Electroanatomical Voltage and Morphology Characteristics in Post-Infarction Patients Undergoing Ventricular Tachycardia Ablation: A Pragmatic Approach Favoring Late Potentials Abolition

DOI: 10.1161/CIRCEP.114.002551

1

Electroanatomical Voltage and Morphology Characteristics in Post-Infarction

Patients Undergoing Ventricular Tachycardia Ablation: A Pragmatic

Approach Favoring Late Potentials Abolition

Running title: Tsiachris et al.; EAM features in post-MI VT Ablation

Dimitris Tsiachris, MD; John Silberbauer, MD; Giuseppe Maccabelli, MD; Teresa Oloriz, MD;

Francesca Baratto, MD; Hiroya Mizuno, MD; Caterina Bisceglia, MD; Pasquale Vergara, MD;

Alessandra Marzi, MD; Nicoleta Sora, MD; Fabrizio Guarracini, MD; Andrea Radinovic, MD;

Manuela Cireddu, MD; Simone Sala, MD; Simone Gulletta, MD; Gabriele Paglino, MD;

Patrizio Mazzone, MD; Nicola Trevisi, MD; Paolo Della Bella, MD

Arrhythmia Unit and Electrophysiology Laboratories, Ospedale San Raffaele, Milan, Italy

Correspondence:

Paolo Della Bella, MD

Arrhythmia Unit and Electrophysiology Laboratories

Ospedale San Raffaele

Via Olgettina 60

20132 Milan, Italy

Tel: +39-02-26436247

Fax: +39-02-26437326

E-mail: [email protected]

Journal Subject Codes: [22] Ablation/ICD/surgery, [5] Arrhythmias, clinical electrophysiology, drugs

Manuela Cireddu, MD; Simone Sala, MD; Simone Gulletta, MD; Gabriele PPPagagagllinonono, , , MDMDMD;;;

PaPaPatrtrtrizio Mazzone, MD; Nicola Trereevivivisiss , MD; Paolo Della a BeBeB lla, MD

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DOI: 10.1161/CIRCEP.114.002551

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Abstract:

Background - Catheter ablation is an important therapeutic option in post-myocardial infarction

(MI) patients with ventricular tachycardia (VT). We analyzed the endo-epicardial

electroanatomical mapping (EAM) voltage and morphology characteristics, their association

with clinical data and their prognostic value in a large cohort of post-MI patients.

Methods and Results - We performed total and segmental analysis of voltage (bipolar dense

scar-DS and low voltage areas, unipolar low voltage and penumbra areas) and morphology

characteristics (presence of abnormal late-LPs and early potentials-EPs) in 100 post-MI patients

undergoing EAM-based VT ablation (26 endo-epicardial procedures) from 2010-12. All patients

had unipolar low voltage areas while 18% had no identifiable endocardial bipolar DS areas.

Endocardial bipolar DS area >22.5 cm2 best predicted scar transmurality. Endo-epicardial LPs

were recorded in 2/3 patients, more frequently in non-septal myocardial segments and were

abolished in 51%. Endocardial bipolar DS area >7 cm2 and endocardial bipolar scar density

>0.35 predicted epicardial LPs. Isolated LPs are located mainly epicardially and EPs

endocardially. As a primary strategy, LPs and VT-mapping ablation occurred in 48%, only VT-

mapping ablation in 27%, only LPs ablation in 17% and EPs ablation in 6%. Endocardial LP

abolition was associated with reduced VT recurrence and increased unipolar penumbra area

predicted cardiac death.

Conclusions - Endocardial scar extension and density predict scar transmurality and endo-

epicardial presence of LPs, although DS is not always identified in post-MI patients. LPs, most

frequently located in non-septal myocardial segments were abolished in 51% resulting in

improved outcome.

Key words: ablation, myocardial infarction, ventricular tachycardia

p p y p

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DOI: 10.1161/CIRCEP.114.002551

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Introduction

Implantable cardioverter-defibrillator (ICD) therapy can prevent sudden cardiac death due to

sustained ventricular tachycardia (VT) late after myocardial infarction (MI)1. However, patients

experiencing ICD shocks have a decreased quality of life and increased mortality compared to

patients without shocks2,3. Catheter ablation is an important therapeutic option in patients with

VT late after MI4,5. The majority of inducible VTs in these patients are unmappable6. A variety

of alternative substrate-based methods have evolved, to overcome the shortcomings of activation

and entrainment mapping6-12. “Substrate” ablation during sinus rhythm consists of late potential

(LP) abolition, elimination of local abnormal ventricular activities (LAVAs), conduction channel

ablation, linear isthmus ablation, electrical isolation of low voltage area and scar

homogenization, all identified by electroanatomical mapping (EAM)6-12.

The purpose of the present study was to analyze the endo-epicardial EAM voltage and

morphology characteristics in order to describe the appropriateness of each substrate ablation

strategy, the interrelationship of EAM characteristics, their association with clinical data and

their prognostic value in a large cohort of post-MI patients undergoing EAM-based catheter

ablation for VT.

Methods

Study population

One hundred and sixty consecutive patients with post-MI drug-refractory VT were referred for

catheter ablation at the VT Unit at the San Raffaele Hospital, Milan between January 2010 and

December 2012. Of these, 60 patients were excluded as they had a non-Carto® 3 (Biosense-

Webster, Diamond Bar, CA, USA) based procedure. The study therefore included 100 patients

with analyzable Carto® 3 substrate maps that provide local activation time and both bipolar (30-

ablation, linear isthmus ablation, electrical isolation of low voltage area and scar

homogegeg nizatit on,,, ala l identified by electroanatomicaal l mapping (EAM)6-12. .

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DOI: 10.1161/CIRCEP.114.002551

4

500Hz) and unipolar (1-240Hz) voltage data. The study period ended in December 2013

allowing at least six months of follow-up in every patient. The study was approved by the

institutional review committee, and all patients gave written informed consent.

VT ablation set-up

Details regarding the status of coronary artery disease and presence of comorbidities were

recorded in all patients. The diagnosis and location of MI were established by the history,

pathological Q waves on ECG, regional wall-motion abnormalities or perfusion defects on

imaging that correlated with coronary angiography (>70% stenosis of an epicardial coronary

artery).

Arrhythmia presentation was classified as either electrical storm, incessant, or

paroxysmal VT as previously described13. Amiodarone was stopped 48 hours before the

procedure. Procedures were performed under general anesthesia. Sub-xiphoid epicardial access

was undertaken after a prior failed endocardial procedure if an epicardial circuit was suspected

(n=16) or as protocol-guided first-line approach (n=10). In the latter cases, no clinical data or a

prior failed procedure indicated the need for epicardial procedure. Double LV access (retrograde

aortic and transseptal) was standard. The transseptal sheath was left heparinized in the left atrium

when not used.

Electroanatomical mapping

Voltage analysis

High-density substrate mapping with a 5 mm fill threshold in low bipolar voltage areas (LVA)

and 10 mm elsewhere was performed using the Carto® 3 workstation and a 3.5 mm open

irrigated catheter with contact force assessment since available (Navistar Thermocool, Biosense-

Webster, Diamond Bar, CA, USA). In patients with ventricular pacing, EAM was performed

Arrhythmia presentation was classified as either electrical storm, incessannnt,t, oor r

paroxyxyysmal VVT asas previously described13. Amiodaarorone was stopped 48 hohours before the

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DOI: 10.1161/CIRCEP.114.002551

5

during spontaneous rhythm, if feasible. LV endo- and epicardial bipolar dense scar (DS) was

and areas with a bipolar voltage >0.5 mV and

<1.5 mV were defined as bipolar border zone (Figure 1). Endo- and epicardial unipolar scar

were areas with a unipolar voltage <8 mV14. Area measurements were achieved using the area

measurement tool. Endo- and epicardial bipolar scar density was defined as the ratio of the

bipolar DS area to total LVA, an index assumed to reflect the density of the myocardial fibrosis

within the infarct region. Matching dense scar identified on the endocardium and epicardium was

presumed to be transmural scar. We defined as unipolar penumbra area the unipolar scar beyond

the bipolar LVA15.

Further offline analyses were undertaken after segmenting the LV endocardial shell into

17 segments and the LV epicardial shell into 12 segments using the design line tool16. Each

segment was considered to be analyzable only if fill threshold criteria were met and the

predominant bipolar and unipolar voltage type was noted.

Electrogram analysis

A color-coded map of sinus rhythm activation delay was drawn on the same anatomical shell by

manual tagging the latest activity of all electrograms (LPs map). The definition of LPs included

either continuous fragmented activity bridging from the main component within the QRS to the

latest signal recorded outside the QRS, without a definite voltage cutoff (fractionated LPs), or

isolated potentials recorded after the QRS offset (isolated LPs). Baseline LPs maps were used to

define the localization and size of LP areas and were compared to re-maps created post-ablation

(Figure 1).

Early potentials (EPs) were defined as fractionated (EGM containing >4 sharp

deflections) or isolated (two or more sharp EGMs separated by an isolelectric segment) within

Further offline analyses were undertaken after segmenting the LV endocaaardrddiaiaiall l shshshelelellll ininintto

17 segggments and d tht e LV epicardial shell into 12 segeggmem nts using the desiigngng line tool16. Each

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DOI: 10.1161/CIRCEP.114.002551

6

the QRS; pacing was systematically attempted at these sites looking for morphology match with

any induced VT and for latency between the stimulus and the QRS (>40 msec). Pacing was

undertaken at just above the capture threshold aiming for near-field capture only. The

predominant electrogram (EGM) type was also noted for each segment. LP abolition was a

primary target in all patients and ablation of selected EPs secondary or adjunctive.

VT ablation strategy

After high-density substrate mapping, programmed ventricular stimulation with up to 4

extrastimuli from the right ventricular apex and multiple LV sites was performed and repeated at

the end of the procedure. By study design, we aimed to achieve the combined procedural end

point of VT noninducibility and LP abolition in all cases. Our VT ablation strategy is outlined:

1. In patients with tolerated or hemodynamically non-tolerated VT, VT was ablated using

activation and entrainment mapping. Ablation continued in SR aiming at complete abolition

of LPs when present or EPs when indicated.

2. In patients with non-inducible or hemodynamically non-tolerated VT, ablation was

performed during SR, targeting LP areas when present and EPs when indicated.

For each segment, the reason for ablation was also recorded including one or more of the

following; VT mapping, LPs and EPs.

Follow-up

In patients with a successful ablation, prior amiodarone was not reinstituted and beta-blocker

therapy maintained. VTs were mostly recorded through home-monitoring while outpatient

follow-up visits were scheduled at 3 months and then 6-monthly intervals or whenever

symptoms recurred. Primary study end-points were VT recurrence and occurrence of cardiac

death.

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DOI: 10.1161/CIRCEP.114.002551

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Statistical analysis

We analyzed EAM voltage and EGM characteristics separately in the endocardium and in the

epicardium, focusing on the predictors of epicardial presence of DS and LPs by constructing

ROC curves. We also related clinical and EAM characteristics in patients with LPs compared to

those without LPs (even according to infarct site) and we conducted segmental voltage and EGM

analysis aiming to detect differences in the endocardium compared to the epicardium and

furthermore dividing the LV shell into anterior, septal and inferolateral parts. Continuous

variables were presented as either means (+/-SD) or medians (with Q1-Q3) and categorical

variables as numbers and percentages. Comparisons between groups were undertaken using the

t-test or non-parametric tests for continuous variables and Fisher’s exact or Chi-squared tests for

proportions as indicated.

Analysis of ablation characteristics along with the above findings may help assessing the

appropriateness of different substrate ablation strategies. Cox proportional hazards analyses were

used to assess the prognostic role only of endocardial EAM characteristics building clinical

rather than statistical models. Differences were considered statistically significant at the 2-sided

p<0.05 level. All statistical analyses were performed using the SPSS version 15.0 statistical

software (SPSS Inc, Texas, Ill, USA).

Results

No difference was observed in any of the background characteristics between the enrolled

(n=100) and excluded (n=60) patients (Supplementary Table 1). Of the 100 included patients,

thirty-six patients had an anterior MI and 64 had an inferolateral MI with 17 having had at least

one prior failed catheter ablation procedure. Among inferolateral infarcts, RCA was the culprit

vessel in 43 patients, LCx in 17 patients and both RCA and LCx in 4 patients.

-test or non-parametric tests for continuous variables and Fisher’s exact or Chi-sssquauu rereed d d tetetestststs ss foff r

proporrtions asa indndicated.

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DOI: 10.1161/CIRCEP.114.002551

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Scar analysis

The mean endocardial surface area was 236.1±58 cm2. Of that, 10.2% was bipolar DS, 21.8%

was bipolar LVA and 46.7% was unipolar scar. Endocardial penumbra was present in all but one

patients and mean area was 51.6 cm2 (24.9%). While unipolar scar was present in all cases, 18%

of the post-MI patients had no evidence of endocardial bipolar DS. In 14 of these, bipolar LVA

was recorded and endocardial LPs were present in 5. All these 18 patients had a history of MI (9

anterior and 9 inferolateral), regional wall motion abnormalities (mean LVEF=37%) and

established coronary artery disease (8 had 3-vessel and 7 had 2-vessel disease) while 13 of them

were revascularized (5 with CABG and 8 with PCI).

Among the 26 patients with available epicardial maps, 8 had no bipolar DS and 4 neither

LVA nor DS. Epicardial penumbra was absent in 5/26 patients. Based on ROC curve analyses,

endocardial bipolar DS area was the only predictor of the epicardial presence of bipolar DS (area

under the curve - AUC 0.75, CIs 0.56-0.95, p=0.040) with an optimal value of 22.5 cm2

(sensitivity 61.1% and specificity 87.5%). Endocardial penumbra area had no predictive value

for the epicardial presence of either DS or LVA.

Segmental scar analysis

Within the study population, 1597 out of 1700 endocardial segments fulfilled fill threshold

criteria and were included in the EGM analysis. DS was the predominant bipolar voltage type in

14.3% of the segments and border zone in 20%. Unipolar scar was present in 60.1%. In all

bipolar DS segments, there was also unipolar scar. In contrast, in 23.9% of unipolar scar

segments there was underlying predominant bipolar DS, in 32.3% bipolar border zone and in

43.8% endocardial penumbra (normal bipolar amplitude).

Among the 26 patients with available epicardial maps, 8 had no bipolar DSDSDS aandndnd 444 neneneititithhher

LVA nor DSS. Epppicicardial penumbra was absent in 5/5/262 patients. Based on n ROC curve analyses,

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DOI: 10.1161/CIRCEP.114.002551

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Presence of LPs

Endocardial LPs were recorded in 66% (n=66) of the patients and epicardially in 17/26 (65.4%).

Prevalence of epicardial LPs was not different between research protocol patients and those with

a prior failed procedure as the indication for epicardial mapping (80% vs. 56%, p=0.21).

Abolition of endocardial LPs was achieved in 51/66 (77.3%) and of epicardial LPs in 10/17

(58.8%) patients. We identified 3 patients in whom LPs were abolished endocardially and

persisted epicardially. Of them, 1 remained inducible at the end of the procedure.

Patients with endocardial LPs had greater endocardial bipolar DS (p<0.001), bipolar

LVA (p=0.001) and ablation area (p=0.029) as well as increased endocardial bipolar scar density

(p<0.001) compared to those without LPs (Table 1). Similarly, patients with epicardial LPs

compared to those without exhibited increased endocardial bipolar DS area (p<0.001) and

bipolar scar density (p=0.006), as well as epicardial bipolar DS (p=0.008), bipolar LVA

(p=0.011), unipolar scar areas (p=0.001) and bipolar scar density (p=0.034), despite the

decreased power to detect a difference based on the small number of patients in each group

(Table 2) (Supplementary Table 2). Accordingly, there was no difference in either endocardial or

epicardial penumbra areas according to the presence of endocardial or epicardials LPs.

Based on ROC curve analyses, endocardial bipolar DS area (AUC 0.80, CIs 0.63-0.98,

p=0.011) and endocardial bipolar scar density (AUC 0.82, CIs 0.65-0.98, p=0.008) predicted the

epicardial presence of LPs with optimal values of 7 cm2 (sensitivity 88.2% and specificity

66.7%) and 0.35 (sensitivity 52.9% and specificity 100%), respectively. Notable, a value of

endocardial bipolar DS area greater than 38 cm2 had 100% specificity (Figure 2). Endocardial

penumbra did not predict the epicardial presence of LPs.

p<0.001) compared to those without LPs (Table 1). Similarly, patients with epicccarardiddialalal LLLPsPsPs

compara ed to thosse e without exhibited increased endodocardial bipolar DS aarerea (p<0.001) and

bibibipooolar scar dddenennsisisitytt (((p=p=p=0.0.0.0000006))),, , asasas wwwelelell ll asasas eepipipicacacardiaaal bbipopopolalalar r r DSDD (((p=p=p=0.00.000008)8)8),, , bipopopolalalar r r LVLVL A A A

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DOI: 10.1161/CIRCEP.114.002551

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Segmental EGM analysis

LPs were predominantly present in 10% of the 1597 endocardial segments (in 5.2% fractionated

LPs and in 4.8% isolated LPs), EPs in 22.1% (in 19.3% fractionated EPs and in 2.8% isolated

EPs) and normal EGMs in 66.8% of the segments (no EGM type was identified in 1.1% of the

segments due to diffuse DS). Unipolar scar was present in all segments with LPs. Underlying

bipolar DS was present in 60% of segments with LPs, border zone in 33.8% and endocardial

penumbra in 6.2% (normal bipolar amplitude). In 98.3% of segments with EPs there was

underlying unipolar scar. Bipolar DS was present in 32.3% of segments with EPs and border

zone in 67.7%.

LPs were also predominantly present in 12.3% of the epicardial segments (in 2.2%

fractionated LPs and in 10.1% isolated LPs), EPs in 13.5% (in 9.4% fractionated EPs and in

4.1% isolated EPs), normal EGMs in 71.9% and diffuse dense scar in 2.2%. Importantly, among

the 12.3% of epicardial segments with LPs, isolated LPs were found in 10.1% (82.1%) whereas

this percent was 48% with respect to the epicardium. Focusing on the distribution of LPs in the

17-segment shell we exhibited a significant shift towards the inferolateral segments taking into

account the whole study population (Figure 3).

Analysis according to infarct site

Patients with anterior infarcts (n=36) compared to those with inferolateral infarcts (n=64) were

younger (-3.8 years, p=0.021), had lower LVEF (-3.9%, p=0.049), a greater prevalence of LV

aneurysm (+28%, p<0.001) and exhibited increased total endocardial surface area (p=0.012),

endocardial LV volume (p=0.001) and unipolar scar (p<0.001) (Table 3). Patients with anterior

compared to those with inferolateral MIs had no difference in the proportion of segments with

bipolar DS (14.5% vs. 14.2%, p=0.8) and segments with LPs (8.7% vs. 10.9%, p=0.07).

LPs were also predominantly present in 12.3% of the epicardial segmentsss (((ininin 222.2.2.2%%%

fractiono ated LLPs aand in 10.1% isolated LPs), EPs iin n 13.5% (in 9.4% fractctioi nated EPs and in

4.4.4.1%%% isolated dd EPEPEPsss),)) nnnororormamamalll EGGGMsMsMs iiin nn 717171.9.9. % %% ananand dddifffffuseee dededensnsnse e scsccarar iiin nn 2.2.2.2%2%2%. Immmpopoportrtrtanana ttlylyly, amamamononong g

hhhe e 12121 .3% of eepiicaaardiaaal ssegmmmenennts wwititith h LPPPs, iiisooolateeed LPsPsPs weweereee fouuunnnd in 11010.1. %%% (8(( 2.1%%%)) whwhwhereeasss

his perceeentnn wasss 448% wwwitii h respspspecee t to the epipp cacacardddiuiuium.mm Focususu ing gg on theheh distribbbutu iooon nn of LPs in the

17177-sesesegmgmgmenenentt t shshs elele ll wewewe eeexhxhibibbitittededed aaa sssigiggninifificacacantntnt ssshihiftftt tttowowowararardsdsds ttthehee iinfnferererololo atataterereralala sssegegegmemementntntss s tatatakikikingngng iintntntooo



DOI: 10.1161/CIRCEP.114.002551

11

LV segments’ analysis was also performed after dividing LV shell into anterior (4/17),

septal (5/17) and inferolateral (8/17) segments. DS was present in 26.8% of the anterior

segments, in 16% of the septal and in 7.4% of the inferolateral segments in patients with anterior

MIs. Accordingly, LPs were present in 20.7% of the anterior segments, in 5% of the septal (5%)

and in 4.9% of the inferolateral. Regarding patients with inferolateral MIs, DS was found in

22.5% of the inferolateral, in 9.3% of the septal and in 2.9% of the anterior segments. Likewise,

LPs were present in 19.3% of the inferolateral, in 4.9% of the septal (4.9%) and in 0.8% of the

anterior (Figure 4).

Ablation characteristics

At baseline monomorphic VT was induced during PVS in 61 patients, during creation of the

substrate map in 14 patients while 11 had baseline incessant VT. The median number of VTs in

each procedure was 2 and at least one non-tolerated VT was present in 38 patients.

Ablation was performed during activation mapping in 75% of the patients. This includes

also limited mapping of non-tolerated VTs when the ablation catheter was placed in the area of

latest activity during SR, showing mid-diastolic potential during VT. LPs were targeted in all

patients with areas of LPs (2/3 of the study population). EPs were targeted in 23% of the patients

whenever there was latency (stimulus to QRS >40msec) or morphology matched with induced

VTs during pacemapping maneuvers.

Focusing on the primary ablation strategy, 48% of the patients underwent both ablation of

LPs and VT mapping and 27% underwent only VT mapping in the absence of LPs. In 17% of the

study population, no VT mapping was available and ablation of LPs constituted the principal

ablation strategy. Ablation of EPs was the basic strategy in 6% of the post-MI patients with

absence of VT mapping and LPs.

At baseline monomorphic VT was induced during PVS in 61 patients, during creeeatattioioionn n ofofof ttthehehe

ubstrata e mappp inn 114 patients while 11 had baseline iincn essant VT. The mededian number of VTs in

eaeaachhh proceduuurerere wwwasaa 222 aaandndnd aaat tt leleeasasast tt ononone e nonononn-tototolelelerateeed VT T T wawawas s s prpp esessenenent tt inini 333888 pap tiiienenentststs. .d

Ablatioi n wwwas ppperrrformememed dd duririingngn acctivvatatiion mamam pppppinining iinin 75%%% of thheee ppapattitienennts. TThThiiis iiinccludddesss

also limitittedede mapapappipipinggg ooof f f non-toolelelerated VTs whwhwhenenn ttthehehe ablatttioii n cathettteree was plplplaceddd in the area of

aaatttesesestt t acacactitit viviv tytyty dddurururinining g g SRSRSR,,, shshs owowowiningg g mimiddd-didid asasastototoliliccc popopotetetentntntiaiaall dududuriringngng VVVT.T.T. LPLPLPsss wewewererere tttararargegegeteteted d d ininin aaallll



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VT recurrence

No patients were lost to follow-up with a median follow-up time of 628 (404-902) days. Thirty-

two (32%) had a VT recurrence during the follow-up period with a median recurrence time of 73

(14-217) days. Focusing on the prognostic value only of EAM characteristics, endocardial LP

presence (HR 0.398, p=0.009) and LP abolition (HR 0.260, p=0.001) were associated with

reduced VT recurrence. In the multivariate analysis with the above two EAM characteristics as

the sole selected variables, LP abolition was the only predictor of reduced VT recurrence (HR

0.274, p=0.010).

Cardiac death

Five patients died from non-cardiac and 7 (7%) from cardiac causes during the study period (6

due to cardiac decompensation and 1 sudden death). Among EAM characteristics, endocardial

LP presence (HR 0.204, p=0.047), endocardial penumbra area (HR=1.018, p=0.001) and

unipolar scar (HR=1.013, p=0.034) were related with cardiac death. In the multivariate analysis

with the above three EAM characteristics as the sole selected variables, endocardial LP presence

(HR 0.177, p=0.041) acted as a prophylactic predictor while increased endocardial penumbra

area (HR=1.028, p=0.044) as an adverse predictor of cardiac death.

Discussion

In the present study we analyzed the EAM voltage and morphology characteristics in post-MI

patients undergoing catheter ablation for VT focusing on the identification and ablation of LPs as

a principal procedural endpoint. We concluded that LPs are present in two-thirds of post-MI

patients with larger and more solid scars and they are most frequently located in non-septal

myocardial segments. The above endocardial EAM features predict also the existence of a

potential arrhythmogenic substrate in the epicardium. Abolition of LPs is feasible in half cases

Five patients died from non-cardiac and 7 (7%) from cardiac causes during the stttudududy y pepeperiririododod (((666

due too cardiaca dececompensation and 1 sudden deathh).).). Among EAM characacteristics, endocardial

LLLPPP pppresence (((HRHRHR 000.22040404,, p=p=p=0.00 0404047)7)7),,, enene dododocacc rdrdrdiaiaial ll penununumbmbrarara aaarererea a (HHHR=R=R=1.11 0101018,8,8 p=0=0=0.0.0.0010101) ) ) anannddd

ununnipppolo ar scar (((HRRR===1.0001333, p===0.0.0300 4) wwwerrre relaaateeed wwwitthth cccararardddiaaac deaaathhh. In thehehe mmmululltit variiiatattee anananalysssisss r

with the aaabobb ve ttthrhh ee EEEAMAMA chaarararacteristics as ththt e e e sososolelele seleccctett d variabbblell s,, endododocardddial LP pppresence

HHRR R 0.0.0.1717177,7,7, ppp=000.0.0.0414141))) acacactetetedd d asasas aaa ppprororophphp ylyly acacactitit cc c prprpredededicicctototorr r whwhw ilileee inincrcrcreaeaeasesesedd d enenendododocacacardrddiaiaall pepepenununumbmbmbrarara



DOI: 10.1161/CIRCEP.114.002551

13

and is associated with lower VT recurrence rate.

Evolution of substrate-based ablation strategies

Inherent limitations of VT inducibility as an ablation target, such as effects of anti-

arrhythmic/sedation/general anesthetic therapy, stimulation protocol pacing site dependence and

inconsistent clinical/non-clinical VT/VF induction stressed out the need for systematic studies of

the substrate9,17. Based on the surgical experience, early attempts targeted scar border zone

creating ‘linear ablation lines’ through the DS until reaching the normal myocardium or valve

continuity6. Further research focused on identification of critical VT isthmuses and conducting

channels between unexcitable scar areas7,8.

More recent substrate ablation strategies focused on EGM characteristics beyond scar

identification. In this setting, we have consistently presented that complete LPs abolition based

on remapping, in combination with VT noninducibility, constitutes an excellent procedural end-

point9,17. Likewise, the elimination of LAVAs, defined by us as LPs and EPs, has also been

associated with a better outcome10. These approaches require the ablation of all substrates, not

only the substrate acting as a VT isthmus at the moment of the procedure. Towards this direction,

the more aggressive in terms of the ablation and less electrophysiologically oriented endo–

epicardial scar homogenization technique has provided promising results11. On the other hand,

there have been attempts to minimize the required ablation lesions either by targeting the

abnormal EGMs with the shortest delay between the far-field component and the delayed local

component (eliminating neighboring and remote areas of slow conduction) or by electrical

isolation of the scar area (<1.5 mV) by means of linear ablations encircling the scar18-20.

Scar characteristics in post-MI patients

In the present study we used the gold standards of EAM cut-off values derived from studies that

More recent substrate ablation strategies focused on EGM characteristicss bbbeyeye ononond d d scscscaara

dentifif cationn. Inn tthis setting, we have consistentlyyy prprp esented that complletete LPs abolition based

ononon rrremappinggg, ininin cccommmbibibinananatititionon wwwititith h h VTVTVT nnnonnnininindudd cibbbilllityyy,,, cococonsnsnstitt tuuutetetes s ananan exexexcecec llenennt t t prprprocococedddurururalalal eeendndnd-

popooinnntt9,17. Likeewiiseee, theee eeelimiinananatit on ooof f LALAAVAAAs,,, defffinnned d d bybyby uuus asa LLLPPs anddd EEEPsss,, hhhas allsosoo beeeeen

associatededed with a a a betttererer oooutcomememe10. These apappprprp oaoaoachchchesee requququiri e the abbblall tion of f f all sususubstrates, , not

onononlylyy ttthehee sssubububstststrararatetete aaactctctiningg g asasas aaa VVVTTT isissththt mumumuss s atatat ttthehee mmmomomomenenentt t ofofo ttthehee ppprororocececedududurerere... ToToTowawawardrddss s thththisisis dddirirececectitit ononon



DOI: 10.1161/CIRCEP.114.002551

14

validated EAM data according to late-enhanced scar in magnetic resonance imaging (MRI)21,22.

Surprisingly, we identified a significant, previously not recognized, proportion of patients

without evident endocardial bipolar DS, despite fulfilling the diagnostic criteria of ischemic

cardiomyopathy. Indeed, MRI scar areas have been exhibited to be larger in 1/3 of post-MI

patients and visual analysis has showed a clear mismatch between EAM bipolar and MRI scar

areas23. Beyond the under-recognition of EAM scar, absence of DS could be attributed to the

underlying presence of either hibernated myocardium, early re-perfused myocardium,

remarkable collateral circulation or the presence of concomitant cardiomyopathy24. LPs were

found in only 6/18 patients with absent bipolar DS and EPs in additional 3 patients, limiting

significantly the ablation targets in SR.

Of utmost importance, we show that the size of endocardial bipolar DS area is the best

predictor of epicardial bipolar DS. Specifically, scar transmurality should be suspected when DS

area exceeds 10% area of endocardial surface area, in accordance with MRI measurements of

late-enhanced scar (8%)23.

EGM characteristics in post-MI patients

Specific areas of LPs are recognized in 2/3 of post-MI patients and complete LP abolition is

accomplished in half of the total post-MI population at least endocardially. LPs are expected to

be found in post-MI patients with larger and more solid scars, based on the increased endocardial

bipolar scar density. Such areas of transmural scar, as assessed by echo or computed

tomography, have been correlated to areas of LAVAs in post-MI patients25. In our study, scar

transmurality and density predict reliably the presence of epicardial LPs, indicating the possible

requirement for a more complex procedure. The fact that we recognized epicardial LPs as often

in research protocol patients as in those with a previous failed endocardial procedure enhances

ignificantly the ablation targets in SR.

Of uttmom stst importance, we show that the sizze e of endocardial bipoolalar DS area is the best

prprpredddictor of eeepipipicacacardrr iaiaalll bibibipopopolall r r DSDSDS.. . SpSpSpecececififificccalalallylyly, scccarrr traaansnsnsmumumurarr liiitytyty ssshohoh ulululddd beb sssusususpepepectctctededd wwwhehehenn n DSDD

ararreaeaa eexceeds 110%%% areaaa ooof endododocac rdiaiaal l sssurrrfacee aaareaaa, iiin aaaccccccordadadanceee wwwith MRMRMRI mememeasurremememennntts offf

ate-enhaaancncn ed scacacar (8(( %)%)%)23.

EGEGEGMMM chchcharararacacacteteteririristststicicicsss ininin ppposososttt-MIMIMI pppatatatieieientntntsss



DOI: 10.1161/CIRCEP.114.002551

15

even more the significance of these findings.

Based on segmental analysis, 2/3 of LPs are found over segments with DS while only 7%

of them in “normal” myocardium and above unipolar scar (penumbra). On the other hand, 2/3 of

EPs are located in the border zone and the remaining 1/3 in DS regions. We also exhibited a

more frequent localization of LPs in non-septal segments of the endocardial shell (anterior

segments in anterior MIs and inferolateral segments in inferolateral MIs), possibly attributed to

the latency of normal activation in the lateral wall, as well as to the greater proportion of

transmural scar in these segments26. We also identified that 80% of LPs in the epicardium are

isolated LPs whereas isolated and fractionated LPs are evenly distributed in the endocardium.

Recent findings identified isolated LPs in sites of heterogeneous islets within DS27. EPs are

found mainly in the endocardium reflecting a possible “bridge” along channels leading to latest

activity and their lower prevalence at epicardial sites might indicate their intramyocardial

distribution. Subsequently epicardial isolated LPs could just reflect the resulting conduction

pattern. From a pathophysiologic point of view, surviving cells surrounded by fibrosis in areas of

inhomogeneous scars are poorly coupled to the rest of the myocardium and constitute the

substrate of LPs and EPs. It has recently been exhibited that the presence of LPs rather than EPs

increases the specificity for identifying the clinical VT isthmus28.

Appropriateness of each ablation strategy in post-MI patients

VT and LPs ablation was the principal ablation strategy in 48%, VT mapping alone in 27%, LPs

ablation alone in 17% and ablation of EPs was the basic strategy in only 6% of the post-MI

patients, despite the fact that EPs were recognized in a significantly larger LV area (22.1% vs.

10% of endocardial segments) compared to LPs. Although not all areas of LPs contain critical

isthmuses for VT maintenance, LPs and selected EPs as defined in the present study, provide an

Recent findings identified isolated LPs in sites of heterogeneous islets within DSSS272727... EPEPEPsss ararareee

found mainlyyy in ththe endocardium reflecting a possiiblb e “bridge” along chahannels leading to latest

acacactiivvvity and ttthhheieieirrr loll wewewerrr prprprevevevallenenencecece aaat t epepepicici ararardididialaa sitttesss mmigigighththt iiindnn icccaaate e e thththeieieirrr inini tramamamyoyoyocacacardddiaiaialll

didiiststrriribution. SuS bbbseeequeeentttly epppicccardialall isolllateddd LLLPs cooouldldd jjjusttt rrrefleeecttt the rrressusultlttininng condndnduucucttiooon

pattern. FFFroror m a papapathopopophyhyhysiologogogicii pppoint of viewewe ,, sususurvrvrviving g g cec lls surrrrouoo nded bbby yy fiiibrbb osis in areas of

nnhohoomomomogegegeneneneouououss s scscscarararss s arararee e popopoorororlylyy cccouououplplp ededed tttooo ththt ee e rerereststst oooff ththt ee e mymymyocococararardidid umumum aaandndd cococonsnsnstitit tutututetete ttthehehe



DOI: 10.1161/CIRCEP.114.002551

16

ideal substrate for VT ablation, since such abnormal EGMs are found more frequently in post-MI

patients with spontaneous VT compared to those without arrhythmias29. One may hypothesize

that these sites of slow conduction, that are initially incapable of supporting VT, will form

critical isthmuses in the future, representing the necessary if not sufficient arrhythmogenic

substrate for reentrant VT.

Of course, this generalized approach towards VT ablation extends the required ablation

zone more than specific critical isthmus and channels ablation but less than complete LAVAs

elimination and endo-epi scar homogenization. Based on the fact that our mean LVA area was >

50cm2 (22% of total endocardium), achievement of scar homogenization, beyond its subjective

interpretation, necessitates an extended damage in the myocardium, compared to the half of

ablated area observed in our study. Targeting only the entrance of conducting channels, i.e the

earliest of LPs or encircling and electrically isolating the scar are attractive alternatives, since

they minimize the required ablation lesions, but their value has to be proven in larger

populations18-20. Moreover, electrical scar isolation is unlikely to be universally feasible with

current ablation technology.

We consider that LPs abolition should constitute the primary target for substrate ablation,

since LPs abolition is a clear end-point amenable to objective evaluation and LPs are more

closely related to clinical VT isthmuses28. Notably, LPs ablation adds to most cases of VT

mapping and constitutes the only option in one quarter of post-MI patients. In contrast, LAVAs

elimination is liable to a more subjective interpretation as with current EAM systems it is

impossible to provide a complete annotation of presence and distribution of LAVAs before and

after ablation.

EPs elimitation should adjunctively be performed after a definite electrophysiologic proof

nterpretation, necessitates an extended damage in the myocardium, compared too o ththhee hahahalflflf ooof f f

ablatedd area oobsererved in our study. Targeting onlyyy ttheh entrance of conduuctc ing channels, i.e thea

eaeaarllliiiest of LPPPss ororor eeenccciririrclclclinining g g anannd d d elelelececectrtrricicicalaa lyyy iiisososolatiiinggg thehehe ssscacacar rr arre e e atatttrtrtracacactititiveveve altttererernananatititivevv s,s,s, sssininincecece

hhheyeyey mminimizze e thhhe requuuirrred aaablblblataa ion n lelel sssiooons, bbuuut thhheiirr vvvalalaluuue hhhaaas tooo bbbe proooveeen n ininn largeeer

populationonons18-20... MoM reeeovovover, , elececctrtt ical scar isolololatttioioion n n isi unlikikikely yy to beee unu iversasasallyyy fefef asible with

cucucurrrreeentntnt aaablblb atatatioioonn n tetetechchchnononololoogygygy.. .



DOI: 10.1161/CIRCEP.114.002551

17

of their involvement in the VT circuit, in patients without LPs (especially those with septal scars)

and in cases of persistent VT inducibility after LPs abolition. The development of an improved

multipolar recording technology that can identify slow conduction entrances into the scar and

allow observing dynamic changes in the slow conducting channels during ablation could allow

reliable and prompt EP characterization and subsequent documentation of their disappearance

post ablation.

Prognostic value of EAM characteristics

DS extension, with a cut-off value of 25 cm2, has been proven to be a potent predictor of VT

recurrences in post-MI patients8. Such an association was not observed in our study population,

where LP abolition was associated with reduced VT recurrence. Last but not least, we had the

opportunity to assess for the first time the prognostic value of EAM characteristics for cardiac

death. Specifically, an increased unipolar scar exceeding bipolar LVA (penumbra) reflects

diffuse disorganized myocyte loss and is associated with increased mortality, whereas

endocardial LP presence improves prognosis possibly through a successful VT ablation

procedure.

Limitations

This is a single center prospective analysis of our current ablation strategy not a randomized

controlled trial assessing one strategy versus another. Moreover, epicardial maps were less than

the endocardial maps and by virtue of this sampling error, there could be a systematic selection

bias in the results and a decreased power in the specific analysis. Additionally, we have not used

a competing risks model for VT recurrence and we acknowledge that there may be confounding

variables since we have not performed a statistical model building. The prospective data

collection in consecutive patients and the large sample size of patients with detailed EAM

where LP abolition was associated with reduced VT recurrence. Last but not leasstst, wewewe hhhadadad ttthehehe

opporttunity yy tot assssess for the first time the prognostiticc value of EAM chararacteristics for cardiac

dededeattth.h Specififificacaalllllly,yy aaann n ininincrcrcreaeae seseed d d unununipipipolololararar scccararar exceeeeeedinngg g bibibipopopolar rr LVLVLVA AA (p(p(penene ummmbrbrbra)a)a) rererefllececectttsss

didiiffffffuususe disorggganiiizeeed mymymyoco yte ee lolol ss aandndn is assoooccciateeed wwititith h h iiincccreeeaseeed morttaaliiity,y,y, wwwhereeeasass

endocardddiaiaial LP ppprer sennncecece imppprooovevv s progggnosisss popoossssssibibiblylyy thrououo ghgg a succccecc ssful VTVV aaablbb ation

prprprocococedededururure.e.e.



DOI: 10.1161/CIRCEP.114.002551

18

analysis constitute the strengths of this study.

Conclusion

Although DS is not always identified in post-MI patients, its endocardial extension and density

predict not only scar transmurality but also the presence of LPs either in the endocardium or in

the epicardium. Endocardial LPs, more often present in non-septal segments and their abolition

predicted VT recurrence predominantly in patients with inferolateral MIs, while the size of

unipolar penumbra area was associated with cardiac mortality.

Acknowledgments: We would like to thank Claudio Albertini and Sebastiano Colombo for their

technical support and all the staff at the San Raffaele VTU and ICU for their tireless work and

professionalism.

Conflict of Interest Disclosures: Dr. Della Bella is a consultant for St. Jude Medical and has

received honoraria for lectures from Biosense Webster, St Jude Medical and Biotronik. Drs.

Silberbauer and Oloriz are Advanced European Heart Rhythm Association Fellows with grants

funded by Biosense Webster.

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2012;23::62626 1-6227.77

10100.. . JaJaJaïsïsïs PPP,, , MaMaMaurururyy y P,P,P, KKKhahaairiryy y P,P,P, SSSacacacheheerr r F,F,F, NNNauauaultltt III,,, KoKoKomamamatststsuu u Y,Y,Y, HHHocococininii M,M,M, FFForororclclc azazaz AAA,,, JaJaJadidididididi AAAS,S,S, WWeerasooryia R Shah A Derval N Cochet H Knecht S Miyazaki S Linton N Rivard L



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17177. SSSilberbaueueuer r r J,J,J, OOlolooriririz z z T,T,T, MMacacaccacacabebebellllliii G,GG TTTsisisiacaa hrrris D,, BaBaBarararatttttto F,F,F, VVVerere gagagararara P, MiMiMizuzuzunonono HHH, ,BBiB scscceglia C, Marrrzii A, Sooora NNN, GGuarararrrraciiinii F, RRRadinnnovvvic cc A,A,A, CCCirrredddudu M, SSallaa SSS, GGGullleetettatata SSS, PPPagglglinnnoG,G,G, MMMazzone PP, TTTreeevisiii NNN, Deeellalala Belllalala PPP. NNonnninnnducccibbbilititity y y andd lal tee ppotenttiialll aabobobolil tionnn: aaa nnnovvvel combmbmbinininededed ppprororogngngnososstititic c c prprprocococedurururalalal eendndnd poioiointntnt fffororor cccatatathhheteteter r ababablalalatititiononon oof f f popopostststinininfaaarcrcrctitiiononon vvvenenentttricicicululararar achycardididia.a Circrcrc Arrhyhyhythtt m Elececectrophyyysiol. 2020201444;7;7;7:4:4: 24-43533 .

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28. Mountantonakis SE, Park RE, Frankel DS, Hutchinson MD, Dixit S, Cooper J, Callans D, Marchlinski FE, Gerstenfeld EP. Relationship between voltage map "channels" and the location of critical isthmus sites in patients with post-infarction cardiomyopathy and ventricular tachycardia. J Am Coll Cardiol. 2013;61:2088-2095.

29. Haqqani HM, Kalman JM, Roberts-Thomson KC, Balasubramaniam RN, Rosso R, Snowdon RL, Sparks PB, Vohra JK, Morton JB. Fundamental differences in electrophysiologic and electroanatomic substrate between ischemic cardiomyopathy patients with and without clinical ventricular tachycardia. J Am Coll Cardiol. 2009;54:166-173.

25. Komatsu Y, Cochet H, Jadidi A, Sacher F, Shah A, Derval N, Scherr D, Pascalelee PP, RoRoteteen n L,L Denis A, Ramoul K, Miyazaki S, Daly M, Riffaud M, Sermesant M, Relan J, Ayyyacachehhe NNN,,, KiKiKim mm S, Montaudon M, Laurent F, Hocini M, Haïssaguerre M, Jaïs P. Regional myocardiaalll wwawallllll ttthihihinnnnnninining ggat mulltidetectc or ccomo puted tomography correlates toto arrhythmogenic subsbstrt ate in postinfarction veentntntriririccular r tatat cchc ycycycaardia: assessment of structural annnddd electrical subbstss rate. CCCirc Arrhythm ElElEleccctrophysiiololo .. 2220100 3;3;;6:6:6:3434342-2-2-35550.0.0.

26266. KKoK matsu Y,Y DDaly M,MM Sacccheheher F, DDDerrrvaaal NNN, PPPascccallle PPP, RRRoteten n L,,, SSScherrrr DDD, JJJadadadidi A,A,A, RRamamamoulll KKK,Deenininis ss A,A,A, JJJeseseseelel LLL,,, ZeZeZelllllleeerhohohoff SSS, , LiLiLim m m HSHSHS, , ShShShahahah AAA, CoCoCochchcheetet HHH,, HoHoHocicinnni MMM, HHHaïsïsïssasas guguguerererrerere MMM, , , JaJaaïsïsïs PPP. Electrophyhyhysiologogogici chahaharararacterizatatation of local aaabnbnbnororormamm l ventntntricular accctitt vities iiin nn popopostss infarction ventricuuulalalar r r tatatachchchycycycararardididiaa a wiwiwiththth rrresesespepepectcct ttto o o thththeieieirrr anananatattomomomiiic c c lololocacacatititiononon... HeHeHearararttt RhRhRhytytythmhmhm.. 202020131313;1;1;10:0:0 16161630-16166373737...



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Table 1: Procedural and mapping characteristics according to endocardial LP presence or not

Endocardial presence of LPs

(n=66)

Endocardial absence of LPs

(n=34)

Background p

Anterior myocardial infarction (%) 31.8 44.1 0.22

Left ventricular ejection fraction (%) 31.8±9.6 33.4±9.4 0.42

Procedural data

Epicardial access (%) 30.3 17.6 0.181

Procedure time (min) 243.1±72.4 206.3±71.8 0.018

2 (1-3) 1 (1-3) 0.55

Non-tolerated VT 39.1 38.2 0.93

1 (0-1.2) 1 (0-1) 0.72

Electroanatomical data

ENDO surface area (cm2) 240.7±58.2 227.2±57.3 0.27

ENDO points 402.5±169 356.7±159 0.195

ENDO LV volume (cm3) 253.7±84.4 234.3±85.5 0.28

ENDO BIP dense scar area (cm2) 23 (13.7-39) 4.5 (0.2-15.7) <0.001

ENDO BIP low voltage area (cm2) 52.7 (40.7-73.5) 25 (8-59.7) 0.001

ENDO Absence of BIP dense scar (%) 7.6 38.2 <0.001

ENDO BIP scar density 0.32 (0.23-0.36) 0.14 (0.01-0.30) <0.001

ENDO Unipolar scar area (cm2) 111.5 (81-141.2) 100 (37.7-134.2) 0.074

ENDO Penumbra area (cm2) 50.5 (32.3-70) 47.5 (19-94.2) 0.73

Ablation area (cm2) 25.2±12.4 19.3±12.7 0.029

Ablation time (min) 28.9±14.7 23.7±12.1 0.076

VT end (%) 10.8 8.8 0.76

LPs=Late potentials, VT=Ventricular tachycardia, ENDO=endocardial, BIP=bipolar

Non-tolerated VT 39.1 38.2 0.0.0.939393

1 (0-1.2) 1 (0-1) 0.72

Ellececectrtrtroananaatototomimiicacacal data

EEENDNDDO surface e arara eeea (((cmcmcm222))) 244000.7±±±55858.2.22 222222777.2±±±575757 3.3 00.0 27272

ENENENDDDO pointss 4440222.5±5±5±16116999 335666.7±7±±11159 00.199955

ENDODODO LLLVVV volulumeme (((cmcm333))) 252525333.7±7±7±848484 44.4 232323444.333±85855 55.5 000.282828

ENDO BBBIPIPIP dededensnsnseee scscscararar ararareaeaea ((cmcmcm222))) 232323 (((131313.7.7.7-3-3-39)9)9) 4.4.4.555 (0(0(0.2.2.2-1-115.55 7)7)7) <<<0.001

ENENENDODODO BBBIPIPIP lllow v llolttage area (((cm222))) 525252 77.7 (((404040 77.7 77-7333.5)5)5) 252525 (((888-595959 77.7))) 000.000000111



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Table 2: Procedural and mapping characteristics according to epicardial LP presence or not

Endo-epicardial procedures

Epicardial presence of LPs (n=17)

Epicardial absence of LPs (n=9)

Background pAge 70.7±5.1 68.4±5.3 0.28 Anterior myocardial infarction (%) 35.3 44.4 0.64 LV ejection fraction (%) 29.2±10 35.0±8.3 0.154 Procedural dataProcedure time (min) 306.7±41 287.5±90 0.46

2 (0.5-3) 3 (1-3) 0.87 Non-tolerated VT 29.4 66.7 0.067 Electroanatomical dataENDO surface area (cm2) 252.1±70 211.0±47 0.130 ENDO points 356.6±186 337.7±131 0.79 ENDO LV volume (cm3) 280.8±102 225.4±78 0.170 ENDO BIP dense scar area (cm2) 33 (11-52) 5 (0-21.5) 0.009 ENDO BIP low voltage area (cm2) 55 (31.5-84.5) 19 (3-67) 0.085 ENDO absence of BIP dense scar 11.8 44.4 0.060 ENDO BIP scar density 0.36 (0.23-0.40) 0.11 (0.00-0.29) 0.006 ENDO Unipolar scar area (cm2) 127 (71.5-147.5) 85 (26.5-136.5) 0.22 ENDO Penumbra area (cm2) 45 (31.2-77.5) 52 (14.5-100) 0.71 ENDO LP area (cm2) 17.5 (12.5-27.7) 8 (4-20.2) 0.122 ENDO LPs (%) 94.1 44.4 0.004 EPI BIP dense scar area (cm2) 18 (5-53) 1 (0-12.5) 0.008 EPI BIP low voltage area (cm2) 45 (23-94.5) 14 (0-27.5) 0.011 EPI BIP scar density 0.19 (0.11-0.34) 0.07 (0.00-0.22) 0.034 EPI Unipolar scar area (cm2) 99 (53.5-141.5) 20 (6-67.5) 0.001 EPI Penumbra area (cm2) 32 (27-54.5) 7 (0-40) 0.085 ENDO Ablation area (cm2) 25 (14-35) 22.6±16.3 0.63 ENDO Ablation time (min) 26.4±20 31.6±9 0.47 EPI Ablation area (cm2) 10 (5.5-21) 0 (0-4.5) <0.001 EPI Ablation time (min) 11 (6-22.5) 0 (0-5) 0.001

LPs=Late potentials, LV=Left ventricular, VT=Ventricular tachycardia, ENDO=endocardial, BIP=bipolar, EPI=epicardial

Electroanatomical dataENDO surface area (cm2) 252.1±70 211.0±47 0.0.0.1313130 00ENDO points 356.6±186 337.7±131 0.79 ENNNDODODO LLLVVV vovovollulumememe (((cm3) 280.8±8±8±10002 2222225.5 4±78 0.170 ENENENDDDO BIP densesese sscccar r ararareaeaa (((cmcmm2))) 333333 (11-552)2 5 5 5 (0(0( -21.1.1.5)5)5) 0.0.0.0000009 ENENE DDDO BIP low voooltttage arrrea (ccmmm2) 5555 ((331.55-8884.4 5))) 11919 (33--6677) 0.008085 ENNNDODODO aabsbsenenncecece off f BBBIP dddennnse scccarara r 111 ..8 444 .4.44 0..0060600 ENDO BIIIPPP scar dddenee sitytyy 0.36366 (0.0.0.232323-0-0- .40)) 0.11 (0( .0.0.00-0...2922 ) 0.006 ENDO UnUnUniiipopopolaaarr r scscscararar ararareaeaea (((cmcmcm222))) 12122777 (7(71.1.555-1-1-1474747.5.55))) 858585 (((262626.5.5.5-1-1-1363636.5.5.5) ) ) 0.22ENENENDODODO PPPenenumumbbrbraa arareaea (((cmcm222))) 454545 (((313131 22.2 77-7777.5)5)5) 525252 (((141414 55.5 11-1000000))) 000.717171



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Table 3: Presentation characteristics according to infarct site

Anterior (n=36) Inferior (n=64)

Background pMales, % 91.7 98.4 0.097Age 68±8.4 71.8±7.5 0.021LV ejection fraction (%) 29.8±9.1 33.7±9.6 0.049Chronic renal disease % 52.8 35.9 0.101Atrial fibrillation % 27.8 43.8 0.113LV aneurysm (%) 38.9 10.9 <0.001Revascularisation (%)None 25 31.3 0.69CABG 19.4 25PCI 44.4 32.8CABG & PCI 11.1 10.9Implantable Cardioverter Defibrillator (%)None 8.3 6.3 0.060Single chamber 22.2 25Dual chamber 27.8 50Cardiac Resynchronization Therapy-Defibrillator 41.7 18.8Presentation (%)Electrical storm current 11.1 18.8 0.31Electrical storm history 38.9 32.8 0.54Incessant VT 19.4 10.1 0.23Shocks 41.7 48.4 0.51Symptomatic VT 27.8 21.9 0.50Procedural dataEpicardial 27.8 25 0.76Procedure time (min) 233.9±84.6 228.8±67.9 0.74VTs in procedure ( ) 2 (1-3) 2 (1-3) 0.65Non-tolerated VT 41.7 37.1 0.65Electroanatomical dataENDO surface area (cm2) 255.5±60 225.2±53.8 0.012ENDO points 365.1±162.8 399.2±169.4 0.33ENDO LV volume (cm3) 285.0±89.3 226.2±75 0.001ENDO BIP dense scar area (cm2) 20 (2.2-58) 16.5 (5.2-32.7) 0.44ENDO BIP low voltage area (cm2) 60 (23.2-102.7) 47 (24.2-60.7) 0.07ENDO Unipolar scar area (cm2) 132 (99-176.5) 87.5 (64.2-126.7) <0.001ENDO LPs (%) 58.3 70.3 0.22ENDO LP area (cm2) 15 (7.5-21) 16.5 (8.5-27) 0.44Epicardial LPs (%) 60 68.8 0.64ENDO Ablation area (cm2) 24.5±14.6 22.4±11.7 0.43ENDO Ablation time (min) 27.3±15.1 27.1±13.6 0.93

LV=Left ventricular, CABG=Coronary artery bypass grafting, PCI=Percutaneous Coronary Intervention,VT=Ventricular tachycardia, ENDO=endocardial, BIP=bipolar, LPs=Late potentials

None 8.3 6.3 0.0.0.0606060Single chamber 22.2 25Dual chamber 27.8 50Cardiacacc RRResese ynynynchc rororoninn zation Therapy-Defibrillator 41.7 18.8Prrresesseeentationnn (((%))EEEleccctrical storm cucuurrrrenntt 1111..1.1 18.8.8.8 0.31313ElEEleccctrical storm hiistttory 3888..999 32322.88 0.5554ncececessssssanaa t VTTT 11919.4.4. 10.1.1.1 0.22323

Shocksksks 41411 77.7 484848.44 0.00 515151Symptomamamattitic c c VTVTVT 272727.8.8.8 212121.9.99 0.50Procedurralall dddatattaaEEpicardial 27 8 25 0 76



DOI: 10.1161/CIRCEP.114.002551

25

Figure Legends:

Figure 1: Anteroposterior view of a large anteroapical epicardial (A) and endocardial (B) bipolar

scar (in panels A,B red color is dense scar, purple is normal and the yellow-green area is low

voltage). A large endocardial dense scar predicts the presence of epicardial dense scar and areas

of late potentials epicardially (C,D) and endocardially (E,F) (in panels C-F red color is within

QRS electrogram and purple is late potential) . Isolated late potentials are more often found in

the epicardium (D) and fractionated late potentials in the endocardium (F). The remap (G-J)

verifies successful late potentials abolition epicardially (H) and endocardially (J).

Figure 2: Based on ROC curve analyses, endocardial bipolar dense scar (DS) area predicted the

epicardial presence of both DS and late potentials (LPs) with optimal values of 22.5 cm2

(sensitivity 61.1% and specificity 87.5%) and 7 cm2 (sensitivity 88.2% and specificity 66.7%),

respectively.

Figure 3: Dense scar was the predominant bipolar voltage type in 14.3% and late potentials in

10% of the endocardial segments. In the 17-segment shell, dense scar is distributed more often in

the inferoseptal and inferolateral segments while a shift in the distribution of LPs is observed in

the inferolateral segments.

Figure 4: Dense scar is also distributed in septal segments in either anterior or inferolateral

infarcts. However, late potentials are located in non-septal segments of the endocardial shell

possibly due to the latency of normal activation in the lateral compared to the septal wall.

Figuree 2: Basa edd oon ROC curve analyses, endocarddiaial bipolar dense scarr (D(D( S) area predicted the

epeppicccardial preeeseeencncnceee ofofof bbbototothh h fff DSDSS anananddd lalal tetete pppotttenenentititials (LLLPs))) wiwiwiththth ooptpttimimimalalal vvvalalalueueu s ofofof 222222 5.5.5 ccmmm2

sssenenensiss tivity 61.1 1%%% anddd ssppeciffficcicity 87.7.7 5%%%))) andd 77 cmmm22 (senenensisitiiiviiity 8888.2% aaandd ssspepepecificiiitytyy 666.6.7%))),

espectivevevelylyly.











SUPPLEMENTAL MATERIAL

Supplementary table 1. Comparison of the presentation characteristics between the enrolled

and the excluded study population.

Overall

Population

(N=160)

Study

Population

(n=100)

Excluded

Population

(n=60) P

Background

Male Gender (%) 96 96 97 1.00

Age, yrs 70±8.1 70.5±8.1 69.1±8.1 0.30

LV ejectrion fraction (%) 32.1±9.5 32.3±9.6 31.6±9.4 0.65

Hypertension (%) 73 75 70 0.49

Diabetes (%) 23 23 22 0.84

Stroke (%) 7 7 7 1.00

Peripheral disease (%) 23 22 23 0.84

Pulmonary disease (%) 14 10 20 0.075

Thyroid disease (%) 34 28 43 0.047

Chronic renal disease (%) 39 42 35 0.40

Valvular heart disease (%) 43 40 47 0.40

Atrial fibrillation (%) 41 38 47 0.28

LV aneurysm (%) 24 21 30 0.199

LV aneurysmectomy (%) 4 2 7 0.198

Prior amiodarone (%) 68 66 70 0.60

Admission amiodarone (%) 7 38 35 0.70

Revascularisation (%)

None 27 29 23 0.58

CABG 23 23 23

PCI 36 37 35

CABG & PCI 14 11 18

New York Heart Association Class (%)

I 17 18 15 0.58

II 45 48 40

III 31 28 37

IV 7 6 8

Coronary vessel disease (%)

Single 31 30 32 0.43

Double 25 29 20

Triple 44 41 48

Implantable Cardioverter Defibrillator (%)

None 6 7 5 0.86

Single chamber 23 24 22

Dual chamber 44 42 48

CRT-D 26 27 25

Presentation (%)

0.96

Shocks 46 46 45

Electrical storm 16 16 17

Incessant VT 14 14 15

Symptomatic VT 24 24 23

LV=Left ventricular, CABG=Coronary artery bypass grafting, PCI=Percutaneous Coronary

Intervention , CRT-D=Cardiac Resynchronization Therapy-Defibrillator, VT=Ventricular

tachycardia

Supplementary table 2. Presentation characteristics according to endocardial LP presence or not.

Endocardial presence

of LPs (n=66)

Endocardial absence

of LPs (n=34)

Background P

Males, % 93.9 100 0.14

Age 71.3±7.4 68.8±9.0 0.15

LV aneurysm (%) 23.5 22.2 0.94

QRS duration (ms) 163.4±36.9 162.3±39.6 0.94

Chronic renal disease (%) 45.5 35.3 0.32

Atrial fibrillation (%) 33.3 47.1 0.18

Admission amiodarone (%) 43.9 26.5 0.08

Revascularisation %

None 30.3 26.5 0.68

CABG 25.8 17.6

PCI 33.3 44.1

CABG & PCI 10.6 11.8

New York Heart Association Class (%)

I 15.2 23.5 0.13

II 54.5 35.3

III 27.3 29.4

IV 3 11.8

Coronary vessel disease (%)

Single 32.8 20.6 0.28

Double 31.3 26.5

Triple 35.9 52.9

Presentation (%)

Electrical storm current 18.2 11.8 0.40

Electrical storm history 37.9 29.4 0.40

Incessant VT 16.7 8.8 0.28

Shocks 45.5 47.1 0.87

Symptomatic VT 19.7 32.4 0.16

CABG=Coronary artery bypass grafting, PCI=Percutaneous Coronary Intervention , CRT-

D=Cardiac Resynchronization Therapy-Defibrillator, VT=Ventricular tachycardia

Mazzone, Nicola Trevisi and Paolo Della BellaAndrea Radinovic, Manuela Cireddu, Simone Sala, Simone Gulletta, Gabriele Paglino, Patrizio

Mizuno, Caterina Bisceglia, Pasquale Vergara, Alessandra Marzi, Nicoleta Sora, Fabrizio Guarracini, Dimitris Tsiachris, John Silberbauer, Giuseppe Maccabelli, Teresa Oloriz, Francesca Baratto, Hiroya

Potentials AbolitionUndergoing Ventricular Tachycardia Ablation: A Pragmatic Approach Favoring Late Electroanatomical Voltage and Morphology Characteristics in Post-Infarction Patients

Print ISSN: 1941-3149. Online ISSN: 1941-3084 Copyright © 2015 American Heart Association, Inc. All rights reserved.

Dallas, TX 75231is published by the American Heart Association, 7272 Greenville Avenue,Circulation: Arrhythmia and Electrophysiology

published online May 28, 2015;Circ Arrhythm Electrophysiol.

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Electroanatomical Voltage and Morphology Characteristics in Post-Infarction Patients Undergoing Ventricular Tachycardia Ablation: A Pragmatic Approach Favoring Late Potentials Abolition