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”.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.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.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. 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.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.51 However, in cases of
failure to place the LV lead in the coronary sinus, due to absence,
tortuosity, or diameter <3mm of lateral or posterolateral vein
or angle <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 >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.52 An impressive reduction of QRS duration was
recorded (from 183±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 <40%
by Boczar et al. (2019).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 ≥ 120 msec and LVEF ≤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.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.