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\begin{document}

\title{Site-Specific Ventricular Tachycardia Inducibility}



\author[1]{Asad Aboud}%
\author[1]{Robert Abraham}%
\author[1]{oluwaseun adeola}%
\author[2]{Ikutaro Nakajima}%
\author[3]{Ryohsuke Narui}%
\author[4]{Tomofumi Nakamura}%
\author[1]{Arvindh Kanagasundram}%
\author[1]{Travis Richardson}%
\author[5]{William Stevenson}%
\affil[1]{Vanderbilt University Medical Center}%
\affil[2]{Saint Marianna University School of Medicine}%
\affil[3]{The Jikei University School of Medicine}%
\affil[4]{Tokyo Metropolitan Toshima Hospital}%
\affil[5]{Vanderbilt Heart and Vascular Institute}%


\vspace{-1em}



  
  \date{June 18, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Introduction Programmed electrical stimulation is an essential part of
VT ablation procedures but VT is not always inducible, usually for
reasons that are not clear. We sought to review pacing site-specific
failure of programmed electrical stimulation (PES) to induce
scar-related ventricular tachycardia (VT). Methods A series of patients
in whom aggressive programmed stimulation from traditional RV pacing
sites failed to induce VT, but VT was easily inducible from a
non-traditional site are reviewed. Computer simulations in a simple
2-dimensional model of reentry were performed. Results Six patients who
had no inducible sustained VT from the RV apex/outflow tract with at
least 3 extrastimuli, but relatively easily induced VT from the LV,
basal RV, epicardium, or atrium are described. In 5 of these patients,
the site that induced VT was closer to the likely reentry circuit region
based on mapping and ablation. Computer simulations illustrated that the
spatial relation between the pacing site and the entrance and exits of a
reentry isthmus can determine the ease of initiation of reentry by
determining the time available for recovery of excitability at the
initial region of block. Conclusions The site of PES has a marked effect
on inducibility of VT in some patients such that PES from the RV apex
and outflow regions will fail to expose clinically relevant VTs. The
frequency with which this occurs is not certain. Stimulation from
alternative sites is a reasonable consideration in selected patients.%
\end{abstract}%



\sloppy


\textbf{Site-Specific Ventricular Tachycardia Inducibility}

\textbf{Short title:} Site Specific VT Inducibility

\textbf{Authors Names} :

Asad A. Aboud, MD\textsuperscript{1}, Robert L. Abraham,
MD\textsuperscript{1}, Oluwaseun Adeola, MD\textsuperscript{1}, Ikutaro
Nakajima, MD, PhD\textsuperscript{2}; Ryohsuke Narui, MD,
PhD\textsuperscript{3}, Tomofumi Nakamura, MD\textsuperscript{4},
Arvindh N. Kanagasundram, MD\textsuperscript{1}, Travis Richardson,
MD\textsuperscript{1}, William G. Stevenson, MD\textsuperscript{1}

\begin{enumerate}
\tightlist
\item
  Vanderbilt Heart and Vascular Institute, Nashville, TN, USA
\item
  Division of Cardiology, St. Marianna University School of Medicine,
  Kawasaki, Japan.
\item
  Division of Cardiology, The Jikei University School of Medicine,
  Tokyo, Japan.
\item
  Heart Center, Tokyo Metropolitan Toshima Hospital, Tokyo, Japan.
\end{enumerate}

\textbf{Corresponding author:}

Asad Aboud, MD

Clinical Fellow, Cardiac Electrophysiology

Vanderbilt University Medical Center

1211 Medical Center Drive MCE 5414

Nashville, TN 37232-8802

Asad.a.al.aboud@vumc.org

\textbf{Sources of Funding:} None

\textbf{Disclosure:} The authors have no conflicts to disclose.

Abstract

\textbf{Introduction}

Programmed electrical stimulation is an essential part of VT ablation
procedures but VT is not always inducible, usually for reasons that are
not clear. We sought to review pacing site-specific failure of
programmed electrical stimulation (PES) to induce scar-related
ventricular tachycardia (VT).

\textbf{Methods}

A series of patients in whom aggressive programmed stimulation from
traditional RV pacing sites failed to induce VT, but VT was easily
inducible from a non-traditional site are reviewed. Computer simulations
in a simple 2-dimensional model of reentry were performed.

\textbf{Results}

Six patients who had no inducible sustained VT from the RV apex/outflow
tract with at least 3 extrastimuli, but relatively easily induced VT
from the LV, basal RV, epicardium, or atrium are described. In 5 of
these patients, the site that induced VT was closer to the likely
reentry circuit region based on mapping and ablation. Computer
simulations illustrated that the spatial relation between the pacing
site and the entrance and exits of a reentry isthmus can determine the
ease of initiation of reentry by determining the time available for
recovery of excitability at the initial region of block.

\textbf{Conclusions}

The site of PES has a marked effect on inducibility of VT in some
patients such that PES from the RV apex and outflow regions will fail to
expose clinically relevant VTs. The frequency with which this occurs is
not certain. Stimulation from alternative sites is a reasonable
consideration in selected patients.

Keywords: Ventricular Tachycardia, Programmed Electric Stimulation,
Site-Specific Induction, VT Ablation, VT Simulation

Introduction

Programmed electrical stimulation (PES) of the ventricle is an important
tool for initiation of ventricular tachycardia (VT) during ablation
procedures. It is used to confirm the diagnosis, guide the procedural
approach, and assess the effect of ablation.\textsuperscript{1} The
absence of inducible VT following VT ablation is associated with lower
risk of recurrence.\textsuperscript{2} Some observations, however, call
into question the reliability of programmed stimulation for these
purposes. Some VTs are not inducible in the electrophysiology laboratory
despite aggressive PES. When this occurs, ablation is typically guided
by targeting the presumptive VT substrate based on electroanatomic
voltage mapping, electrogram characteristics, and/or pace-mapping.
Secondly, it is well recognized that a clinical VT may be rendered no
longer inducible immediately after ablation, and then be inducible again
a few days later. In one study this occurred in 18.2\% of patients for
whom ablation was deemed acutely successful.\textsuperscript{3}

Inducibility of VT is related to the aggressiveness of the PES. Using
multiple drive cycle lengths and up to 3 or 4 extrastimuli, PES has a
high sensitivity for inducing VT in patients who have had this
arrhythmia spontaneously.\textsuperscript{4} The site of stimulation
also plays a role. The initial ventricular stimulation site is typically
the RV apex (RVA) and then the RV outflow tract (RVOT) if VT is not
inducible from the RVA. This approach is widely adopted after earlier
studies demonstrated the incremental yield of programmed electric
stimulation (PES) from two RV sites.\textsuperscript{5} Before the era
of catheter ablation, Josephson and colleagues reported that up to 11\%
of patients studied in the electrophysiology laboratory for VT had VTs
that could be induced only with left ventricular (LV) and not with right
ventricular stimulation.\textsuperscript{6} While their series did not
find any electrocardiographic predictors of the need for LV stimulation,
it is likely that site-specific inducibility varies with the location of
the reentry circuit as well as with tissue conduction properties.

We describe here a case series of patients in whom inducibility was
exquisitely sensitive to the site of stimulation and discuss the
implications for VT ablation studies and patient management.

Methods

From patients referred for VT ablation, 6 patients were identified who
had VT inducible from outside of the right ventricular apical or outflow
region. Patients underwent electrophysiological studies and ablation
according to the previously published method.\textsuperscript{7--10} An
informed consent was obtained prior to the ablation procedure. Either
Monitored Anesthesia Care (MAC) or general anesthesia was delivered by a
dedicated anesthesia team throughout the procedure. Electroanatomic maps
were constructed using a 3D mapping system (CARTO3, Biosense Webster)
and intracardiac echocardiography (ICE). Programmed electric stimulation
protocol involved 1-3 extrastimuli after two paced cycle length
(typically 400 and 600ms) from two sites (typically the RV apex or
septum and the RVOT). Additional stimulation sites and use of 4
extrastimuli were chosen at the discretion of the operator. Data
collection was performed under protocols approved by the institutional
review board. This research adheres to the ethical guidelines specified
in Helsinki Declaration as revised in 2013.

\emph{Computer simulation}

A simple, anatomically fixed reentry circuit was constructed in a custom
software model of a cardiac tissue plane using the Matlab programming
environment (Matlab R2020a, The Mathworks, Inc., Natick, MA). A
propagation model was created consisting of an 1281 x 1281 matrix of
excitable elements. The nominal dimensions of the simulation matrix are
40 mm x 40 mm with an imbedded 20 mm diameter circular scar. Within the
non-conducting scar is an asymmetric gap of conducting elements. The
matrix is isotropic except for a difference in refractory period within
the scar gap. The excitable elements are 31.25 \selectlanguage{greek}µ\selectlanguage{english}m in diameter, though
this is an arbitrary size chosen to provide as dense a matrix as
possible within the constraints of the available computational
resources. To allow more physiologic circular wavefronts within the
rectangular simulation matrix, each activated element activates a
roughly circular cluster of adjacent elements. The 16-element-radius
size of this cluster was chosen to allow a wavefront as smooth as
possible within the available computational constraints. Each active
element activates its non-refractory cluster of neighboring elements
immediately at each iteration interval, thus the conduction velocity
through the matrix is determined by the cluster size and the iteration
interval. That interval was chosen arbitrarily to be 4 ms to provide a
reentry cycle length through the scar gap of \textasciitilde{}300 ms.
The conduction velocity within the scar gap is identical to that of the
surrounding. After being excited, each element remains refractory to
subsequent activation for an interval of 100 ms, though this interval is
arbitrary and was chosen to facilitate visualization of a sequence of
activation wavefronts. The refractory time within the scar conduction
gap is 260 ms.

Programmed stimulation of the cardiac tissue plane is simulated by
exciting specified locations within the tissue plane with a typical
pacing protocol. In order to assess the range of VT inducibility,
stimulation was tested at sequential points around the entire
circumference of the scar while maintaining a constant distance from the
outer edge of the scar. In these simulations, the last impulse of a 300
ms drive train is followed by a 220 ms extrastimulus. The simulation
continues until no tissue is in the excited state or until a stable
re-entrant circuit is demonstrated.

Case Description

\textbf{Case 1:}

A 57 year-old man without known cardiac disease presented with a wide
complex tachycardia (WCT) at a rate of 270 bpm requiring external
cardioversion. Cardiac magnetic resonance imaging (MRI) revealed a
mildly dilated LV and low-normal LV systolic function. Further
evaluation showed no evidence of myocardial ischemia or arrhythmia on
exercise stress testing.

At EPS, no arrhythmia was inducible despite burst and extra stimulus
pacing from the RA, RVA, and RVOT. PES included up to 3 extrastimuli to
a minimum coupling interval of 180 ms following two drive cycle lengths
with and without isoproterenol (up to 12 mcg/min eliciting sinus
tachycardia of 140 bpm). An RV voltage map identified a very small area
of low bipolar voltage (\textless{}1.5 mv) at the basal inferolateral RV
raising concern for arrhythmogenic RV cardiomyopathy. Pericardial access
was obtained and epicardial mapping revealed an extensive area of low
voltage (\textless{}1.5mV, Figure 1). PES was then performed from the RV
epicardium with 3 extrastimuli following a drive train of 350ms which
reproducibly induced sustained monomorphic VT (cycle length 235ms) that
was terminated with burst pacing. Following combined endocardial and
epicardial ablation targeting the low voltage substrate, VT was no
longer inducible with up to 3 extrasimuli from either the RV endocardium
or epicardium.

\textbf{Case 2:}

A 79 year-old man with ischemic cardiomyopathy, cardiac
resynchronization therapy ICD, and coronary artery bypass graft (CABG)
surgery, presented with recurrent VT despite antiarrhythmic drug
therapy, three prior endocardial ablation procedures, investigational
irrigated intramural needle ablation, and bilateral cervical
sympathectomy.\textsuperscript{11} In preparation for planned surgical
epicardial ablation, non-invasive programmed stimulation (NIPS) was
performed using his ICD to further characterize the ventricular
arrhythmia. During light sedation, NIPS from the RV apical septal lead
site with up to 3 extrastimuli down to ventricular refractoriness
following drive cycle lengths of 400 and 600 ms failed to induce VT
(Figure 2 Panel A). PES was then performed from the lateral LV utilizing
the coronary sinus lead, where a pacing drive train of 600 ms without
extrastimuli induced sustained monomorphic VT that had a RBBB right axis
configuration, consistent with an apical lateral exit from his apical
infarct scar (Figure 2 Panel B). VT was terminated with burst pacing. He
subsequently underwent surgical epicardial mapping and cryoablation of a
large LV epicardial scar, which rendered the VT non-inducible.

\textbf{Case 3:}

A 63 year-old woman with apical hypertrophic cardiomyopathy (HCM)
presented with nearly incessant VT at 115 bpm (RBBB superior axis) that
failed to respond to beta blockers, amiodarone and mexiletine. VT was
controlled with lidocaine that was stopped six hours prior to the study
and she arrived in the EP laboratory in sinus rhythm. PES from the RVa
with up to 3 extra stimuli down to refractoriness following a drive
cycle length of 600 ms failed to induce VT. Polymorphic VT was induced
with 400ms drive cycle length and two extra stimuli requiring external
defibrillation. A substrate modification approach was planned and access
to the LV was obtained by transseptal puncture. Burst pacing from the
rim of the LV apical aneurysm at a cycle lengths of 300 ms readily
induced the previously observed VT (Figure 3, panel A). Entrainment
mapping was consistent with an isthmus at the lateral border of the
aneurysm where the VT was successfully terminated (Figure 3, panel B).
VT was no longer inducible following endocardial and epicardial ablation
targeting the isthmus region.

\textbf{Case 4:}

A 64 year old man with ischemic cardiomyopathy and recurrent VT despite
amiodarone, mexiletine and two prior ablation procedures presented for
repeat VT ablation. PES from the RV apex with up to three extrastimuli
down to refractoriness or a minimum coupling interval of 180 ms at two
drive cycle lengths (400 and 600 ms) did not induce VT. A substrate
approach was planned and LV mapping revealed a large low voltage
(\textless{} 1.5mV) inferior and lateral scar. PES from the septal
border zone of the scar with up to two extrastimuli following a basic
drive cycle length of 600 ms induced four different sustained
monomorphic VTs with cycle lengths of 268ms to 566ms and QRS
morphologies consistent with origin from the mid-lateral and
mid-inferoseptal aspects of the infarct scar. Following ablation, VTs
were no longer inducible with PES from either the RV or LV. NIPS two
days after the procedure via the RV lead of the patient's defibrillator
did not induce VT.

\textbf{Case 5:}

A 44 year old man with previously normal ventricular function and a high
burden of symptomatic premature ventricular contractions (PVCs) from
various RV sites despite multiple previous ablations presented for
repeat ablation. He was found to have a small area of endocardial
low-voltage (\textless{}1.5 mV) at the anterior RV outflow region. PES
from the RV apex and basal septum with up to 4 extrastimuli following a
drive cycle length of 350ms did not induce any ventricular arrhythmia in
the baseline state or following isoproterenol and epinephrine infusions.
However, PES from the inferior RV free wall readily induced sustained
monomorphic VT. Subsequent cardiac MRI and FDG PET were consistent with
sarcoidosis. The details of his clinical course have been previously
reported.\textsuperscript{12}

\textbf{Case 6:}

A 36 year old man with a history of repaired Tetralogy of Fallot and
recurrent VT despite sotalol therapy and prior catheter ablation
presented for repeat ablation. PES from the RV apex and RV outflow tract
with up to 4 extra stimuli following drive cycle lengths as short as 300
ms with and without isoproterenol (up to 4mcg/min that elicited sinus
tachycardia of \textasciitilde{} 130 bpm) failed to induce VT. Single
atrial extrastimuli during isoproterenol infusion induced sustained
clinical VT (Figure 4). Programmed stimulation was then performed from
the basal inferior RV septum and reproducibly induced VT. Activation and
entrainment mapping revealed a circuit utilizing the infundibular septum
requiring ablation from the RV and aortic root for interruption, as
previously reported.\textsuperscript{13}

\textbf{Illustrative Computer Simulation}

Programmed stimulation with a single extrastimulus following a basic
drive was simulated for sites around the anatomic reentry circuit shown
in figure 5 and Video 1. In this model, proximity to the entrance/exit
regions of the channel determine whether reentry will occur in response
to an extrastimulus. S1 wavefronts propagate through the channel, the S2
wavefront blocks and fails to enter the adjacent entrance to the
channel, but propagates to the other side with a sufficient to allow
entry into the channel and initiation of reentry. This is an
oversimplification of the complex anatomic and electrophysiologic
heterogeneity in VT-causing substrate, but illustrates the marked effect
that pacing site can have on inducibility of a simple circuit.

Discussion

This case series illustrates the potential importance of the site of
stimulation when attempting to induce VT. In some patients,
non-inducibility may be due to the inability of paced wavefronts from
remote sites to engage potential reentry circuits, despite the use of
multiple extrastimuli and adrenergic agents. The concept of enhanced VT
induction probability by the addition of more stimulation sites,
including the LV has been described
previously.\textsuperscript{5,6,14,15} PES from the RV endocardium and
LV epicardium has previously been compared in patients following
surgical treatment of VT.\textsuperscript{16} The authors concluded that
stimulation from either site yielded comparable results. The study was
done post operatively, however, and was geared towards evaluating
whether post-operative residual VT was predictive of future VT
recurrence.

All six patients we describe in our case series had clinical VTs that
were not induced with PES from the common RV sites (Table 1). All
subjects had scar related re-entrant VT that was successfully induced
from different alternate sites which markedly affected their subsequent
clinical management. In five of the six patients (cases 1-5), the
clinical VT was induced when PES was performed at a site anatomically
closer to the expected critical VT isthmus. This observation supports
that the proximity of the pacing site to the reentry circuit as an
important factor beyond the probabilistic nature of PES yield in some
patients. The pacing site is likely an important determinant of whether
an extrastimulus wavefront will both reach the VT exit site sufficiently
early to block due to refractoriness, and then propagate into the
entrance and through the critical isthmus with sufficient delay to allow
recovery at the exit site to allow VT initiation. This is likely related
to both the anatomic and electrophysiologic properties of the scar and
surrounding tissue as well as the distance from the stimulation site to
various points in the circuit. At a stimulation site remote to the scar,
or one where propagation velocity of the intervening tissue between the
site and the circuit is slow, the paced wavefront may not reach the
isthmus within the critical time window required to initiate VT.
Conversely, by moving the stimulation site closer to the circuit, the
paced wavefront is more likely to reach the critical isthmus and exit
site with the appropriate relative timing to initiate reentry (figures 5
and video 1). Although our series suggests that close proximity to the
reentry circuit is an important factor, perhaps by allowing premature
stimuli to reach the circuit with less delay propagating through
surrounding tissue, the direction from which the stimulated wave front
arrives at the circuit is also likely important and a remote site may be
more effective than a close site in some cases.

The sixth case illustrates the importance of the electrophysiologic
properties of the intervening tissue between the stimulation site and
the circuit in contrast to simple anatomic proximity. This patient had
VT from the basal RV septum induced with atrial stimulation but not with
aggressive stimulation from the RV apex and RVOT. In this case, right
bundle branch block was present so atrial pacing activated the ventricle
over the left bundle during atrial pacing, and perhaps resembled LV
stimulation. The importance of atrial stimulation in the induction of
idiopathic fascicular VT, which utilizes parts of the conduction system,
has been described previously.\textsuperscript{17} Here, we posit that
the conduction system was not formally involved in the circuit but did
allow the paced wavefront to quickly engage the ventricular tissue
proximate to the circuit despite its origin in the atrium.

The potential value of PES from different sites, including the RV
epicardium in patients with suspected Arrhythmogenic Right Ventricular
Cardiomyopathy (ARVC) is well demonstrated in the first case. The
separation of the epicardial and endocardial layers in ARVC with long
conduction delays from epicardium to endocardium have been previously
described,\textsuperscript{18} but, to our knowledge, this is the first
reported case of epicardial-specific VT inducibility in a patient with
suspected ARVC.

This case series illustrates that alternate sites for PES, perhaps that
are in close anatomic or electrophysiologic proximity to potential
reentry circuits, are a reasonable consideration when trying to induce a
clinical arrhythmia in patients with previously documented VT or in
assessing arrhythmia risk in some patients with concern for VT (as
illustrated by case 5). Alternative sites might also be considered when
it is desirable to induce a specific clinical VT morphology, when only
others are inducible with initial PES; as in patients who have repeated
recurrence of a clinical VT after substrate guided ablation. Further
studies are needed to evaluate the optimal pacing sites for assessing
the value of inducibility during/following ablation procedures.

\textbf{Limitations}

The intent of this series is to illustrate the potential importance of
alternative stimulation sites when assessing VT inducibility. It is
unclear how often VT is only inducible from sites other than the RVA or
RVOT. This is a retrospective case series without randomization of
alternate stimulation sites or control for other factors which are
inevitably changing during the course of the ablation procedure
including the sympathetic tone, filling conditions, level of sedation,
and absorption of local anesthetic, that can affect VT inducibility. The
programmed stimulation was done as the procedure dictated. Hence it is
difficult to provide guidance as to a specific approach to the problem.

The use of some alternate pacing sites may increase procedural risk. For
example, most epicardial pacing sites require pericardial access. LV
endocardial stimulation requires retrograde aortic or transseptal access
to the LV, with the risks that this entails. In most cases, it seems
likely that the additional risk is not warranted.

Clinical Implications: The site of PES has a marked effect on
inducibility of VT in some patients. In some patients, PES from the RV
apex and outflow regions will fail to expose clinically relevant VTs.
The frequency with which this occurs is not certain. Stimulation from
alternative sites is a reasonable consideration in selected patients.
Our observations suggest that this may be especially useful when
performing ablation in patients whose VT is not inducible despite
previously documented clinical VTs. A PES site anatomically closer to
the suspected reentry circuit is reasonable. Further studies are
warranted to clarify the utility and selection of alternate pacing
sites.



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1998;83:795--805.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure 1: The discrepancy between the RV endocardial (Panel A) and
epicardial (Panel B) voltage maps is illustrated in this patient with VT
and suspected ARVC. Purple indicates bipolar voltage \textgreater{} 1.5
mV. While PES from the RVa (Panel C) did not induce VT, VT was readily
induced with PES from the RV epicardium (Panel D). Maroon tags are
ablation sites.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 2. Non-invasive programmed stim from the RV ICD lead with up to 3
extrastimuli following a drive train of 400ms could not induce VT in
this patient with ischemic cardiomyopathy and known history of VT (Panel
A). PVCs were also present and pacing from the LV lead at 600ms
intermittently fusing with PVCs readily induced the clinical VT in the
same patient.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Figure 3. LV voltage maps (left panels) showing the pacing site location
(distal electrodes of the mapping catheter) in a patient with
hypertrophic cardiomyopathy and apical aneurysm are shown. A, the right
panel shows the clinical VT was readily induced in this patient with
burst pacing from the border of the LV apical aneurysm. The catheter
position during stimulation is illustrated in the electroanatomic map on
the left and middle of the panel. B, the right panel shows the local
signal at the VT isthmus site where the clinical VT was successfully
ablated. The left and middle of the panel show the catheter position at
the isthmus site, which is in close proximity to the stimulation site
that induced the clinical VT.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Figure 4: Panel A: programmed electrical stimulation did not induce VT
from the RV apex despite using 4 extra stimuli with isoproterenol
infusion in this patient with a history of repaired Tetralogy of Fallot
and clinical VT. Panel B, a single atrial extrastimulus during
isoproterenol infusion readily induced VT.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

Figure 5: The relationship between the stimulation site and VT
inducibility is illustrated using a computer model. In this model,
unexcitable regions (black) create an asymmetrical channel, wider at the
left-hand side, than at the right, creating anatomy that facilitates
left to right conduction through the channel.\textsuperscript{19} Panel
A. Simulations of the same stimulation sequence of stimuli were
conducted to determine the range of sites over which re-entry was
induced. Stimulation at sites along the blue line successfully induced
VT, while stimulation from sites along the red line failed to do so.
Panel B. Two separate simulations are shown with programmed stimulation
applied at the \textasciitilde{}11 o'clock (Stimulation Site 1 where no
VT was induced) and 2 o'clock positions (Stimulation Site 2 where VT was
induced). The leading edge of the excitation wavefront is black and the
trailing edge of refractoriness fades to green - yellow. The last beat
of the drive train (S1) at 300ms (panel a) and the onset and propagation
of the extrastimulus beat (S2) at 220ms (panels b-e) are shown. With
stimulation from Site 1 close to the broad end of the channel, the paced
wavefronts encounter the ends of the channel with a timing that
prevented reentry for all extrastimuli down to refractoriness. This is
due to block of the S1 wavefront at the narrow end of the channel
shortly before arrival of the S2 wavefront, such that the channel is
refractory for the S2 wavefront. In contrast, Stimulation Site 2 is
close to the narrow end of the channel. A premature stimulus encounters
block at the narrow end, propagates to the entrance, then through the
isthmus with sufficient time for the initial site of block to recover,
and emerges from the channel producing the first reentrant beat.

Table 1: Clinical characteristics\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
\textbf{Case Number} & \textbf{Age} & \textbf{Gender} & \textbf{Type of
CM} & \textbf{Ejection Fraction} & \textbf{AADs at the time of ablation}
& \textbf{Sites of stimulation: No VT Induction} & \textbf{Successful VT
induction site} & \textbf{Site of ablation} & \textbf{Procedural
outcomes}\tabularnewline
\midrule
\endhead
1 & 57 & M & ARVC & 56\% (mild LV dilation) & None & RVa, RVOT & RV
epicardium & RV endo and epicardium & No inducible VT\tabularnewline
2 & 79 & M & ICM & 20-25\% & Mexiletine and Dofetilide (held 48h) & RVa,
RVOT & LV epicardium & LV epicardium & No inducible VT\tabularnewline
3 & 69 & F & HCM & 55-65\% (apical aneurysm) & Amiodarone and Mexiletine
(held 48h) & RVa, RV base & LV endocardium & LV endo and epicardium & No
inducible VT\tabularnewline
4 & 64 & M & ICM & 30-49\% & Amiodarone and Mexiletine (held 48h) & RVa,
RVOT & LV endocardium & LV endocardium & No inducible VT\tabularnewline
5 & 44 & M & Sarcoid & ~normal & ~none & RVa, RV base & RV anterior wall
& N/A & No ablation. ICD inserted\tabularnewline
6 & 36 & M & TOF & ~normal & ~Sotalol (held) & RVa, RVOT & RA,
Inferobasal RV & RV endocardium, RCC & No inducible VT\tabularnewline
\bottomrule
\end{longtable}

ARVC: Arrhythmogenic Right Ventricular Cardiomyopathy, HCM: Hypertrophic
Cardiomyopathy, ICD: Implantable cardioverter defibrillator, ICM:
Ischemic Cardiomyopathy, LV: left ventricle, NICM: Non-ischemic
Cardiomyopathy, RA: right atrium, RCC: the right coronary cusp of the
aortic valve, RVa: Right ventricular apex, TOF: Tetralogy of Fallot, VT:
Ventricular tachycardia.

\selectlanguage{english}
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