use of a novel endoscopic catheter for direct visualization and

DOI: 10.1161/CIRCULATIONAHA.112.112540

1

Use of a Novel Endoscopic Catheter for Direct Visualization and Ablation in

an Ovine Model of Chronic Myocardial Infarction

Running title: Betensky et al.; Direct Visualization Catheter

Brian P. Betensky, MD; Miguel Jauregui, MD; Bieito Campos, MD; John Michele, BS;

Francis E. Marchlinski, MD; Leslie Oley, MS; Bryan Wylie, MS; David Robinson, BS;

Edward P. Gerstenfeld, MS, MD

Section of Cardiac Electrophysiology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia PA

Correspondence:


University of California, San Francisco

500 Parnassus Avenue

MU-East 4, Box 1354

San Francisco, CA 94143

Tel: 415-476-5706

Fax: 415-476-6260

E-mail: [email protected]

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

Francis E. Marchlinski, MD; Leslie Oley, MS; Bryan Wylie, MS; David Robibinssonon, , BSBS;;


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Abstract:

Background - Defining the arrhythmogenic substrate is essential for successful ablation of scar-

related ventricular tachycardia (VT). The visual characteristics of endocardial ischemic scar

have not been described in vivo. The goal of this study was to 1) quantify the visual

characteristics of normal tissue, scar border zone and dense scar in vivo using a novel endoscopic

catheter that allows direct endocardial visualization and 2) correlate visual attributes of

myocardial scar with bipolar voltage.

Methods and Results - Percutaneous transient balloon occlusion (150mins) of the mid-LAD

coronary artery was performed in an ovine model. Animals were survived for 41.5±0.7 days.

Detailed bipolar voltage maps of the left ventricle were acquired using NavX. Video snapshots

of the endocardium were acquired at sites distributed throughout the left ventricle. Visual tissue

characteristics of normal (>1.5mV), border (0.5-1.5mV) and dense scar (<0.5mV) were

quantified using image processing. Radiofrequency (RF) lesions (10-20W, 30secs) were

delivered under direct visualization. Mean white-threshold pixel area was lowest in normal tissue

(189,969 ± 41,478pixels2), intermediate in scar border zone (255,979 ± 36,016pixels2) and

highest in dense scar (324,452 ± 30,152pixels2, p<0.0001 for all pairwise comparisons). Tissue

"whiteness", characteristic of scar, was inversely correlated with bipolar voltage (p<0.0001).

During RF lesions, there was a significant increase in white-thresholded pixel area of the visual

field after ablation (average increase 85,381 ± 52,618 pixels2; P<0.001).

Conclusions - Visual characteristics of chronic infarct scar in vivo using a novel endoscopic

catheter correlate with bipolar electrogram voltage. Irrigated RF lesions in normal endocardial

tissue and post-infarction zone can be visualized and quantified using image processing. This

technology shows promise for visually based delivery of RF lesions for the treatment of scar-

based VT.

Key words: ablation; animal model; catheter ablation; myocardial infarction; ventricular tachycardia

Introduction

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characteristics of normal (>1.5mV), border (0.5-1.5mV) and dense scar (<0.5mVVV)) weww rerere

quantified using image processing. Radiofrequency (RF) lesions (10-20W, 30secs) were

delivered under direct visualization. Mean white-threshold pixel area was lowest in normal tissue

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Mapping of poorly tolerated ventricular tachycardia (VT) combines reconstruction of cardiac

anatomy and scar using electroanatomic voltage mapping (EAM) and pacemapping to locate VT

exit sites.1-2 Ablative therapy uses an anatomic approach of lesion delivery in a linear fashion

through the infarct border zone and may include ablation of late and fractionated potentials

presumed to represent zones of slow conduction capable of sustaining VT.3-6 Despite the advent

of these “substrate modification” techniques that allow ablation of VT that is not tolerated

hemodynamically, the long-term result of VT ablation remains suboptimal. In the recent

randomized VTACH study, the 2-year success rate after ablation of VT in patients with ischemic

cardiomyopathy was 47%.7 In addition to an evolving substrate, some of the limitations of

substrate-based ablation include indirect localization of myocardial scar using voltage mapping,

poor catheter-myocardial contact during radiofrequency (RF) delivery, difficulty delivering

contiguous lesions and challenges in achieving adequate lesion depth in dense scar.

Given the largely anatomic approach to ablation of poorly tolerated VT in many centers,

direct visualization of the myocardium may offer advantages to the indirect visualization offered

by current EAM systems. These advantages include direct visualization of infarct heterogeneity

and location, catheter stability, lesion development and lesion contiguity. A novel endoscopic

catheter (IRIS Cardiac Ablation Catheter, Voyage Medical Inc., Redwood City, CA) allows

direct visualization of endocardial tissue during mapping and delivery of irrigated

radiofrequency ablation. Using this catheter in an ovine model of myocardial infarction, we

hypothesized that 1) we could quantify and differentiate the visual characteristics of normal

endocardium, infarct border zone and dense scar; 2) scar characteristics defined by visual

assessment would correlate with bipolar voltage recorded from the catheter tip, and 3) we could

visualize and quantify ablative lesions delivered to normal tissue, infarct border zone and scar.

ubstrate-based ablation include indirect localization of myocardial scar using vooolltltagaga ee mamamappppppiniing,g,

poor catheter-myocardial contact during radiofrequency (RF) delivery, difficulty delivering

coontntntigigiguououoususus llleeesioonsnsns aand challenges in achieving aaadeded qquate lesion ddepepe th iiinn n ddense scar.

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We also assessed the size of ablative lesions delivered with this novel catheter at different power

settings.

Methods

Study design

The study was performed in ovine following creation of a myocardial infarction using transient

balloon occlusion of the left anterior descending coronary artery. This study was approved by the

University of Pennsylvania Institutional Animal Care and Use Committee and was performed

within ULAR institutional guidelines.

Catheter Description

The IRIS catheter is designed for visualization of anatomical structures within the heart, cardiac

mapping, and delivery of RF energy to myocardial tissue for the treatment of cardiac

arrhythmias. The catheter is an open irrigation, direct visualization catheter consisting of a

steerable 12.5 Fr catheter with a distal self-expanding flexible hood (6.8mm), open aperture in

the center of the hood face (3mm), and an integrated high-resolution flexible fiberscope and

illumination bundle (Figure 1). The catheter has 4 electrodes (2 mm inter-electrode bipolar

spacing) on the hood surface and an additional 8 electrodes on the outside of the hood to allow

for localization of the catheter using an impedance-based mapping system. With the hood in

contact with the endocardium, a constant saline flush (5-10cc/min) is used to keep the hood free

of blood and allows for direct visualization of the endocardial surface. The video images are

displayed on a monitor in the lab and recorded by an external system for digital archive and

review. Brightness settings and camera focus were calibrated at the start of each experiment to

optimize tissue clarity. The catheter handle contains a steering device that combines a primary

Catheter Description

The IRIS catheter is designed for visualization of anatomical structures within the heart, cardiac

mapppppinining,g,g, aaandndd delelliviviveery of RF energy to myocardidialalal ttissue for the treatmtmmenenent of cardiac

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unidirectional curve of up to 180 degrees with a 4-way steering mechanism that allows for fine

movements of the catheter tip in 3 dimensions.

The hood contains a 2.7 mm electrode; when radiofrequency energy is delivered to the

electrode, the saline serves as a medium to conduct current to the tissue, i.e. a “virtual” RF

electrode. This allows irrigated ablation from the 6.8mm diameter catheter hood without direct

electrode contact with the endocardium, with the effective “electrode” area being the 3mm hood

aperture. During ablation, saline irrigation is maintained at up to 25cc/minute using an irrigation

pump.

Myocardial Infarction Protocol

All animals were placed under general anesthesia. After induction with ketamine and

buprenorphine, all animals were intubated and placed under general anesthesia with inhaled

isoflurane 1-2% and mechanically ventilated. Vascular access was obtained through the femoral

artery and vein using standard hemostatic sheaths. Temperature was maintained at > 37 degrees

Celsius using a warming blanket and warmed saline. An intracardiac echo catheter (AcuNav,

Siemens Medical, Mountain View, CA) was used to visualize the left ventricle during infarct

creation. A quadripolar pacing catheter was advanced to the right ventricular apex in case pacing

was needed. Each sheep received lidocaine (50mg IV bolus) followed by a continuous infusion

at 1mg/minute. The left main coronary artery was engaged with a hockey-stick guide sheath and

a coronary angiogram was performed using iopamidol contrast media. An appropriately sized

angioplasty balloon (2.5-3mm diameter x 10-20mm length) was advanced just distal to the

second diagonal branch and inflated for 150 minutes. The mean arterial pressure was maintained

>70mmHg throughout the infarction using an IV neosynephrine drip titrated to effect. At the end

of the procedure, all hemostatic sheaths were removed and the sheep was extubated and

All animals were placed under general anesthesia. After induction with ketaminee annndd

buprenorphine, all animals were intubated and placed under general anesthesia with inhaled

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recovered.

Endocardial Mapping

After 4-6 weeks survival, sheep were taken back to the catheterization lab and intubated under

general anesthesia, with intravenous and arterial access as described above. A coronary sinus

catheter was placed at the start of each experiment and used a NavX reference for geometry

reconstruction (Figure 2). An intracardiac echocardiography catheter was used in all cases for

guiding transseptal access and infarct visualization (Figure 2). A heparin bolus of 10,000 units

was administered and repeat boluses were given throughout the procedure to maintain an ACT >

250 seconds. Transseptal puncture was performed with a standard 8 Fr sheath and then changed

over a wire to a custom 14 Fr fixed, 110 degree curve sheath (Voyage Medical Inc., Redwood

City, CA) in order to access the left ventricle. After initial mapping was performed, the

intracardiac echocardiography catheter was exchanged for a right ventricular quadripolar pacing

catheter positioned at the RV apex, in order to perform programmed electrical stimulation.

The eight electrodes located on the hood exterior allowed catheter tip localization with

the NavX mapping system (St Jude Medical, Minnetonka, MN), and the 4 electrodes on the IRIS

hood were used to simultaneously record bipolar voltage. A left ventricular geometry was

created and then a detailed bipolar voltage map was superimposed on the LV geometry (Figure

2). Dense scar (<0.5mV), border zone (0.5-1.5mV) and healthy tissue (>1.5mV) were defined

using previously described voltage cutoffs.4, 8 Individual recording sites were distributed

throughout the LV at points of stable apposition of the catheter hood with the myocardium. At

each site a video image was captured and the location was tagged and electrograms recorded on

the NavX system for offline analysis. Mean bipolar electrogram voltage was calculated by

averaging the 4 bipolar electrode pairs (1,2; 2,3; 3,4; 4,1) on the catheter tip and was correlated

over a wire to a custom 14 Fr fixed, 110 degree curve sheath (Voyage Medical IInnnc.,,, RRRedededwowowoodood

City, CA) in order to access the left ventricle. After initial mapping was performed, the

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with the simultaneous visual snapshot of the myocardium at each site (Figure 3).

Image Processing

Video snapshots of each region were acquired off-line using Corel VisualStudio 12. Bitmap

images were imported into the Fiji Package for ImageJ, an open source Java-based image

processing application developed by the National Institutes of Health.9 Individual color images

were contrast enhanced and color thresholded to best approximate red-white tissue borders.

Thresholding parameters were pre-set to "default" mode with an “HSB” color space. Saturation

and brightness were initially fixed at 0-255. Hue was the first parameter assessed by setting the

color range to 0-15. The upper limit was then decreased in a stepwise fashion until "red" regions

appeared to breakthrough between the "black" regions and the "white" regions. Once this was

established, the saturation parameter was adjusted to avoid counting the 4 white electrodes. The

image was then converted to 8-bit format for particle analysis. Images were analyzed in a

random chronologic order. Pixel measurement settings were standardized for ensuring consistent

particle analysis measurements. All images with blood in view were excluded, as to not falsely

affect tissue whiteness.

Radiofrequency Lesion Delivery

Following completion of geometric and voltage data acquisition, a series of radiofrequency

lesions were delivered to regions of healthy, border and dense scar tissue for 30 seconds each at

powers of 10 Watts, 15 Watts and 20 Watts. During RF energy delivery irrigation was

maintained at 25cc/minute. Constant power delivery was maintained for each lesion; no attempt

was made to titrate power delivery based on visual findings in order to determine histopathologic

correlation to the different power settings. Local bipolar electrograms were recorded before and

immediately after RF delivery. The time to tissue blanching (TTB), defined as the time until the

appeared to breakthrough between the "black" regions and the "white" regions. OOOncncnce thththisisis wwwasas

established, the saturation parameter was adjusted to avoid counting the 4 white electrodes. The

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field of view through the central 6mm aperture was completely white, was recorded by 2

independent observers. It was hypothesized that this measure, reflective of scar formation during

ablation, would differ among normal myocardium, border zone and dense scar.10-11

Gross Anatomy and Histopathology

At the conclusion of the mapping and lesion study, while under a deep plane of anesthesia, sheep

were euthanized and the hearts were explanted. The hearts were then incised posteriorly to

provide a postero-anterior view of the endocardial surface. Scar distribution and RF lesions were

visually inspected and then marked using colored sutures to denote power delivery for each

lesion. The hearts were then immersed in 10% buffered formalin. Following fixation, the RF

lesions were identified, grossly trimmed and the width and depth of each lesion was measured

with a hand caliper. Trimmed sections were embedded in paraffin, cut 4mm thick and stained

with Masson’s trichrome (Histo Tec Laboratory, Hayward, CA). Histology slides were evaluated

with a light microscope and histopathologic findings were recorded.

Statistical analysis

To accommodate the repeated measurements on each animal, linear mixed models were used to

compare tissue types and assess the association of tissue whiteness and voltage. Pairwise

comparisons between groups were corrected for multiple testing using the Sidak method. The

Kenward-Roger approximation was used to account for small sample sizes and sensitivity to the

assumed variance-covariance structure was checked using robust standard errors. Voltage was

log transformed to linearize the relationship to whiteness. The significance of the overall tissue

whiteness change from before to after ablation as well as lesion width and depth were also

assessed using mixed model analyses as described above. The analysis included terms for tissue

type, power and their interaction. Analyses were performed using SPSSv16.0 statistical software

esions were identified, grossly trimmed and the width and depth of each lesion wwwas ss mememeasasasururureeded d

with a hand caliper. Trimmed sections were embedded in paraffin, cut 4mm thick and stained

wiwiththh MMMasassososon’n’n’s trtrricicichhrome (Histo Tec Laboratory,y,y HHaayward, CA). HHHistotoololologgy slides were evaluated

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(SPSS, Chicago, Illinois) and SASv9.2 (SAS Institute, Cary, North Carolina).

Results

Eight male Hunter-Dorset sheep were included in this study. Animals were survived for a mean

of 41.5±0.7 days after infarct creation. Detailed bipolar endocardial voltage maps were acquired

in each animal. In the 8 animals, visual images and mean bipolar voltage were examined and

compared at 148 sites: normal tissue (n=75), border zone (n=49) and dense scar (n=24). At an

additional 60 sites (normal=32, border=20, dense scar=8) bipolar voltage and image analysis

were performed before and after RF ablation.

Visual Characterization of Tissue Types

Visually, there were clear differences among the tissue types under direct visualization, with

healthy myocardium appearing pink/red, dense infarct white, and infarct border zone with

red/white intermingled fibers (Figure 3). These qualitative findings were quantified by counting

the “whiteness” of each visual field after white-thresholding. The mean white-thresholded pixel

area (range 97,569 - 398,002 pixels2) was significantly different among healthy endocardium,

border zone and dense scar (Figure 4A, p<0.0001 for all pairwise comparisons). Mean peak-to-

peak bipolar voltage (range 0.16-19.64mV) was inversely correlated with mean white-

thresholded pixel area. With each doubling of voltage, white-thresholded pixel area was

estimated to decrease by about 62,100 pixels (p<0.001) (Figure 4B).

Visual Characterization of Radiofrequency Lesions

Delivery of RF lesions (n=60) were visualized in real-time using the IRIS catheter (Figure 5). RF

lesions were marked by an initial quiescent period, followed by marked, rapid tissue whitening

starting at the center of the visual field and radiating outward. Small micro-bubbles could be seen

developing during higher power energy delivery. At the highest power (20W), a nonaudible

Visual Characterization of Tissue Types

Visually, there were clear differences among the tissue types under direct visualization, with

healalththhy y y mymymyococcara dididiumumu appearing pink/red, dense ininnfafafarct white, and infaarcrcrctt t border zone with

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steam “pop” was observed only once during RF delivery. Microbubbles were visualized and

increased in volume prior to the steam pop occurring. Endocardial coagulum or thrombi were

not observed during ablation. After each lesion was delivered, the catheter could be navigated

around the lesion borders, which were clearly demarcated in vivo. Each lesion was delivered

individually, separate from the others to allow for later histological analysis of lesion size. There

was a significant increase in white-thresholded pixel area of the visual field both within each

tissue type (P<0.001 for each type) and overall (average increase 85,381 ± 52,618 pixels2;

P<0.001) after ablation. Visually, even lesions appearing in dense scar were readily apparent.

Despite subjective appearance of more robust visual field whitening during the highest

power (20W lesions), the TTB was not significantly correlated with tissue type when all lesions

were grouped together (dense scar 16.3±10.4 vs. border zone 12.6±7.0 vs. normal 14.7±4.8 secs,

p=0.339).

Histopathology of the left ventricle and RF lesions

Sections of the ventricle had large regions of chronic infarct scar tissue, as well as regions that

had acute coagulative necrosis of the myocardial fibers. The scar tissue (infarct) as represented

by regions of fibrous connective tissues mixed with a collagenous matrix. Zones of persisting

normal myocardial fibers were interspersed within the chronic scar. The acute ablation foci were

well demarcated, consisting of swollen and dark myocardial fibers with loss of cellular detail

along with interstitial edema and congestion/hemorrhage (Figure 6). Ablation lesions were

either individually localized separated by zones of healthy myocardial tissue or adjacent to and

within infarct scars. In the latter case, RF application targeted the surviving myocardial fibers

still persisting in previously infarcted tissue. These isolated sheets of myofibers sustained

complete thermal necrosis (Figure 6).

power (20W lesions), the TTB was not significantly correlated with tissue type wwhwhenene aalllll lllesesesioioionsn

were grouped together (dense scar 16.3±10.4 vs. border zone 12.6±7.0 vs. normal 14.7±4.8 secs,

p==0.0.0.3333339)9)9).

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Of the 62 lesions delivered, 45 lesions were identified during histopathologic

examination. Sizeable lesions were achieved across all tissue types (width 6.5±2.0mm, range

2.0-16.0mm; depth 5.2±1.9mm, range 2-10mm). Lesion width (10W vs 15W vs. 20W adjusted

mean ± SEM; 5.2±0.8mm vs. 6.1±0.6mm vs. 8.1±0.6; p=0.01) and depth (2.9±0.7 vs.5.4±0.6mm

vs. 5.8±0.6mm, p=0.0003) increased with increasing power (Figure 7).

Discussion

We found that a novel endoscopic catheter allows real-time visualization of the left ventricular

endocardium during mapping and irrigated radiofrequency ablation. Direct visualization allowed

the operator to differentiate among electrogram-defined dense scar, border zone and normal

tissue in an ovine model of chronic myocardial infarction. The difference in tissue characteristics

among these regions was readily apparent visually, and these visual findings could be quantified

using image processing demonstrating a direct inverse correlation between visual field

“whiteness” and bipolar electrogram voltage. Direct visualization was also performed during

irrigated RF ablation, with qualitative and quantitative whitening of the visual field occurring

during ablation. RF lesion visualization was most pronounced in normal tissue, but also readily

apparent in dense scar. Microbubble formation was rarely seen at higher powers, and in one case

presaged a steam pop.

These findings introduce a new paradigm in catheter ablation. Initially, catheter ablation

was guided indirectly by fluoroscopy and electrograms recorded from the electrode tip. The

advent of electroanatomic mapping allowed one to construct a virtual geometry, and with

computed tomographic or magnetic resonance image registration, an indirect representation of

the cardiac chamber anatomy and catheter location.12-15 Intracardiac ultrasound provided the

first real time feedback of anatomy during ablation, however the anatomic rendering was limited

he operator to differentiate among electrogram-defined dense scar, border zonee aaandndnd nnnororormamamal l ld

issue in an ovine model of chronic myocardial infarction. The difference in tissue characteristics

amonongg g thththesesesee rer gigiiononons s was readily apparent visuaalllllyy,y, and these visual fifindndndinii gs could be quantified

uususinnng g imagee prproococeesssisiinngng dddemememonononstststrarar tititingngng aa ddiririrecece tt ini veveverrse e cococorrrrrrelelelatatioioion n bebebetwtwtweeeen vivivisususualalal fffieiei lllddd

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by the resolution and field of view of ultrasound.16-19 Now, direct visualization of the endocardial

surface is feasible during mapping and ablation. This has many important implications. Many

arrhythmias are targeted using a combination of electrical and anatomic information, including

atrial fibrillation, atrial flutter, papillary muscle VT and VT in ischemic cardiomyopathy.

Ablation of VT that is poorly tolerated hemodynamically is performed using a combination of

pacemapping and linear ablation through the scar border zone. Some have advocated scar

“homogenization”, with ablation of all portions of electrically active scar or late potentials that

might harbor future VT circuits. The IRIS endoscopic catheter can be used to rapidly construct a

voltage map that identifies the location of scar and border zone. Ablation can then be performed

through regions of border zone with direct visual confirmation. In addition, ablation of other

areas of presumably viable tissue throughout the scar can be performed empirically.

There may be other advantages to direct visualization during ablation. Visualization

ensures catheter contact during ablation, since one cannot visualize the endocardium until

contact is achieved and the saline flush clears blood from the field of view. This will likely

enhance the depth and consistency of ablative lesions. Furthermore, tissue blanching during

radiofrequency delivery actually confirms the tissue has reached an adequate temperature for

irreversible thermal necrosis. It has been previously demonstrated that tissue optical properties

change as the tissue is heated based on increased light scattering from denatured proteins and

changes to mitochondria (what we observe as “blanching”). These visual/optical changes have

been found to occur in the 50-60oC range.10-11, 20-21

Visual feedback during ablation also may prevent complications via early visualization of

thrombus and avoidance of steam pops due to downward titration of power when aggressive

micro-bubbles appear. Linear, contiguous lesions may also be assured by visually connecting

hrough regions of border zone with direct visual confirmation. In addition, ablaatitiionnn oof f f otototheheher r r

areas of presumably viable tissue throughout the scar can be performed empirically.

ThThThererere e mamaayy y beb other advantages to direct vvivissuualization duririingnn aablblblaatation. Visualization

ennsuuurer s cathetterer coonontatatactct ddduruurininnggg ababblalalatitioonn, sinncceee onee ccannnnnootot vvvisssuaualliizzee tthehehe eendndocococarardidiiumumum uuntntililil

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enhance the dededeptptpth h h ananand d d cocc nsnsnsisisstett ncncncy y y ofofo aaablblb atatativivivee e lelel sisis ononons.s FuFuFurtrtrthehehermrmrmorore,e,e, tttisisissususue e e blblanananchchchinining g g during


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individual lesions. Previous lesions can also be revisited quite easily should the catheter be

repositioned. Contact with certain challenging anatomic structures, such as the papillary muscle,

can be confirmed prior to ablation. Furthermore, ablation through the “virtual” electrode saline

irrigant may also have advantages over contact electrodes. Energy delivery is more uniform and

efficient, since the RF energy is delivered directly to the myocardium in the field of view. This is

in contrast to contact irrigated catheter ablation, where energy delivery may vary significantly

depending on catheter orientation due to the variable electrode/myocardial interface and loss of

energy to the surrounding blood pool.22 Lastly, the flat 6 mm distal hood surface is also less

likely to lead to cardiac perforation; we have never seen a perforation despite aggressive catheter

manipulation in this animal model.

Prior work

Two visualization catheters have been reported previously, including CardioFocus Endoscopic

Ablation System (CardioFocus Inc., Marlborough, Massachusetts), and the FLEXview system

(Boston Scientific Cardiac Surgery, Santa Clara, CA).23-24 CardioFocus uses a small endoscope

to allow visualization through a balloon placed in the pulmonary vein ostium. This system is

designed specifically for PV isolation and such a balloon cannot be maneuvered around a cavity

such as the left ventricle. The FLEXview system is a gastroenterology endoscopy catheter that

was adapted for use in epicardial visualization. This catheter did not have the ability for fine

mapping, recording of electrical signals, nor ablation. None of these studies addressed scar based

models of VT.

Limitations

There are several limitations to the endoscopic catheter system. Visualization requires

endocardial contact; no visualization occurs when manipulating the catheter inside the LV

manipulation in this animal model.

Prior work

Twwooo vvvisisisuauaualililizazazationonon ccatheters have been reported prprpreevviously, includddini g g CaCaCarrdioFocus Endoscopic

AAAbllalation Systeemmm (CCarardidioFoFoFocococususus IIncncnc..,., MMMaarrlbooroooughhh, MaMaasssssacachuhuhusesettttts))), anand dd tthhe e FLFLFLEXEXXviviviewewew ssyysysteetemmm

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o allow visuauaalilil zazaz tititionono ttthrhh ouuughghgh aaa bbbalallololoononn ppplalalacececed d d ininn ttthehehe ppulululmomomonananaryryry veieiein n n ososostititiumumum.. ThThThisisis sysysystem is


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cavity. We used an electroanatomic mapping system to guide catheter manipulation, localization,

and rendering of the voltage map to define the location of endocardial scar. These combined

modalities may increase the cost of the procedure, however with additional use it is likely that

the endoscopic catheter could be used without a mapping system. A large amount of saline is

given throughout these procedures, as a constant infusion is need both during mapping and

ablation. This may be reduced in future versions of the catheter.

The absolute value for tissue “whiteness” was determined offline. Further investigation

is warranted to determine whether more automated software capable of real-time, online

quantification for visual-based mapping is feasible and to establish clinical reference values for

different tissue types. Although visual blanching is the hallmark of lesion formation and

progressively deeper lesions were achieved at higher powers, a statistically significant

correlation between lesion depth and change in tissue whiteness pre/post ablation or time to

initial blanch was not observed in this study. Thus, further research is needed to develop visually

based criteria that may help to predict lesion depth. Lastly, we recognize that the optical

properties of endocardial tissue varies between cardiac chambers and that there may exist

species-specific differences in the “whiteness” of ventricular endocardium at baseline,

potentially limiting the generalizability of our results to humans with chronic myocardial

infarction.

Conclusions

A novel endoscopic catheter is capable of direct endocardial visualization during mapping and

ablation in an ovine model of chronic myocardial infarction. Using this catheter, we were able to

visualize and quantify differences in tissue characteristics among normal myocardium, border

zone, and dense scar. Irrigated RF lesions were visualized during and after ablation in both

different tissue types. Although visual blanching is the hallmark of lesion formaattitiononn aaandndnd

progressively deeper lesions were achieved at higher powers, a statistically significant

coorrrrrelelelatatatiioionnn bebebetwweeeeeenn lesion depth and change in tttiisisssuue whiteness prprpre/popooststst ablation or time to

nnittiiaial blanch wwaaas nnotot oobsbsbsererervevveddd ininn tthhihis sttuudyyy. TTThuss, furrrththherer rrreesseaearcrchh isis nnneeeededeed d d toto dddevevvelelloopop vvissisuauaually

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properties of f enenendododocacacardrddiaiaal titiissssssueueu vvvarara ieieies bebeb twtwtweeeeeen n n cacaardrdr iaiai c chchchamamambebebersrsrs aandndnd ttthahahatt t thththererre e e mamamay y y exe ist


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normal tissue and dense scar. Integration of direct visualization with current mapping techniques

may enable visually guided ablation of heterogeneous scar capable of supporting VT. This

technology shows promise for visually based delivery of contiguous RF lesions for the treatment

of scar-based VT.

Acknowledgments: We thank Dr. Narayan R. Raju, DVM, PhD, DACPV (PRL, Inc., San Bruno, CA) for performing the histopathology for the study and Dr Charles McCulloch PhD for statistical analysis.

Funding Sources: The funding for this study was provided by an investigator initiated research grant from Voyage Medical, Inc. to Dr. Gerstenfeld.

Conflict of Interest Disclosures: Dr. Marchlinski is on the scientific advisory board ofVoyage Medical Inc.Dr. Wylie is an employee of Voyage Medical Inc. Dr. Oley is an employee of Voyage Medical Inc. Dr. Robinson is an employee of Voyage Medical Inc. Dr. Gerstenfeld has an investigator initiated research grant from Voyage Medical Inc. and is on the Scientific Advisory Board of Voyage Medical Inc.

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1.1 DDeDelacretaz EE, Sttteveennssson WGWGW . CaCaC ththeeeteeer abbblaaationnn ooof vveneentrtrtriiicuulularrr taaachyycacardrdiiaia iin paaatit eenentts wwwitthhh cocoorooonann ryy heaaartrr ddiiseeeaseee: PPPartrt ii: MaMaM ppppppining.g. PaP cccinngng CCCliinn EElEleecectrtrroppphyhyysiiool. 20000101;2;2244:4:121 611--112277777.

222. JJJosososepepephshshsononon MMMEEE, WWWaxaxaxmamamannn HLHLHL, CaCaCaininin MMMEEE, GGGararardndndnererer MMMJJJ, BBBuxuxuxtototonnn AEAEAE. VeVeVentntntririricucuculalalarrr acacactititivavavatititiononon during ventrriciciculululararar eeendndndococcararrdididialala ppacaccininngg. IIIii.i RRRolololeee ofofof pppacacace-e-mammapppppinininggg totot lllocococalalalizizize ee ororigigigininin ooof ff vvev ntricular


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1333. GGeG psteinn LL, HaHaHayammm GG, BBBennn-HHaiim m SASAA. AAA nnnoveeel memethththododod fooor nnononnfluoororooscscoopopicic catattheeeteteer--bbaseeeddd ellececectrtrroaoao nanatototomimmicacaal mamam pppppinini gg oofof ttthehehe hhheaearrtrt. InInIn vvvittrororo aaanddd innn vivivivovovo aaaccccc uururacacacy y y rrressusultlts.s.s CiCiC rcrccuululattiiionnn.199797;9;955:161611-1-16222.2.

1414 KrKrumum DD GoGoelel AA HaHaucuckk JJ SSchchweweititzezerr JJ HHararee JJ AAttttararii MM DDhahalala AA CoCoololeyey RR AkAkhthtarar MM


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Figure Legends:

Figure 1. Voyage IRIS Ablation Catheter. The 12.5 Fr catheter has a flexible 6.8mm hood

(magnified view) that allows direct endocardial visualization once blood is flushed from the

hood using saline irrigation. Ablation is performed via a 2.7 mm electrode at the base of the

hood. Bipolar electrograms can be recorded using electrodes on the face of the hood.

Figure 2. Voltage Mapping. Top: NavX voltage map (0.1 – 1.5mV) of left ventricular

endocardium after percutaneous anteroseptal myocardial infarction. Purple represents normal

23. Phillips KP, Schweikert RA, Saliba WI, Themistoclakis S, Raviele A, Bonso o A,A,A, RRRosoossisisillllllooo A,A, Burkhardt JD, Cummings J, Natale A. Anatomic location of pulmonary vein elecctrtrricicicalal disconnection with balloon-based catheter ablation. J Cardiovasc Electrophysiol. 2008;19:14-18

244. . ZeZeZenananatititi MMMAAA, SSShhahalaby A, Eisenman G, Nosbissscchch JJ, McGarvey JJJ,, Ottaa a TT.T. Epicardial left veveentnttriricular mamm pppppinining g usussinini gg g susus bxbxxipipiphohoh idid vvidideoeo ppperericiccaarrdiososcococopypypy. AnAnnnn ThThororracaca SSururrggg.. 20202 0707;8;884:4:4 21212106060 -22100707.

FiFigugurere LLegegenendsds::


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endocardium. Note the heterogeneous anteroseptal scar. Bottom Left: Fluoroscopy image of

IRIS catheter in LV abutting the endocardium (red arrow). Bottom Right: Intracardiac

echocardiographic image demonstrating catheter articulation and endocardial positioning during

ablation in the inferoseptal LV (red arrow). ICE = intracardiac echocardiography; CS = coronary

sinus

Figure 3. Representative Examples of Direct Endocardial Visualization. Direct endocardial

visualization using the IRIS Cardiac Ablation Catheter in three voltage-defined tissue types and

corresponding ImageJ-thresholded images and recorded bipolar electrograms. The peak-to-peak

amplitude of the electrograms and white-thresholded pixel count of each visual field is shown.

Figure 4. Correlation of Tissue-Whiteness with Electrogram Bipolar Voltage. A. Mean white-

thresholded pixel area was significantly different between three bipolar electrogram-defined

tissue types, potentially enabling independent identification of tissue type by visual criteria

alone. B. Mean local peak-to-peak bipolar voltage was inversely correlated with visual tissue

“whiteness” (p<0.0001).

Figure 5. Sequential Real-Time Endocardial Radiofrequency Lesion Development. Examples of

stereotypical appearance of lesions created over time in the infarct border zone at 10W, 15W and

20W power delivery.

Figure 6. Lesion pathology. A: Gross image of lesions made with the IRIS catheter in a healthy

heart. The lesion was delivered at 10W for 30 seconds and measured 5.7mm in width x 3mm

amplitude of the electrograms and white-thresholded pixel count of each visual fifiieleldd d iiss sshohohownwnw ..

Fiigugugurerere 444. CoCoCorrrrellatatatioioi n of Tissue-Whiteness withh EEEleeectrogram Bippoloo ar VVVoololtage. A. Mean white-

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depth. B: Lesion histopathology: photomicrograph illustrates an ellipsoidal area of acute RF

ablation below the endocardial surface (E) leading to tissue alteration including cellular

coagulation (A) with interstitial swelling and edema. This is followed by a paler band (*) of

ablated tissue ablation separating it from a darker (^) leading edge of the acute ablation

(compacted / congestion) beyond which is a lighter zone of tissue contraction leading to healthy,

normal myocardium. C: Gross image of lesions made in an anteroseptal area of myocardial

infarction. These lesions were delivered at 10w for 30 seconds and measures 5.7mm in width and

3mm depth. D: Histopathology: ablation lesion (A) and scar border (*) leading to infarct zone

(I). Chronic scar appears pale (light blue). Normal cardiomyocytes which have undergone acute

coagulation necrosis are characterized by dark blue homogeneous bands with a lack of cellular

detail and swollen cytoplasm.

Figure 7. Lesion depth as a function of power. Mean lesion depth increased with progressively

higher delivered power (p<0.001).

coagulation necrosis are characterized by dark blue homogeneous bands with a llaaack kk ofoff ccelelellululullalar r

detail and swollen cytoplasm.

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Oley, Bryan Wylie, David Robinson and Edward P. GerstenfeldBrian P. Betensky, Miguel Jauregui, Bieito Campos, John Michele, Francis E. Marchlinski, Leslie

Chronic Myocardial InfarctionUse of a Novel Endoscopic Catheter for Direct Visualization and Ablation in an Ovine Model of

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2012 American Heart Association, Inc. All rights reserved.

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SUPPLEMENTAL MATERIAL

Movie Legend

Movie 1: Left panel: Electroanatomic voltage map of the swine left ventricle showing

catheter position on the mid-septum. Right panel: Video of the scar border zone during

radiofrequency ablation. Note the heterogeneous appearance of the scar tissue at

baseline and the whitening that occurs during ablation.

use of a novel endoscopic catheter for direct visualization and

Documents