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Visual Balloon-Guided Point-By-Point Ablation:Reliable, Reproducible, and Persistent Pulmonary Vein Isolation
Dukkipati et al.: Visually-Guided AF Ablation
Srinivas R. Dukkipati, MD1, Petr Neuzil MD, PhD2, Jan Skoda MD2, Jan Petru MD2, Andre
d’Avila, MD, PhD1, Shephal K. Doshi, MD3, Vivek Y. Reddy, MD1
1The Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New
York, 2Homolka Hospital, Prague, Czech Republic, 3Saint John’s Hospital, Santa Monica,
California
Address for correspondence:
Vivek Y. Reddy, MD
Mount Sinai Hospital
One Gustave L. Levy Place, Box 1030
New York, NY 10029
Phone: (212) 241-7114
Fax : (646) 537-9691
E-mail: [email protected]
Journal Subject Codes: [5] Arrhythmias, clinical electrophysiology, drugs; [22] Ablation/ICD/surgery
of MeMeMeMeMeMeM dididididicicicicicinenenenenenene, , , ,,,, NNNNNNN
SHospital, Prague, Czech Republic, 3Saint John’s Hospital, S
California
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ABSTRACT
Background — While conceptually straightforward, placing point-to-point contiguous
radiofrequency lesions to achieve pulmonary vein isolation (PVI) is technically challenging in
patients with paroxysmal atrial fibrillation (PAF). Furthermore, chronic efficacy is limited by
late PV reconnections. A novel compliant balloon ablation catheter (BAC) able to deliver
visually-guided short arcs/spots of laser energy was tested in initial pre-clinical and clinical cases
to determine if visual guidance could predict reliable and persistent PVI.
Methods and Results — This study consisted of i) an experimental porcine phase with both
acute (n=15 pigs) and 4-week chronic (n=10) data, and ii) a single-center clinical feasibility
phase (n=27 PAF patients), again with acute and 3-month chronic data. Under endoscopic
guidance, point-by-point peri-venous ablation was performed in a contiguous and overlapping
manner. Each porcine PV was longitudinally sectioned for detailed histological analysis. At 3-
months post-ablation, patients underwent a pre-specified remapping procedure regardless of
symptomotology. In the acute and chronic animals, 29/30 (97%) PVs were electrically isolated
after placing the initial circumferential lesion set. For the 4-week chronic animals, 80% of PVs
remained isolated; lesions were histologically circumferential in 120/120 (100%) PV sections,
and transmural in 116/120 (96.7%) PV sections (average transmurality = 99.0 5.5%). In
patients, 100% of the PVs were isolated after 1.3 attempts/PV – 84% of them (85/101) isolated
after the initial visually-guided lesion set. At 3 months, 61/68 (90%) PVs continued to be
electrically isolated.
Conclusions — Using a visually-guided, compliant balloon ablation catheter with point-by-point
ablative capability, PV isolation can be achieved in a reliable, reproducible, and persistent
manner.
Key words: Atrial Fibrillation, Catheter Ablation, Laser, Pulmonary Veins, Visual Guidance
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esions were histologically circumferential in 120/120 (100
ine PV was longitudinally sectioned for detailed histologica
n, patients underwent a pre-specified remapping procedu
n the acute and chronic animals, 29/30 (97%) PVs were ele
tial circumferential lesion set. For the l 4-week chronic anim
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INTRODUCTION
Pulmonary vein (PV) isolation is the mainstay of catheter based therapy for atrial
fibrillation (AF).1-11 However, achieving electrical PV isolation with point-by-point ablation is
technically challenging. Recently, balloon catheters utilizing multiple energy sources have been
utilized to facilitate PV isolation.12-17 While many of these balloons share similar characteristics,
the laser balloon is unique in its ability to provide real-time endoscopic visualization and to
deliver laser energy at operator-determined locations around the PV-left atrial junction.17
Although clinically promising, the first generation laser balloon ablation catheter (BAC)
was limited in its ability to deliver optimal lesions due to balloon noncompliance and the large
90o – 120o ablative arc. This translated to suboptimal balloon contact and difficulty in delivering
sufficient energy along the large ablative arc due to risk of thrombus formation from ablation at
areas with overlapping blood. Accordingly, the rate of acute PV isolation in the clinical series
was only 91% with an AF recurrence rate of 60%.Because of these limitations, the balloon was
redesigned to 1) maximize balloon-tissue contact by making a balloon of adjustable diameter and
compliance, and 2) allow the delivery of spot laser lesions. This second generation balloon was
evaluated in a two-phase study. The pre-clinical phase involved electrophysiological and
histological assessment of the lesions delivered by the balloon in a series of acute and chronic
porcine experiments. The clinical phase involved a single center evaluation in patients
undergoing catheter ablation for paroxysmal atrial fibrillation with a prespecified PV remapping
procedure at ~3 months regardless of intervening symptomatology. Thus, in addition to the
acute procedural performance of this BAC, we are also able to report on the 3-month
permanency of electrical PV isolation.
METHODS
The pre-clinical experiments were approved by the Institutional Animal Care and Use
Committees. The clinical phase was approved by the human ethics committee at Homolka
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an AF recurrence rate of 60%.Because of these limitation ,
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allow the delivery of spot laser lesions This second genera
ing blood. Accordingly, the rate of acute PV isolation in t
an AF recurrence rate of 60%.Because of these limitations,
ximize balloon-tissue contact by making a balloon of adjusta
allow the delivery of spot laser lesions This second genera by guest on May 12, 2018
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Hospital. The authors had full access to and take full responsibility for the integrity of the data.
All authors have read and agree to the manuscript as written.
Endoscopic Ablation System with Adaptive Contact (EASAC): The EASAC
(CardioFocus, Inc., Marlborough, Massachusetts) consists of the following major components:
(i) delivery sheath, (ii) balloon ablation catheter (BAC), (iii) endoscope, (iv) lesion generator,
and (v) cooling console. The delivery sheath is a deflectable 12-Fr ID sheath with the capability
of 180º deflection. The BAC (Figure 1) is a variable diameter, compliant balloon with a flexible
tip (to minimize the possibility of mechanical trauma). Contained within the balloon are
multiple lumens within the central shaft for the endoscope, lesion generator, and cooling
conduits. The balloon is constantly cooled with circulating D2O.
The BAC is positioned at the PV ostium and inflated (Figure 2A&B) to provide good
contact. A 2-Fr endoscope is located at the proximal portion of the balloon and provides real-
time visualization of the face of the balloon (Figure 2C). Regions of the balloon in contact with
blood appear red, and regions in contact with tissue blanch white. The field of view is partially
obscured in the area behind the central shaft. This partially obscured view is located 180o
opposite the radiopaque “L” marker on the balloon catheter shaft and allows positional
correlation between the fluoroscopic and the endoscopic images. The lesion generator consists
of an optical fiber within the central shaft that generates a 30o arc of light that is projected onto
regions of balloon contact. This arc serves as an aiming beam for laser delivery, and can be
easily advanced/retracted and rotated along the balloon face with endoscopic visualization. Once
an appropriate location is selected, laser energy (980 nm) is delivered through the same optical
fiber to ablate the target tissue. Multiple lesions are delivered in an overlapping manner to
achieve circumferential ablation (Figure 2D).
Pre-Clinical Phase – Ablation Procedure: After an overnight fast, 25 pigs (15 acute, 10
chronic) were induced with 1.4 mg/kg Telazol, 1.1 mg/kg acetylpromazine, and 0.05 mg/kg IM
lelesisisissis onononnn g g g g gggenenenenenenenerererererererataaataaa
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nd regions in contact with tissue blanch white The field of
positioned at the PV ostium and inflated (Figure 2A&B)
doscope is located at the proximal portion of the balloon an
f the face of the balloon (Figure 2C). Regions of the balloo
nd regions in contact with tissue blanch white The field of by guest on May 12, 2018
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atropine. The animals were intubated and ventilated with oxygen and 1.5-2.5% Isoflurane.
Femoral venous access was obtained and transseptal puncture was performed using a
Brockenbrough needle under fluoroscopic guidance. The deflectable 12-Fr sheath was advanced
into the LA over a 0.035” or 0.038” guidewire. Intravenous heparin was given as a continuous
infusion and boluses to maintain an ACT>300 sec. The deflectable sheath was positioned at the
ostium of the target PV. Contrast was injected through the sheath to assess PV anatomy and
diameter. A circular mapping catheter (Biosense-Webster, Inc., Diamond Bar, California) was
placed in the PV to evaluate electrograms at baseline and post-ablation to assess for electrical
isolation.
The BAC was delivered through the deflectable sheath and inflated at the ostium of the
target PV. The right superior (RSPV), and sometimes the left superior (LSPV), were targeted for
ablation; the decision to target a PV was based on the presence of baseline PV electrograms. The
porcine right inferior (RIPV) and left inferior (LIPV) were not targeted as PV electrograms are
rarely, if ever, present. Additionally in pigs, the esophagus is located much more posteriorly to
the LA than seen in humans, and esophageal injury is never seen. However, the course of the
right phrenic nerve is similar to humans and injury is possible during ablation. Therefore, during
ablation around the RSPV, phrenic nerve pacing was performed with a catheter placed in the
superior vena cava. Using endoscopic visualization, the aiming beam was manipulated around
the PV and laser energy was delivered in a contiguous, overlapping, and circumferential manner
to achieve PV isolation.
The dose of laser energy available for use ranged between 5.5 – 16 Watts/cm at 20-30 sec
duration per lesion. When ablation in regions with overlapping blood was required, the lowest
energy of 5.5 Watts/cm for 30 sec per lesion was used (this is based upon pre-clinical data
indicating safety despite blood overlap at this dose). To ablate the tissue located at the partially
distorted region behind the central shaft, the BAC was partially deflated, rotated, and then
reinflated to allow full visualization of this obscured region. Following circumferential ablation
PV isolation was assessed with the circular mapping catheter. If electrical breakthrough was
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n humans and esophageal injury is never seen However t
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or (RIPV) and left inferior (LIPV) were not targeted as PV
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observed, the BAC was repositioned in the PV ostium to ablate in the region of breakthrough and
achieve PV isolation. At 30 min post-ablation, PV isolation was confirmed again and PV
angiography was repeated to again assess PV diameters.
The acute animals were sacrificed and pathological examination was performed. The
chronic animals were recovered and brought back for a repeat procedure at 4 weeks to assess
PV diameters and electrical isolation by the methods described above. For these chronic
experiments, at the time of the second procedure, the animals were sacrificed and pathological
examination was performed.
Pre-Clinical Phase – Pathological Examination: The explanted heart and surrounding
tissue, were subjected to gross examination. In all animals, the LA and PVs were examined to
assess location and circumferentiality of the lesions. The LA and PVs, as well as any abnormal
tissue were fixed with 10% formalin for histological examination. The PVs were opened
longitudinally at the superior-most aspect (12 o’clock position) and sectioned (8-15 slices/PV) in
a circumferentially longitudinal pattern parallel to blood flow. The sections underwent paraffin
processing and were stained with either hematoxylin-eosin (H&E), Movat pentachrome, or
Masson’s trichrome stains. The slides were examined by light microscopy and evaluated for
thermal injury and necrosis.
Clinical Phase – Study Design. The clinical phase was a prospective, open label, non-
randomized, single center study of patients with symptomatic, recurrent, paroxysmal AF. The
inclusion criteria were: age 18-75 years, and recurrent paroxysmal atrial fibrillation that was
refractory to at least one antiarrhythmic drug (Class I – IV). All patients were otherwise deemed
to be candidates for radiofrequency catheter ablation. Key exclusion criteria included: a prior
PV isolation procedure, presence of intracardiac thrombus or spontaneous echo contrast,
myocardial infarction or cardiac surgery in the prior 3 months, moderate to severe valvular
disease, left ventricular ejection fraction <30%, LA diameter >5 cm, PV diameter >30 mm (for
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longitudinal pattern parallel to blood flow The sections un
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with 10% formalin for histological examination. The PV
superior-most aspect (12 o’clock position) and sectioned (8
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oval PVs, the mean of the PV major and minor dimension was used), or stroke/transient ischemic
attack in previous 6 months. Pre-procedural CT scans were performed to assess LA and PV
anatomy and size.
A total of 27 patients underwent ablation with the BAC. Following the procedure, all
patients were discharged on warfarin, and at times, low molecular weight heparin until the
international normalized ratio was 2.0. Following the procedure, antiarrhythmic medications
were either discontinued or reduced in dosage for 1 month after which they were completely
discontinued. There was a 1 month blanking period following ablation. All patients were
discharged with an event monitor for weekly transmissions and for recurrence of AF symptoms.
Post-procedure clinic visits were performed at 1 and 3 months. A repeat CT scan was performed
at 3 months to assess for PV stenosis. At ~3 months after the index procedure, patients were
brought back for a repeat procedure to assess for the permanency of PV isolation. This second
procedure was performed regardless of the intervening symptomatology.
Clinical Phase – Ablation and Remapping Procedures: The ablation and remapping
procedures were performed in a modified manner to the methods described for the preclinical
experiments. All procedures were performed under conscious sedation. Two transseptal
punctures were performed; one for the deflectable sheath and BAC, and the second for the
circular mapping catheter. Intracardiac echocardiography was used during the procedures to
facilitate transseptal puncture and BAC positioning. During ablation of the RSPV, pacing from
the superior vena cava was performed to minimize risk of phrenic nerve palsy. In all patients, an
esophageal temperature probe was placed to monitor esophageal heating and ablation was
stopped when the temperature reached 38.5oC. After inflation of the BAC, laser energy was
delivered around the PV ostium in a contiguous, overlapping, and circumferential manner. After
completion of a single circumferential lesion set, PV electrical isolation was assessed with the
circular mapping catheter. If breakthrough was present, further ablation with the BAC was
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ase Ablation and Remapping Procedures: The ablation
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performed at sites of electrical breakthrough. After PV isolation was achieved, it was reassessed
at 30 min post-ablation.
The remapping procedures were also performed under conscious sedation. After a
transseptal puncture, PV isolation was assessed with a circular mapping catheter. If electrical
breakthrough was identified, a second transseptal puncture was performed. Then ablation was
performed with a externally-irrigated radiofrequency ablation catheter (Celsius or Navistar
ThermoCool, Biosense-Webster, Inc., Diamond Bar, CA). All data are expressed as mean ±
standard deviation.
RESULTS
Pre-Clinical Phase – Acute Porcine Experiments: Among 15 pigs, a total of 20 PVs (15
RSPV, 5 LSPV) were targeted for ablation. The BAC conformed well to the PV ostia and antra
and provided adequate contact and visualization (Figure 2). With the initial visually-guided
placement of an overlapping circumferential ablation lesion set, 19/20 (95%) PVs were
electrically isolated. After identifying the area of electrical breakthrough using a circular
mapping catheter, the remaining PV was isolated with additional balloon laser lesions. The
mean number of ablation lesions needed to isolate each PV was 31.0±14.1 with a mean ablation
time of 24.7±11.9 min. All PVs (100%) remained electrically isolated after 30 minutes post-
ablation. The mean PV diameter change was -2.5±7.7% (limits -22.2 to +8.3%).
Gross pathological examination of the PVs revealed well-demarcated circumferential and
contiguous lesions. Interestingly, grossly visual gaps were identified in 7/20 (35%) PVs (Figure
3) despite the fact that all PVs were electrically isolated. Histological examination was
performed in 13/15 pigs (12 RSPV, 5 LSPV). The histological lesion characteristics observed
are shown in Table 1. On a per vein basis, histological acute lesion transmurality was
80.8±16.2% (limits 57.0-100%). When assessed by histological sections (n=187), the mean
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re targeted for ablation. The BAC conformed well to the PV
uate contact and visualization (Figure 2). With the initial
overlapping circumferential ablation lesion set, 19/20 (9
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transmurality was 84.6±27.8% (limits 0.0-100%). Of the PV sections, 122/187 (65.2%) had
completely transmural lesions while only 8/187 (4.3%) had no lesion. The maximal lesion depth
observed was 12.7 mm which represented a completely transmural lesion. On histological
examination, all injury was confined to the PV antra without extension into the PVs. One animal
had a lung lesion in a location directly adjacent to the PV antrum. There was no phrenic nerve
injury or thrombi seen on either the BAC or atrial tissue.
Pre-Clinical Phase – Chronic Experiments: In 10 pigs, 10 PVs (all RSPV) were
targeted for ablation. All PVs (100%) were electrically isolated on first attempt and remained
isolated 30 minutes post-ablation. Based on the finding of visual gaps in the acute animal
experiments, more overlapping lesions (30-50% overlap) were delivered in the chronic series.
When remapped after 4 weeks, 8/10 PVs (80%) were still electrically isolated. On gross
pathological examination, the lesions appeared contiguous and circumferential although they
were more difficult to discern because they had a whiter, less intense appearance than those
observed acutely (Figure 4A). On a per vein basis, the chronic mean lesion transmurality was
98.8±2.1% (limits 94.6-100%). When analyzed by histological PV sections (n=120), the mean
lesion transmurality was 99.0±5.5% (limits 59.8-100%). Complete lesion transmurality was
present in 96.7% of PV sections with lesion depths of up to 12.0 mm. The lesions were
completely circumferential without any gaps by histology. In the two animals with recovered
electrical conduction, the circular mapping catheter identified breakthrough in the
anterior/inferior portion of the RSPV. One animal was ablated using low-dose energy (5.5 W/30
sec) in this region and had a 59.8% transmural lesion (total wall thickness = 10.5 mm) in this
region by histology. The second animal had showed 100% transmural lesions in the sampled PV
sections; presumably, the area of chronic conduction gap was between the sampled slices.
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fter 4 weeks, 8/10 PVs (80%) were still electrically isol
nation, the lesions appeared contiguous and circumferentid
to discern because they had a whiter, less intense appea
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In all 10 animals, ablation lesions extended beyond the atrial wall onto the adjacent
pulmonary artery (Figure 4B) and in 6 animals there was extension of thermal injury into the
PV. Lung injury was seen in 3 animalsand there was no phrenic injury seen. The mean change
in chronic PV diameters was -2.6±19.0% (limits -33.9 to +21.7%).
Clinical Phase – Patient Demographics: The baseline patient demographics are shown
in Table 2. The mean age of the cohort was 52.7±12.6 years (limits 25-66). All patients had
paroxysmal AF with a mean duration of symptoms of 6.7±7.1 years, and 77.8% (21/27 patients)
failed 1 class I or III antiarrhythmic drug. Nine patients (33.3%) were taking warfarin, 1
(3.7%) aspirin, and 6 (22.2%) low molecular weight heparin just prior to the procedure.
Clinical Phase – Visually-Guided Ablation: There were a total of 101 PVs in 27
patients – all PVs were targeted for ablation. The variable diameter and compliant nature of the
balloon provided adequate contact for visualization (Figure 5) and made it amenable for use
with diverse PV anatomies (Supplemental Table 1, Figures 6 & Supplemental Figure 1).
With visual guidance, 84.2% (85/101) PVs were isolated with the initial visually-guided
circumferential placement of contiguous point-by-point lesions. By using the circular mapping
catheter to identify the point of electrical breakthrough, the remaining PVs were isolated; thus,
100% of PVs were ultimately isolated. The average number of attempts to isolate each vein was
1.3. All PVs remained isolated after a minimum of 30 minutes post-ablation. The mean
fluoroscopy time per patient was 17.3 6.3 minutes, mean ablation time was 110.9 29.6 minutes,
and total laser energy delivery time was 65.9 14.9 minutes.
Nine patients had esophageal temperature rises >38.5oC prompting cessation of energy
delivery. The temperature rises occurred posterior to the: LIPV in 4 patients, LCV in 3, at the
junction of the LSPV/LIPV in 1, and LSPV and LIPV in 1. There were no significant
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were targeted for ablation. The variable diameter and compli
dequate contact for visualization (Figure 5) and made it a
natomies (Supplemental Table 1, Figures 6 & Supplem
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temperature rises >38.5oC with ablation near the right sided PVs seen. There were no instances
of loss of phrenic nerve capture during ablation of the right sided veins. No major adverse
events were seen including cardiac tamponade, strokes or transient ischemic attacks, or bleeding.
Clinical Phase – PV Remapping and Follow-Up. Of the 27 patients, 23 were at least 3
months post-ablation. Of these 23, 18 agreed to undergo PV remapping at a mean of 11.1±0.9
weeks post-ablation. In these patients, persistent electrical isolation was present in 61/68 PVs
(89.7%). In toto, resumption of electrical conductivity was observed in 6 patients and 7 veins – 5
patients had one reconnection each, while the remaining patient had two PV reconnections
(Supplemental Table 2). All PVs were completely isolated in 12/18 (66.7%) patients. Each of
the reconnected PVs had a single area of focal reconnection. An analysis of the location of these
gaps is shown in Supplemental Figure 2. The distribution of reconnections observed on a per
vein basis was: 2 in the LSPV, 2 in the RSPV, and 3 in the RIPV. There were no reconnections
involving the LIPV, left or right common PVs. On a per vein basis, the success of chronic PV
isolation was 86.7% (13/15) for the LSPV, 100% (15/15) for the LIPV, 88.2% (15/17) for the
RSPV, and 82.4% (14/17) for the RIPV. There was 100% chronic PV isolation in the 3 left
common and 1 right common PVs.
At 3 months, 4/23 patients had recurrent AF symptoms with documentation of the
episodes in 3. All of the patients with recurrence were remapped and 2 of 4 had PV
reconnections (Supplemental Table 2). The remaining 2 patient had documented recurrence of
AF, however, all PVs were electrically isolated suggesting a non-PV trigger for the AF. These 2
were the only patients still on a Class I or III antiarrhythmic drug. There was no significant PV
stenosis >30% as assessed by CT scans at 3 months. There was also no evidence of other
12/18 (66.7%%%%%)) ) ) ) ) ) p
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upplemental Figure 2. The distribution of reconnections o
the LSPV, 2 in the RSPV, and 3 in the RIPV. There were
left or right common PVs. On a per vein basis, the succe
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complications: including phrenic damage, atrial esophageal fistula, gastric dysmotility, and
thromboembolism/stroke.
DISCUSSION
In patients with paroxysmal AF, the goal of catheter based therapy is to achieve
permanent PV electrical isolation.1-11 Despite, a high rate of acute isolation, the incidence of
recurrent AF related to PV reconnections is substantial.18-20 In the present study, we have shown
that with visual-guidance, 100% of targeted PVs could be isolated using the variable diameter,
compliant balloon with the capability of real-time endoscopic visualization during point-by-point
ablation using laser energy. Furthermore, with adequate lesion overlap, a high degree of lesion
circumferentiality and transmurality could be achieved. In the chronic preclinical experiments,
lesions were 100% circumferential and 99% transmural in the sampled PV histological sections.
This likely translated to the high rate of chronic PV isolation seen at remapping (80% in the
preclinical experiments, 90% in patients). These favorable results were achieved safely without
any major adverse events.
Feasibility of PV Isolation. In patients with paroxysmal AF, visually-guided PV
isolation using a balloon ablation catheter utilizing laser energy delivery was previously shown
to be possible.17 Although clinically promising, acute PV isolation was feasible in only 91% of
PVs and there was a high rate of clinical recurrence, with only 60% of patients remaining free of
AF without antiarrhythmic drugs at 12 months. These results could be explained in-part by the
suboptimal area of balloon/tissue contact and a large 90o-120o ablative arc which often
necessitated low energy delivery due to overlapping blood and concern for thrombus formation.
In the present study, a compliant balloon with a variable diameter and a point-by-point ablative
capability was used. These changes translated in the ability to isolate 100% of targeted PVs
acutely in both the preclinical and clinical experiments.
With visual guidance alone, 97% of PVs in pigs and 84% of PVs in humans were isolated
after placement of the initial encircling lesion set. In pigs, acute lesions created with laser
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circumferential and 99% transmural in the sampled PV histo
ed to the high rate of chronic PV isolation seen at remappt
ents, 90% in patients). These favorable results were achieve
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energy were more readily identifiable with endoscopic visualization, than in humans. The acute
lesions in humans appeared paler and less intense than in pigs, and were frequency difficult to
discern. Additionally, the area of balloon/tissue contact was also better in pigs. These factors
likely account for the observed difference.
Lesion Characteristics. Although all PVs were isolated, visual gaps in the ablation line
were observed in 35% of PVs in the acute preclinical series, highlighting the fact that isolation
can often be achieved in the absence of a completely circumferential lesion set. Whether these
PVs would have been chronically reconnected, or whether there might have been lesion
progression is unanswered in these experiments. Based on these observations, in the subsequent
chronic preclinical and clinical experiments, there was an attempt to achieve a 30-50% lesion
overlap. Thus in the chronic pigs, no gaps were identified either visually or by histology.
Complete lesion transmurality was seen in 65% of sampled PV sections in the acute pigs, and
97% of PV sections in the chronic pigs. While more lesion overlap may partially account for this
difference, it is more likely that the full extent of injury is more readily appreciated following
lesion maturation. The chronic pig experiments highlight that it is possible to achieve complete
lesion circumferentiality and tranmurality using the visually-guided BAC.
Efficacy & Safety. At ~3 months, 90% of PVs remained electrically isolated and 83% of
patients were free of AF. All PVs were isolated in 67% of remapped patients. These favorable
results are likely due to improved balloon characteristics as previously described. These findings
also compare favorably to the other available balloon ablation technologies, particularly the
cryoballoon.12,13Unlike with the visually-guided BAC, often more than one cryoballoon was used
in conjunction with another catheter for “spot ablation”, to achieve isolation of all the PVs. The
most common reported adverse event with the cryoballoon is reversible right phrenic nerve
palsy. In the present study, one balloon was often enough to isolate all PVs and there were no
major adverse events, including phrenic nerve injury.
Limitations. In animals, the ablation lesions are more readily visible and balloon/tissue
contact is better than in humans. Therefore, with visual-guidance alone, a high proportion of
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The chronic pig experiments highlight that it is possible to ac
nsmurality was seen in 65% of sampled PV sections in the ac
in the chronic pigs. While more lesion overlap may partially
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veins were isolated. While a similar trend was seen in humans, notable differences included
difficulty in visually discerning the lesion; thus overlap was often based more on overlap of each
laser spot with the subsequent laser spot. In patients, although the endpoint was persistent PV
isolation at ~3 month remapping, the procedures were done in a single center with 27 patients.
Therefore, more experience with this particular balloon ablation catheter in multiple centers is
needed to more accurately determine the long-term efficacy and safety. Also, the 3 month
timepoint was chosen as a reasonably late after the initial procedure; however, we cannot rule
out the possibility that more reconnections might be seen at later timepoints. Finally, while only
18, and not all, patients presented for the remapping study, it should be noted that any potential
bias is more likely to be against the device. That is, it is more likely that symptomatic patients
would show up for the second procedure; thereby artificially decreasing the true chronic isolation
rate on an intention-to-treat basis.
CONCLUSIONS
Using a compliant, variable diameter, visually-guided laser balloon with point-by-point
ablative capability, acute PV isolation can be safely achieved in all PVs. The properties of the
balloon make it amenable to address diverse PV sizes and anatomies. With visual-guidance and
placement of overlapping and contiguous lesions, circumferential and transmural lesions can be
reproducibly achieved which translates to persistent electrical isolation in ~90% of PVs.
FUNDING SOURCES
This study was supported by CardioFocus, Inc.
DISCLOSURES
Vivek Y. Reddy, Petr Neuzil, and Shephal K. Doshi: Research grant support from CardioFocus,
Inc.
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Table 1. Histological Lesion Characteristics in the Pre-Clinical Acute and Chronic Porcine Experiments.
Acute Chronic
Pulmonary Veins # of PVs 17 10 Mean Lesion Depth, mm 2.4±0.8 5.0±0.9 Mean Atrial Wall Thickness, mm 3.0±1.0 5.1±0.9 Mean Lesion Transmurality, % 80.8±16.2 98.8±2.1
Histological Sections # of Sections 187 120 Mean Lesion Depth, mm 2.4±2.0 5.0±2.6 Mean Atrial Wall Thickness, mm 3.1±2.5 5.1±2.7 Mean Lesion Transmurality, % 84.6±27.8 99.0±5.5 values are mean±standard deviation
99999999999999
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Table 2. Clinical Phase – Patient Demographics.
Patient Data (N = 27)
Age, mean ± SD (limits) 52.7 ± 12.6 (25 – 66) Gender, M/F 18 / 9 Duration of AF, mean ± SD yrs (limits) 6.7 ± 7.1 (0.3 – 30.0) Coronary Artery Disease, n (%) 1 (3.7%) Hypertension, n (%) 14 (51.9%) Congestive Heart Failure, n (%) 6 (22.2%) Diabetes Mellitus, n (%) 0 (0%) Stroke, n (%) 0 (0%) Structural Heart Disease, n (%) 0 (0%) Ejection Fraction, mean ± SD (limits) 67± 7% (45 – 80%)LA Diameter, mean ± SD (limits) 4.5 ± 0.7 (3.0 – 5.6)History of Atrial Flutter, n (%) 6 (22.2%) Antiarrhythmic Medications Class I 13 (48.1%) Class II 14 (51.9%) Class III 6 (22.2%) Class IV 4 (14.9%)
* LA diameter (N=20, ejection fraction (N=22). One patient had a LA diameter of 5.6 cm and represented a protocol deviation.
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13 (48.1%)
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FIGURE LEGENDS
Figure 1. The Visually-Guided Laser Balloon Ablation Catheter. A schematic representation
of the catheter is shown in (A). Within the central shaft are the 2F endoscope, lesion generator,
and cooling conduits for circulating D2O. The radiopaque “L” marker is located 180o opposite to
the partially obscured view location seen on endoscopic visualization. The balloon catheter is
shown in (B). The catheter also consists of a variable diameter and compliant balloon, and an
atraumatic and flexible tip. The adjustable aiming point is also shown in a view from the tip of
the catheter (C). This aiming point can be manipulated in a circumferential and longitudinal
manner to control the site of laser energy delivery.
Figure 2. Positioning of the Balloon Ablation Catheter and Endoscopic Views. (A) The
deflectable sheath and circular mapping catheter is situated at the ostium of the LSPV of a pig.
The anatomy of the PV is identified with injection of dye through the sheath. (B) The balloon
ablation catheter is shown situated at the ostium of the LSPV and conforms well to the shape of
the PV ostium and antrum (arrow). Endoscopic views from a different animal with the balloon
in the LSPV are shown in (C) and (D). The area of good balloon contact around the vein is pale
and the area with blood is red. The partially obscured view due to the central shaft is also shown
(white, dashed lines). The aiming point is manipulated around the ostium of the PV and
determines site of laser energy delivery. The ablation lesions are also visualized.
Figure 3. Gross Examination of the Pulmonary Veins Following Laser Ablation Using the
Balloon Ablation Catheter. The explanted left atrium of a pig following laser balloon ablation
of the RSPV and LSPV is shown in (A). The left atrium is inverted to display the endocardial
surface. The ablation lesions are seen around the PVs and appear to be contiguous and
circumferential. However, on closer examination a visual gap in the ablation line was identified
(B) and (C). While this was not fully appreciated during the procedure, careful retrospective
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review of the endoscopic films identified the gap which occurred due to insufficient lesion
overlap in the area. Interestingly, despite the visible gap, the PV was electrically isolated.
Figure 4. Gross and Histological Assessment of Chronic Lesions. (A) Circumferential and
contiguous lesions around the pulmonary vein (PV) of a pig are shown 4 weeks post-ablation.
The lesions are paler and less intense than those seen acutely. (B) A histological section
(Masson’s trichrome stain) showing a transmural lesion adjacent to the PV ostium is shown
(arrow). The lesion extends into the adjacent lung and pulmonary artery.
Figure 5. Balloon Contact and Visualization. A 3D CTA reconstruction of the left atrium of a
patient who underwent ablation is shown in the right anterior oblique (A) and posteroanterior (B)
projections. The RIPV of the patient has multiple proximal branches (1-4). The compliant
balloon catheter was placed in the RIPV and conformed well to the size and shape of the PV
ostium (C). An endoscopic view through the balloon catheter showed not only good contact
with the area around the PV ostium, but was also able to delineate the numerous branches of the
RIPV (D).
Figure 6. A Single Balloon Catheter Conforming to Multiple PVs. (A) The baseline 3D CTA
reconstruction of the left atrium of a patient who underwent ablation is shown in the
posteroanterior projection is shown. This patient had an LSPV (yellow dashed line), LIPV, and a
single RCV (white dashed line). The variable radius and compliant nature of the balloon was
able to conform to the different size and shapes of the LSPV (B) and RCV (C) allowing for
successful pulmonary vein isolation. (D) The post-ablation electroanatomical map in the
posteroanterior view of the left atrium of the same patient is shown. Superimposed on the 3D
CTA is a bipolar voltage map following electrical isolation of all veins. The color range of the
voltage map spans from 0.1mV (gray) to 1.0mV (purple) and delineates the level of electrical
isolation.
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Y. ReddySrinivas R. Dukkipati, Petr Neuzil, Jan Skoda, Jan Petru, Andre d'Avila, Shephal K. Doshi and Vivek
Pulmonary Vein IsolationVisual Balloon-Guided Point-By-Point Ablation: Reliable, Reproducible, and Persistent
Print ISSN: 1941-3149. Online ISSN: 1941-3084 Copyright © 2010 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 26, 2010;Circ Arrhythm Electrophysiol.
http://circep.ahajournals.org/content/early/2010/05/26/CIRCEP.109.933283World Wide Web at:
The online version of this article, along with updated information and services, is located on the
http://circep.ahajournals.org/content/suppl/2010/05/26/CIRCEP.109.933283.DC1Data Supplement (unedited) at:
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is online at: Circulation: Arrhythmia and Electrophysiology Information about subscribing to Subscriptions:
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requested is located, click Request Permissions in the middle column of the Web page under Services. FurtherCenter, not the Editorial Office. Once the online version of the published article for which permission is being
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SUPPLEMENTAL MATERIAL
Supplemental Table 1. Number and Type of PVs Targeted for Ablation
Number Treated
(N = 101)
LSPV 21
LIPV 21
LCPV 6
RSPV 25
RIPV 25
RCPV 2
LA Roof Vein 1
Supplemental Table 2. Chronic PV Isolation in Patients with Remapping Procedures.
LSPV LIPV LCV RSPV RIPV RCV AF
Symptoms Documented
1 + + + + No No
2 + + + No No
3 + + + – No No
4 + + + + No No
5 + + + + No No
6 + + – + No No
7 + + + + No No
8 + + + Yes Yes
9 + + + + No No
10 + + + + No No
11 + + – No No
12 + + + + No No
13 + + + + Yes Yes
14 – + + + Yes No
15 + + + No No
16 + + + + No No
17 – + + – No No
18 + + – + Yes Yes
Total 13/15 15/15 3/3 15/17 14/17 1/1
86.7% 100% 100% 88.2% 82.4% 100%
Supplemental Figure 1
Supplemental Figure 2
SUPPLEMENTAL FIGURE & VIDEO LEGENDS
Supplemental Figure 1. 3D CTA Reconstructions of the Left Atria Illustrating the
Different PV Anatomies that were Targeted. These posteroanterior views of the left atrium
show typical PV variants that were successfully targeted with the balloon ablation catheter.
There were patients with separate ostia for all 4 PVs (upper left), a right common vein (upper
right), a left common vein (bottom left), and a small left middle vein (arrow, bottom right).
Supplemental Figure 2. An Illustration Highlighting Areas of Chronic PV Reconnection.
An anteroposterior illustration of the left atrium and pulmonary veins showing the areas of
chronic PV reconnections that were seen in 6 of 18 patients during the remapping procedures.
There were no reconnections involving the right or left common veins, or the LIPV.
Movie 1. Endoscopic Visualization of PV Branches. The endoscopic view of the branches
of the right inferior PV described in Figure 5 are seen.
Movie 2. Endoscopic Visualization During Point-by-Point Ablation. The balloon catheter is
at the ostium of the right superior PV; shown are the fluoroscopic image (top left), an
intracardiac ultrasound image (bottom left), and the endoscopic view (right). The laser ablation
lesions are shown being created (from ~1 o’clock to ~5 o’clock); in the interests of time, the
video is shown at accelerated speed.