.

A concept that is emerging is the use of ICD leads for delivering CSP. 244 , 245 However, the long-term safety and efficacy of this approach needs to be evaluated.

 Po+i alAYblock

22

Patient education and shared decision-making

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 vices, but there is also transvenous vs. leadless pacing. The emergence of CSP in the form of HBP and LBBAP adds even more choices to the decision-making process, making it more complex.

This document therefore reinforces the importance of patient-centred care and shared decision-making between patients and clinicians. 1 , 246 When implanting a pacemaker or CRT, the patient’s preferences, values, and goals of care must be considered and carefully balanced with the best available evidence and the individual risks and benefits.

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 their caregivers can understand. The physician should explore to gether with the patient which of the alternatives best fits their medical needs and personal preferences and goals. It is important to recognize that while shared decision-making should be encouraged, it cannot be imposed; some patients may decide to not engage in the process for various reasons which must be respected. If CSP is considered in the setting of device revision or replacement, it is important to keep in mind that a patient’s personal preferences and expectations may have changed as compared to when the device was first implanted. Therefore, they must be assessed again as part of the shared decision-making process.

Whenever new technologies or approaches for treatment are avail able, shared decision-making including the communication of evidence becomes even more important because there are not only potential benefits associated with them but there typically is less evidence and there is uncertainty regarding mid- and long-term outcomes and risks. Hence, as CSP is still lacking evidence from large, randomized trials, it is of outmost importance to be transparent about what is known and not yet known about this recent pacing modality. Patients should be able to not only understand the potential benefits it may offer compared with more well-established pacing techniques, but also be aware of the lack of evidence that exists regarding aspects such as lead longevity, impact on the device’s battery, experiences with lead removal and the possibil ity of yet unknown long-term risks of CSP. Furthermore, they must be aware of risks associated with the implanter’s experience in CSP; many patients are being treated by physicians who are new to this pacing mo dality and so the operator’s learning curve is another aspect that should not be neglected.

An important aspect of patient’s education should take place follow ing CSP implantation. This is especially relevant in an emergency setting, in particular, when the patient is in a medical centre that is not familiar with new CSP technologies. Such efforts can include supplying the pa tient with a card and / or digital records of the new pacing hardware and programming, as well as establishing a central medical entity that can be approached by patients, as well medical staff in need for specific instruc tions. Finally, establishing in-person and online medical education ap proaches to transfer the knowledge on the new pacing technologies to a broad spectrum of medical personnel could improve patients’ care and long-term safety.


Future perspectives

As CSP continues to gain traction, several ongoing RCTs are underway (see Figure 11 and Supplementary material online, Table S9 ). Several small-/mid-sized studies are expected to be completed soon, while lar ger studies with hard primary endpoints are anticipated to conclude by the end of the decade. The outcomes of these RCTs have the potential to significantly influence the future pacing guidelines directing the broader implementation of CSP in clinical practice across various pa tient groups. Cost-effectiveness analyses of these RCTs will clarify pos sible long-term economic benefits of CSP, potentially influencing reimbursement models. Additionally, there are trials studying treat ment strategies involving CSP such as a pace-and-ablate strategy com pared with AF ablation as well as studies evaluating different types of leads used for CSP.

Although CSP is gaining increasing adoption, many aspects of CSP implantation are likely to be improved in the near future. The pacing leads currently used for CSP were initially designed for conventional endocardial pacing sites, and concerns remain regarding their long-term performance. 10 In particular with LBBAP, the lead is screwed deeply into the septum, creating novel forms of mechanical stress on these leads. Despite several pacing leads being approved for CSP by regulatory boards, data on the impact of these new use conditions on long-term lead performance are scarce. Early conductor fractures, especially with LBBAP, have been reported in case studies or as single-centre experiences. 247 – 251 The recent LIFE-LBBAP study, 252 a large international multicentre registry, showed a lead survival probability of $99.7\%$ at mid-term follow-up, with lead fracture rates varying be tween 0.04 and $0.4\%$ , depending on the lead design. Some of these early conductor fractures with LBBAP have been attributed to implant-related conditions, such as kinking of the lead during septal deployment or excessive angulation within the septum, while others might result from fatigue due to repeated bending over time. 248 , 251 Identifying these mechanisms can guide future developments in CSP-specific lead designs. Prototypes of new dedicated CSP lead de signs are in the pipeline, and the feasibility of using ICD leads for LBBP (HV-LBBAP) 244 , 245 , 253 and leadless CSP systems are being ex plored. 254 , 255 Until dedicated CSP leads become available, proper lead handling and awareness of the potential higher risk of lead failure are advised. Further data on long-term lead performance are needed to implement CSP in future guidelines.

ESC/EHRA clinical consensus statement

|CSP|Atrioventricular block|Heart failure|Heart failure|Heart failure|Heart failure|Heart failure|||| |---|---|---|---|---|---|---|---|---|---| |CSP|LVEF ≥50%|LVEF 40-49%|LVEF 40-49%|LVEF |||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP|||||||||| |CSP||||||||||

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 which allow continuous pacing during lumenless lead deployment, and de livery catheters with a range of shapes to better suit variable anatomies.

For implanting centres lacking a dedicated electrophysiology record ing system, affordable laptop/programmer/tablet-based solutions cap able of continuously recording multilead ECGs and electrograms (both filtered and unfiltered), delivering pacing and equipped with digital callipers for precise measuring of time intervals $(\mathsf{V}_{6}\mathsf{R}\mathsf{V}\mathsf{V P T}$ , $\mathsf{V}_{6}\mathrm{-}\mathsf{V}_{1}$ inter peak intervals, QRS duration, etc.) and current of injury amplitude, would greatly facilitate implantation. Ideally, these systems may auto matically perform these measurements on a beat-to-beat basis during lead deployment, which would standardize them, streamline the pro cedure, and reduce the need for specialized personnel. Eventually, arti ficial intelligence might help to identify conduction system capture or physiological pacing at implantation and follow-up.

Dedicated pulse generators designed for CSP are being developed and 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 monitoring of CIEDs offers several advantages over traditional in-office visits, including the early detection of lead failures, device malfunctions,

and significant arrhythmias through automated alerts. For patients with CIEDs, remote monitoring is part of standard of care. 1 , 256 More data are needed on the usability of remote monitoring specifically in CSP.

Data on the safety of extracting CSP leads are limited, and data on extraction of CSP leads with long lead dwell times are needed. In the recent international TECSPAM study, the success and safety of extract ing HBP and LBBAP leads were high, although the average lead dwell time was only 2 years. Retained distal fragments might pose a risk during the extraction of fractured lead segments, indicating the need for ex pertise with femoral extraction tools in CSP lead extraction. 257 Additionally, specific extraction tools may be needed in the future to extract CSP leads with longer dwell times.

There are scant data regarding CSP in populations such as children, patients with complex congenital heart disease, or specific conditions such as genetic conditions or sarcoidosis. There is a need for more data collection in these populations in the future.

Conclusions

The field of CSP is rapidly moving forward. We are continuing to gain a better understanding of its physiological principles and basic

24

mechanisms (for which there is yet much to learn). Following the cur rently available data from observational studies and small short-term RCTs which report encouraging results for this pacing modality, the foundations to provide solid evidence have been laid for large ongoing RCTs which will serve to strengthen recommendations in future guide lines. In the meantime, our Clinical Consensus Statement aims to pro vide guidance for patient indications in daily clinical practice, bearing in mind that knowledge in this field is rapidly evolving.

Supplementary material

Supplementary material is available at Europace online.

Funding

None declared.

Conflict of interest: A.A. declares speaker’s honoraria from Boston Scientific and Bayer and speaker honoraria from Medtronic, Abbott, and Biotronik. C.W.I. reports the following—advisory board: Impulse-Dynamics, Medtronic, Zoll, honoraria for presentations, re imbursement for travel/congress costs: Abbott, Biotronik, Boston Scientific, Impulse-Dynamics, Medtronic, Microport, and Zoll. D.K. re ceives Honoraria and Research Support Medtronic and Abbott. H.B. reports institutional fellowship and research support, speaker’s bur eau, and advisory boards from Abbott, Biotronik, Boston Scientific, Medtronic, and Microport. J.C.D. reports speaker and proctoring hon oraria for Medtronic, Boston Scientific, and Biotronik. M.G. has parti cipated in Medtronic advisory boards, for which he has received minor compensation. J.K. declares speaker honoraria and/or consultancy fees from Abbott, Biotronik, Boston Scientific, and Medtronic and ad visory board (Medtronic). J.D.P. reports speaker fees and honoraria from Medtronic, Boston Scientific, Abbott, and Biotronik. K.C. reports advisory boards with Medtronic and Abbott and shares with VDI Technologies Inc. M.P.-L. has received speaker honoraria from Medtronic. Y.M. is a consultant for Edwards Lifesciences (Irvine, California). All remaining authors have declared no conflicts of interest.

Data availability

Data availability does not apply since no patient data are involved.

References

1. Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM et al. 2021 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. Europace 2022; 24 :71–164. 2. Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS et al. On-treatment comparison between corrective His bundle pacing and biventricular pa cing for cardiac resynchronization: a secondary analysis of the His-SYNC pilot trial. Heart Rhythm 2019; 16 :1797–807. 3. Lustgarten DL, Crespo EM, Arkhipova-Jenkins I, Lobel R, Winget J, Koehler J et al. His-bundle pacing versus biventricular pacing in cardiac resynchronization therapy pa tients: a crossover design comparison. Heart Rhythm 2015; 12 :1548–57. 4. Kronborg MB, Mortensen PT, Poulsen SH, Gerdes JC, Jensen HK, Nielsen JC. His or para-His pacing preserves left ventricular function in atrioventricular block: a double-blind, randomized, crossover study. Europace 2014; 16 :1189–96. 5. Occhetta E, Bortnik M, Magnani A, Francalacci G, Piccinino C, Plebani L et al. Prevention of ventricular desynchronization by permanent para-Hisian pacing after atrioventricular node ablation in chronic atrial fibrillation: a crossover, blinded, rando mized study versus apical right ventricular pacing. J Am Coll Cardiol 2006; 47 :1938–45. 6. Kron J, Bernabei M, Kaiser D, Nanda S, Subzposh FA, Zimmerman P et al. Real-world performance of conduction system pacing compared with traditional pacing. Circ Arrhythm Electrophysiol 2023; 16 :411–2. 7. Keene D, Anselme F, Burri H, Perez OC, Curila K, Derndorfer M et al. Conduction system pacing, a European survey: insights from clinical practice. Europace 2023; 25 : euad019. 8. Kircanski B, Boveda S, Prinzen F, Sorgente A, Anic A, Conte G et al. Conduction system pacing in everyday clinical practice: EHRA physician survey. Europace 2023; 25 :682–7. 9. Jastrzebski M, Kielbasa G, Cano O, Curila K, Heckman L, De Pooter J et al. Left bundle branch area pacing outcomes: the multicentre European MELOS study. Eur Heart J 2022; 43 :4161–73. 10. Burri H, Jastrzebski M, Cano O, Curila K, de Pooter J, Huang W et al. EHRA clinical con sensus statement on conduction system pacing implantation: endorsed by the Asia Pacific Heart Rhythm Society (APHRS), Canadian Heart Rhythm Society (CHRS), and Latin American Heart Rhythm Society (LAHRS). Europace 2023; 25 :1208–36. 11. Trines SA, Moore P, Burri H, Goncalves Nunes S, Massoullie G, Merino JL et al. 2024 updated EHRA core curriculum for physicians and allied professionals. A statement of the European heart rhythm association (EHRA) of the ESC. Europace 2024; 26 : euae243. 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. 13. Wiggers CJ. The muscular reactions of the mammalian ventricles to artificial surface stimuli. Am J Physiol 1925; 73 :346–78. 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 Cardiol 2006; 47 :282–8. 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 through the interventricular septum. Circ Arrhythm Electrophysiol 2016; 9 :e003344. 17. Tops LF, Schalij MJ, Holman ER, van Erven L, van der Wall EE, Bax JJ. Right ventricular pacing can induce ventricular dyssynchrony in patients with atrial fibrillation after atrio ventricular node ablation. J Am Coll Cardiol 2006; 48 :1642–8. 18. Sweeney MO, Hellkamp AS, Ellenbogen KA, Greenspon AJ, Freedman RA, Lee KL et al. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among pa tients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation 2003; 107 :2932–7. 19. Lamas GA, Lee KL, Sweeney MO, Silverman R, Leon A, Yee R et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002; 346 :1854–62. 20. Wilkoff BL, Cook JR, Epstein AE, Greene HL, Hallstrom AP, Hsia H et al. Dual-chamber pacing or ventricular backup pacing in patients with an implantable de fibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) trial. JAMA 2002; 288 :3115–23. 21. Kiehl EL, Makki T, Kumar R, Gumber D, Kwon DH, Rickard JW et al. Incidence and predictors of right ventricular pacing-induced cardiomyopathy in patients with com plete atrioventricular block and preserved left ventricular systolic function. Heart Rhythm 2016; 13 :2272–8. 22. Khurshid S, Epstein AE, Verdino RJ, Lin D, Goldberg LR, Marchlinski FE et al. Incidence and predictors of right ventricular pacing-induced cardiomyopathy. Heart Rhythm 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 atrioventricular block and normal left ventricular function. J Cardiovasc Electrophysiol 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 ventricular block: results of the Protect-Pace study. Eur Heart J 2015; 36 :856–62. 25. Beer D, Sharma PS, Subzposh FA, Naperkowski A, Pietrasik GM, Durr B et al. Clinical outcomes of selective versus nonselective His bundle pacing. JACC Clin Electrophysiol 2019; 5 :766–74. 26. Abdelrahman M, Subzposh FA, Beer D, Durr B, Naperkowski A, Sun H et al. Clinical outcomes of His bundle pacing compared to right ventricular pacing. J Am Coll Cardiol 2018; 71 :2319–30. 27. Su L, Wang S, Wu S, Xu L, Huang Z, Chen X et al. Long-term safety and feasibility of left bundle branch pacing in a large single-center study. Circ Arrhythm Electrophysiol 2021; 14 :e009261. 28. Curila K, Jurak P, Halamek J, Prinzen F, Waldauf P, Karch J et al. Ventricular activation pattern assessment during right ventricular pacing: ultra-high-frequency ECG study. J Cardiovasc Electrophysiol 2021; 32 :1385–94. 29. Jastrzebski M, Kielbasa G, Moskal P, Bednarek A, Rajzer M, Curila K et al. Right bundle branch pacing: criteria, characteristics, and outcomes. Heart Rhythm 2023; 20 : 492–500. 30. Curila K, Prochazkova R, Jurak P, Jastrzebski M, Halamek J, Moskal P et al. Both selective and nonselective His bundle, but not myocardial, pacing preserve ventricular electrical synchrony assessed by ultra-high-frequency ECG. Heart Rhythm 2020; 17 :607–14. 31. Arnold AD, Shun-Shin MJ, Ali N, Keene D, Howard JP, Chow JJ et al. Left ventricular activation time and pattern are preserved with both selective and nonselective His bundle pacing. Heart Rhythm O2 2021; 2 :439–45. 32. Zhang J, Guo J, Hou X, Wang Y, Qian Z, Li K et al. Comparison of the effects of se lective and non-selective His bundle pacing on cardiac electrical and mechanical syn chrony. Europace 2018; 20 :1010–7. 33. Bednarek A, Ionita O, Moskal P, Linkova H, Kielbasa G, Prochazkova R et al. Nonselective versus selective His bundle pacing: an acute intrapatient speckle-tracking strain echocardiographic study. J Cardiovasc Electrophysiol 2021; 32 :117–25.

ESC/EHRA clinical consensus statement

34. Curila K, Poviser L, Stros P, Jurak P, Whinnett Z, Jastrzebski M et al. LVSP and LBBP result in similar or improved LV synchrony and hemodynamics compared to BVP. JACC Clin Electrophysiol 2024; 10 :1722–32. 35. Heckman LIB, Luermans J, Curila K, Van Stipdonk AMW, Westra S, Smisek R et al. Comparing ventricular synchrony in left bundle branch and left ventricular septal pa cing in pacemaker patients. J Clin Med 2021; 10 :822. 36. Curila K, Jurak P, Jastrzebski M, Prinzen F, Waldauf P, Halamek J et al. Left bundle branch pacing compared to left ventricular septal myocardial pacing increases inter ventricular dyssynchrony but accelerates left ventricular lateral wall depolarization. Heart Rhythm 2021; 18 :1281–9. 37. Rijks JHJ, Heckman L, Westra S, Cornelussen R, Ghosh S, Curila K et al. Assessment of ventricular electrical heterogeneity in left bundle branch pacing and left ventricular sep tal pacing by using various electrophysiological methods. J Cardiovasc Electrophysiol 2024; 35 :2282–92. 38. Meiburg R, Rijks JHJ, Beela AS, Bressi E, Grieco D, Delhaas T et al. Comparison of novel ventricular pacing strategies using an electro-mechanical simulation platform. Europace 2023; 25 :euad144. 39. Zhu H, Qin C, Du A, Wang Q, He C, Zou F et al. Comparisons of long-term clinical outcomes with left bundle branch pacing, left ventricular septal pacing, and biventricu lar pacing for cardiac resynchronization therapy. Heart Rhythm 2024; 21 :1342–53. 40. Diaz JC, Tedrow UB, Duque M, Aristizabal J, Braunstein ED, Marin J et al. Left bundle branch pacing vs left ventricular septal pacing vs biventricular pacing for cardiac resyn chronization therapy. JACC Clin Electrophysiol 2024; 10 :295–305. 41. Liu W, Fulati Z, Tian F, Xu N, Cheng Y, Zhao Y et al. Relationship of different left bun dle branch pacing sites and clinical outcomes in patients with heart failure. Heart Rhythm 2025 (EPUB ahead of print). 42. Ali N, Arnold AD, Miyazawa AA, Keene D, Chow JJ, Little I et al. Comparison of meth ods for delivering cardiac resynchronization therapy: an acute electrical and haemo dynamic within-patient comparison of left bundle branch area, His bundle, and biventricular pacing. Europace 2023; 25 :1060–7. 43. Arnold AD, Shun-Shin MJ, Keene D, Howard JP, Sohaib SMA, Wright IJ et al. His re synchronization versus biventricular pacing in patients with heart failure and left bundle branch block. J Am Coll Cardiol 2018; 72 :3112–22. 44. Salden F, Luermans J, Westra SW, Weijs B, Engels EB, Heckman LIB et al. Short-term hemodynamic and electrophysiological effects of cardiac resynchronization by left ven tricular septal pacing. J Am Coll Cardiol 2020; 75 :347–59. 45. Vijayaraman P, Hughes G, Manganiello M, Johns A, Ghosh S. Non-invasive assessment of ventricular electrical heterogeneity to optimize left bundle branch area pacing. J Interv Card Electrophysiol 2023; 66 :1103–12. 46. Azzolini G, Bianchi N, Vitali F, Malagù M, Balla C, De Raffele M et al. A comparative assessment of myocardial work performance during spontaneous rhythm, His bundle pacing, and left bundle branch area pacing: insights from the EMPATHY study. J Cardiovasc Dev Dis 2023; 10 :444. 47. Vijayaraman P, Rajakumar C, Naperkowski AM, Subzposh FA. Clinical outcomes of left bundle branch area pacing compared to His bundle pacing. J Cardiovasc Electrophysiol 2022; 33 :1234–43. 48. Tan ESJ, Soh R, Boey E, Lee JY, de Leon J, Chan SP et al. Comparison of pacing perform ance and clinical outcomes between left bundle branch and His bundle pacing. JACC Clin Electrophysiol 2023; 9 :1393–403. 49. Wu S, Su L, Vijayaraman P, Zheng R, Cai M, Xu L et al. Left bundle branch pacing for cardiac resynchronization therapy: nonrandomized on-treatment comparison with His bundle pacing and biventricular pacing. Can J Cardiol 2021; 37 :319–28. 50. Hua W, Fan X, Li X, Niu H, Gu M, Ning X et al. Comparison of left bundle branch and His bundle pacing in bradycardia patients. JACC Clin Electrophysiol 2020; 6 :1291–9. 51. Vijayaraman P, Longacre C, Kron J, Subzposh F, Zimmerman P, Butler K et al. Conduction system pacing associated with reduced heart failure hospitalizations and all-cause mortality compared with traditional right ventricular pacing in the Medicare population. Heart Rhythm 2025; 22 :735–43. 52. Cai M, Wu S, Wang S, Zheng R, Jiang L, Lian L et al. Left bundle branch pacing post atrioventricular junction ablation for atrial fibrillation: propensity score matching with His bundle pacing. Circ Arrhythm Electrophysiol 2022; 15 :e010926. 53. Pillai A, Kolominsky J, Koneru JN, Kron J, Shepard RK, Kalahasty G et al. Atrioventricular junction ablation in patients with conduction system pacing leads: a comparison of His-bundle vs left bundle branch area pacing leads. Heart Rhythm 2022; 19 :1116–23. 54. Yuan Z, Cheng L, Wu Y. Meta-analysis comparing safety and efficacy of left bundle branch area pacing versus His bundle pacing. Am J Cardiol 2022; 164 :64–72. 55. Zhuo W, Zhong X, Liu H, Yu J, Chen Q, Hu J et al. Pacing characteristics of His bundle pacing vs. Left bundle branch pacing: a systematic review and meta-analysis. Front Cardiovasc Med 2022; 9 :849143. 56. Vijayaraman P, West M, Dresing T, Oren J, Abbey S, Zimmerman P et al. Safety and performance of conduction system pacing: real-world experience from a product sur veillance registry. Heart Rhythm 2025; 22 :318–24. 57. Abdin A, Werner C, Burri H, Merino JL, Vukadinovic D, Sawan N et al. Outcomes of left bundle branch area pacing compared to His bundle pacing as a primary pacing strategy: systematic review and meta-analysis. Pacing Clin Electrophysiol 2023; 46 1315–24. 58. Vazquez PM, Mohamed U, Zanon F, Lustgarten DL, Atwater B, Whinnett ZI et al. Result of the physiologic pacing registry, an international multicenter prospective ob servational study of conduction system pacing. Heart Rhythm 2023; 20 :1617–25. 59. Ye Y, Gao B, Lv Y, Xu TT, Zhang SS, Lu XL et al. His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a prospective crossover comparison. J Geriatr Cardiol 2023; 20 :51–60. 60. Marinaccio L, Vetta F, Ginocchio G, Maria Marchese G, Marchese D. Electrocardiographic diagnosis of acute myocardial ischemia during His bundle pacing. Anatol J Cardiol 2022; 26 :328–30. 61. Curila K, Stros P, Herman D, Vesela J, Prochazkova R, Osmancik P et al. Electrocardiogram changes due to myocardial infarction in a patient with selective His bundle pacing. Kardiol Pol 2019; 77 :237. 62. Deluca F, Marcantoni L, Pastore G, Valenza S, Porcelli G, Zanon F. Acute myocardial infarction in a patient with permanent left bundle branch pacing. J Electrocardiol 2024; 87 :153804. 63. Zaidi SMJ, Sohail H, Satti DI, Sami A, Anwar M, Malik J et al. Tricuspid regurgitation in His bundle pacing: a systematic review. Ann Noninvasive Electrocardiol 2022; 27 : e12986. 64. Hu Q, You H, Chen K, Dai Y, Lu W, Li Y et al. Distance between the lead-implanted site and tricuspid valve annulus in patients with left bundle branch pacing: effects on postoperative tricuspid regurgitation deterioration. Heart Rhythm 2023; 20 :217–23. 65. Burri H, Jastrzebski M, Vijayaraman P. Electrocardiographic analysis for His bundle pa cing at implantation and follow-up. JACC Clin Electrophysiol 2020; 6 :883–900. 66. Sharma PS, Naperkowski A, Bauch TD, Chan JYS, Arnold AD, Whinnett ZI et al. Permanent His bundle pacing for cardiac resynchronization therapy in patients with heart failure and right bundle branch block. Circ Arrhythm Electrophysiol 2018; 11 : e006613. 67. Vijayaraman P, Cano O, Ponnusamy SS, Molina-Lerma M, Chan JYS, Padala SK et al. Left bundle branch area pacing in patients with heart failure and right bundle branch block: results from international LBBAP collaborative-study group. Heart Rhythm O2 2022; 3 :358–67. 68. Vinther M, Risum N, Svendsen JH, Mogelvang R, Philbert BT. A randomized trial of His pacing versus biventricular pacing in symptomatic HF patients with left bundle branch block (His-alternative). JACC Clin Electrophysiol 2021; 7 :1422–32. 69. Vijayaraman P, Ponnusamy S, Cano O, Sharma PS, Naperkowski A, Subsposh FA et al. Left bundle branch area pacing for cardiac resynchronization therapy: results from the international LBBAP collaborative study group. JACC Clin Electrophysiol 2021; 7 :135–47. 70. Keene D, Arnold AD, Jastrzebski M, Burri H, Zweibel S, Crespo E et al. His bundle pa cing, learning curve, procedure characteristics, safety, and feasibility: insights from a large international observational study. J Cardiovasc Electrophysiol 2019; 30 :1984–93. 71. Teigeler T, Kolominsky J, Vo C, Shepard RK, Kalahasty G, Kron J et al. Intermediate-term performance and safety of His-bundle pacing leads: a single-center experience. Heart Rhythm 2021; 18 :743–9. 72. Vijayaraman P, Dandamudi G, Worsnick S, Ellenbogen KA. Acute His-bundle injury current during permanent His-bundle pacing predicts excellent pacing outcomes. Pacing Clin Electrophysiol 2015; 38 :540–6. 73. Vijayaraman P, Dandamudi G, Zanon F, Sharma PS, Tung R, Huang W et al. Permanent His bundle pacing: recommendations from a multicenter His bundle pacing collabora tive working group for standardization of definitions, implant measurements, and follow-up. Heart Rhythm 2018; 15 :460–8. 74. Vijayaraman P, Naperkowski A, Subzposh FA, Abdelrahman M, Sharma PS, Oren JW et al. Permanent His-bundle pacing: long-term lead performance and clinical outcomes. Heart Rhythm 2018; 15 :696–702. 75. Su L, Wu S, Wang S, Wang Z, Xiao F, Shan P et al. Pacing parameters and success rates of permanent His-bundle pacing in patients with narrow QRS: a single-centre experi ence. Europace 2019; 21 :763–70. 76. Vijayaraman P, Subzposh FA, Naperkowski A. Atrioventricular node ablation and His bundle pacing. Europace 2017; 19 :iv10–6. 77. De Leon J, Seow SC, Boey E, Soh R, Tan E, Gan HH et al. Adopting permanent His bundle pacing: learning curves and medium-term outcomes. Europace 2022; 24 : 606–13. 78. Sritharan A, Kozhuharov N, Masson N, Bakelants E, Valiton V, Burri H. Procedural out come and follow-up of stylet-driven leads compared with lumenless leads for left bun dle branch area pacing. Europace 2023; 25 :euad295. 79. Li X, Zhu H, Fan X, Wang Q, Wang Z, Li H et al. Tricuspid regurgitation outcomes in left bundle branch area pacing and comparison with right ventricular septal pacing. Heart Rhythm 2022; 19 :1202–3. 80. Vijayaraman P, Naperkowski A, Ellenbogen KA, Dandamudi G. Electrophysiologic in sights into site of atrioventricular block: lessons from permanent His bundle pacing. JACC Clin Electrophysiol 2015; 1 :571–81. 81. Ponnusamy SS, Murugan M, Ganesan V, Vijayaraman P. Predictors of procedural failure of left bundle branch pacing in scarred left ventricle. J Cardiovasc Electrophysiol 2023; 34 : 760–4.

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82. Bhatt AG, Musat DL, Milstein N, Pimienta J, Flynn L, Sichrovsky T et al. The efficacy of His bundle pacing: lessons learned from implementation for the first time at an experi enced electrophysiology center. JACC Clin Electrophysiol 2018; 4 :1397–406. 83. Vijayaraman P, Cano O, Koruth JS, Subzposh FA, Nanda S, Pugliese J et al. His-Purkinje conduction system pacing following transcatheter aortic valve replacement: feasibility and safety. JACC Clin Electrophysiol 2020; 6 :649–57. 84. Sharma PS, Subzposh FA, Ellenbogen KA, Vijayaraman P. Permanent His-bundle pacing in patients with prosthetic cardiac valves. Heart Rhythm 2017; 14 :59–64. 85. Bednarek A, Kiełbasa G, Moskal P, Ostrowska A, Bednarski A, Sondej T et al. Left bun dle branch area pacing improves right ventricular function and synchrony. Heart Rhythm 2024; 21 :2234–41. 86. Nagarajan VD, Ho SY, Ernst S. Anatomical considerations for His bundle pacing. Circ Arrhythm Electrophysiol 2019; 12 :e006897. 87. Andreas M, Burri H, Praz F, Soliman O, Badano L, Barreiro M et al. Tricuspid valve dis ease and cardiac implantable electronic devices. Eur Heart J 2024; 45 :346–65. 88. Jastrzebski M, Moskal P, Bednarek A, Kielbasa G, Vijayaraman P, Czarnecka D. Programmed His bundle pacing: a novel maneuver for the diagnosis of His bundle cap ture. Circ Arrhythm Electrophysiol 2019; 12 :e007052. 89. Liang Y, Yu H, Wang N, Liang Z, Xu B, Gao Y et al. Cycle length criteria for His-bundle capture are capable of determining pacing types misclassified by output criteria. Heart Rhythm 2019; 16 :1629–35. 90. Jastrzebski M, Moskal P, Curila K, Fijorek K, Kukla P, Bednarek A et al. Electrocardiographic characterization of non-selective His-bundle pacing: validation of novel diagnostic criteria. Europace 2019; 21 :1857–64. 91. Curila K, Jurak P, Vernooy K, Jastrzebski M, Waldauf P, Prinzen F et al. Left ventricular myocardial septal pacing in close proximity to LBB does not prolong the duration of the left ventricular lateral wall depolarization compared to LBB pacing. Front Cardiovasc Med 2021; 8 :787414. 92. Ali N, Saqi K, Arnold AD, Miyazawa AA, Keene D, Chow JJ et al. Left bundle branch pacing with and without anodal capture: impact on ventricular activation pattern and acute haemodynamics. Europace 2023; 25 :euad264. 93. Sato T, Togashi I, Ikewaki H, Mohri T, Katsume Y, Tashiro M et al. Diverse QRS morph ology reflecting variations in lead placement for left bundle branch area pacing. Europace 2023; 25 :euad241. 94. Upadhyay GA. QRS morphologies in V1 and V6 during left bundle branch area pacing: assessing the patterns. Europace 2023; 25 :euad284. 95. Burri H, Kozhuharov N, Jastrzebski M. Proximal and distal right bundle branch pacing: insights into conduction system physiology. HeartRhythm Case Rep 2023; 9 :372–5. 96. Parlavecchio A, Vetta G, Coluccia G, Pistelli L, Caminiti R, Crea P et al. Success and complication rates of conduction system pacing: a meta-analytical observational com parison of left bundle branch area pacing and His bundle pacing. J Interv Card Electrophysiol 2024; 67 :719–29. 97. Albertsen AE, Mortensen PT, Jensen HK, Poulsen SH, Egeblad H, Nielsen JC. Adverse effect of right ventricular pacing prevented by biventricular pacing during long-term follow-up: a randomized comparison. Eur J Echocardiogr 2011; 12 :767–72. 98. Yu CM, Chan JY, Zhang Q, Omar R, Yip GW, Hussin A et al. Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 2009; 361 : 2123–34. 99. Zweerink A, Zubarev S, Bakelants E, Potyagaylo D, Stettler C, Chmelevsky M et al. His-optimized cardiac resynchronization therapy with ventricular fusion pa cing for electrical resynchronization in heart failure. JACC Clin Electrophysiol 2021; 7 :881–92. 100. Kirkfeldt RE, Johansen JB, Nohr EA, Moller M, Arnsbo P, Nielsen JC. Risk factors for lead complications in cardiac pacing: a population-based cohort study of 28,860 Danish patients. Heart Rhythm 2011; 8 :1622–8. 101. Mei DA, Imberti JF, Vitolo M, Bonini N, Serafini K, Mantovani M et al. Systematic review and meta-analysis on the impact on outcomes of device algorithms for minimizing right ventricular pacing. Europace 2024; 26 :euae212. 102. Mizner J, Waldauf P, Grieco D, Linkova H, Ionita O, Vijayaraman P et al. A randomized comparison of HBP versus RVP: effect on left ventricular function and biomarkers of collagen metabolism. Kardiol Pol 2023; 81 :472–81. 103. Wang J, Liang Y, Wang W, Chen X, Bai J, Chen H et al. Left bundle branch area pacing is superior to right ventricular septum pacing concerning depolarization-repolarization reserve. J Cardiovasc Electrophysiol 2020; 31 :313–22. 104. Zhang J, Wang Z, Cheng L, Zu L, Liang Z, Hang F et al. Immediate clinical outcomes of left bundle branch area pacing vs conventional right ventricular pacing. Clin Cardiol 2019; 42 :768–73. 105. Yao L, Qi Y, Xiao S, Liu R, Wo J. Effect of left bundle branch pacing on left ventricular systolic function and synchronization in patients with third-degree atrioventricular block, assessment by 3- dimensional speckle tracking echocardiography. J Electrocardiol 2022; 72 :61–5. 106. Gonzalez-Matos CE, Rodriguez-Queralto O, Zaraket F, Jimenez J, Casteigt B, Valles E. Conduction system stimulation to avoid left ventricle dysfunction. Circ Arrhythm Electrophysiol 2024; 17 :e012473. comes of left bundle branch area pacing compared to right ventricular pacing: results from the Geisinger-Rush conduction system pacing registry. Heart Rhythm 2022; 19 : 3–11. 108. Tan ESJ, Soh R, Lee J-Y, Boey E, Ho K-H, Aguirre S et al. Clinical outcomes in conduc tion system pacing compared to right ventricular pacing in bradycardia. JACC Clin Electrophysiol 2023; 9 :992–1001. 109. Li X, Zhang J, Qiu C, Wang Z, Li H, Pang K et al. Clinical outcomes in patients with left bundle branch area pacing vs. right ventricular pacing for atrioventricular block. Front Cardiovasc Med 2021; 8 :685253. 110. Okubo Y, Sakai T, Miyamoto S, Uotani Y, Oguri N, Furutani M et al. Mid-term clinical outcomes of left bundle branch area pacing compared to accurate right ventricular septal pacing. J Interv Card Electrophysiol 2025; 68 :55–63. 111. Niu HX, Liu X, Gu M, Chen X, Cai C, Cai M et al. Conduction system pacing for post transcatheter aortic valve replacement patients: comparison with right ventricular pa cing. Front Cardiovasc Med 2021; 8 :772548. 112. Dell’Era G, Baroni M, Frontera A, Ghiglieno C, Carbonaro M, Penela D et al. Left bun dle branch area versus conventional pacing after transcatheter valve implant for aortic stenosis: the LATVIA study. J Cardiovasc Med (Hagerstown) 2024; 25 :450–6. 113. Okubo Y, Miyamoto S, Uotani Y, Ikeuchi Y, Miyauchi S, Okamura S et al. Clinical impact of left bundle branch area pacing in heart failure with preserved ejection fraction and mid-range ejection fraction. Pacing Clin Electrophysiol 2022; 45 :499–508. 114. Qu Q, Sun JY, Zhang ZY, Kan JY, Wu LD, Li F et al. His-Purkinje conduction system pacing: a systematic review and network meta-analysis in bradycardia and conduction disorders. J Cardiovasc Electrophysiol 2021; 32 :3245–58. 115. Abdin A, Aktaa S, Vukadinovic D, Arbelo E, Burri H, Glikson M et al. Outcomes of con duction system pacing compared to right ventricular pacing as a primary strategy for treating bradyarrhythmia: systematic review and meta-analysis. Clin Res Cardiol 2022; 111 :1198–209. 116. Liu X, Li W, Wang L, Tian S, Zhou X, Wu M. Safety and efficacy of left bundle branch pacing in comparison with conventional right ventricular pacing: a systematic review and meta-analysis. Medicine (Baltimore) 2021; 100 :e26560. 117. Herbert J, Kovacsovics A, Brito R, Masson N, Burri H. Mid-term performance of His bundle pacing and usefulness of backup leads. Europace 2024; 26 :euae168. 118. Vijayaraman P, Patel N, Colburn S, Beer D, Naperkowski A, Subzposh FA. His-Purkinje conduction system pacing in atrioventricular block: new insights into site of conduction block. JACC Clin Electrophysiol 2022; 8 :73–85. 119. Curtis AB, Worley SJ, Adamson PB, Chung ES, Niazi I, Sherfesee L et al. Biventricular pa cing for atrioventricular block and systolic dysfunction. N Engl J Med 2013; 368 :1585–93. 120. Kindermann M, Hennen B, Jung J, Geisel J, Bohm M, Frohlig G. Biventricular versus con ventional right ventricular stimulation for patients with standard pacing indication and left ventricular dysfunction: the Homburg biventricular pacing evaluation (HOBIPACE). J Am Coll Cardiol 2006; 47 :1927–37. 121. Filho MM, de Siqueira SF, Costa R, Greco OT, Moreira LF, D’Avila A et al. Conventional versus biventricular pacing in heart failure and bradyarrhythmia: the COMBAT study. J Card Fail 2010; 16 :293–300. 122. Upadhyay GA, Vijayaraman P, Nayak HM, Verma N, Dandamudi G, Sharma PS et al. His corrective pacing or biventricular pacing for cardiac resynchronization in heart fail ure. J Am Coll Cardiol 2019; 74 :157–9. 123. Pujol-Lopez M, Jimenez-Arjona R, Garre P, Guasch E, Borras R, Doltra A et al. Conduction system pacing vs biventricular pacing in heart failure and wide QRS pa tients: LEVEL-AT trial. JACC Clin Electrophysiol 2022; 8 :1431–45. 124. Vijayaraman P, Pokharel P, Subzposh FA, Oren JW, Storm RH, Batul SA et al. His-Purkinje conduction system pacing optimized trial of cardiac resynchronization therapy vs biven tricular pacing: HOT-CRT clinical trial. JACC Clin Electrophysiol 2023; 9 :2628–38. 125. Ajijola OA, Upadhyay GA, Macias C, Shivkumar K, Tung R. Permanent His-bundle pa cing for cardiac resynchronization therapy: initial feasibility study in lieu of left ventricu lar lead. Heart Rhythm 2017; 14 :1353–61. 126. Sharma PS, Dandamudi G, Herweg B, Wilson D, Singh R, Naperkowski A et al. Permanent His-bundle pacing as an alternative to biventricular pacing for cardiac re synchronization therapy: a multicenter experience. Heart Rhythm 2018; 15 :413–20. 127. Li Y, Yan L, Dai Y, Zhou Y, Sun Q, Chen R et al. Feasibility and efficacy of left bundle branch area pacing in patients indicated for cardiac resynchronization therapy. Europace 2020; 22 :ii54–60. 128. Qian Z, Wang Y, Hou X, Qiu Y, Wu H, Zhou W et al. Efficacy of upgrading to left bun dle branch pacing in patients with heart failure after right ventricular pacing. Pacing Clin Electrophysiol 2021; 44 :472–80. 129. Rademakers LM, Bouwmeester S, Mast TP, Dekker L, Houthuizen P, Bracke FA. Feasibility, safety and outcomes of upgrading to left bundle branch pacing in patients with right ventricular pacing induced cardiomyopathy. Pacing Clin Electrophysiol 2022; 45 :726–32. 130. Pujol-Lopez M, Jimenez Arjona R, Guasch E, Borras R, Doltra A, Vazquez-Calvo S et al. Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunc tion and AV block. Pacing Clin Electrophysiol 2022; 45 :1115–23.

ESC/EHRA clinical consensus statement

131. Vijayaraman P, Zalavadia D, Haseeb A, Dye C, Madan N, Skeete JR et al. Clinical out comes of conduction system pacing compared to biventricular pacing in patients re quiring cardiac resynchronization therapy. Heart Rhythm 2022; 19 :1263–71. 132. Diaz JC, Sauer WH, Duque M, Koplan BA, Braunstein ED, Marin JE et al. Left bundle branch area pacing versus biventricular pacing as initial strategy for cardiac resynchro nization. JACC Clin Electrophysiol 2023; 9 :1568–81. 133. Ezzeddine FM, Pistiolis SM, Pujol-Lopez M, Lavelle M, Wan EY, Patton KK et al. Outcomes of conduction system pacing for cardiac resynchronization therapy in pa tients with heart failure: a multicenter experience. Heart Rhythm 2023; 20 :863–71. 134. Vijayaraman P, Sharma PS, Cano O, Ponnusamy SS, Herweg B, Zanon F et al. Comparison of left bundle branch area pacing and biventricular pacing in candidates for resynchronization therapy. J Am Coll Cardiol 2023; 82 :228–41. 135. Liang Y, Xiao Z, Liu X, Wang J, Yu Z, Gong X et al. Left bundle branch area pacing ver sus biventricular pacing for cardiac resynchronization therapy on morbidity and mor tality. Cardiovasc Drugs Ther 2024; 38 :471–81. 136. Graterol FR, Pujol-Lopez M, Borras R, Ayala B, Uribe L, Guasch E et al. Predictors of failed left bundle branch pacing implant in heart failure with reduced ejection fraction: importance of left ventricular diameter and QRS morphology. Heart Rhythm 2024; 21 : 2571–8. 137. Glikson M, Jastrzebski M, Gold MR, Ellenbogen K, Burri H. Conventional biventricular pacing is still preferred to conduction system pacing for atrioventricular block in pa tients with reduced ejection fraction and narrow QRS. Europace 2023; 26 :euad337. 138. Pujol-Lopez M, Jimenez-Arjona R, Garcia-Ribas C, Borras R, Guasch E, Regany-Closa M et al. Longitudinal comparison of dyssynchrony correction and ‘strain’ improvement by conduction system pacing: LEVEL-AT trial secondary findings. Eur Heart J Cardiovasc Imaging 2024; 25 :1394–404. 139. Vijayaraman P, Herweg B, Verma A, Sharma PS, Batul SA, Ponnusamy SS et al. Rescue left bundle branch area pacing in coronary venous lead failure or nonresponse to bi ventricular pacing: results from international LBBAP collaborative study group. Heart Rhythm 2022; 19 :1272–80. 140. Joza JBH, Andrade JG, Linz D, Ellenbogen KA, Vernooy K. Pacemaker implantation and atrioventricular node ablation for the treatment of atrial fibrillation in the era of con duction system pacing. Eur Heart J 2024; 45 :4887–901. 141. Tan ES, Rienstra M, Wiesfeld AC, Schoonderwoerd BA, Hobbel HH, Van Gelder IC. Long-term outcome of the atrioventricular node ablation and pacemaker implantation for symptomatic refractory atrial fibrillation. Europace 2008; 10 :412–8. 142. Wood MA, Kay GN, Ellenbogen KA. The North American experience with the ablate and pace trial (APT) for medically refractory atrial fibrillation. Europace 1999; 1 :22–5. 143. Kirkutis A, Poviliŭnas A, Griciene P, Polena S, Yang S, Yalamanchi G et al. Cardiac rate normalization in chronic atrial fibrillation: comparison of long-term efficacy of treat ment with amiodarone versus AV node ablation and permanent His-bundle pacing. Proc West Pharmacol Soc 2004; 47 :69–70. 144. Wang T, Fang T, Cheng Z. Comparison of the efficacy and safety endpoints of five ther 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 of patients with chronic atrial fibrillation undergoing radiofrequency catheter ablation of the atrioventricular junction. Am J Cardiol 1997; 80 :1606–9. 146. Morady F, Calkins H, Langberg JJ, Armstrong WF, de Buitleir M, el-Atassi R et al. A pro spective randomized comparison of direct current and radiofrequency ablation of the atrioventricular junction. J Am Coll Cardiol 1993; 21 :102–9. 147. Olgin JE, Scheinman MM. Comparison of high energy direct current and radiofrequency catheter ablation of the atrioventricular junction. J Am Coll Cardiol 1993; 21 :557–64. 148. Brignole M, Gianfranchi L, Menozzi C, Bottoni N, Bollini R, Lolli G et al. Influence of atrioventricular junction radiofrequency ablation in patients with chronic atrial fibrilla tion and flutter on quality of life and cardiac performance. Am J Cardiol 1994; 74 :242–6. 149. Jensen SM, Bergfeldt L, Rosenqvist M. Long-term follow-up of patients treated by radiofrequency ablation of the atrioventricular junction. Pacing Clin Electrophysiol 1995; 18 :1609–14. 150. Edner M, Caidahl K, Bergfeldt L, Darpo B, Edvardsson N, Rosenqvist M. Prospective study of left ventricular function after radiofrequency ablation of atrioventricular junc tion in patients with atrial fibrillation. Br Heart J 1995; 74 :261–7. 151. Fitzpatrick AP, Kourouyan HD, Siu A, Lee RJ, Lesh MD, Epstein LM et al. Quality of life and outcomes after radiofrequency His-bundle catheter ablation and permanent pace maker implantation: impact of treatment in paroxysmal and established atrial fibrilla tion. Am Heart J 1996; 131 :499–507. 152. Bubien RS, Knotts-Dolson SM, Plumb VJ, Kay GN. Effect of radiofrequency catheter ablation on health-related quality of life and activities of daily living in patients with re current arrhythmias. Circulation 1996; 94 :1585–91. 153. Darpo B, Walfridsson H, Aunes M, Bergfeldt L, Edvardsson N, Linde C et al. Incidence of sudden death after radiofrequency ablation of the atrioventricular junction for atrial fibrillation. Am J Cardiol 1997; 80 :1174–7. 154. Brignole M, Gianfranchi L, Menozzi C, Alboni P, Musso G, Bongiorni MG et al. Assessment of atrioventricular junction ablation and DDDR mode-switching pace maker versus pharmacological treatment in patients with severely symptomatic parox ysmal atrial fibrillation: a randomized controlled study. Circulation 1997; 96 :2617–24. 155. Buys EM, van Hemel NM, Kelder JC, Ascoop CA, van Dessel PF, Bakema L et al. Exercise capacity after His bundle ablation and rate response ventricular pacing for drug refractory chronic atrial fibrillation. Heart 1997; 77 :238–41. 156. Twidale N, McDonald T, Nave K, Seal A. Comparison of the effects of AV nodal ab lation versus AV nodal modification in patients with congestive heart failure and un controlled atrial fibrillation. Pacing Clin Electrophysiol 1998; 21 :641–51. 157. Lee SH, Chen SA, Tai CT, Chiang CE, Wen ZC, Cheng JJ et al. Comparisons of quality of life and cardiac performance after complete atrioventricular junction ablation and atrioventricular junction modification in patients with medically refractory atrial fibril lation. J Am Coll Cardiol 1998; 31 :637–44. 158. Kay GN, Ellenbogen KA, Giudici M, Redfield MM, Jenkins LS, Mianulli M et al. The ablate and pace trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. APT inves tigators. J Interv Card Electrophysiol 1998; 2 :121–35. 159. Marshall HJ, Harris ZI, Griffith MJ, Gammage MD. Prospective, randomized study of atrioventricular node ablation and mode-switching, dual chamber pacemaker implant ation using two different algorithms in patients with paroxysmal atrial fibrillation. Europace 1999; 1 :20–1. 160. Weerasooriya R, Davis M, Powell A, Szili-Torok T, Shah C, Whalley D et al. The Australian intervention randomized control of rate in atrial fibrillation trial (AIRCRAFT). J Am Coll Cardiol 2003; 41 :1697–702. 161. Leon AR, Greenberg JM, Kanuru N, Baker CM, Mera FV, Smith AL et al. Cardiac resyn chronization in patients with congestive heart failure and chronic atrial fibrillation: ef fect of upgrading to biventricular pacing after chronic right ventricular pacing. J Am Coll Cardiol 2002; 39 :1258–63. 162. Linde C, Leclercq C, Rex S, Garrigue S, Lavergne T, Cazeau S et al. Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J Am Coll Cardiol 2002; 40 :111–8. 163. Puggioni E, Brignole M, Gammage M, Soldati E, Bongiorni MG, Simantirakis EN et al. Acute comparative effect of right and left ventricular pacing in patients with permanent atrial fibrillation. J Am Coll Cardiol 2004; 43 :234–8. 164. Simantirakis EN, Vardakis KE, Kochiadakis GE, Manios EG, Igoumenidis NE, Brignole M et al. Left ventricular mechanics during right ventricular apical or left ventricular-based pacing in patients with chronic atrial fibrillation after atrioventricular junction ablation. J Am Coll Cardiol 2004; 43 :1013–8. 165. Doshi RN, Daoud EG, Fellows C, Turk K, Duran A, Hamdan MH et al. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol 2005; 16 :1160–5. 166. Brignole M, Gammage M, Puggioni E, Alboni P, Raviele A, Sutton R et al. Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fib rillation. Eur Heart J 2005; 26 :712–22. 167. Orlov MV, Gardin JM, Slawsky M, Bess RL, Cohen G, Bailey W et al. Biventricular pacing improves cardiac function and prevents further left atrial remodeling in patients with symptomatic atrial fibrillation after atrioventricular node ablation. Am Heart J 2010; 159 :264–70. 168. Brignole M, Botto G, Mont L, Iacopino S, De Marchi G, Oddone D et al. Cardiac re synchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial. Eur Heart J 2011; 32 :2420–9. 169. Brignole M, Pentimalli F, Palmisano P, Landolina M, Quartieri F, Occhetta E et al. AV junction ablation and cardiac resynchronization for patients with permanent atrial fib rillation and narrow QRS: the APAF-CRT mortality trial. Eur Heart J 2021; 42 :4731–9. 170. Deshmukh P, Casavant DA, Romanyshyn M, Anderson K. Permanent, direct His-bundle pacing: a novel approach to cardiac pacing in patients with normal His-Purkinje activation. Circulation 2000; 101 :869–77. 171. Deshmukh PM, Romanyshyn M. Direct His-bundle pacing: present and future. Pacing Clin Electrophysiol 2004; 27 :862–70. 172. Occhetta E, Bortnik M, Marino P. Permanent parahisian pacing. Indian Pacing Electrophysiol J 2007; 7 :110–25. 173. Huang W, Su L, Wu S, Xu L, Xiao F, Zhou X et al. Benefits of permanent His bundle pacing combined with atrioventricular node ablation in atrial fibrillation patients with heart failure with both preserved and reduced left ventricular ejection fraction. J Am Heart Assoc 2017; 6 :e005309. 174. Wang S, Wu S, Xu L, Xiao F, Whinnett ZI, Vijayaraman P et al. Feasibility and efficacy of His bundle pacing or left bundle pacing combined with atrioventricular node ablation in patients with persistent atrial fibrillation and implantable cardioverter-defibrillator therapy. J Am Heart Assoc 2019; 8 :e014253. 175. Su L, Cai M, Wu S, Wang S, Xu T, Vijayaraman P et al. Long-term performance and risk factors analysis after permanent His-bundle pacing and atrioventricular node ablation in patients with atrial fibrillation and heart failure. Europace 2020; 22 :ii19–26. 176. Senes J, Mascia G, Bottoni N, Oddone D, Donateo P, Grimaldi T et al. Is His-optimized superior to conventional cardiac resynchronization therapy in improving heart failure? Results from a propensity-matched study. Pacing Clin Electrophysiol 2021; 44 :1532–9. 177. Huang W, Wang S, Su L, Fu G, Su Y, Chen K et al. His-bundle pacing vs biventricular pacing following atrioventricular nodal ablation in patients with atrial fibrillation and

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reduced ejection fraction: a multicenter, randomized, crossover study-the ALTERNATIVE-AF trial. Heart Rhythm 2022; 19 :1948–55. 178. Ivanovski M, Mrak M, Meznar AZ, Zizek D. Biventricular versus conduction system pa cing after atrioventricular node ablation in heart failure patients with atrial fibrillation. J Cardiovasc Dev Dis 2022; 9 :209. 179. Vijayaraman P, Mathew AJ, Naperkowski A, Young W, Pokharel P, Batul SA et al. Conduction system pacing versus conventional pacing in patients undergoing atrioven tricular node ablation: nonrandomized, on-treatment comparison. Heart Rhythm O2 2022; 3 :368–76. 180. Qi P, An H, Lv Y, Geng Y, Chen S, Li S et al. His-Purkinje conduction system pacing and atrioventricular node ablation in treatment of persistent atrial fibrillation refractory to multiple ablation procedures: a case report. SAGE Open Med Case Rep 2023; 11 : 2050313X231172873. 181. Palmisano P, Ziacchi M, Dell’Era G, Donateo P, Ammendola E, Aspromonte V et al. Ablate and pace: comparison of outcomes between conduction system pacing and bi ventricular pacing. Pacing Clin Electrophysiol 2023; 46 :1258–68. 182. Chaumont C, Azincot M, Savoure A, Auquier N, Hamoud RA, Popescu E et al. His bun dle pacing versus left bundle branch area pacing in patients undergoing atrioventricular node ablation: a prospective and comparative study. Arch Cardiovasc Dis 2024; 117 : 505–13. 183. Jacobs M, Bodin A, Spiesser P, Babuty D, Clementy N, Bisson A. Single-center experi ence of efficacy and safety of atrioventricular node ablation after left bundle branch area pacing for the management of atrial fibrillation. J Interv Card Electrophysiol 2024; 67 :1865–76. 184. Zweerink A, Bakelants E, Stettler C, Burri H. Cryoablation vs. radiofrequency ablation of the atrioventricular node in patients with His-bundle pacing. Europace 2021; 23 :421–30. 185. Mahajan A, Trivedi R, Subzposh FA, Vijayaraman P. Feasibility of His bundle pacing and atrioventricular junction ablation with left bundle branch area pacing as backup. Heart Rhythm 2024; 21 :1180–1. 186. Rodríguez Muñoz D, Crespo-Leiro MG, Fernández Lozano I, Zamorano Gómez JL, Peinado Peinado R, Manzano Espinosa L et al. Conduction system pacing and atrioven tricular node ablation in heart failure: the PACE-FIB study design. ESC Heart Fail 2023; 10 :3700–9. 187. Sweeney MO, Bank AJ, Nsah E, Koullick M, Zeng QC, Hettrick D et al. Minimizing ven tricular pacing to reduce atrial fibrillation in sinus-node disease. N Engl J Med 2007; 357 : 1000–8. 188. Salden F, Huntjens PR, Schreurs R, Willemen E, Kuiper M, Wouters P et al. Pacing therapy for atrioventricular dromotropathy: a combined computational-experimental-clinical study. Europace 2022; 24 :784–95. 189. Salden F, Kutyifa V, Stockburger M, Prinzen FW, Vernooy K. Atrioventricular dromo tropathy: evidence for a distinctive entity in heart failure with prolonged PR interval? Europace 2018; 20 :1067–77. 190. Boriani G, Tukkie R, Manolis AS, Mont L, Purerfellner H, Santini M et al. Atrial antita chycardia pacing and managed ventricular pacing in bradycardia patients with paroxys mal or persistent atrial tachyarrhythmias: the MINERVA randomized multicentre international trial. Eur Heart J 2014; 35 :2352–62. 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 chronization therapy. Europace 2008; 10 :797–800. 193. Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 2010; 363 :2385–95. 194. Zareba W, Klein H, Cygankiewicz I, Hall WJ, McNitt S, Brown M et al. Effectiveness of cardiac resynchronization therapy by QRS morphology in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT). Circulation 2011; 123 :1061–72. 195. Giraldi F, Cattadori G, Roberto M, Carbucicchio C, Pepi M, Ballerini G et al. Long-term effectiveness of cardiac resynchronization therapy in heart failure patients with un favorable cardiac veins anatomy comparison of surgical versus hemodynamic proced ure. J Am Coll Cardiol 2011; 58 :483–90. 196. Daubert J-C, Saxon L, Adamson PB, Auricchio A, Berger RD, Beshai JF et al. 2012 EHRA/HRS expert consensus statement on cardiac resynchronization therapy in heart failure: implant and follow-up recommendations and management: a registered branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society; and in collaboration with the Heart Failure Society of America (HFSA), the American Society of Echocardiography (ASE), the American Heart Association (AHA), the European Association of Echocardiography (EAE) of the ESC and the Heart Failure Association of the ESC (HFA). Endorsed by the governing bodies of AHA, ASE, EAE, HFSA, HFA, EHRA, and HRS. Europace 2012; 14 :1236–86. 197. Leclercq C, Burri H, Delnoy PP, Rinaldi CA, Sperzel J, Calò L et al. Cardiac resynchro nization therapy non-responder to responder conversion rate in the MORE-CRT MPP trial. Europace 2023; 25 :euad294. 198. Teng AE, Lustgarten DL, Vijayaraman P, Tung R, Shivkumar K, Wagner GS et al. Usefulness of His bundle pacing to achieve electrical resynchronization in patients with complete left bundle branch block and the relation between native QRS axis, dur ation, and normalization. Am J Cardiol 2016; 118 :527–34. 199. Sharma PS, Ellison K, Patel HN, Trohman RG. Overcoming left bundle branch block by permanent His bundle pacing: evidence of longitudinal dissociation in the His via re cordings from a permanent pacing lead. HeartRhythm Case Rep 2017; 3 :499–502. 200. Moustafa AT, Tang AS, Khan HR. Conduction system pacing on track to replace CRT? Review of current evidence and prospects of conduction system pacing. Front Cardiovasc Med 2023; 10 :1220709. 201. Barba-Pichardo R, Manovel Sanchez A, Fernandez-Gomez JM, Morina-Vazquez P, Venegas-Gamero J, Herrera-Carranza M. Ventricular resynchronization therapy by direct His-bundle pacing using an internal cardioverter defibrillator. Europace 2013; 15 :83–8. 202. Zanon F, Abdelrahman M, Marcantoni L, Naperkowski A, Subzposh FA, Pastore G et al. Long term performance and safety of His bundle pacing: a multicenter experi ence. J Cardiovasc Electrophysiol 2019; 30 :1594–601. 203. Upadhyay GA, Cherian T, Shatz DY, Beaser AD, Aziz Z, Ozcan C et al. Intracardiac delineation of septal conduction in left bundle-branch block patterns. Circulation 2019; 139 :1876–88. 204. Whinnett ZI, Shun-Shin MJ, Tanner M, Foley P, Chandrasekaran B, Moore P et al. Effects of haemodynamically atrio-ventricular optimized His bundle pacing on heart failure symptoms and exercise capacity: the His optimized pacing evaluated for heart failure (HOPE-HF) randomized, double-blind, cross-over trial. Eur J Heart Fail 2023; 25 :274–83. 205. Li Y, Chen K, Dai Y, Li C, Sun Q, Chen R et al. Left bundle branch pacing for symptom atic bradycardia: implant success rate, safety, and pacing characteristics. Heart Rhythm 2019; 16 :1758–65. 206. Wu S, Sharma PS, Huang W. Novel left ventricular cardiac synchronization: left ven tricular septal pacing or left bundle branch pacing? Europace 2020; 22 :ii10–8. 207. Chen J, Ezzeddine FM, Liu X, Vaidya V, McLeod CJ, Valverde AM et al. Left bundle branch pacing vs ventricular septal pacing for cardiac resynchronization therapy. Heart Rhythm O2 2024; 5 :150–7. 208. Mirolo A, Chaumont C, Auquier N, Savoure A, Godin B, Vandevelde F et al. Left bun dle branch area pacing in patients with baseline narrow, left, or right bundle branch block QRS patterns: insights into electrocardiographic and echocardiographic features. Europace 2023; 25 :526–35. 209. Wang Y, Zhu H, Hou X, Wang Z, Zou F, Qian Z et al. Randomized trial of left bundle branch vs biventricular pacing for cardiac resynchronization therapy. J Am Coll Cardiol 2022; 80 :1205–16. 210. Ferreira Felix I, Collini M, Fonseca R, Guida C, Armaganijan L, Healey JS et al. Conduction system pacing versus biventricular pacing in heart failure with reduced ejection fraction: a systematic review and meta-analysis of randomized controlled trials. Heart Rhythm 2024; 21 :881–9. 211. Friedman DJ, Al-Khatib SM, Dalgaard F, Fudim M, Abraham WT, Cleland JGF et al. Cardiac resynchronization therapy improves outcomes in patients with intraventricu lar conduction delay but not right bundle branch block: a patient-level meta-analysis of randomized controlled trials. Circulation 2023; 147 :812–23. 212. Chen X, Li X, Bai Y, Wang J, Qin S, Bai J et al. Electrical resynchronization and clinical outcomes during long-term follow-up in intraventricular conduction delay patients ap plied left bundle branch pacing-optimized cardiac resynchronization therapy. Circ Arrhythm Electrophysiol 2023; 16 :e011761. 213. Jastrzębski M, Foley P, Chandrasekaran B, Whinnett Z, Vijayaraman P, Upadhyay GA et al. Multicenter hemodynamic assessment of the LOT-CRT strategy: when does combining left bundle branch pacing and coronary venous pacing enhance resynchro nization? Primary results of the CSPOT-study. Circ ArrhythmElectrophysiol 2024; 17 : e013059. 214. Chung ES, Katra RP, Ghio S, Bax J, Gerritse B, Hilpisch K et al. Cardiac resynchroniza tion therapy may benefit patients with left ventricular ejection fraction ${>}35\%$ a PROSPECT trial substudy. Eur J Heart Fail 2010; 12 :581–7. 215. Cha YM, Lee HC, Mulpuru SK, Deshmukh AJ, Friedman PA, Asirvatham SJ et al. Cardiac resynchronization therapy for patients with mild to moderately reduced ejec tion fraction and left bundle branch block. Heart Rhythm 2024; 21 :2250–9. 216. Yu GI, Kim TH, Cho YH, Bae JS, Ahn JH, Jang JY et al. Left bundle branch area pacing in mildly reduced heart failure: a systematic literature review and meta-analysis. Clin Cardiol 2023; 46 :713–20. 217. Ye Y, Chen X, He L, Wu S, Su L, He J et al. Left bundle branch pacing for heart failure and left bundle branch block patients with mildly reduced and preserved left ventricu lar ejection fraction. Can J Cardiol 2023; 39 :1598–607. 218. Zeng J, He C, Zou F, Qin C, Xue S, Zhu H et al. Early left bundle branch pacing in heart failure with mildly reduced ejection fraction and left bundle branch block. Heart Rhythm 2023; 20 :1436–44. 219. Vijayaraman P, Zanon F, Ponnusamy SS, Herweg B, Sharma P, Molina-Lerma M et al. Conduction system pacing compared with biventricular pacing for cardiac resynchro nization therapy in patients with heart failure and mildly reduced left ventricular ejec tion fraction: results from international collaborative LBBAP study (I-CLAS) group. Heart Rhythm 2025. (EPUB ahead of print)

ESC/EHRA clinical consensus statement

220. Chen X, Jin Q, Qiu Z, Qian C, Liang Y, Wang J et al. Outcomes of upgrading to LBBP in CRT nonresponders: a prospective, multicenter, nonrandomized, case-control study. JACC Clin Electrophysiol 2024; 10 :108–20. 221. Vijayaraman P, Herweg B, Ellenbogen KA, Gajek J. His-optimized cardiac resynchroni zation therapy to maximize electrical resynchronization: a feasibility study. Circ Arrhythm Electrophysiol 2019; 12 :e006934. 222. Jastrzebski M, Moskal P, Huybrechts W, Curila K, Sreekumar P, Rademakers LM et al. Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT): results from an international LBBAP collaborative study group. Heart Rhythm 2022; 19 :13–21. 223. Jastrzebski M, Kielbasa G, Curila K, Moskal P, Bednarek A, Rajzer M et al. Physiology-based electrocardiographic criteria for left bundle branch capture. Heart Rhythm 2021; 18 :935–43. 224. Jastrzebski M, Baranchuk A, Fijorek K, Kisiel R, Kukla P, Sondej T et al. Cardiac resyn chronization therapy-induced acute shortening of QRS duration predicts long-term mortality only in patients with left bundle branch block. Europace 2019; 21 :281–9. 225. Zweerink A, Burri H. His-optimized and left bundle branch-optimized cardiac resynchro nization therapy: in control of fusion pacing. Card Electrophysiol Clin 2022; 14 :311–21. 226. Deshmukh A, Sattur S, Bechtol T, Heckman LIB, Prinzen FW, Deshmukh P. Sequential His bundle and left ventricular pacing for cardiac resynchronization. J Cardiovasc Electrophysiol 2020; 31 :2448–54. 227. Parale C, Bootla D, Jain A, Satheesh S, Anantharaj A, Ahmed AS et al. Comparison of electrocardiographic parameters between left bundle optimized cardiac resynchroni zation therapy (LOT-CRT) and left bundle branch pacing-cardiac resynchronization therapy (LBBP-CRT). Pacing Clin Electrophysiol 2023; 46 :840–7. 228. Burri H, Prinzen FW, Gasparini M, Leclercq C. Left univentricular pacing for cardiac resynchronization therapy. Europace 2017; 19 :912–9. 229. Somma V, Ha FJ, Palmer S, Mohamed U, Agarwal S. Pacing-induced cardiomyopathy: a systematic review and meta-analysis of definition, prevalence, risk factors, and manage ment. Heart Rhythm 2023; 20 :282–90. 230. Kaza N, Htun V, Miyazawa A, Simader F, Porter B, Howard JP et al. Upgrading right ventricular pacemakers to biventricular pacing or conduction system pacing: a system atic review and meta-analysis. Europace 2023; 25 :1077–86. 231. Merkely B, Hatala R, Merkel E, Szigeti M, Veres B, Fabian A et al. Benefits of upgrading right ventricular to biventricular pacing in heart failure patients with atrial fibrillation. Europace 2024; 26 :euae179. 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 trial. Eur Heart J 2023; 44 :4259–69. 233. Wang N, Ma PP, Jing ZM, Chen Y, Jia JJ, Zhao FL et al. Predictors of pacing-induced cardiomyopathy detection and outcomes demonstration after conduction system pa cing upgrade on patients with long-term persistent atrial fibrillation. Pacing Clin Electrophysiol 2023; 46 :684–92. 234. Shan Y, Lin M, Sun Y, Zhang J, Jiang H, Fu G et al. The specific value of upgrading to left bundle branch area pacing in patients with pacing-induced cardiomyopathy or non-pacing-induced cardiomyopathy related upgrade status: a retrospective study. Pacing Clin Electrophysiol 2023; 46 :761–70. 235. Gardas R, Golba KS, Soral T, Biernat J, Kulesza P, Sajdok M et al. The effects of His bun dle pacing compared to classic resynchronization therapy in patients with pacing-induced cardiomyopathy. J Clin Med 2022; 11 :5723. 236. Zheng R, Yao H, Lian L. His-Purkinje conduction system pacing for pacing-induced car diomyopathy: a systematic literature review and meta-analysis. J Interv Card Electrophysiol 2023; 66 :1005–13. 237. Yang YH, Wang KX, Ma PP, Zhang RF, Waleed KB, Yin X et al. His-purkinje system pacing upgrade improve the heart performances in patients suffering from pacing-induced cardiomyopathy with or without permanent atrial fibrillation. Int J Cardiol 2021; 335 :47–51. 238. Ye Y, Wu S, Su L, Sheng X, Zhang J, Wang B et al. Feasibility and outcomes of upgrading to left bundle branch pacing in patients with pacing-induced cardiomyopathy and infra nodal atrioventricular block. Front Cardiovasc Med 2021; 8 :674452. 239. Vijayaraman P, Herweg B, Dandamudi G, Mittal S, Bhatt AG, Marcantoni L et al. Outcomes of His-bundle pacing upgrade after long-term right ventricular pacing and/or pacing-induced cardiomyopathy: insights into disease progression. Heart Rhythm 2019; 16 :1554–61. 240. Burri H, Starck C, Auricchio A, Biffi M, Burri M, D’Avila A et al. EHRA expert consensus statement and practical guide on optimal implantation technique for conventional pa cemakers and implantable cardioverter-defibrillators: endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin-American Heart Rhythm Society (LAHRS). Europace 2021; 23 :983–1008. 241. Sticherling C, Ellenbogen KA, Burri H. Stepping back for good reasons: a reappraisal of the DF-1 connector for defibrillator leads. Europace 2024; 26 :euae057. 242. Ponnusamy SS, Ramalingam V, Ganesan V, Syed T, Kumar M, Mariappan S et al. Left bundle branch pacing-optimized implantable cardioverter-defibrillator (LOT-ICD) for cardiac resynchronization therapy: a pilot study. Heart Rhythm O2 2022; 3 :723–7. 243. Clementy N, Bodin A, Ah-Fat V, Babuty D, Bisson A. Dual-chamber ICD for left bundle branch area pacing: the cardiac resynchronization and arrhythmia sensing via the left bundle (cross-left) pilot study. J Interv Card Electrophysiol 2023; 66 :905–12. 244. Imnadze G, Fink T, Eitz T, Bocchini Y, Antonyan L, Harutyunyan K et al. Standard de fibrillator leads for left bundle branch area pacing: first-in-man experience and short-term follow-up. JACC Clin Electrophysiol 2024; 10 :2263–8. 245. Ponnusamy SS, Ganesan V, Vijayaraman P. Feasibility, safety, and short-term follow-up of defibrillator lead at left bundle branch area pacing location: a pilot study. Heart Rhythm 2024; 21 :1900–6. 246. Chung MK, Fagerlin A, Wang PJ, Ajayi TB, Allen LA, Baykaner T et al. Shared decision making in cardiac electrophysiology procedures and arrhythmia management. Circ Arrhythm Electrophysiol 2021; 14 :e007958. 247. Mahajan A, Pokharel P, Vijayaraman P. Lead-to-lead interaction leading to left bundle branch area pacing lead failure. HeartRhythm Case Rep 2023; 9 :72–5. 248. Ozpak E, Van Heuverswyn F, Timmermans F, De Pooter J. Lead performance of stylet-driven leads in left bundle branch area pacing: results from a large single-center cohort and insights from in vitro bench testing. Heart Rhythm 2024; 21 :865–73. 249. Rangaswamy VV, Ponnusamy SS. Late distal conductor fracture of the lumenless pacing lead after left bundle branch area pacing. Heart Rhythm 2024; 21 :490–1. 250. Thaler R, Sinner MF, Joghetaei N, Fichtner S. Early sudden distal conductor fracture of a stylet-driven lead implanted for left bundle branch area pacing. HeartRhythm Case Rep 2023; 9 :28–30. 251. Zou J, Chen K, Liu X, Xu Y, Jiang L, Dai Y et al. Clinical use conditions of lead deploy ment and simulated lead fracture rate in left bundle branch area pacing. J Cardiovasc Electrophysiol 2023; 34 :718–25. 252. De Pooter J, Breitenstein A, Özpak E, Haeberlin A, Hofer D, Le Polain de Waroux JB et al. Lead integrity and failure evaluation in left bundle branch area pacing (LIFE-LBBAP study). JACC Clin Electrophysiol 2025; 11 :158–70. 253. Huybrechts WLH, Bergonti M, Saenen JB, Miljoen H, Van Leuven O, Van Assche L et al. Left bundle branch area defibrillator (LBBAD): a first-in-human feasibility study. JACC Clin Electrophysiol 2023; 9 :620–7. 254. Elliott MK, Jacon P, Sidhu BS, Smith LJ, Mehta VS, Gould J et al. Technical feasibility of leadless left bundle branch area pacing for cardiac resynchronization: a case series. Eur Heart J Case Rep 2021; 5 :ytab379. 255. Wijesuriya N, Elliott MK, Mehta V, Sidhu BS, Strocchi M, Behar JM et al. Leadless left bundle branch area pacing in cardiac resynchronisation therapy: advances, challenges and future directions . Front Physiol 2022; 13 :898866. 256. Ferrick AM, Raj SR, Deneke T, Kojodjojo P, Lopez-Cabanillas N, Abe H et al. 2023 HRS/EHRA/APHRS/LAHRS expert consensus statement on practical management of the remote device clinic. Europace 2023; 25 :euad123. 257. Vijayaraman P, Trivedi RS, Koneru JN, Sharma PS, De Pooter J, Schaller RD et al. Transvenous extraction of conduction system pacing leads: an international multicen ter (TECSPAM) study. Heart Rhythm 2024; 21 :1953–61.