Panel A: Shows one patient with S-HBP where a transient but complete
correction of acute RBBB appears to occur with S-HBP with recurrence as
voltage was lowered to 3.5 V. However, if corrected and uncorrected
beats are compared (first and second beats) there are subtle differences
(L1 voltage and initial r in V1) suggesting that septal activation may
have been different in corrected beat and an alternate pathway may have
been activated.
Panel B: In remaining 3 patients with RBBB (one acute and 2 chronic) did
not resolve with selective His bundle pacing at any pacing voltage.
Panel C: In one patient, chronic RBBB resolves partially, however with
transient NS-HBP (3rd and 4th beats)
but recurs abruptly as selective HBP occurs with voltage still at 5V.
In patients in S-HBP group, the site of block was distal to pacing lead
and was not resolved with S-HBP.
Note HVAT intervals in NS-HBP and S-HBP of 93msec and 97 msec
respectively.
Discussion
The observation that both acute and chronic right bundle branch block
(RBBB) remained uncorrected with selective His bundle pacing (S-HBP)
clearly suggests that site of RBBB was distal to pacing lead tip (Fig.
1-4). Intra-operative study of conduction times and velocity would
indicate that the mean H-V intervals of 53±11 ms obtained in our study
would place the lead tip in proximal His bundle; 2-3 cm from the
bifurcation of His bundle into bundle branches and the ventricular
septum (6). Even so, the RBBB was partially or completely corrected in
all patients with non-selective (NS)-HBP where a characteristic ‘delta’
wave indicating that a parallel pathway, in addition to the His bundle,
is also being activated (Fig. 1-4). From same pacing site, even in acute
RBBB ostensibly located in close proximity to pacing lead, conduction
block was rarely corrected with S-HBP.
Correction of RBBB appeared to correlate with pacing voltage, as higher
pacing voltage (5V) resulted in complete correction of RBBB in 22
patients while only 10 showed complete correction at lower voltage.The voltage effect including a unique pattern of
progressive beat by beat correction of RBBB with higher voltage was seen
only during NS-HBP . Complete recurrence of RBBB was seen only
with S-HBP never with NS-HBP (Fig. 1,4).
NS-HBP group showing lower capture threshold of the delta wave
(1.3±0.5V,) had more patients with complete resolution of RBBB (9/14
patients) as compared to NS-S HBP group where the delta wave had higher
capture threshold (2.4±0.8V) and only 3/11 patients had complete
correction of RBBB.
Voltage related resolution of slow conduction has been observed in
injured Purkinje fibers where higher voltage is required to generate a
propagating impulse (7-10) and our observations during NS-HBP suggests
that the parallel pathway may have properties similar to specialized
conduction fibers. Increased pacing threshold is also predicted by
virtual electrode polarization (VEP) theory and is felt to occur as a
result of tissue damage (11,12). Based on planar model of cardiac
muscle, the VEP theory does not explain how higher voltage would result
in improvement of conduction particularly in His Purkinje system.
In our study, in acute RBBB in which injured His bundle fibers are in
close proximity to pacing lead tip a clinically significant VEP
effect was not readily apparent in S-HBP where conduction is
exclusively via His bundle.
The explanation why the parallel pathway in NS-HBP demonstrates voltage
dependent phenomenon, may lie in the work of Effimov group which shows
evidence of parallel pathways in the His region (13). The His bundle and
surrounding area shows a rich density of gap junction proteins (Cx43,
Cx40, and Cx45) extending from right lower extension (RLE) of the AV
node to the interatrial septum and the latter has more than twice the
expression of CX-43 compared to the His bundle (13,14). Thus, a
molecular compartmentalization exists in the peri- Hisian region
which connects directly to a specific Cx43‐positive domain of the His
bundle (13). Hucker et al. have suggested that as these molecular
pathways are not encased in fibrous tissue, pacing the RLE would not
only activate the His bundle but may require lower voltage than direct
pacing of His bundle itself (13).
Thus, one may speculate that the pacing lead may disrupt and activate
subendocardial tissues rich in gap junction proteins which may behave as
a parallel specialized conduction pathway injured by the active fixation
process.
Thus, If one assumes as our observations suggest, that
conduction through normal pathway (His bundle) results in RBBB and
conduction through parallel pathway results in correction of RBBB then
robust conduction through the parallel pathway at higher voltage may
completely resolve RBBB while at lower pacing voltage, slower conduction
in the parallel pathway would allow conduction through His bundle to
manifest the RBBB and progressive slowing in the parallel pathway would
result in progressively greater RBBB (Fig.1,4).
Two possible mechanisms whereby interaction between the two wavefronts
may resolve RBBB is depicted in Figure 6. In one possibility, early
excitation of the RV free wall may decrease or abolish ECG evidence of
RBBB. This mechanism is suggested by the counterclockwise rotation of
the NS-HBP complex (Table 1, Fig. 3), a consistent feature of NS-HBP
(15) it may result from an early rightward wavefront.
The work of Durrer et al (16,17) and more recently of Almeida et al
(18,19) lays out the specialized conduction pathway to early RV free
wall pre-excitation in NS-HBP. In normal QRS activation (Fig.6),
following left to right septal activation, the wavefront proceeds to the
septal border of the crista supraventricularis (CSV) and meets the RV
free wall wavefront exiting from right bundle branch (16-19)
(Fig. 6, left upper panel). During NS-HBP early activation of
septum would also result in activation proceeding anteriorly to the
crista supraventricularis (CSV) which alone connects the septum to RV
free wall (20). This early activation wavefront, upon finding the RV
free wall unexcited because of RBBB, would proceed to pre-excite the RV
free wall (fig. 6, right upper panel), thus decreasing the duration of
the S wave in Lead 1 without actually resolving the conduction delay at
the distal site. This mechanism also explains why allpatients, particularly those in whom conduction block may be
located more distally in the right bundle branch, showed at least
partial ‘correction’ of RBBB .
The right lower panel in figure 6 shows another mechanism where the
parallel pathway bypasses a more proximally related site of block. This
mechanism may be a more plausible explanation of complete correction of
RBBB. The transition from actively bypassing a more proximal RBBB to
just passive pre-excitation of RV free wall at lower voltage may explain
the change from complete resolution of RBBB to partial resolution of
RBBB.
More than one parallel pathway with different capture thresholds would
also explain the voltage dependent phenomenon.
The novel effect of NS-HBP in correcting a distal RBBB may seemingly be
at odds with previous reports which suggest that given the longitudinal
dissociation of the His bundle (21,22) only pacing the His bundle distal
to site of block would correct bundle branch block (1,2). However, it
appears that the narrowed QRS they described as ‘normal range, not
normal activation’ (1), ‘with stim-Q interval shorter than H-V
interval’ (1,2), would be similar to the NS-HBP QRS complex we observed
with high voltage pacing. It is also likely that our use of 12 lead ECG
with filter setting of 0-100 Hz allowed easier visualization of the
delta wave as opposed to fewer leads with filter setting of 0-20 Hz in
previous studies (1).
El Sherif et al also reported that in some cases higher pacing voltage
was required to narrow the QRS complex and in discussing their results
state that longitudinal dissociation in His bundle itself would only
explain their conclusions if the transverse interconnections between the
longitudinally dissociated fibers (23,24) become functionally
inoperative and the conduction block was indeed located in proximal His
bundle in all patients (2).
In summary, our previous observation that ventricular activation time
decreases with increased pacing voltage in NS-HBP (5,15) (manuscript in
review), is extended in this study with the novel finding of greater
reduction of RBBB with higher voltage and there appears to be a stark
difference between selective and non-selective His bundle pacing on
correction of distal block. While we have attempted to explain the
mechanisms involved with our current understanding of the A-V conduction
system, the answers may well lie in the less well understood molecular
biology of the His region (13, 14, 25). Further studies are needed to
understand non-selective His bundle pacing, which appears to be
distinctly different from the septal paced complex with HVAT of 146 ±26
ms reported by Vassallo et al (26), or the description of the ‘wide
paced septal complex’ to which the term ‘non-selective His bundle
pacing’ was originally applied. (27).
Fig. 6: Myocardial activation models in normal QRS, with non-selective
His bundle pacing.