The CRT considered a crucial treatment modality
for HF may be pro-arrhythmic, since pacing from
epicardium increases TDR.[
7] In responders to CRT,
this early increase has been shown to decrease in
the long-term, presumably as a result of reverse
remodeling.[
12] In the present study, our objective was
to investigate the impact of CRT on conventional and
recently defined ventricular repolarization parameters
from the perspective of different LV pacing polarities
in both acute and long-term and to examine novel
arrhythmia predictive parameters taking depolarization
into account. We also attempted to identify whether
there were reflections on arrhythmic events.
Different pacing polarities lead to different
distribution of activation in the ventricle. The activation
wave of a bipolar depolarization detracts with the third
force of the distance, while a unipolar wave attenuates
with the square of the distance.[13] This difference
caused by polarity particularly influences the initiation of the re-entry mechanism in the scar tissue. Although
the first capture point in the epicardium can be the
same, the subepicardial layers captured by the virtual
electrode may differ. Additionally, the presence of
scar tissues may affect the conduction vectors and can
change the transmural activation sequence within such
heterogeneous myocardium.[14] Yang et al.[5] reported a
higher basal endocardial strain with bipolar pacing and
found more uniform global strain compared to unipolar
pacing. They also revealed that there were differences
in the mechanical activation sequence in terms of LV
pacing polarity, probably affecting vectoral activation
and ventricular repolarization patterns.
Myocardial activation sequence reverses during
biventricular pacing in conventional CRT patients.
As a consequence of this reverse activation, early
repolarization of epicardium, delayed activation and
repolarization of midmyocardial M cells lead to a
significant increase in TDR.[7] The Increased TDR
can be measured non-invasively using parameters,
such as Tpeak-Tend (TpTe or Tpe) and Tp-Te/QT.[15]
Furthermore, it was shown that the QT dispersion
which reflects regional heterogeneity in myocardial
repolarization is associated with life-threatening
arrhythmias and SCD. However, TpTe has been
demonstrated to be superior to QT and QT dispersion
in predicting VTs.[16] The TDR seems to play a key
arrhythmogenic role not only in CRT’s HF patients,
but also in those with SCD, myocardial infarction, long
QT syndrome, and Brugada syndrome.[17] Recently, Tpec (TpTe corrected according to the Bazett formula)
was suggested to be more sensitive measurement in
predicting the risk of SCD and Tpec of more than
90 msec was determined to be associated with an
approximately three-fold increased risk.[18] In the light
of these data, we investigated both Tpec and Tpec/QTc
value that, to the best of our knowledge, has not been
evaluated previously.
In our study, Tpec/QTc showed a significant postprocedural
increase in the true bipolar group, while
a decrease was observed in the unipolar/extended
bipolar group. The difference between the two groups
decreased in the long-term, but remained statistically
significant. There was no significant difference in
the remaining ventricular repolarization parameters
between the groups. As a clinical reflection of this
observation, four of five patients with electrical storm
were in the true bipolar LV configuration. Sustained
and NSVTs were observed more frequently in the
bipolar group. The greater influence of Tpec/QTc in
the early period after CRT supports that a significant
part of the increase in TDR is temporal. The point
that draws our attention in this regard is that electrical
storm occurred in four (80%) of our five patients
within the first 100 days.
In another aspect, TDR does not take into account
depolarization and action potential in HF patients
whose myocardium are electrically and mechanically
heterogeneous and transmural activation sequence is
abnormal due to scar tissues. Recently, it has been
suggested that, in arrhythmogenic right ventricular
dysplasia and Brugada syndrome, QT/QRS ratio
defined as cardiac electrophysiological balance
index can be used to predict arrhythmia, as it
takes depolarization into consideration.[19] In this
context, it was recommended that TpTe/QRS and
TpTe/(QRS × QT) parameters may be used, since
the TpTe interval has been shown to be more
precise in predicting arrhythmic risk rather than the
QT interval.[20] In the present study, we evaluated
Tpec/QRS and Tpec/(QTc × QRS) as well as
aforementioned novel markers. To the best of our
knowledge, this was not previously evaluated in CRT
patients.
The LV pacing polarity has also a substantial
role in the pathophysiology of arrhythmogenesis
other than TDR. Asvestas et al.,[21] in a patient who
presented with a monomorphic electrical storm two
years after CRT, completely terminated the storm by changing the LV pacing configuration from the
true bipolar to the extended bipolar (unipolar). The
authors suggested that the bipolar configuration
(D1-M2) caused the initiation of the one-way block
and re-entry circuit due to its proximity to the critical
isthmus in the scar tissue, and they prevented the
onset of the re-entry circuit by pacing from extended
bipolar. Considering the novel arrhythmia markers
along with depolarization and TDR in our study, we
observed that, in the bipolar group, where electrical
storm and sustained VTAs were predominantly
observed, the TpTe/QRS, Tpec/ QRS, Tpec/QRS ¥
QTc, TpTe/QRS ¥ QTc values increased more than
the unipolar group. We persuaded that these markers
may be used to predict arrhythmia, if supported by
larger studies.
The main limitation of the present study is its
relatively small sample size. The second limitation is the
relatively high ischemic etiology (44.4%). The presence
of ischemic scar tissues, as well as the heterogeneity
of myocardium may have influenced the transmural
activation sequence and VTAs. However, it should be
kept in mind that the CRT patient population in daily
practice is quite heterogeneous, as in this study. Bias
in choosing the LV pacing configuration can be also
considered a limiting factor; many factors, such as the
branch of the existing CS, the risk of phrenic nerve
stimulation, avoiding anodal capture, and optimization
of LV pacing thresholds are taken into consideration
in the decision-making process. Furthermore, given
the nature of the study, we cannot ignore the impact
of extrinsic and intrinsic variables, such as use of
antiarrhythmic agents, coronary anatomy, and LV lead
position on the outcomes.
In conclusion, left ventricular pacing polarity
significantly affects Tpec/QTc, but not other ventricular
repolarization parameters. Novel arrhythmia predictors
(TpTe/QRS, Tpec/QRS, TpTe/(QRS × QTc) and
Tpec/(QRS × QTc)) are more influenced in bipolar
pacing associated with more frequent ventricular
tachyarrythmias.
Declaration of conflicting interests
The authors declared no conflicts of interest with respect
to the authorship and/or publication of this article.
Funding
The authors received no financial support for the research
and/or authorship of this article.