Heart Failure Reviews
https://doi.org/10.1007/s10741-023-10296-4
Conduction system pacing: promoting the physiology to prevent heart
failure
Han Naung Tun1 · Hafiza Khan2 · Daryna Chernikova3 · Yury Mareev4,5 · Santabhanu Chakrabarti6 · May Thant7 ·
Antonio Cannata8
Accepted: 24 January 2023
© The Author(s) 2023
Abstract
Cardiac conduction system pacing provides physiological ventricular activation by directly stimulating the conduction
system. This review describes the two types of conduction system pacing: His bundle pacing (HBP) and left bundle area
pacing (LBAP). The most significant advantage of HB pacing is that it can provide a regular, narrow QRS; however, the
disadvantages are challenging implantation and a high risk of re-intervention due to lead dislodgement and the development of high pacing threshold. LBAP provides optimum physiological activation of the left ventricle by engaging the left
bundle/fascicular fibers. LBAP is more physiological than traditional RV apical pacing and could be an attractive alternative
to conventional cardiac resynchronization therapy (CRT). The advantages of LBAP are a relatively more straightforward
implantation technique than HBP, better lead stability and pacing thresholds. HBP and LBAP are more physiological than
right ventricular pacing and may be used instead of conventional pacemakers. Both HBP and LBBP are being investigated
as alternatives to conventional CRT.
Keywords His bundle pacing · Left bundle area pacing · Cardiac resynchronization · Heart failure
Introduction
Conventional cardiac resynchronization therapy (CRT) is
an essential part of treating selected patients with HFrEF
and ventricular dyssynchrony due to wide QRS. However,
conventional CRT requires implantation of an extra lead
in the coronary sinus, which sometimes may be challenging and less feasible due to unsuitable anatomy, phrenic
nerve stimulation, and unacceptably high local thresholds.
Moreover, the left ventricular epicardial stimulation may not
2
Cardiac Electrophysiology, Baylor Scott & White The Heart
Hospital, TX, Plano, USA
Han Naung Tun
htun@uvm.edu; annasxhan@gmail.com
3
Cardiology Department, City Hospital, Heroiv Ukrainy, 17
Street, 84300, Kramatorsk, Donetsk, Ukraine
Hafiza Khan
Hafiza.Khan@bswhealth.org
4
Daryna Chernikova
kardio4815926@gmail.com
Department of Cardiology, National Medical Research
Centre for Therapy and Preventive Medicine, Moscow,
Russia
5
Yury Mareev
mareev84@gmail.com
Robertson Centre for Biostatistics, University of Glasgow,
Glasgow, UK
6
Division of Cardiology, Department of Medicine, University
of British Columbia, Heart Rhythm Services, 211-1033
Davie Street, Vancouver, BC V4N 0J9, Canada
7
Royal Blackburn Hospital, Health Education England,
Northwestern Deanery, Haslingden Rd, Blackburn BB2 3HH,
UK
8
Department of Cardiovascular Sciences, Faculty of Life
Sciences & Medicine, King’s College - London, London, UK
* Antonio Cannata
antonio.cannata@kcl.ac.uk; anto.cannata@gmail.com
Santabhanu Chakrabarti
schakrabarti@providencehealth.bc.ca
May Thant
drmaysandarthant@gmail.com
1
UVM Medical Centre, Larner College of Medicine,
University of Vermont, Given Medical Bldg, E-126, 89
Beaumont Ave, Burlington, VT 05405, USA
13
Vol.:(0123456789)
Heart Failure Reviews
entirely resolve the electrical dyssynchrony [1, 2]. Epicardial
placement of LV lead has been suggested as an alternative
method in the case of transvenous procedure failure during
CRT device implantation, but it may cause lead failure and
rather highly reported complications such as infection [5].
These challenges with conventional CRT led to the development of a new concept of pacing—the conduction system
pacing (namely His bundle pacing (HBP) and left bundle
area pacing (LBAP)), which can also be alternatives to conventional right ventricular pacing in selected patients.
Clinical anatomy of physiological pacing
The His bundle (HB) is a thin structure penetrating the central fibrous body of the heart and has two main anatomical
variants. The type I HB, present in 46.7% of subjects, when
the AV bundle is covered by a thin layer of myocardial fibers
and runs along the lower border of the membranous septum.
Conversely, the type II HB runs within the muscular part
of the interventricular septum below the pars membranacea
[2, 3]. Both atrial and ventricular portions of the HB can be
accessed for permanent conduction system pacing [1]. The
HB has significant positional variations relative to the membranous septum [1], influencing selective His bundle pacing
(S-HBP) or nonselective His bundle pacing (NS-HBP) during permanent HBP procedure.
LBB’s anatomical features determine the feasibility of
LBBP as a potential physiological pacing modality. In contrast to HBP, LBBP that is determined by the capture of the
LBB and distal conduction system tissues has a much wider
target zone for area pacing that is likely to be beyond the site
of the block in distal HB [5]. In contrast to right ventricular apical pacing, HBP does not induce interventricular or
intraventricular asynchrony and does not provoke myocardial perfusion disorders [6].
Development and early experience
of human HBP and LBBP
Implementing physiological pacing techniques directly activating the conduction system has been and continues to be a
crucial issue in managing cardiac conduction disease. Hence,
electrophysiological challenges arose as development progressed. Nearly 5 decades ago Narula et al. reported that the
pacing impulse to ventricular activation time (PI-R) during the
procedure was the same as the H-V time during normal sinus
rhythm [7]. Subsequently, the ability of HBP to generate truly
physiological ventricular activation would allow this technique
to become a full-fledged alternative to cardiac resynchronization therapy (CRT) [8] and has been recommended as a rescue
modality for failed biventricular pacing [9].
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Since 2006, several reports which described the use of
HBP in clinical practice have been published [10]. These
reports have led to further investigation of the effectiveness of
permanent HBP in patients requiring pacing and device-paced
HF therapy [11]. After that, the benefits of permanent HBP
were proved in multiple studies. In particular, the first systematic analysis of a large pool of patients demonstrated a high
success for HBP concerning the sustaining of cardiac function with the potential for significant improvement in LVEF
in patients with systolic dysfunction and heart failure [12].
However, due to significant procedural limitations and technical complexities of HBP associated with the risk of causing
distal conduction block, high capture threshold, and low sensed
R wave amplitude (Fig. 1), researchers and clinicians have faced
the necessity to develop a better pacing modality for delivering
physiological pacing, the LBAP therapy [13]. After that, the
advantages of the LBAP technique in patients with cardiomyopathy have been demonstrated across several studies [14].
Mechanisms for LBBB reversal with His
bundle pacing
His bundle pacing (HBP) has arisen as a novel and alternative method for cardiac resynchronization therapy (CRT) in
patients with heart failure (HF) and left bundle branch block
(LBBB). The main reason for implementing effective ventricular resynchronization and more physiological activation
is the obvious improvement in cardiac function. This method
can also significantly reduce QRS duration and restore normal intrinsic activation patterns in patients with ventricular
conduction delays, as demonstrated by Ali et al. [21].
Thus, for the first time, the concept of longitudinal dissociation with the fibers within the His bundle committed to the left
bundle with asynchronous conduction resulting in an LBBB
pattern was described. The study showed that localized lesions
within the His bundle induced LBBB. Meanwhile, stimulation of the HB proximal to the intra-His lesion could lead to
ventricular depolarization. HB stimulation at a site distal to
the lesion, in turn, resulted in narrow QRS complexes due to
synchronous impulse conduction to LBB and RBB. These fundamental concepts confirmed the feasibility of HBP, including in advanced His to ventricular electrogram interval (HV)
disease stages [6].
In some cases, the factors like the higher lead revision rate
or pacing thresholds can prevent HBP from reversing LBB.
Concerning the mechanisms for HBP narrowing or reversing
BBB, there are the following:
• The pacing lead is placed distal to the site of BBB fibers
within the HB are ordered in strands predestined for the
LBB or RBB. The position of a pacing lead can reverse
conduction delays within the HB [25].
Heart Failure Reviews
Fig. 1 Advantages and disadvantage of His bundle pacing (HBP) vs left bundle branch pacing (LBBP)
• The connection between source and sink: the block is
overcome with sufficient stimulus for activation of distal
dormant tissue based on the source-sink connection during pacing versus intrinsic impulse propagation [25].
• Retrograde activation: the activation of the His-Purkinje
system happens through the capture of an upper septal
branch that permits onward antegrade activation beyond
a block site [25].
evaluated, it was proved that temporary HBP did not lead to
an increase in QRS duration (in comparison with temporary
biventricular pacing) [28]. A randomized study by Ellenbogen
and Huizar demonstrated that LVEF was significantly higher
after 12 months of His pacing in patients compared with AVB,
narrow QRS, and LVEF > 0.40 as compared with RVP [29].
Evaluating the long-term lead performance of His pacing,
Chen et al. reported successful HBP in 80% of cases with
markedly lower death or HF hospitalization in HBP compared
to RVP patients at five years of follow-up [30].
Acute and chronic effects of HBP and LBBP
In a prospective crossover study, Catanzariti et al. proved
that during direct HBP, physiologic distribution of myocardial blood flow was preserved more in comparison with right
ventricular apical pacing [26]. In another crossover trial, the
evaluation of myocardial perfusion and mitral regurgitation
showed significant improvement in the assessed indicators.
Still, HBP, in this case, had no effect on LV systolic function
[27]. The results of the study by Zanon et al., meanwhile,
demonstrated that HBP mode in comparison with RV apical
pacing in patients undergoing permanent implantation of a
HBP lead contributed to improvement in LV systolic function
and echocardiographic indices of ventricular synchrony [12].
In a more recent study, where the effects of HBP in patients
with LV systolic dysfunction, first-degree atrioventricular
block (AVB), and either RBBB or narrow QRS complex were
HBP and LBBP in CRT‑eligible populations
Several prospective randomized studies proved the effects of
BVP in reducing mortality rates and heart failure hospitalization, improving quality of life, and increased exercise capacity. However, the CRT non-response is up to 30% in all CRT
candidates [31]. In patients with narrow QRS or moderate
QRS prolongation (i.e., < 130 ms), BVP can cause prolongation of ventricular activation time and worsen dyssynchronous
activation [32]. Furthermore, right ventricular pacing should
not be applied to patients with impaired LVEF to avoid the
development of pacing-induced cardiomyopathy. Since BVP
does not deliver true physiological pacing, it has not demonstrated superiority over RVP in patients with LVEF > 45%,
according to the results of the BIOPACE trial [33].
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Heart Failure Reviews
A multicenter study by Ali et al. evaluated the feasibility and
outcomes of the LBBAP method in CRT-eligible patients or
those who underwent unsuccessful CRT. In this cohort study,
all patients had NYHA class II to IV, baseline LVEF ≤ 50%,
and indications for ventricular pacing and/or CRT. Based on
the results, LBBAP was associated with reduced paced QRS
duration, improving clinical and echocardiographic outcomes.
Hence, LBBAP can be a feasible, safe, and potentially an alternative option for CRT [21]; however, this option needs to be
tested in large clinical trials.
In a randomized crossover study, Gasparini et al. demonstrated no significant difference in clinical and echocardiographic improvements while applying HBP compared with
BVP [34]. However, certain disadvantages of HBP, such as
higher pacing thresholds and the inability to correct distal
LBBB, were a limitation for using this technique, as demonstrated by Leclercq et al. comparing HBP with BVP [35].
pacing improves quality of life New York Heart Association
classification, left ventricular ejection fraction, and left ventricular volumes. However, despite strong clinical evidence
regarding the efficacy of biventricular pacing, it is estimated
that approximately 1/3 of patients have no clinical benefit or
response to CRT via LV lead placement (Table 1).
HBP
Conduction system pacing, either via His bundle pacing or
more recently left bundle branch pacing, has emerged as a
viable alternative to traditional left ventricular CRT in patients
with congestive heart failure. His bundle pacing via activation
of the His-Purkinje conduction system and resultant physiologic ventricular activation has been promoted as a favorable
alternative to Bi ventricular pacing strategy in patients with
and without heart failure (Fig. 2).
LBBAP
Clinical perspectives of His bundle pacing
and left bundle branch pacing area in heart
failure
Cardiac resynchronization therapy is the gold standard in the
management of patients with systolic heart failure and electromechanical dyssynchrony, as evidenced by a wide QRS
duration. For over two decades, the resynchronization method
has been through by ventricular pacing. We have strong data
using prospective randomized studies that show biventricular
Left bundle branch area pacing has been suggested as an
effective alternative to overcome the limitations of His bundle pacing. Left bundle branch pacing allows for physiologic
stimulation of the left bundle component of cardiac conduction system like HBP, however, with improved leads to stability and fewer implant and post-op technologic challenges.
Left bundle branch pacing has a larger target area and somewhat fewer technological implant challenges. Lead stability
and thresholds also appear to be improved compared to His
Table 1 Current limitations of HBP and LBBP in heart failure
HBP
LBBAP
1. Higher pacing thresholds
2. Increased implantation time and fluoroscopy time
3. Lead dislodgement
4. Elevated pacing thresholds at follow-up
5. Rapid battery depletion due to an increase in pacing thresholds
6. Failure to achieve His bundle capture
7. Absence of a unique CPT code resulting in no increase in payment
despite increased physician time utilization, EP lab utilization, and
use of additional sheaths and equipment
8. Lack of large RCT data regarding outcomes in comparison to
traditional CRT
9. Nuanced implant technique, limited to mostly electrophysiologists
10. Not scalable
11. High reintervention rate
12. Concerns regarding aortic valve endocarditis if lead related
infection
1. Learning curve regarding the use of the delivery systems of several
vendors
2. Learning curve regarding the left bundle branch area pacing site and
placement of the lead deep into septal
3. Risk of deep septal lead placement, including but not limited to
perforation into the left ventricle
4. Potential for higher complication rate should the deep intra-septal
lead need to be extracted in the future
5. Absence of big randomized controlled data comparing left bundle
branch area pacing in patients requiring CRT in comparison to traditional
biventricular pacing
6. Accurate understanding of criteria for left bundle branch area capture
by implanting physician
7. Long-term (> 12 months) lead performance with deep septal implantation
of pacing lead
8. Increased procedure time and fluoroscopy time, in the initial implant
learning curve
9. No unique CPT code; hence, no payment for increased physician
procedure time and EP lab time utilization
10. Equipment issues: new lead design and delivery systems are being
designed
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Heart Failure Reviews
Fig. 2 His bundle pacing in CHF
bundle pacing. Nonetheless, it is important to understand
anatomy and fluoroscopic views when implantation of the
lead to achieve accurate left bundle capture.
Vijayaraman et al. recently published their data regarding
the feasibility and outcomes of left bundle branch area pacing for CRT in a multicenter international collaborative study.
LBBP was attempted in 325 patients with LVEF < 50% and an
indication for CRT. CRT was successfully achieved in 277 of
these patients (85%). QRS configuration at baseline was left
bundle branch block in 39%, and non-left bundle branch block
in 46%. Procedure times were 105 ± 54 min, and fluoroscopy
time was acceptable at 19 ± 15 min. Importantly, left bundle
branch area pacing thresholds were 0.6 ± 0.3 V @0.5 ms, and
R wave amplitude was acceptable at 10.6 ± 6 mV at implantation. Sensing and thresholds remain stable during the followup of approximately 6 months. The importantly clinical and
echocardiographic response was observed in 72 to 73% of the
patients who achieved left bundle branch pacing. This study
proved that left bundle branch pacing is a feasible alternative for
cardiac resynchronization therapy providing acceptable pacing
and sensing parameters both in the short and long term with no
excessive procedure times and successful clinical outcomes.
Recent randomized LBBP-RESYNC study (40 pts) showed
that patient randomized to LBBP has higher LVEF improvement. In this study, 10% LBBP patients were crossover to
biventricular CRT and 20% of biventricular CRT were crossover to LBBB pacing due to the problems with lead placement.
Which on the one hand showed that is not always possible to
perform both of techniques in one patient but in case of the
impossibility of one of the methods it is possible to change to
another. Both HBP and LBAP could be helpful also in patients
without HF in whom we expect a high rate of RV stimulation.
HBP is the most physiological pacing modality that restores
normal ventricular activation and has been demonstrated to
achieve greater hemodynamic response over BVP in patients
[44]. Confirmation of LBB capture is essential to distinguish
LBBP from LVSP, as LBBP ensures rapid LV activation propagation via conduction system rather than myocardial endocardium and hence improves ventricular electrical synchrony.
Pacing strategies for HF and AF patients
Atrial fibrillation (AF), the most common arrhythmia, increases
the risk of death and hospitalization in 76% of HF patients, and
the structural and neurohormonal changes in HF make, in turn,
the development and progression of AF much more likely [15].
AF ablation was associated with a significant improvement in
LVEF, independent of the severity of left ventricular dysfunction [16].
In a study, Molhoek et al. patients with AF showed a milder
degree of response to CRT compared to those with sinus
rhythm. However, the long-term survival rate was comparable among these two groups of patients [36, 37]. According
to the guidelines, CRT should be performed in patients with
HF and LVEF ≤ 35% with NYHA class III or IV if they are
in AF and have intrinsic QRS ≥ 130 ms, provided a strategy
to ensure biventricular capture is in place. Meanwhile, AV
junction ablation should be added in the case of incomplete
biventricular pacing (< 90–95%) due to conducted AF [38].
An intrinsic and irregular spontaneous AF rhythm
reduces the percentage of effectively biventricular paced
captured beats, making CRT delivery more challenging in
those patients with AF [39]. Nevertheless, the deleterious
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Heart Failure Reviews
hemodynamic effects of irregular, spontaneous rhythm could
be eliminated by AVJ ablation delivery. Hence, in the context
of CRT in patients with HF and concomitant AF, many studies have shown AVJ ablation’s benefits for optimization of
CRT procedure [40]. The MUSTIC AF trial is considered the
first randomized trial showing potential benefits of CRT in
HF patients with permanent AF by determining biventricular stimulation as a preferred mode compared to RV [41].
An observational study by Gasparini et al. demonstrated
that significant improvements in LVEF, the left ventricular
end-systolic volume (LVESV), and exercise capacity were
observed in AF patients who underwent AVJ ablation [37,
38]. Deshmukh et al. demonstrated further improvement in
LV dimensions with His pacing in patients with impaired
LV systolic function and AF prior to AV node ablation and
achieved procedural success in 60% of cases [36, 37].
On the other side, in selected patients with AF and HF,
especially with uncontrolled heart rate, the “ablate-andpace” strategy can be beneficial, resulting in improvement of
LVEF and the NYHA functional class [17]. However, potential downsides of such a strategy are the risk of progressive
left ventricular dyssynchrony, deterioration of LVEF, and
the risk of sudden death after AV node ablation [18]. To
prevent mechanical ventricular dyssynchrony and further HF
aggravation, cardiac resynchronization therapy (CRT) is an
effective option, although patients with AF show a milder
degree of improvement with CRT compared with patients
with sinus rhythm [19].
In patients with HF and sinus rhythm, PR prolongation is
a prospective issue for pacing. A PR ≥ 200 ms is significantly
associated with 58% higher mortality in the long term regardless of QRS duration [20]. According to the results of the studies, the prevalence of prolonged PR in patients with HF and
CRT stands at 18–52% [21].
The benefits of HBP in HF can potentially apply to patients
with narrow QRS and PR prolongation by providing AV synchrony without inducing ventricular dyssynchrony [22]. The
EuroHeart Failure survey identified that about 75% of patients
hospitalized with a suspected diagnosis of HF had normal
QRS duration (≤ 120 ms) [23]. Meanwhile, up to 50% of HF
patients with a narrow QRS complex show echocardiographic
evidence of ventricular dyssynchrony and hence might benefit from CRT, resulting in frequent off-label use of CRT
[24]. Noteworthy, HBP has a higher success rate in patients
with symptomatic AV block if the level is nodal compared to
infranodal [4]. Anatomy of the mechanism of pacing procedures should be considered during maneuvers to ensure that
the lead is positioned distal to the site of diseased HB [4].
At present with the development of dedicated tools for
direct HBP, the success rate of implantations has become
more than 90%. Moreover, in most cases, the acceptable
pacing thresholds can be achieved [37]. Su et al. evaluated
the long-term performance of HBP following AV node
13
ablation in patients with AF and HF. It was demonstrated
that HBP combined with AV node ablation was effective
in AF patients with drug-refectory HF. Furthermore, high
pulmonary artery systolic pressure (PASP), elevated serum
creatinine (Scr), and low LVEF at baseline were established
as independent predictors of the composite endpoint of allcause mortality or HF hospitalization [38].
The study by Vinther et al. observed HF patients with
LBBB, demonstrated that His-CRT provided similar clinical
improvement in comparison with BiV-CRT at the expense of
higher pacing thresholds [39]. One more study successfully
achieved permanent HBP in 80% of patients with AF, with
narrow QRS duration, both HF with a preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).
The results of the study demonstrated a reduction in hospital
admissions as well as an improvement in cardiac function [40].
Physiological pacing in patients with heart
failure with preserved ejection fraction
Increase heart rate (HR) may have the potential to reduce the
risk for heart failure hospitalization, atrial fibrillation (AF),
and cerebrovascular stroke as these outcomes are increased in
patients with a normal or preserved ejection fraction on HRlowering treatments. Therefore, lower HR elevation employing physiological conduction system pacing in patients with
HFpEF will decrease left atrial and left ventricular filling
pressures. There is an ongoing randomized trial that is investigating whether pacing with a higher heart rate is beneficial
for patients with HFpEF and pacemakers with intrinsic AV
conduction or CRT. Also, physiological pacing (CRT or His)
could be beneficial in patients with HF, LVEF 35–50%, and
indications for pacemaker implantation with high expected
percent of pacing (BLOCK HF study) [42]. Again, physiologic
accelerated pacing as a treatment in patients with heart failure
with preserved ejection fraction (PACE HFpEF) trial is now
under investigation hypothesizes that a personalized lower HR
elevation employing physiological conduction system pacing
in patients with HFpEF will decrease left atrial and left ventricular filling pressure [43].
Conclusion
Implementing physiological pacing techniques directly activating the conduction system has been and continues to be a
crucial issue in managing cardiac conduction disease. HBP is
the most physiological pacing modality that restores normal
ventricular activation and has been demonstrated to achieve
greater hemodynamic response over BVP in patients. HBP
combined with AV node ablation showed effectiveness in AF
patients with drug-refectory HF. Left bundle branch area pacing
Heart Failure Reviews
has been suggested as an effective alternative to overcome the
limitations of His bundle pacing. But, left bundle branch pacing
and His bundle pacing have a larger target area and somewhat
fewer technological implant challenges. In fact, future studies
and large-scale clinical trials are expected to validate HBP and
LBBP’s safety, reliability, and long-term performance for physiological pacing in several groups of patients.
Author contribution HNT: conceptualization and writing; HK: writing
and critical review; DC: writing and critical review; YM: writing and
critical review; SC: writing and critical review; MT: writing and critical
review; AC: conceptualization and writing.
8.
9.
10.
11.
Availability of data and materials No dataset generated.
Declarations
12.
Ethical approval No ethical approval needed.
Competing interests The authors declare no competing interests.
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