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\begin{document}

\title{Conduction System Pacing: How far are we from the ``electrical'' bypass?}



\author[1]{Evangelos Sdogkos}%
\author[2]{Konstantinos Iliodromitis}%
\author[3]{Andrew Xanthopoulos}%
\author[3]{Filippos Triposkiadis}%
\author[3]{John Skoularigis}%
\author[2]{Harilaos Bogossian}%
\author[1]{Ioannis Vogiatzis}%
\affil[1]{General Hospital of Veroia}%
\affil[2]{Evangelisches Krankenhaus Hagen Haspe}%
\affil[3]{University Ηospital of Larissa}%


\vspace{-1em}



  
  \date{May 16, 2024}


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\selectlanguage{english}
\begin{abstract}
Conduction system pacing is an alternative practice to conventional
right ventricular apical pacing. It is a method that maintains
physiologic ventricular activation, based on a correct
pathophysiological basis, in which the pacing lead bypasses the lesion
of the electrical fibers, and the electrical impulse transmits through
the intact adjacent conduction system. For this reason, it might
reasonably characterized by the term ``electrical bypass'' compared to
the coronary artery bypass in revascularization therapy. In this review
reference is made to the sequence of events that conventional right
ventricular pacing may cause adverse outcomes. Furthermore, there is a
reference to alternative strategies and pacing sites. Interest focuses
on the modalities for which there is data from the literature, namely
for the Right Ventricular (RV) septal pacing, the His Bunde pacing
(HBP), and the Left Bundle Branch pacing (LBBP). A more extensive
reference is about the HBP, for which there are the most updating data.
We analyze the considerations that limit HBP wide application in three
axes, and we also present the data for the implantation and follow-up of
these patients. Then, the indications with their most important studies
to date are described in detail, not only in their undoubtedly positive
findings but also in their weak aspects, because of which, this pacing
mode has not yet received a strong recommendation for implementation.
Finally, there is a report on LBBP, focusing mainly on its points of
differentiation from HBP.%
\end{abstract}%



\sloppy


\textbf{1. Introduction}

Conduction system pacing (CSP) was a subject of intense discussion at
the European Society of Cardiology (ESC) Congress 2021 due to an
ever-growing interest in the past five years, both in the literature and
clinical practice.\textsuperscript{1} This is because of the deeply
established knowledge that chronic conventional right ventricular (RV)
pacing is responsible for an increased risk of provoking and worsening
heart failure with hospitalizations, as also atrial fibrillation or even
causing death.\textsuperscript{2} The fact that conventional RV apical
pacing (RVA pacing), through inter-ventricular dyssynchrony, promotes
the appearance rather sooner than later of Pacing-Induced Cardiomyopathy
makes it responsible for the disturbance of the diastolic and systolic
function of both right and left ventricle, with the subsequent adverse
impact on patients. (\textbf{Figure 1} )

For the prevention of this phenomenon, alternative pacing strategies and
sites have been proposed. On the one hand, pacing different areas of the
myocardium outside the apex of the RV (non-apical RV pacing) by
targeting the interventricular septum at various higher positions, such
as this happens with the Right Ventricular Outflow Tract (RVOT) septal
pacing, the Mid and High RV Septal (RVS) pacing, but also Para-Hisian
pacing, and from the other attempt pacing parts of the conduction system
(Conduction System Pacing - CSP), as with Left Bundle Branch Area pacing
(LV Septal pacing or Left Bundle Branch pacing), but also His Bundle
pacing (HBP). (\textbf{Figure 2} )

\textbf{2. Non-apical RV pacing}

RV septal pacing is the only one during the last decade for which
randomized studies have been conducted both for indications of
high-grade atrioventricular (AV) block disorders and cardiac
resynchronization therapy. Regarding the first indication, the
Protect-Pace study compared RV apical and septal
pacing.\textsuperscript{3} There were randomized 240 patients with
preserved Left Ventricular Ejection Fraction (LVEF) \textgreater{} 50\%,
requiring high-burden RV pacing \textgreater{} 90\%, for two years of
follow-up. The study concluded that LVEF decreased in both groups
(apical and septal) to the same non-statistically significant degree. At
the same time, there was no significant difference in heart failure
hospitalizations, mortality and atrial fibrillation burden as well as
biomarkers levels, such as Brain Natriuretic Peptide (BNP). On the
contrary, a longer time was required for the RV septal implantation
procedure with an increase up to doubling the fluoroscopy time.

Regarding RV septal pacing compared to RVA for the application of
cardiac resynchronization therapy (CRT), the randomized study performed
was the SEPTAL CRT study.\textsuperscript{4} 263 patients were
randomized for septal and apical pacing in the CRT context. The results
showed non-inferiority of septal, compared to the apical position of the
RV electrode, in terms of reduction of echocardiographically determined
left ventricular end-systolic volume (LVESV) and composite clinical
endpoint of deaths and hospitalizations for heart failure, at a 6-month
follow-up. The above two studies were the cause that RV septal pacing
did not officially approve for routine implementation in permanent
pacemaker implantations.

The precise placement of the RV electrode in a septal position is a
matter that is not easy to ascertain through the fluoroscopy currently
used. Nevertheless, in addition to the above two randomized studies, a
meta-analysis of all available studies demonstrated a benefit of
non-apical RV pacing, compared to apical, in patients who had
pre-implantation reduced LVEF
\textless{}40\%.\textsuperscript{5}Furthermore, in an observational
study, in 2200 patients having 3822 active-fixation pacing and
defibrillation leads, the apical location of the RV lead, especially for
female gender and age \textgreater{}80 years, appeared to be
statistically associated with cardiac perforation.\textsuperscript{6}
Therefore, the effort to place the electrode in a non-apical position
with the data so far is not systematically recommended for every patient
needing pacing therapy but should perhaps be considered for these
specific categories. The summarized data for non-apical RV pacing
instead of RV apical pacing is in \textbf{Table 1} .

\textbf{3. Conduction system pacing: An ``Electrical Bypass''}

Therefore, given that the pacing of the RV myocardium beyond the apex is
not always associated with favorable clinical endpoints, the effort to
find and pace the conduction system in order to avoid Pacing-Induced
Cardiomyopathy is deemed essential. CSP comprises His bundle pacing
(HBP) and Left Bundle Branch Area pacing (LBBAP). This technique is
based on a pathophysiologically correct theory and could be considered
an ``Electrical Bypass''. (\textbf{Figure 3} ) The role of the venous
graft used in revascularization therapy is represented in this setting
by the pacing lead. By bypassing a lesion of the native pacing system,
which usually occurs in the area of the AV node, with the pacemaker
lead and transmitting the stimulus downward through the remaining intact
part of the system, results in faster transmission of the electrical
impulse with the normal mode, but also simultaneous stimulation of both
ventricles, and therefore the avoidance of the unfavorable phenomenon of
dyssynchrony. As a result, CSP could be characterized as an ``ideal''
form of pacing. Speaking of an ideal pacing method, this should be
easily applicable to all patients with AV system disorders, without
complications, and with long-term beneficial clinical endpoints, namely,
a form of pacing where the answer to the question ``when and to whom
patients'' is ``always and to everyone''!

This idea is not new. More than half a century before, in 1970, Narula
et al. in a series of 30 patients with conduction disturbances in the AV
node, through the transvenous technique, found the His Bundle, mapped
it, measured the corresponding intervals, and successfully induced
pacing.\textsuperscript{7} Nevertheless, permanent HBP has applied 30
years afterward, in 2000, in a series of 18 patients, with impaired left
ventricular systolic function and atrial fibrillation before AV node
ablation.\textsuperscript{8} Successful pacing was achieved in 14
patients, with satisfactory results as far as the improvement of left
ventricular dimensions and LVEF from 20 to 31\%. However, despite the
good outcomes, the HBP procedure did not proceed on a large scale,
recording a plateau in clinical application and literature research.
That is because of the following three considerations, schematically
illustrated in \textbf{Table 2} .

\textbf{4. HBP: ``Why not always and to everyone''?}

\textbf{4.1. Anatomical Considerations}

The first reason this pacing method does not apply widely until now is
the formation and anatomical location of the AV conduction system. The
AV node is located from the perspective of the right atrium within the
triangle of Koch, an area defined by heterogeneous structures. On one
side is the tendon of Todaro in the Eustachian ridge, just below is the
ostium of the coronary sinus, and on the other side is the constantly
moving septal leaflet of the tricuspid valve.\textsuperscript{9} From
this position, the AV node, as it converts into the His Bundle, enters
the electrically inactive fibrous cardiac skeleton, then passes to the
membranous portion of the interventricular septum, where its two
bundles, right and left, after their separation, advance into the
myocardium of the corresponding areas of the septum.

Additionally, it is not only the complex path of the conduction system
but also the dimensions of these formations: the mean length, width, and
thickness of the compact AV node are 3.5 \selectlanguage{ngerman}± 1.2 mm, 4.5 ± 1.1 mm, and 1.2
± 0.3 mm, respectively, and the tubular His Bundle has only a length of
20 mm and a diameter of 4 mm.\textsuperscript{10} But even the placement
of the His Bundle within the myocardium anatomically varies and can be
distinguished into three types: His bundle may run under the membranous
portion of the interventricular septum, it may run within the muscular
portion of the interventricular septum beyond the lower border of its
membranous portion, so in this case, it is hard to achieve pure
selective pacing, and also it may be located beneath the endocardium
with no surrounding myocardial fibers.\textsuperscript{11} Therefore,
the position and course, the minuscule size, and the anatomic variations
of the conduction system are a challenge to be confronted with
fluoroscopy to reveal electrical signals and give a stimulation. That is
precisely where the second consideration for HBP lies.

\textbf{4.2. Technical Considerations}

Fluoroscopy is inaccurate for localizing lead positions compared with
other imaging methods, such as cardiac computed tomography (CT). Indeed,
in a series of 59 heart failure patients undergoing CRT, the agreement
for the left ventricular lead position was observed in 35\% and for the
right ventricular lead position in only 22\% of the patients with
fluoroscopy, respectively.\textsuperscript{12} The agreement within and
between observers was much better and more accurate for cardiac CT
(kappa 0.87 and 0.85 for both left and right ventricular lead position,
respectively). Further, another technical limitation is the implantation
tools for HBP. Although several companies in the pharmaceutical industry
have created pacing leads for His Bundle, the most commonly used HBP
lead is the 69 cm Select Secure\selectlanguage{english} 3830 (Medtronic), a non-stylet-driven
active fixation lead.\textsuperscript{13} This lead can be delivered to
the His bundle region using either the specially-designed
non-deflectable His delivery sheath (C315 43 cm; Medtronic) or a
deflectable sheath (C304 69 cm; Medtronic). A characteristic of this 4.1
Fr (French gauge) bipolar lead is that the 1.8 mm exposed-helical-screw
design forms part of the tip electrode, with 9 mm tip to ring spacing,
allowing easier detection and thus pacing of His Bundle fibers. It has
unipolar mapping capabilities and minuscule size, reducing flow stresses
and valvular motion effects, thus giving maximum stability in that
demanding area.\textsuperscript{14} This lead has the best features
after 50 years of trying pacing His Bundle using primarily fluoroscopic
guidance and afterward electrical mapping for its placement.

As a technique, it does not have any critical complications for the
patient, apart from those related to the vein puncture, as with
conventional pacemakers implantation. However, there are two main
troubles: the possibility of an increase in pacing threshold, which is
observed at about 10\% of the patients, leading to shorter battery-life
duration, as well as the higher rate of lead revisions in an actual
percentage ranging from 6.7 - 8.9 \%, due to loss of capture or
increased threshold. In order to avoid the above two concerns, a
'backup' right ventricular lead can be used. The use of a 'backup' lead
is recommended in HBP in cases of the inexperience of the implanter,
acceptable threshold achieved at the upper limit, at about 2V/1ms,
possible schedule of an AV node ablation shortly, but also in cases of
high-degree or infranodal block, especially in entirely
pacemaker-dependent patients.\textsuperscript{1} Undoubtedly, an extra
third lead for pacing has the advantage of safety, especially in cases
of loss of capture, and it has better sensing compared with the HBP
lead. However, more transvenous hardware for pacing (three versus two
leads) increases the procedure's cost, along with the risk of
complications, both during implantation (ventricular perforation or vein
thrombosis) and after, such as lead damage or risk of endocarditis. From
all the anatomical and technical limitations mentioned, which may lead
to a possible increase in pacing threshold and the need for lead
revisions, arises the third consideration, which is also restrictive of
HBP widespread application.

\textbf{4.3. Programming Considerations}

Minimal dimensions of both the structures and the HBP lead cause a
variety of expressions of attempted CSP.\textsuperscript{15} During the
implantation process, the pacing lead may achieve exclusive stimulation
of the intrinsic conduction system (selective pacing), may stimulate a
part of the system and part of adjacent myocardial fibers (non-selective
pacing) or the neighboring myocardial fibers only, failing directly
stimulate the conduction system (myocardium-only pacing). These
combinations may occur for both the His Bundle and the Left Bundle
Branch area, presenting nine patterns of pacing: Selective HBP,
Non-Selective HBP, Myocardium-Only (Para-hisian) Pacing, Selective Left
Bundle Branch Pacing (LBBP), Non-Selective LBBP, Left Ventricular Septal
Pacing, Right Ventricular Septal Pacing, Mid-septal capture, and Anodal
capture (simultaneous capture of the interventricular septum and left
bundle branch from lead's ring and tip, respectively). Of course, the
arisen question is whether Selective pacing is superior to Non-Selective
pacing in terms of clinical endpoints. In a study of 350 consecutive
patients with successful HBP and \selectlanguage{english}[?]20\% ventricular pacing burden,
Selective and Non-Selective HBP have associated with similar outcomes of
death and heart failure hospitalizations together as a primary endpoint.
However, when heart failure hospitalizations and all-cause mortality
were studied as secondary endpoints separately, Selective pacing
appeared to be superior in the latter.\textsuperscript{16}

Selective and Non-Selective pacing can be recognized through the His
bundle lead threshold check electrocardiographic parameters during the
implantation. These parameters are mainly related to the morphology and
duration of the intrinsic QRS. These electrical responses are hard to
assess by only the implanter, so an additional familiar with the
procedure person needs to estimate these changes, and that's another
reason that makes this procedure demanding.\textsuperscript{15} In
situations with narrow QRS, Selective HBP is easily distinguished with
an isoelectric interval (corresponding to the H-V interval) between the
pacing spike and QRS onset, whereas in Non-Selective HBP, a
'pseudo-delta' wave is observed due to the capture of local myocardium,
before the onset of paced QRS.\textsuperscript{17, 18} In situations of
Bundle Branch Block (BBB) presence, correction of BBB may be observed
during these electrical tests at the pacing
threshold.\textsuperscript{19} Another characteristic of the transition
with reduction of pacing output is that Myocardium only capture instead
of Selective HBP is observed before the loss of capture
(LOC).\textsuperscript{17} Some examples follow for the beneficial
effect of HBP on the electrocardiographic duration of ventricular
depolarization compared to biventricular pacing and conventional apical
RV pacing. The loss of pacemaker capture during threshold control, and
the recording of selective and nonselective pacing on the
electrocardiogram, are also shown. In addition, the position of the
three electrodes in the fluoroscopic view during HBP implantation is
apparent. (\textbf{Examples 1-4} ) Except for QRS duration, other
electrocardiographic parameters are examined, such as H-QRSend =
duration from His potential to QRS offset, LBpo-QRS-LVAT = duration from
left bundle potential to peak of R wave in lateral leads (where the time
of the peak of the R wave in lead V5 or V6 is thought to represent
lateral LV activation time, LVAT), Stim-QRSend = duration from pacing
stimulus to QRS offset, Stim-QRS-LVAT = duration from pacing stimulus to
the peak of R wave in lateral leads, and Stim-V = interval from pacing
stimulus to the onset of QRS.\textsuperscript{15}

Moreover, in cases of conduction system disease with BBB, it is examined
whether or not there is a correction of the pre-existing disorder in the
branches of the His Bundle. Even in cases where there is no complete
correction of the block, the width of the QRS with HBP is narrower than
the initial.\textsuperscript{11} Thus, electrocardiographic criteria
have been proposed based on the various types of pacing in combination
with the intrinsic electrocardiogram, and that is undoubtedly more
demanding than simple conventional pacing.\textsuperscript{20}

In HBP, there are also troubleshooting issues to take care of because
they cause programming considerations, not only during implantation but
also at outpatient follow-up.\textsuperscript{21} Two issues that should
be taken care of during implantation, and have to do with the position
of the His lead, are those of atrial oversensing and ventricular
undersensing. \selectlanguage{greek}Α\selectlanguage{english}ttention should be paid to cases of atrial capture with
the His lead due to loss of His Bundle capture, as there may be
morphologies with a short PR interval (due to proximity to the AV node)
but also with a narrow P-wave morphology (due to simultaneous bi-atrial
activation).\textsuperscript{17} In addition, His leads may produce
pacing artifacts, especially at high pacing thresholds, and morphologies
that may be confusing when reading the electrocardiogram, such as
retrograde P-wave and anodal capture.

Atrial ovesensing should be checked at each follow-up visit, as should
any threshold increases that may occur during the follow-up period. HBP
thresholds are usually higher when compared with other pacing sites, not
only because His Bundle is encased in a fibrous sheath which is
electrically non-conducting but also because of the concomitant His area
disease, including local fibrosis and degeneration. Underlying
conditions, such as right atrial dilatation, septal hypertrophy, or
infiltrative situations, as in sarcoidosis or amyloidosis, should be
considered for threshold issues, as well. Finally, the ports that His
lead is placed in, especially at CRT devices (atrial, right ventricular,
or left ventricular port), should be taken into account so that the
timing intervals are accurately measured, and the correct algorithms are
appliable.\textsuperscript{22, 23} For these reasons, a specialized
Pacemaker Technician is required, who will actively participate with
knowledge and suggestions during the implantation process. In
conclusion, HBP associates with more clinical and technical issues, and
an every six months closer surveillance, which for many elderly patients
may not be so practical, unlike conventional pacemakers, where the
in-office follow-up oughts to be annual.\textsuperscript{1}

\textbf{5. HBP: Implantation and follow-up}

Despite the described difficulties of HBP, there are data from a small
number of centers indeed that show encouraging results for this
implantation technique, as well as for the follow-up of these patients
regarding the variation of the pacing parameters within the time. In a
recently published study including a total of 529 patients, in five
years, with a mean 7-month follow-up, a relatively short learning curve
was recorded, with an overall implant success rate of 81\%, which
improved to 87 \% after completion of 40 cases.\textsuperscript{24} The
mean fluoroscopy time was 11.7 \selectlanguage{ngerman}± 12.0 min, and His capture threshold
decreased. HBP lead re-implantation occurred in 7.5\% of successful
procedures mainly due to threshold rise. It is worth noting that the QRS
duration decreased by 26 msec in patients with an intrinsic QRS
\textgreater{} 120 msec, while on the contrary, an insignificant
increase in the QRS width by 12 msec observed in the patients with a
narrow QRS.

Regarding the efficacy of HBP, in QRS duration change with non-selective
or selective pacing, in the absence of BBB, selective and non-selective
pacing minimally affected QRS duration, whereas, in the presence of BBB,
QRS duration markedly decreased with both patterns of
HBP.\textsuperscript{18} AV block morphology seems to affect the
procedural success and needs to be considered before applying this type
of pacing. In a recently published meta-analysis of 1438 patients, the
implant success rate of the lead in the bundle of His averaged 84.8\%,
considerably higher than that with older stylet-driven leads with which
the success rate reached up to just 70\%. LVEF improved by an average of
5.9\% during follow-up and even more in ventricles with impaired
systolic performance \textless{}50\%, while in preserved LVEFs, no
statistically significant change recorded. Average pacing thresholds
were 1.71 V at implant and 1.79 V at \textgreater{}3 months follow-up,
with various pulse widths.\textsuperscript{25}

Also, according to recently published data, both the intermediate-term
and the long-term performance of HBP leads seem to be quite encouraging
for the implantation success rate and the threshold maintenance.
Nevertheless, threshold increase and the loss of selective pacing have
not been overcome in this study, too, during a follow-up period of 1.5
years, and that may cause a lead revision in rates up to
10\%.\textsuperscript{26} Additionally, in patients' follow-up data for
five years, HBP proved superior to RV pacing in paced QRS duration and
LVEF improvement with significantly lower rates of occurrence of
Pacing-Induced Cardiomyopathy, findings affecting clinical endpoints,
such as death and heart failure hospitalizations, especially in patients
with \textgreater{}40\% ventricular pacing.\textsuperscript{27} A
summary of published trials conducted in the last 15 years on HBP with
clinical and/or echocardiographic follow-up is included in the 2021 ESC
Guidelines' supplementary data on cardiac pacing and cardiac
resynchronization therapy.\textsuperscript{1} Therefore, according to
all mentioned, the question of ``when and in which patients'' it is
worth applying the HBP could be answered based on the following four
axes, as shown in summary in \textbf{Figure 4} .

\textbf{6. Indications of His Bundle Pacing: When and to whom?}

\textbf{6.1. Pacing for bradycardia}

Several small studies have demonstrated the superiority of HBP over RV
pacing in avoiding Pacing-Induced Cardiomyopathy. Even though upgrading
simple RV to biventricular pacing could be a highly effective solution
in patients with post-implant LVEF \textless{}35\%, nevertheless, it is
significantly underutilized even in those with lower preimplant
LVEF.\textsuperscript{28} The echocardiographically estimated LVEF is
used as a study indicator of Pacing-Induced Cardiomyopathy, knowing, of
course, the limitations of this indicator in terms of the impact of
clinical endpoints and mortality in patients with heart
failure.\textsuperscript{29} The older studies by Zanon et al. (2008),
Barba-Pichardo et al. (2010), and Kronborg et al. (2014) recorded an
LVEF improvement in 12, 59, and 32 patients, respectively, mainly with
atrioventricular block, with relatively short follow-up of 3-12 months,
in single-center trials.\textsuperscript{30-32} Sharma et al. (2015) and
Vijayaraman et al. (2018) included 75 patients in each study, recording
less heart failure hospitalization and a trend in lower mortality in
patients with \textgreater{}40\% ventricular pacing, as well as no
difference in patients with atrial fibrillation, in HBP
group.\textsuperscript{27, 33}

The largest study is that of Abdelrahman et al. (2018), a two-center
study that included 304 consecutive patients with HBP and 433 patients
with RV pacing at a sister hospital. In a 2-year follow-up, the study
showed the superiority of HBP in terms of the combined endpoint of
all-cause mortality, heart failure hospitalization, or upgrade to
biventricular pacing. The HBP superiority was even great in patients
with ventricular pacing \textgreater{}20\% (HR 0.71 and 0.65,
respectively).\textsuperscript{34} Additionally, two recently published
studies with a small number of patients with bradycardia have documented
the adequacy of HBP in maintaining LVEF after transcatheter aortic valve
implantation, as well as in comparison with LBBAP.\textsuperscript{35,
36} The commonality of all the above studies is that the data came from
observational, single, or two-center studies, with few patients, with
short follow-up periods. For that reason, most authors emphasize the
need to conduct large, prospective, randomized control trials (RCTs)
comparing HBP to RV pacing to prove beneficial clinical endpoints, such
as reduction in hospitalizations and mortality attributable to HBP in
patients with bradycardia.

\textbf{6.2. ``Ablate and pace'' strategy}

As already mentioned, the first clinical study for HBP was by Deshmukh
et al. (2000), an observational, single-center study. In 18 patients
scheduled for AV node ablation, with narrow QRS and LVEF
\textless{}40\%, with atrial fibrillation, using stylet-driven leads
without a guiding catheter, improvement in LVEF, LV dimensions, and New
York Heart Association (NYHA) Functional Classification
achieved.\textsuperscript{8} Afterwards, Occhetta et al. (2006)
conducted another small study with 16 patients, trying to achieve HBP
again using stylet-driven leads without a guiding catheter, succeeding
only in four of them HBP, while in the rest, para-Hisian pacing only
recorded. In a follow-up period of 6 months, comparing HBP to RV pacing,
the study recorded a better NYHA class, and a 6-min walk test (6MWT),
while no difference observed in LVEF and LVESV.\textsuperscript{37}

Because of the difficulty in approaching the His bundle, subsequent
studies with improved leads conducted by Huang et al. (2017),
Vijayaraman et al. (2017), and Wang et al. (2019) in 42, 40, and 44
patients, respectively.\textsuperscript{38-40} In all three of these
studies, an improvement was noticed in LVEF, left ventricular
dimensions, and NYHA class compared with baseline. The authors pointed
out that AV node ablation may result in capture thresholds increase or
lead dislodgments in a minority of patients and should be taken into
account before implantation since patient safety comes first. Similar
results were shown in the study by Su et al. (2020), who applied HBP
combined with AV node ablation to 81 patients. Additionally,
pre-procedure values of high pulmonary artery systolic pressure (PASP)
\selectlanguage{english}[?]40 mmHg, serum creatinine levels \selectlanguage{english}[?]97 \selectlanguage{greek}μ\selectlanguage{english}mol/L ([?]1.1 mg/dl), or reduced
LVEF \textless{}40\% pointed out as independent predictors of the
composite endpoint of all-cause mortality and heart failure
hospitalization.\textsuperscript{41} Finally, Zweerink et al. (2020)
compared HBP with AV node ablation in 44 patients, applying either
radiofrequency ablation or cryoablation. Although the results regarding
the improvement in LVEF were similar to the previous studies regarding
the ablation technique, cryoablation appeared as more procedural
time-consuming, may require more redo procedures, and does not avoid the
risk of compromising His capture thresholds.\textsuperscript{42} Be that
as it may, all studies in the ``ablate and pace'' indication of HBP
until now have been observational, single-center studies with few
patients and a short follow-up of a few months. Most authors of all
these studies underline the need to conduct large RCTs for this
indication, as for the previous one.

\textbf{6.3. Role in CRT}

The electrocardiographic feature of inter-ventricular dyssynchrony is
the QRS widening, which manifests as either Right BBB (RBBB) or Left BBB
(LBBB). On the other hand, there is the intra-ventricular dyssynchrony,
which refers to the late activation of the lateral regions of the left
ventricular chamber as compared to the interventricular septum, existing
in patients with heart failure, regardless of QRS duration. Especially
for patients with LBBB, the role of biventricular pacing is proven
beneficial, both in narrowing the QRS duration and in clinical
endpoints. In 1977, Narula in 27 patients showed that by pacing the His
bundle, LBBB is corrected, suggesting a longitudinal dissociation in the
His Bundle and proposing the concept of ``sinoventricular
conduction''.\textsuperscript{43} Narula's theory is based on the
hypothesis that stimulation at a constant cycle length, at a slightly
distal site, can abolish the LBBB (constant or rate related) due to
synchronous impulse conduction to both the bundle branches. These early
conclusions confirmed by a recent mapping study from Upadhyay et al.
(2019) with 85 patients. This study reported that LBBB patterns comprise
a set of partial disorders that can range from complete conduction block
when this is intrahisian to no discrete block and intact Purkinje
activation, when the block is more peripheral, in the left anterior and
posterior fascicles. In patients to whom HBP attempted, block correction
achieved in 94\% of patients with left intrahisian block and none with a
peripheral disorder at the level of the fascicles confirming thus the
theory of intracardiac delineation of the septal conduction system,
proposed almost half a century ago.\textsuperscript{44}

The achievement of block reversal with HBP is reached either by placing
the His lead further from the lesion if it is relatively proximal to the
His bundle or by remote electrical activation, considering higher
outputs, with all that this implies for the battery longevity. Moreover,
the same may be achieved by retrograde activation of the His-Purkinje
system via capture of an upper septal branch when His lead is
fortuitously placed in close proximity with one of these many left
bundle septal branches.\textsuperscript{45} Especially when the pacing
is selective, the corrected morphology of paced QRS can be maintained
even with chronic pacing, as also happens with mean thresholds.
Subsequently, this electrocardiographic notification of BBB correction
with HBP in those patients led to studies that attempted to demonstrate
and correlate this correction with clinical benefits.

Several studies, though with few patients, showed non-inferiority of HBP
in CRT compared to biventricular pacing. Barba-Pichardo et al. (2013) in
9 patients, Lustgarten et al. (2015) in 12 patients, Ajijola et al.
(2017) in 16 patients, and Shan et al. (2018) in 16 patients recorded an
improvement in LVEF and LV dimensions and reduction in NYHA class
compared with baseline. \textsuperscript{46-49} In these studies, in
addition to LVEF, an improvement was observed in other echocardiographic
parameters, such as the disappearance of a significant
septal-to-posterior wall delay in colour tissue Doppler, as well the
reduction in isovolumic contraction time, and increase in peak systolic
velocity in Pulsed-wave tissue -Doppler. Secondary endpoints were also
studied, such as the quality of life (QoL), 6MWT, and mitral
regurgitation jet area, with a trend of improvement.

HBP especially gained remarkable worth in CRT as a solution in the case
of failed LV lead implantation. This indication first studied by Giraldi
et al. (2011), wherein 20 patients with unfavorable cardiac veins
anatomy, an alternative CRT was attempted with a surgical
minithoracotomic approach.\textsuperscript{50} The utilization of HBP
lead as a general CRT alternative was also highlighted by Upadhyay et
al. (2019) in a secondary analysis of the His-SYNC Pilot Trial. The
study initially underlined the role of HBP in the QRS duration
improvement and LBBB correction but failed to determine the advantage in
hospitalizations and mortality.\textsuperscript{51} However, in cases of
failure to place the LV lead in the coronary sinus, due to absence,
tortuosity, or diameter \textless{}3mm of lateral or posterolateral vein
or angle \textless{}60* of the lateral vein, HBP could be a reliable
alternative to conventional CRT.

Another promising application of HBP in CRT was studied by Vijayaraman
et al. (2019), with good results regarding QRS duration narrowing in the
His-Optimized CRT study (HOT-CRT). In this study, in 27 heart failure
patients presenting LBBB with QRS duration \textgreater{}140 msec and
LVEF [?]35\%, the RV lead placed in the His Bundle area and the LV lead
synchronized in a time equal to the H-V interval with the His Bundle
lead.\textsuperscript{52} An impressive reduction of QRS duration was
recorded (from 183\selectlanguage{ngerman}±27 msec to 120±16 msec), improvement of LVEF from
24±7\% to 38±10\%, and a change in NYHA functional class from 3.3 to
2.04, in 14- month follow-up. Similar results of this method observed in
11 patients with permanent atrial fibrillation and LVEF \textless{}40\%
by Boczar et al. (2019).\textsuperscript{53}

Finally, the application of HBP showed the same good results in patients
with RBBB, where the conventional CRT has a weaker class of
recommendation. Sharma et al. (2018), in 39 heart failure and RBBB
patients with QRS duration \selectlanguage{english}[?] 120 msec and LVEF \selectlanguage{english}[?]50\%, demonstrated a
significant narrowing of QRS from 158+-24 msec to 127+-17 msec, an
increase in LVEF from 31+-10\% to 39+- 13\%, and improvement in NYHA class
from 2.8 to 2 with HBP in 15-month follow-up.\textsuperscript{54} All
the above results for the beneficial effects of HBP in CRT come from
observational, single-center studies, with a limited number of patients
and for a relatively short follow-up period. As in the studies of the
previous indications, for proof of these beneficial effects in primary
clinical outcomes, such as hospitalizations and mortality, the authors
also emphasize the need to carry out large RCTs.

\textbf{6.4. Heart Failure with Narrow QRS and PR Prolongation}

A less studied but significant indication is the application of HBP in
heart failure patients with narrow QRS and atrio-ventricular
dyssynchrony, namely an extensive PR prolongation. Except for
inter-ventricular dyssynchrony, caused by RV pacing, the long
prolongation of the atrial emptying phase also drives to non-optimal
ventricular filling and, therefore, non-optimal application of the
Frank-Starling law. Especially in heart failure patients, that is
important not only for symptoms but also for their adequate cardiac
function, affecting their mortality. After all, in addition to the
simultaneous activation of the two ventricles, the benefit of
biventricular pacing is also due to PR interval
optimization.\textsuperscript{45}

And for this indication of HBP, the data is limited. The randomized,
crossover HOPE-HF trial (His Optimized Pacing Evaluated for Heart
Failure Trial), which is still conducting, includes 160 patients with PR
prolongation (\selectlanguage{english}[?]200 msec), impaired LVEF \selectlanguage{english}[?]40\%, and either narrow QRS
\selectlanguage{english}[?]140 msec or RBBB. The clinical impact of HBP on reducing the PR
interval is studied.\textsuperscript{55} As primary endpoint is
considered the change in exercise capacity. Secondary endpoints include
changes in LVEF, QoL scores, B-type natriuretic peptide values, and
daily patient activity levels. In another recently published study,
Strocchi et al. (2020), in 24 LBBB heart failure patients recruited for
CRT upgrade (96\% males, mean LVEF 34\% +- 10\%), have compared HBP with
LBBAP, LV septal pacing, biventricular endocardial and biventricular
epicardial pacing, regarding ventricular activation changes. HBP showed
clear superiority over the other pacing methods in ventricular
synchrony, while noteworthy is that for left bundle pacing, AV delay
optimization resulted in a reduction of RV activation
times.\textsuperscript{56} Undoubtedly, for these studies, as well as
for all the above related to HBP, the lack of large RCTs that would
relate the impact of these findings on hospitalizations or mortality is
a disadvantage and should be investigated in the coming years.

\textbf{7. Left bundle branch area pacing: just an alternative to HBP or
an independent pacing method?}

LBBAP is considered an alternative, so far, to HBP, with both these
methods constituting the two components of CSP. LBBAP includes LV septal
pacing and LBBP. There are no studies to date for LV septal pacing,
having a clinical follow-up, as opposed to RV septal pacing. Left bundle
branch pacing, compared to HBP, presents several
differentiations.\textbf{(Figure 5)} Mostly this is due to anatomical
reasons. As opposed to the small size of the His bundle, the left bundle
branch extends comparatively to a much larger area in the
interventricular septum, which has two anatomical explanations. That is
because, on the one hand, the left bundle branch subdivides into two
main fascicles, the left anterior and the left posterior fascicle. At
the same time, other sources divide the left bundle branch into three
fascicles concluding with the left septal fascicle. On the other hand,
there is a rich network of fibers among these structures, creating a
wide range of variations. As a result, this part of the conduction
system can be stimulated in an easier way successfully than the His
bundle area.\textsuperscript{10, 57}

In addition to the anatomical ones, there are technical reasons making
LBBP easier. The infrahisian conduction system and the proximal right
and left bundle branches are enveloped in an insulating sheath of lesser
thickness than the penetrating bundle of His. In contrast, most
peripheral branches are located in the myocardium, thus requiring a much
smaller threshold for selective stimulation, with a consequent
significant impact on battery longevity. Also, for LBBP, as in HBP, the
method used for the pacing lead implantation is fluoroscopy. The only
difference is the wider target area in the interventricular septum and,
therefore, the fewer requirements for lead placement
accuracy.\textsuperscript{58} Other technical issues differentiate the
LBBP implantation procedure from HBP's. In challenging cases, fixing a
lead into the His bundle as an anatomical landmark may be
helpful.\textsuperscript{15} Special technical feature of the
implantation technique of LBBP is the fulcrum sign of the pacing lead,
which makes the lead and its subsequent parameters more stable. Sheath
angiography is also helpful by gently pulling back the catheter and
administering a contrast agent to establish the correlation of lead and
septum positions and identify the depth penetrated by the bipolar lead
with its active helix. The most commonly used lead is Select Secure\selectlanguage{english}
3830, as in HBP, with 9 mm tip to ring spacing and 1.8 mm the exposed
helix. The w-shaped QRS configuration of pacing the right ventricular
septum at the initial fixation site indicates LBBP.

This technique is also demanding to program. Apart from the threshold,
better parameters are recorded regarding sensing, which is also
maintained in the follow-up, especially concerning atrial oversensing
and ventricular undersensing, in contrast to HBP. In addition, LBBP
offers ease in the need for future AV node ablation in heart failure
patients with refractory atrial fibrillation and a rapid average heart
rate despite optimal medical therapy in contrast with HBP that this may
not be possible. LBBP, as an alternative method, may be successful in
blocks that are too distal to be treated with HBP, although these blocks
are not that frequent. A recent publication, in a series of 333
consecutive patients with AV block referred for pacemaker implantation,
recorded the prevalence of the site of conduction
block.\textsuperscript{59} The study found that the exact site of
conduction block was nodal in 55\% and infranodal in 45\% of the cases,
which in turn, distributed in intra-Hisian 89\%, infra-Hisian 4\%, and
indeterminate 7\% of the patients. Therefore, although infra-Hisian
blocks are rare, LBBP is an alternative pacing modality for these
patients.

Compared to HBP, where complications are minimal, the LBBP technique's
complications may be life-threatening to the patient. There have been
reported cases of septal perforation to the LV chamber (during the
procedure, but also post-procedure in case of excessive slack of the
pacing lead), LBBP lead dislocation, especially when there is not
adequate slack of the lead, right bundle branch injury, septal injury or
hematoma, and coronary artery injury, especially when the pacing lead is
placed deep in the proximal septum, causing even myocardial
infarction.\textsuperscript{60} Moreover, LBBP lead fracture may occur,
causing loss of pacing, with unpleasant consequences, especially for
pacemaker-dependent patients. However, the rate of all these
procedure-related complications of LBBP is still low.

Therefore, LBBP is currently being tested not only as an alternative
method to HBP in case of technical difficulties, such as a high HBP
threshold at implant, but also as a primary pacing method, with all the
corresponding indications described for HBP.\textsuperscript{61} Success
rate is very high (\textgreater{}90 \%), and the achieved capture
thresholds are low (\textless{} 1 Volt at 0.4 msec), which maintain in
the follow-up. At the same time, beneficial results have also been found
in echocardiographic parameters, such as LVEF and left ventricular
volume measurements. Various studies have pointed out this in the last
few years. The main indications for LBBP concern bradycardia and CRT.
Zhang et al. (2019) in 11 patients, Wu et al. (2020) in 32 patients,
Huang et al. (2020) in 61 patients, and Vijayaraman et al. (2021) in 277
patients with impaired LVEF \textless{}50\% and LBBB found a notable
improvement in LVEF, NYHA class, BNP plasma level, but also lower
capture threshold and higher R-wave sensing amplitude in comparison to
HBP patients.\textsuperscript{62-65} Padala et al. (2020) in 305
patients showed low rates of lead dislodgement over two weeks with LBBP,
while similar findings of complications were also recorded by Su et al.
(2021) in 632 patients, with a follow-up of 8.6
months.\textsuperscript{66, 67} Finally, LBBP was even tested in cases
after unsuccessful or suboptimal HBP but also after TAVR implantation in
a few patients, with encouraging results regarding improvement in LVEF
and reduction in QRS duration over follow-up,
respectively.\textsuperscript{35, 61}

All the above results, as also the recorded post-procedure stability of
electrical parameters, suggest that LBBP is a feasible and effective
pacing method with promising results for the near future. Nevertheless,
the fact that these data come from observational, single-center studies
with a small number of patients and a short follow-up explains why LBBP
is not included as an official indication in the latest 2021 ESC
Guidelines on cardiac pacing. That's why it's highlighted, as for HBP,
the need to conduct large RCTs, which will correlate these findings with
clinical endpoints such as heart failure hospitalizations and mortality.

\textbf{8. Looking to the Future}

The great interest in CSP in recent years logically directs towards the
issues that make difficulties so that this type of pacing prevails as
the dominant one for all prospective patients who may need this type of
intervention.\textsuperscript{15} Given the complicated anatomy of the
area where the conduction system locates, new tools are tested by all
manufacturers, both for HBP and LBBP. The tests concern the sheaths that
guide the pacing lead and the lead model itself. Stylet-driven leads,
tested in the past, are already being tested again to locate the area of
interest with greater precision and stability, bypassing the existing
anatomical and hemodynamic difficulties.\textsuperscript{68} Moreover,
efforts to circumvent the difficulties of locating the conduction system
with fluoroscopy are being made by testing new 3D electro-anatomical
mapping systems.\textsuperscript{69} Recently published data is also
encouraging for an electrogram-only guided approach to HBP with minimal
fluoroscopy and high success rates compared to the classical
method.\textsuperscript{70} But of course, the need for data collection
through conducting large RCTs, which will prove the significant benefit
of this pacing in clinical endpoints of hospitalizations and mortality,
should not be overlooked. For this reason, studies are constantly
conducted in this direction. Thus, for the question concerning CSP
``when and to whom'', the answer one day may be ``always and to all''.

\textbf{9. Conclusion}

Classic RV pacing may induce the systolic and diastolic dysfunction of
both ventricles with consequent adverse clinical endpoints. CSP is a
method that maintains physiologic ventricular activation. It has a
correct pathophysiological basis, and for a long time, the scientific
community has been interested in circumventing its anatomical and
technical difficulties. The knowledge is there, and as the interest is
there, the only thing missing is the right tool so that it is possible
to access this area whenever needed, with satisfactory pacing
parameters, without complications, and of course, with indisputable
proof of its good clinical outcomes. Thus, after coronary artery bypass
grafting, which revolutionized the field of coronary artery
revascularization, electrical lesions in the conduction system might be
dealt with a corresponding ``electrical bypass'' feasible for all
indications and in all patients who need this pacing treatment.

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\textbf{Figures}

\textbf{Figure 1.} The detrimental effects of chronic RV apical pacing\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

RV: right ventricular

\textbf{Figure 2} : Alternative pacing strategies and sites\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

RV: right ventricular, RVOT: Right Ventricular Outflow Tract, LV: left
ventricular

\textbf{Figure 3:} An ``Electrical Bypass''\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Figure 4:} Indications of His Bundle Pacing\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

HBP: His bundle pacing, RV: right ventricular, LVEF: Left ventricular
ejection fraction, LBBB: Left bundle branch block, RBBB: Right bundle
branch block, LV: left ventricular

\textbf{Figure 5:} Differentiations of LBBAP compared to HBP\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

LBBAP: Left bundle branch area pacing, LBBP: Left bundle branch pacing,
LV: left ventricular, RV: right ventricular, IVS: interventricular
septum, LBB: Left bundle branch, RBB: Right bundle branch, MI:
myocardial infarction

\textbf{Example 1:} Twelve-lead electrocardiogram (ECG) at baseline and
following BVP, HBP and apical RV pacing. The baseline ECG demonstrates a
QRS duration of 86 ms. During BVP and HBP the QRS duration remains
narrow, 100ms and 92ms, respectively, in contrast to its significant
widening during apical RV pacing, where it reaches 196ms. BVP;
biventricular pacing; HBP; His Bundle pacing; RV; Right ventricular\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image6/image6}

\end{center}
\end{figure}

\textbf{Example 2:} Twelve-lead electrocardiogram (ECG) of His Bundle
Pacing. Loss of capture is demonstrated during threshold check.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image7/image7}

\end{center}
\end{figure}

\textbf{Example 3:} Twelve-lead electrocardiogram (ECG) shows the QRS
morphology at baseline, as well as with Selective and Non-Selective His
Bundle Pacing. The noted QRS duration widening during Non-Selective
Pacing is due to the existence of the pseudo-delta wave, which is not
observed in Selective Pacing (146 ms versus 100 ms, respectively).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image8/image8}

\end{center}
\end{figure}

\textbf{Example 4:} Fluoroscopic projection showing the position of the
leads. RA, right atrium; HB, His bundle; RV, right ventricle; AP,
Anteroposterior; LAO, Left Anterior Oblique\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image9/image9}

\end{center}
\end{figure}

\textbf{Table 1:} Data for non-apical RV pacing

Data only for RV Septal pacing\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Drawbacks (-)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Drawbacks (-)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Drawbacks (-)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Benefits (+)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Indications\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
high-grade atrioventricular block\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
cardiac resynchronization therapy\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
meta-analysis results: pre-implantation LVEF \textless{}40\% females age
\textgreater{}80 years\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Randomized studies\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Protect-Pace study\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
SEPTAL CRT study\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Patients\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
240\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
263\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Results\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Decrease in LVEF, no difference in HF hospitalizations, AF, BNP, and
mortality\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
No difference in reduction of LVESV and composite clinical endpoint of
deaths and HF hospitalizations\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

RV: right ventricular, CRT: cardiac resynchronization therapy, LVEF:
left ventricular ejection fraction, HF: heart failure, AF: atrial
fibrillation, BNP: brain natriuretic peptide, LVESV: left ventricular
end-systolic volume

\textbf{Table 2:} His bundle pacing: ``Why not always and to everyone''?

His bundle pacing's considerations\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Anatomical & \vtop{\hbox{\strut complex formation and anatomical
location of AV conduction system minuscule dimensions His bundle
association within the myocardium - under the membranous portion of
IVS}\hbox{\strut - within the muscular portion of IVS}\hbox{\strut -
beneath the endocardium}}\tabularnewline
Technical & \vtop{\hbox{\strut Procedure related: - fluoroscopy for
localizing lead positions}\hbox{\strut - implantation
tools}\hbox{\strut - HBP lead (stylet, non-stylet driven)}\hbox{\strut -
His delivery sheath (deflectable, non-deflectable) Parameters related: -
increase in pacing threshold}\hbox{\strut - lead stability --
dislodgement}}\tabularnewline
Programming & \vtop{\hbox{\strut Selective pacing Non-Selective pacing
Myocardium-only pacing Selective HBP Non-Selective HBP Myocardium-Only
(Para-hisian) Pacing Selective Left Bundle Branch Pacing Non-Selective
LBBP Left Ventricular Septal Pacing Right Ventricular Septal Pacing
Mid-septal capture Anodal capture variety of ECG responses during
threshold checks requires extra person, except implanter, during the
procedure correction or not of BBB troubleshooting issues (during
procedure \& at outpatient follow-up) - atrial
oversensing}\hbox{\strut - ventricular undersensing}\hbox{\strut -
pacing artifacts which port the His lead is placed in (especially at
CRT) specialized Pacemaker Technician is required closer surveillance is
suggested every six months}}\tabularnewline
\bottomrule
\end{longtable}

AV: atrioventricular, IVS: interventricular septum, RV: right
ventricular, HBP: His bundle pacing, LBBAP: Left bundle branch area
pacing, LBBP: Left bundle branch pacing, ECG: electrocardiographic, BBB:
bundle branch block, CRT: cardiac resynchronization therapy

\selectlanguage{english}
\FloatBarrier
\end{document}

