Esophageal Cooling in Radiofrequency Cardiac Ablation: Pilot Study
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Riverside Medical Center

 
 
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Esophageal cooling in radiofrequency cardiac ablation: Pilot study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator: Dr. Brad Suprenant 
Investigators: Dr. Bradley Clark 
Contact Information: 815-939-9400 
Site(s) where study will be performed: Riverside Medical Center 
Protocol Version Number & Date: 1.1 / March 20, 2018 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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List of Acronyms 
 
Activated Clotting Time 
ACT 
Advanced Cardiovascular Life Support 
ACLS 
Adverse Event 
AE 
Atrioventricular 
AV 
Esophageal Cooling Device 
ECD 
Food and Drug Administration 
FDA 
Luminal Esophageal Temperature 
LET 
Principal Investigator 
PI 
Pulmonary Vein Isolation 
PVI 
Radiofrequency (Ablation) 
RF 
Serious Adverse Event 
SAE 
Transesophageal Echocardiography 
TEE 
Unanticipated Problem 
UP 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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1. Study Summary 
 
Title 
Esophageal cooling in radiofrequency cardiac ablation: Pilot 
study 
Protocol Number 
RMC IRB # 187 
Study Design 
Randomized, Single-Blind, Interventional, Post-Market pilot 
study 
Study Duration 
1 Year 
Sample Size 
6 
Primary Objective 
To assess the reduction in the occurrence and severity of 
esophageal injury in patients who have the EnsoETM inserted 
into the esophagus during Radiofrequency (RF) ablation. 
Secondary Objectives 
To assess the safety of the EnsoETM and efficacy of ablation 
when the EnsoETM is used to regulate temperature 
Exploratory Objectives 
To assess the EnsoETM’s ease of use during ablation 
 
2. Introduction 
2.1. Background Information 
2.1.1. Atrial and Ventricular Arrhythmias 
 
Atrial and ventricular arrhythmias include a broad range of atypical myocardial 
conduction which are named based on their site of origin.  Intervention for these 
arrhythmias include medications and/or ablation strategies.  Of primary interest is the 
atrial arrhythmia termed atrial fibrillation.  This type of arrhythmia involves multiple 
points of origin typically in the left atrium and the base of the pulmonary veins at the 
junction of the left atrium.  The most common ablative strategy includes pulmonary vein 
isolation which involves heating (RF ablation) or cooling of the posterior aspect of the 
left atrium which lies near the esophagus. 
 
2.1.2. EnsoETM Device Description 
 
The EnsoETM is a silicone tube with three lumens that is placed in the esophagus. 
Distilled water is circulated through the two cooling lumens, while the third lumen 
connects to wall suction and is used for standard gastric decompression. The EnsoETM is 
composed of standard medical-grade silicone, and it is a single-use, disposable, non-
implantable device with an intended duration of use of 36 hours or less. In 2015, Attune 
Medical, LLC received approval from the FDA on their de novo request for classification 
of the Esophageal Cooling Devices (ECD) named EnsoETM. This class II device is used 
to apply a specified temperature to the endoluminal surface of the esophagus via an 
external controller. This study will be utilizing the EnsoETM, because it is designed to fit 
the Gaymar Medi-Therm III Conductive Hyper/Hypothermia SystemNaiman. There are 
three contraindications for this device: (1) patients with known esophageal deformity or 
evidence of esophageal trauma, (2) patients with known ingestion of acidic or caustic 
poisons within the prior 24 hours, and (3) patients with less than 40 kg of body 
mass.Naiman, Shanley 
 

 
 
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2.1.2.1. 
Regulatory Status 
 
 
   
The Food and Drug Administration (FDA) identifies the EnsoETM as: 
 
Esophageal thermal regulation device. An esophageal thermal regulation device is a 
prescription device used to apply a specified temperature to the endoluminal surface of 
the esophagus via an external controller. This device may incorporate a mechanism for 
gastric decompression and suctioning. The device is used to regulate patient temperature. 
 
Indications for Use: 
 
The EnsoETM is a thermal regulating device, intending to:  
 Connect to a Gaymar Medi-Therm III Conductive Hyper/Hypothermia System to 
control patient temperature, and 
 Provide gastric decompression and suctioning 
 
Limitations: 
 
Prescription use only: Federal (USA) law restricts this device to sale by or on the order of a 
physician. 
 
The EnsoETM may cause or exacerbate esophageal tissue damage in patients with esophageal 
deformity or evidence of esophageal trauma, or in patients who have ingested acidic or caustic 
poisons within the prior 24 hours. 
 
The safety and effectiveness of the EnsoETM have not been evaluated in patients with less than 
40 kg of body mass 
 
The EnsoETM should only be used by healthcare professionals with training in the use of 
orogastric tubes and the use of the Gaymar Medi-Therm III Conductive Hyper/Hypothermia 
System. 
 
The EnsoETM is intended for esophageal placement. Inserting the EnsoETM in the trachea, 
bronchi, or lungs can result in serious harm. 
 
Attachment of the EnsoETM to unapproved or unintended connections can result in serious 
patient harm 
 
The presence of the EnsoETM may interfere with other devices in the esophagus or mouth. Dual 
placement of other devices in the esophagus with the EnsoETM in place, such as an enteral 
feeding tube, may result in patient harm. 
 
Large patients with body mass greater than 120 kg may exhibit slower responses to intended 
temperature changes. Small patients with a body mass less than 60 kg may exhibit faster cooling 
than anticipated, and may exhibit slower rewarming than anticipated. 
 

 
 
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2.1.3. Prior Clinical Studies 
 
The first case of esophageal trauma associated with left atrial posterior wall ablation for 
atrial fibrillation was reported in 2003 (Lequerica JL B. E., 2008).  Since then there have 
been a myriad of interventions in hopes of preventing such damage.  This ranges from 
mechanical manipulation of the esophagus to esophageal cooling with various 
mechanisms including ice water lavage.  This also includes the development of a cooled 
intraesophageal balloon with mixed results  (Berjano EJ, 2005) (Lequerica JL B. E., 
2008) (Lequerica JL B. E., 2008) (Tsuchiya T, 2007) ].  Further in-vitro evaluation of 
animals has been performed using a controlled saline circulating system (EPSac) which 
spares the esophagus from collateral thermal injury (Arruda MS, 2009). The novel idea of 
cooling the esophagus to prevent transmural damage has been documented as 
overwhelmingly positive.  The most notable clinical evaluation of an esophageal cooling 
mechanism was performed by Tsuchiya et. which included a cooled water-irrigated 
intraesophageal balloon. (Tsuchiya T, 2007) A limitation of this study included the 
inability to assess the deeper muscular layer of the esophagus for evidence of injury.  
Several limitations to the above mentioned approaches include cost, physician 
availability, displacement of the esophagus, and ability to monitor the luminal esophageal 
temperature (LET). 
 
2.2. Rationale 
 
Left atrial ablation is a standard therapy in the management of atrial fibrillation; however 
esophageal injury is a known potential consequence of this procedure.[1-4] Delivery of the 
radiofrequency energy necessary to perform left it real ablation has the potential to cause 
injury to the nearby esophagus and its associated vagal innervation, with injuries including 
ulceration, hematoma, spasm, disorders of esophageal motility, and atrial-esophageal fistula 
(the latter representing the extreme consequence of esophageal thermal injury due to 
posterior left atrial ablation).[1, 2]  Esophageal mucosal lesions are commonly reported with 
an incidence ranging widely from 3%to 60%, and recent observations suggest a potential 
contribution of the transesophageal echocardiogram probe to esophageal injury seen after 
catheter ablation.[5]  Although ablation of the left atrium poses the greatest risk, right atrial 
ablation also has the potential to allow esophageal damage to occur. 
 
Although luminal esophageal temperature monitoring is one proposed measure to reduce the 
incidence of esophageal injury during atrial fibrillation ablation, the success of temperature 
monitoring has varied widely.[6, 7]  It is fairly well established that effective measuring of 
the esophageal temperature depends on the position of the temperature probe relative to the 
heated cardiac tissue and also on good contact with the esophageal mucosa.[8]  However, the 
esophagus often is mobile and shifts sideways by >2 cm in a patients undergoing catheter 
ablation for atrial fibrillation under conscious sedation.[9]  Using fairly sophisticated 
approaches (e.g., deploying an ablation catheter with thermistor tip into the esophagus [as 
both a measurement device and a deflection tool], along with position confirmation using 
intracardiac echo) appears to be the only measurement technique that offers adequate 
protection.[6] This approach does not seem to be a technique that is routinely feasible (due to 
both the cost of equipment and the need for additional operators during the procedure).[6]  

 
 
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Moreover, there is the suggestion that the temperature probe used for esophageal temperature 
monitoring may contribute to a thermal effect and enhance direct tissue heating.[10] 
 
Data from animal models show that the muscular layer is disrupted and necrotic myocytes 
are seen at the border of lesions in the esophagus even when no lesions on the epithelial layer 
were found, suggesting that cooling the deep muscular layer of the esophagus may be needed 
to prevent esophageal injury.[11]   Prevention of esophageal injury via cooling of the 
esophagus has been investigated with mathematical modeling, preclinical models, and in the 
clinical arena.  A finite element model in three dimensions investigating the effects of a 
cooled intra-esophageal balloon suggested that this approach could be a viable method to 
prevent thermal injury to the esophagus during intraoperative ablation of the left atrium.[12]  
Specifically, the authors found that (i) chilling the esophagus by means of a cooled balloon 
placed in the lumen minimizes the lesion in the esophageal wall compared to the cases in 
which no balloon is used (a collapsed esophagus) and with a non-cooled balloon; (ii) the 
temperature of the cooling fluid has a more significant effect on the minimization of the 
lesion than the rate of cooling (the thermal transfer coefficient for forced convection); and 
(iii) pre-cooling periods previous to RF ablation do not represent a significant improvement.  
Finally, the authors also suggest that the use of a cooled balloon could affect the 
transmurality of the atrial lesion, especially in the cases where the atrium is of considerable 
thickness (or in other words, in the presence of an atrium of considerable thickness, when a 
short duration and a low target temperature are programmed, the use of a cooled balloon 
could reduce the possibilities of achieving a transmural lesion in the atrium. 
 
Subsequent study using an agar phantom-based model that was built to provide temperature 
readings at points between the esophageal lumen and the myocardium found that this method 
was able to provide effective thermal protection, although it was noted that the method could 
fail under certain unfavorable topical and procedural conditions.[13]  In this study, a balloon 
utilizing water temperature of 5° C flowing at a rate of 25 mL per minute was used, which 
likely significantly limits the capability of this device to extract heat effectively. 
 
Further study by this same group utilized varying coolant temperatures between 5°C and 
37°C but maintained the coolant flow rate at 25 mL per minute.[14] The authors conclude 
that their results suggest that it is possible to thermally protect the esophagus (including the 
transmural region 2 mm away from the mucosal surface) during radiofrequency cardiac 
ablation by means of a cooling balloon placed in the esophageal lumen utilizing coolant 
temperature of 5°C or less and involving a precooling period of two minutes. 
 
A custom developed system utilizing temperature controlled saline or water circulating at a 
flow rate tween 50 to 300 mL per minute and a temperature of 5 to 25°C was evaluated using 
an in vitro Lamb heart – esophagus preparation, followed by an in vivo model with six 
dogs.[15]  This custom system consisted of a 12 French probe with a distal expandable 
compliant latex sack with a diameter of up to 3 cm fully expanded. The authors found that a 
circulating water temperature of 25° C failed to spare the esophagus from thermal injury. 
However lowering the circulating temperature to 10° C or 5°C spared thermal injury 
(although expanding the balloon diameter by increasing circulating volume substantially to 

 
 
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intentionally displace the esophagus towards the left atrium allowed the development of 
shallow esophageal injury to the external layers of the muscularis).   
 
A clinical study [16] of eight patients used a closed loop system with low flow rates (25 
mL/min) and a water temperature of 4.5±3.1◦C to build upon computer modelling 
demonstrating that a cooled balloon catheter (with a diameter of 10 mm) could transmurally 
cool the esophagus. They found that without cooling, esophageal temperature increased from 
a baseline of 36.4°C up to 40.5°C in under 30 seconds during ablation, whereas with the 
esophageal cooling balloon, esophageal temperature decreased down to 30.2°C with the 
balloon in place, and allowed an increase in temperature to only 33.5°C.  The authors 
conclude that luminal esophageal temperature during the left atrial ablation was lowered by 
esophageal cooling using their catheter to a level where no thermal damage to the esophagus 
would likely be induced.   
 
A study presented in 2007 in abstract form described the use of a saline filled esophageal 
balloon to attempt esophageal protection in an animal model, and found that in four dogs, a 
saline solution of 10°C was not sufficient to prevent thermal injury.[17]  However, details of 
balloon configuration and, more importantly, coolant flow rate, were not provided, and a 
formal manuscript further describing these findings appears not to have yet been submitted. 
 
Free water instillation into the esophagus has been tried with varying success. A study of 100 
patients used very small volumes (5 mL) of ice water as the instilled volume, which was 
injected prior to RF energy delivery, and subsequently when esophageal temperatures 
reached 42°C.[18] The authors found that this approach alleviated the severity of esophageal 
lesions, but did not reduce the incidence: lesions occurred in 20% of the experimental group, 
and 22% of the controls, with three moderate and seven mild in the cooled group and three 
severe, one moderate, and seven mild in the control.   
 
Another study utilized infusion of cooled saline mixed with Gastrografin or Iopamidol, with 
slightly higher, but still limited volumes (10 – 20 mL in repeated injected aliquots with a 
temperature of approximately 10°C).[19]  A total of 318 patients were randomized between 
groups receiving only temperature monitoring without cooling, temperature monitoring with 
cooling when temperature exceeded 43°C, and temperature monitoring with cooling received 
when temperatures exceeded 39°C.  The percentage of patients free from any ulceration or 
erosion in each group was found to be 63.6%, 87.5%, and 95.2%, respectively, and the 
authors conclude that these findings suggest that esophageal damage can be reduced by 
reducing cooling solution into the esophagus via a gastric tube when luminal temperature 
exceeds 39°C during ablation. 
 
In summary, although abundant data suggest that cooling of the esophagus during ablation 
procedures can protect against esophageal injury, no commercially available device has yet 
been shown to perform this task. 
Our intention is to evaluate the use of an esophageal cooling catheter to protect the 
esophagus during atrial fibrillation RF ablation.  This will theoretically eliminate esophageal 
tissue damage.  As noted above, this is not a novel idea, however, there are several 
advantages that this device offers.  The most significant of which includes a large area of 

 
 
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distribution of cooling effect throughout the length of the catheter as well as a large lumen.  
The lumen size provides more rapid thermal energy exchange thus limiting the extent of 
esophageal damage.  There are no metal parts included in this catheter, therefore, eliminating 
the concern for the device acting as a wick for energy transfer and enhanced direct tissue 
heating. (Deneke T, 2011)  The cooling catheter does not require advanced training for 
placement or monitoring and also acts as an oral-gastric tube during the procedure.  This 
device is also cost effective as the cooling source is used by hospitals (nearly ubiquitously) 
for standard cooling blankets. 
 
2.3. Potential Risks and Benefits 
2.3.1. Known Potential Risks 
 
The following potential risks are associated with the use of esophageal thermal regulation 
devices: 
 
 Adverse tissue reaction 
 Gastric distension 
 Injury to the esophagus 
 Harmful hypo/hyperthermia 
 Injury to the trachea 
 Interference with other device in the esophagus or mouth leading to esophageal 
trauma 
 
 
 
The following potential risks are associated with RF ablation: 
 Bleeding or infection at the puncture site(s) 
 Vascular damage from mechanical shear stress on the vessel wall from the 
catheters  
 Myocardial rupture with tamponade 
 Valvular heart damage which might cause regurgitation 
 Arrhythmia possibly requiring pacemaker implantation 
 Venous thromboembolism 
 Stroke or heart attack 
 Pulmonary vein stenosis 
 Acute kidney injury related to dye use during the procedure 
 Atrio-esophageal fistula formation  
 Death in rare cases 
The following potential risks are associated with general surgery: 
 
 Adverse reaction to anesthesia 
 Hematoma or seroma at the operative site 
 Failure to improve 
 Persistent or worsened pain 
 Infection of the wound 

 
 
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 Radiation exposure 
 Wound dehiscence 
 Vascular disorders, including thrombus 
 Bronchopulmonary disorders, including emboli 
 Genitourinary disorders 
 Pneumonia 
 Hemorrhage 
 Myocardial infarction 
 Death 
 
3. Objectives and Purpose 
3.1. Primary Objective 
 
The primary objective of this study is to evaluate the reduction in the occurrence and severity 
of esophageal injury in subjects who had a cooling tube inserted into the esophagus during 
radiofrequency ablation. 
 
3.2. Secondary Objectives 
 
The secondary objective of this study is to assess the safety of the EnsoETM and efficacy of 
ablation when the EnsoETM is used to regulate temperature. 
 
3.3. Exploratory Objectives 
 
This study will assess the EnsoETM’s ease of use during RF ablation. 
 
4. Study Design and Endpoints 
4.1. Description of Study Design 
 
Single-center, randomized pilot study of esophageal temperature management using Attune 
Medical’s EnsoETM during RF ablation vs. RF ablation without the EnsoETM. 
 
4.2. Study Endpoints 
4.2.1. Primary Endpoint 
 Esophageal mucosal damage as assessed by endoscopic evaluation and graded 
using Zagar's modified endoscopic classification scheme.    
 

 
 
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 Radiofrequency ablation of the posterior aspect of the left atrium has been shown 
to cause esophageal mucosal irritation which may be exacerbated by LET 
monitoring and/or TEE.  We believe that cooling of the esophagus will lead to a 
reduction of esophageal damage.  To date there are bench models that suggests 
such an esophageal sub-mucosal protection but this has not been proven in human 
studies.   
 Providing evidence that a reduction in sub-mucosal esophageal damage using the 
ECD may be a precursor to reduction in atrial-esophageal fistula formation.   
4.2.2. Secondary Endpoints 
 1) Safety of the EnsoETM placement as measured by the number of adverse events 
recorded 
 We believe that cooling of the esophagus will lead to a reduction of esophageal 
damage.  The use of an EnsoETM would replace LET monitoring during ablation 
of the posterior aspect of the left atrium.  This endpoint was chosen to prove that 
replacing the LET monitor with a cooling catheter is a safe alternative.   
 This is of primary importance as any evidence of esophageal damage or adverse 
events related to the use of the EnsoETM would deter any further use of this 
approach to Pulmonary Vein Isolation (PVI).   
 2) Altered submucosal tissue architecture as assessed by endoscopic ultrasound 
(EUS) 
 While mucosal injury may suggest significant thermal injury to related to RF 
ablation there is also concern that this injury may be more of a mechanical process 
from TEE and LET monitoring.  We aim to assess the submucosa using EUS for 
differentiation between superficial and deep injury which may provide further 
insight into the risk of atrio-esophageal fistula formation.  A grading scheme has 
not been developed for this type of evaluation so we will assess for individual 
changes with pre-procedure to post-procedure comparison. 
4.2.3. Exploratory Endpoints 

 
 
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 Efficacy of PVI by evaluation of rhythm at 3 months following the procedure.  
 
This endpoint was chosen as a precursor to future larger studies that may 
focus on efficacy to ensure that PVI with EnsoETM is non-inferior to PVI 
with LET.  
 Does the use of an EnsoETM prolong or shorten the overall ablation time? 
 
5. Study Enrollment and Withdrawal 
5.1. Inclusion Criteria 
Patients must meet all of the inclusion criteria to be enrolled as subjects in this study. 
 
 Subject is between ages 18 – 90 years 
 Subject has an atrial or ventricular arrhythmia requiring radiofrequency ablation on 
the posterior aspect of the heart 
 Subject is willing and able to provide informed consent 
 Subject is capable of adhering to the expectations of the study protocol (e.g., 
attending follow-up visit) 
 
 
5.2. Exclusion Criteria 
 
 Subject has known esophageal deformity, or evidence of esophageal trauma, prior 
radiation therapy involving the esophagus, or previous esophageal disease (for 
example, known esophageal varices, cirrhosis, history of esophagectomy, previous 
swallowing disorders or dysphagia, achalasia, known ingestion of acidic or caustic 
poisons within the prior 24 hours etc.). 
 Subject is incarcerated 
 Subject is pregnant or plans to become pregnant 
 Subject has a silicone allergy 
 Subject has esophageal bleeding prior to EnsoETM insertion 
 
5.3. Recruitment Strategy 
 
Patients will be recruited from the Principal Investigator’s clinic when the decision to 
perform RF ablation in order to treat the patient’s condition is made. The Principal 
Investigator (PI) or designee will provide a brief explanation of the study by describing the 
study objectives. If the patient is interested in learning more about the study, the PI will 
initiate the informed consent process. 
 
5.4. Participant Withdrawal 
5.4.1. Reasons for Withdrawing 
 
 Subject’s refusal to participate 
 
5.5. Participant Removal from Study 
 
 Subject has esophageal stricture or ulceration 

 
 
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 Subject death 
 Physician scheduling conflict 
 
 
6. Study Device  
6.1. Acquisition 
 
Study device is currently undergoing evaluation on-site and supply is already available on-
site, with additional available upon request via standard shipping. 
 
6.2. Formulation, Appearance, Packaging, and Labeling 
 
Study device, the EnsoETM, is a non-sterile multi-lumen silicone tube placed in the 
esophagus for the purpose of cooling or warming a patient while simultaneously allowing 
gastric decompression and drainage.  Modulation and control of the patient’s temperature is 
achieved by connecting the EnsoETM to an external heat exchanger. Two lumens connect to 
the external heat exchanger, while a third central lumen provides stomach access for 
connection to a fluid collection device with low intermittent suction for gastric 
decompression.  The EnsoETM is made of standard medical-grade silicone.  It is a single-
use, disposable, non-implantable device with an intended duration of use of 36 hours or less.  
 
Additional details can be found in the attached Instructions for Use which are packaged along 
with the device as a package insert.   
 
6.3. Products Storage and Stability 
 
Describe the study device’s storage needs. Include: 
 
 Storage requirements: Store in a dry and clean place 
 Stability requirements: 5C to 32C, with no humidity requirement. 
 Expiration date: 3-year shelf life 
 
6.4. Preparation 
 
The Manual of Procedures details the preparation of the study device and is attached to this 
protocol as an appendix. 
 
6.5. Administration 
 
Placement of the EnsoETM 
 
The external heat exchanger must be in proper operating condition and must have received 
all the required maintenance.  Failure to ensure that the heat exchanger is in proper condition 
may result in suboptimal performance.  Ensure that no contaminants are present in the heat 
exchanger water. 

 
 
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Measure the patient for EnsoETM placement carefully before use.  Insertion of an excessive 
length of the EnsoETM into the stomach may lead to coiling, kinking, knotting, or breakage 
of the EnsoETM.  To measure the patient for EnsoETM placement, extend the EnsoETM 
from the patient's lips to the earlobe and then from the earlobe to the tip of the xiphoid 
process (xiphisternum).  Mark the location on the EnsoETM. 
Follow the Instructions for Use for the external heat exchanger for all device operations, 
including connections to electric wall power, patient probes, and tube set connections. 
Connect the EnsoETM (Figure 1) to the external heat exchanger in place of a blanket or pad, 
using a Cincinnati Sub-Zero connector hose (CSZ P/N 286) with the connectors as shown in 
Figure 1.  Turn on the external heat exchanger.  
Ensure that the patient has a temperature probe with a monitor in use (for example, a Foley 
catheter temperature probe or a rectal temperature probe).  The temperature probe must be 
connected to the external heat exchanger, as directed in the external heat exchanger‘s 
Instructions for Use.  Ensure that the temperature monitor is functioning correctly and that 
the temperature probe is not damaged, expired, or compromised in any other way.  
Select the control mode and target patient temperature on the external heat exchanger.  
Ensure that water is flowing through the EnsoETM, and that no leaks are present.  Failure to 
initiate water flow prior to insertion may hinder placement of the EnsoETM.  
Lubricate the EnsoETM generously with water soluble lubricant prior to insertion. Do NOT 
use petroleum-based products, because these may be harmful to the respiratory tract.    
Insert the EnsoETM using gentle pressure posteriorly and downwards through the mouth, 
past the oropharynx and into the esophagus.  Gently assist the passage of the EnsoETM with 
light pressure until the required length of tube has been inserted. 
Do not use force during insertion of the EnsoETM, because this may cause bleeding and/or 
damage to the oropharynx or other structures.  If resistance is encountered during insertion of 
the EnsoETM, immediately stop the procedure. 
Confirm placement of the EnsoETM by the following: 
 injecting 5 to 20 mL of air (with a 50 or 60 ml syringe) through the central lumen 
while auscultating over the stomach for a “swoosh” or a “burp” indicating gastric 
placement, 
 aspirating gastric contents with a syringe (using a 50 or 60 ml syringe) through the 
central lumen, and 
 confirming the location and placement of the EnsoETM with an x-ray. 
Secure the EnsoETM with a securement device or tape in accordance with hospital protocol.  
Ensure the EnsoETM and tube set connections are not in contact with the patient’s skin.  
Direct contact between the EnsoETM and exposed skin may cause shivering. 
For stomach decompression, connect the central lumen of the EnsoETM (Figure 1) to low-
intermittent suction using standard suction tubing (not supplied) and adaptor (not supplied).  
Always use the lowest suction setting that will effectively decompress the stomach.  
The central lumen of the EnsoETM is not intended for enteral feeding or for administration 
of oral medication. If the central lumen of the EnsoETM becomes blocked or clogged, 

 
 
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standard approaches for clearing blocked gastric tubes are recommended.  For example, 
disconnect the EnsoETM from wall suction and use a saline flush.  If the standard approaches 
are unsuccessful, it may be necessary to remove and then replace the EnsoETM. 
Monitor patient temperature using both monitors during use. Ensure that the temperature 
monitors are reporting temperatures that are in agreement; if the discrepancy between the two 
monitors is greater than 0.5°C, discontinue treatment and investigate the cause of the 
discrepancy. Replace the temperature probes or secondary monitor if necessary.  Ensure both 
temperature probes remain in place without accidental dislodgement during the entire course 
of patient treatment.  Monitor circulating coolant temperature and ensure that it does not fall 
below 4°C or exceed 42°C. 
6.6. Device Specific Considerations 
 
 Device size: The device has outside diameter less than or equal to 13.3mm, with a 
wall thickness of 0.65mm±0.1mm. 
 Device model: EnsoETM  Model: ECD02 
 Duration of exposure: less than 36 hours 
 Frequency of exposure: Single-use 
 
7. Study Procedures and Schedule  
7.1. Study Procedures/Evaluations 
7.1.1. Study Specific Procedures 
 Study specific imaging with include endoscopic evaluation of the esophagus one 
day before surgery at the time of the pre-op Transesophageal Echocardiography 
(TEE) and again 1-day post-op.  This will include endoscopic esophageal 
intubation with visual assessment of the entire esophagus and grading of lesions.  
Coupled with this procedure will include endoscopic ultrasound assessment of the 
esophagus at the level of the left atrium with specific attention to the sub-mucosal 
layer that separates esophagus from the cardiac tissue.  The patient will undergo 
moderate sedation during this procedure, which will accompany the TEE.  
 The ECD will be placed by trained study staff following endotracheal intubation. 
Proper positioning will be verified.  A temperature probe will be placed to verify 
the patients core temperature.  The target temperature will be set to the core 
temperature at the beginning of the procedure.  Two minutes prior to ablation on 
the posterior wall the target temperature will be changed to the minimum 
temperature setting which will allow for maximal cooling.  Cooling will take 
place throughout the duration of posterior wall ablation.  After ablation in this 
territory is complete the target temperature will return to the patients core 
temperature.  The device will be removed at the completion of the procedure by 
anesthesiology when there is no further need for an orogastric tube. 
 LET monitoring will not be performed in the patients of the intervention group as 
the ECD is prohibitive.  Therefore, ice lavage of the esophagus, as detailed below, 
will not be performed in this group.   
7.1.2. Standard Care Procedures 

 
 
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 Medical History will be obtained by interview and will involve identification of 
contraindications to the use of the ECD.  This includes a history of esophageal 
perforation or varices.  An allergy to silicone will be assessed.   
 The patient’s active medication list will be reviewed as is standard protocol for 
atrial fibrillation ablation, but this is not specific to the study as there are no 
medications that would impact the use of the ECD. 
 All subjects will be on Protonix (40mg; twice daily) immediately following 
surgery for 30 days and anticoagulation for 3 months following surgery. 
 
The physical exam will be performed as is customary for the procedure.  Study 
specific exam is included as part of the airway assessment which is performed on 
a regular basis by anesthesiology.  The oropharynx will be assessed prior to 
placement of the ECD. 
 
The patient will be administered general anesthesia by the anesthesia department 
with hemodynamic monitoring. Two 8-French sheaths placed in the right femoral 
vein. A 7- and a long 9-French sheath will then be placed in the left femoral vein 
and a 7-French sheath placed in the right subclavian vein. Under fluoroscopic 
guidance, a quadripolar catheter is then placed through the left femoral venous 
sheath to the His bundle region. His-bundle electrocardiography is performed 
with measurement of intervals. A decapolar catheter with 2-5-2 spacing is then 
placed through the right subclavian venous sheath and utilized to intubate the 
coronary sinus for left atrial recordings. Ventricular pacing is used to demonstrate 
VA 1:1 conduction. Next, trans-septal puncture is performed with the use of a SL-
1 sheath from Daig, a Baylis needle, and intracardiac echocardiography. Then, a 
separate slightly higher puncture of the atrial septum is performed with 
intracardiac echo guidance into the left atrium also using a Baylis needle and SL-
1 sheath. The participant will be given 5000 units of heparin bolus after the first 
transseptal puncture and again after the second transseptal puncture. The 
participant will then be maintained on heparin infusion with intermittent boluses 
to maintain ACT between 300 and 350 seconds. At this point, a multi-pole loop 
catheter will be placed through the sheath into the left atrium. Three-dimensional 
geometry will be obtained of all four pulmonary veins, left atrial appendage, and 
left atrium. Then, the loop catheter will be placed in the left superior vein and 
ablation will be carried out utilizing an 8 mm distal tip large curve ablation 
catheter from Boston Scientific. Ablation will be carried out with 35 watts of 
energy at 55 degree temperature on the posterior wall and 50 watts of energy and 
55 degree temperature on the anterior wall. The participants with LET monitoring 
may require intermittent boluses of iced lavaged saline through the nasogastric 
tube when the temperature rises above 1 degree centigrade.  Next, ablation will be 
carried out of the left superior pulmonary vein until completely isolated as well as 
the carina. The loop catheter will then be placed in the left inferior pulmonary 
vein and isolation of the left inferior pulmonary vein is obtained as well. The loop 
catheter will then be placed in the right superior pulmonary vein with isolation of 
that catheter and then brought down into the right inferior pulmonary vein with 
entrance block demonstrated from that catheter. All veins then demonstrate exit 
block with additional consolidating ablations as required. All four veins will be 
checked at that point. Next, Isuprel provocation will be initiated. Pacing will be 

 
 
16 | P a g e  
 
performed to the atrioventricular (AV) nodal Wenckebach block rate and to the 
AV nodal effective refractory period. Then the patient is placed on 10-20 mcg of 
Isuprel and repeat burst pacing from the coronary sinus as well as the high right 
atrium is performed. Should atrial fibrillation recur then further ablation is carried 
out from the roof anteriorly from the right superior pulmonary vein to the left 
superior pulmonary vein with bidirectional conduction block detected. A complex 
atrial fractionated electrogram map may be performed to determine fractionated 
areas for further ablation lines.  Should atrial fibrillation persist then anterior 
septal ablation will be carried out for complex atrial fractionated electrograms as 
well as spot ablation within the atrial appendage or atrial appendage isolation if 
required. Should the patient develop mitral isthmus atrial flutter then an ablation 
line will be performed from the left inferior pulmonary vein to the mitral annulus 
posteriorly. Should the patient develop typical atrial flutter, a cavo-tricuspid 
isthmus (CTI) right atrial flutter line may be performed. Other right atrial lesions 
will be targeted as required, including superior vena cava isolation if needed. 
Organized atrial tachycardias will be mapped and ablated as needed. At the 
conclusion of the ablation, heparin is discontinued and catheters removed.  
Sheaths are removed once the (activated clotting time) ACT is below 180 seconds 
or following administration of protamine. At the conclusion of the procedure the 
intracardiac echocardiogram is used to demonstrate no evidence for pericardial 
effusion or fluid.  
 
7.2. Radiographic Procedures/Evaluations 
7.2.1. Esophagoscopy 
The patient will present for endoscopic evaluation the day prior to surgery.  During this 
time the patient will undergo moderate sedation with continual monitoring of vital signs.  
Following adequate sedation the proceduralist will proceed with esophageal intubation 
with visual assessment of the entire esophagus and grading of lesions (Zargar 
classification). Furthermore, the submucosal tissue will be assessed with EUS at the level 
of the left atrium. This procedure will be preceded by TEE with moderate sedation 
maintained. 
 
The day following the PVI the patient will undergo repeat endoscopic evaluation of the 
esophagus in the same manner as detailed above.  The proceduralist will document their 
findings including the condition of the sub-mucosal esophageal tissue as noted by EUS. 
 
7.3. Study Schedule 
7.3.1. Screening/Enrollment/Baseline (Visit 1, Day 0) 
 
Screening/Enrollment/Baseline Visit (Visit 1) 
 Obtain informed consent of potential participant verified by signature on written 
informed consent form 
 Review medical history to determine history based on inclusion/exclusion criteria 
 Review medications history to determine eligibility based on inclusion/exclusion 
criteria 
 Obtain demographic information and tobacco use history 

 
 
17 | P a g e  
 
 Record vital signs, results of examinations, other assessments 
 Perform medical examinations needed to determine eligibility based on 
inclusion/exclusion criteria 
 Schedule EGD 1 day prior to surgery. 
 Schedule follow-up visits for patients who are eligible and available for the 
duration of the study 
 Provide patients with instructions needed to prepare for the first study 
visit/procedure 
 
7.3.2. Endoscopic evaluation and TEE (Visit 2) 
 
The patient will present to the hospital on the day prior to their RF ablation 
procedure as is standard of care for transesophageal echocardiography (TEE).  The 
patient will be prepped for moderate conscious sedation with appropriate monitoring 
of vital signs under the care of a nurse and as directed by the physician.  For this 
study we will add the patient will undergo direct visualization of the esophageal 
mucosa as well as ultrasound assessment of the sub-mucosal tissue in the area of the 
left atrium.  The patient will be sedated to a level of moderate conscious sedation as 
is typical for endoscopic evaluation and TEE.  The endoscopic probe will be passed 
into the esophagus with appropriate imaging obtained throught the length of the 
esophagus.  Then EUS will be used to assess the submucosal tissue 
 
7.3.3. Surgical Procedure Visit (Visit 3) 
 
Subjects will undergo the RF ablation procedure within 30 days of randomization unless 
there is a medically valid reason to the delay the procedure. The procedure is describe 
below. Details of the procedure are referenced in section 7.1.2 of this study protocol. The 
investigator’s procedure note will be included in the study files to gather endpoint and 
exploratory data. 
 
The following day the patient will undergo repeat endoscopic evaluation in the same 
fashion as the prior study with moderate sedation.  This will include visual assessment of 
the esophagus with video imaging as well as EUS at the area of interest near the left 
atrium at the level of the pulmonary veins. 
 
7.3.4. Follow-up Visit (Visit 3) 
 
The first follow-up visit will occur 12 days (+4/-4) days after the surgery procedure. 
 
 Review medical history and medications history 
 Record vital signs 
 Adverse event assessment 
 Assess study eligibility  
 
7.3.5. Final Study Visit (Visit 4)  
 

 
 
18 | P a g e  
 
The final study visit will occur 3 months (+30/-30 days) after the surgery procedure.  
 
 Review medical history and medications history 
 Record vital signs 
 Adverse event assessment 
 PVI Efficacy as assessed through placement of an event monitor 
 Assess study eligibility  
 
7.3.6. Unscheduled Visit 
 
In addition to standard care provided during unscheduled visits, an adverse event 
assessment will be performed to determine whether an adverse event is present. Any 
adverse events will be recorded on the AE case report form. 
 
7.4. Concomitant Medications, Treatments, and Procedures 
 
All concomitant prescription medications taken during study participation will be recorded 
on the case report forms. For this protocol, a prescription medication is defined as a 
medication that can be prescribed only by a properly authorized/licensed clinician. 
Medications to be reported in the CRF are concomitant prescription medications, over-the-
counter medications, and non-prescription medications. 
 
7.5. Rescue Medications, Treatments, and Procedures 
 
If evidence of bleeding with placement of the ECD then the device will be removed. 
 
Surgical exploration and repair of esophageal fistula. 
 
Hemodynamic support including (Advanced Cardiovascular Life Support (ACLS) 
protocol will be implemented as needed. 
 
8. Safety Assessment 
8.1. Specification of Safety Parameters 
 
8.1.1. Definition of Adverse Events (AE) 
 
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related (21 CFR 312.32 
(a)). 
 
8.1.2. Definition of Serious Adverse Events (SAE) 
 
An AE is considered serious if, in the view of the PI, it results in any of the following 
outcomes: 
 
 Death 
 Life-threatening adverse event 
 Inpatient hospitalization or prolongation of existing hospitalization 

 
 
19 | P a g e  
 
 Persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life function 
 Congenital anomaly/birth defect 
 
Important medical events that may not fall under one of these categories may be 
considered serious when, based on upon appropriate medical judgment, they may 
jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. 
 
 
8.1.3. Definition of Unanticipated Problems (UP) 
 
OHRP considers unanticipated problems involving risks to participants or others to 
include, in general, any incident, experience, or outcome that meets all of the following: 
 
 Unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in protocol-related documents, such as the IRB-
approved research protocol and informed consent; and (b) the characteristics of 
the participant population being studied; 
 Related or possibly related to participation in the research (“possible related” 
means there is a reasonable possibility that the incident, experience, or outcome 
may have been caused by the procedures involved in the research); and 
 Suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized. 
 
8.2. Reporting Procedures 
8.2.1. Adverse Event Reporting 
 
If a subject presents with an adverse effect, the PI will evaluate whether or not the event 
is related to the use of the study device by completing an adverse event report. If the PI 
determines the adverse event to be related with the study device, or if the adverse event is 
unexpected, he must: 
 Complete and submit the adverse event report to the IRB in a timely manner (10 
working days after the investigator determines the adverse event is related to the 
study device). 
 
8.2.2. Serious Adverse Event Reporting 
 
All unanticipated adverse device effects are considered Serious Adverse Events (SAEs). 
The PI will submit to the RMC IRB a report of any unanticipated adverse device effect 
occurring during an investigation as soon as possible, but in no event later than 10 
working days after the investigator first learns of the effect.  
 
8.2.3. Unanticipated Problem Reporting 
 

 
 
20 | P a g e  
 
The study investigator shall complete an Adverse Event Report and submit it to the RMC 
IRB as soon as possible, but in no event later than 10 working days after the investigator 
first learns of the effect.  
 
8.3. Classification of an Adverse Event 
8.3.1. Severity of Event 
 
On the Adverse Event Report, the investigator will characterize the severity of each AE as 
mild, moderate, or severe. The investigator will use medical judgment to compare the 
report AE to similar types observed in normal clinical practice. To assess the severity of 
an AE, the following guidelines are to be followed: 
 
 Mild: The AE is transient and easily tolerated by the subject 
 Moderate: The AE causes the subject discomfort and interrupts the subject’s 
daily activities 
 Severe: The AE causes considerable interference with the subject’s usual 
activities; may be incapacitating and may require hospitalization 
 
8.3.2. Relationship with Study Device 
 
On the Adverse Event Report, the PI will characterize the AE’s relationship with the 
study device by indicating one of the following: 
 
 Definitely Related: clearly related to the research 
 Probably Related: likely related to the research 
 Possibly Related: may be related to the research but information not yet available 
to assess the likelihood of this 
 Probably Not Related: doubtfully related to the research 
 Definitely Not Related: clearly not related to the research 
 
8.3.3. Expectedness 
 
The PI will be responsible for determining whether an AE is expected or unexpected. An 
AE will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information described for the study device. This assessment 
 
8.4. Time Period and Frequency for Event Assessment and Follow-Up 
 
What Event is Reported 
When is Event Reported 
By Whom is Event 
Reported 
To Whom is Event Reported 
Fatal or life-threatening 
unexpected, suspected 
serious adverse reactions 
Within 7 calendar days of 
initial receipt of information 
Investigator 
 
Local/Internal IRB 
 
NHLBI and/or Data 
Coordinating Center (DCC) 
 
 
Sponsor or Designee 
 
FDA (if IND study) 
Non-fatal, non-life-
threatening unexpected, 
Within 15 calendar days of 
initial receipt of information 
Investigator 
 
Local/Internal 
IRBs/Institutional Officials 

 
 
21 | P a g e  
 
suspected serious adverse 
reactions 
 
NHLBI and/or DCC 
 
 
Sponsor or Designee 
 
FDA (IND/Marketed 
Products) 
 
All participating 
investigators 
Unanticipated adverse device 
effects 
Within 10 working days of 
investigator first learning of 
effect 
Investigator 
 
Local/internal IRBs 
 
NHLBI and/or DC 
 
 
Sponsor or Designee 
 
FDA (if IDE study) 
Unanticipated Problem that 
is not an SAE 
Within 14 days of the 
investigator becoming aware 
of the problem 
Investigator 
 
Local/internal 
IRBs/Institutional Officials 
 
NHLBI and/or DCC 
All Unanticipated Problems 
Within 30 days of the IRB’s 
receipt of the report of the 
UP from the investigator 
IRB 
 
OHRP 
 
 
Investigator 
 
IRB 
 
 
8.5. Safety Monitoring  
 
If necessary, the PI will collaborate with the Riverside Medical Center IRB to develop a 
safety monitoring plan to ensure the proper conduct of monitoring study data and activities. 
 
9. Statistical Considerations 
9.1. Statistical and Analytical Plans 
 
A detailed statistical analysis plan will be developed and added to the study protocol on a 
later date.   
 
9.2. Measures to Minimize Bias 
9.2.1. Enrollment / Randomization / Masking Procedures 
 
Patients will be randomly assigned on a 1:1 ratio (ECD during RF ablation:No ECD 
device during RF ablation) one of two study groups. A random permuted block will be 
generated to decide the randomization assignments. The rationale for the use of random 
permuted block assignment is to ensure a 1:1 group assignment ratio. 
 
To minimize bias, the individual who evaluates the radiographic imaging will be blinded 
to the study hypotheses and subject’s group assignment, so as not to influence his/her 
evaluation of the condition of the subjects’ esophagus. It is not possible to blind the PI, as 
he will be performing the procedure. Further, the patient will be blinded to the study 
group to which he or she was assigned. Study subjects will be debriefed regarding his or 
her study assignment at the final study visit. The informed consent form will explain this 
process to subjects. The rationale for blinding subjects to their study group assignment is 
to minimize the influence of the Placebo Effect. 

 
 
22 | P a g e  
 
 
10. Source Documents 
 
As part of conducting an IRB-approved study, the PI will permit authorized representatives of 
the Riverside Medical Center IRB and regulatory agencies to examine (and when permitted by 
applicable law, to copy) clinical records for the purposes of quality assurance reviews, audits, 
and evaluations of the study safety, progress, and data validity.  
 
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical study necessary for the reconstruction and evaluation of the study. This 
may include, but is not limited to, hospital records, clinical and office charts, lab notes, 
memoranda, evaluation checklists, pharmacy dispensing records, radiographic imaging, and 
other study-related documents. A case report form will be used to organize all the study data.  
 
11. Ethics/Protection of Human Subjects 
11.1. 
Ethical Standard 
 
The investigator will ensure that this study is conducted in full conformity with Regulations 
for Protection of Human Subjects of Research. 
 
11.2. 
Institutional Review Board 
 
The protocol, informed consent form, and all participant materials will be submitted to the 
Riverside Medical Center IRB for review and approval. Approval of both the protocol and 
the consent form must be obtained before any participant is enrolled. Any amendment to the 
protocol will require review and approval by the IRB before any changes are implemented to 
the study. All changes to the consent form will be IRB approved and a determination will be 
made regarding whether previously consented participants need to be re-consented. 
 
11.3. 
Informed Consent Process 
 
Subject participation in this research is voluntary. Subjects must give informed consent 
before they can be enrolled in this study, and the Principal Investigator is responsible for 
obtaining informed consent before any study-related activities are performed (this includes 
any screening procedures that are not considered conventional care). 
 
The PI will obtain and document the subject’s informed consent in accordance with State and 
Federal regulations and Riverside Medical Center’s Institutional Review Board policies. The 
informed consent form must be approved by the Riverside IRB. 
 
The informed consent process will include the following steps: 
 Be conducted by the PI or designated study team member with appropriate training 
 Avoid any undue influence or coercion of subjects to participate in the study 
 Make it clear to the subject that participation in the study is voluntary and that 
refusing to participate in the study will not result in any loss of benefits 
 Make no statement that the subject’s legal rights are waived by participating 

 
 
23 | P a g e  
 
 Use plain language that is understandable to the subject to describe all aspects of the 
study that subjects need to make an informed decision to participant 
 Provide sufficient time for the subject to consider his/her participation 
 Answer all of the subject’s questions to ensure he/she fully understands the study 
 Provide subjects with new information throughout the study, if applicable 
 Ensure the informed consent form is signed and dated by the subject 
 
Any changes to the informed consent form will be approved by Riverside Medical Center’s 
IRB before use in the informed consent process. 
 
 
11.3.1. Consent and Other Informational Documents Provided to Subjects 
 
Consent forms describing in detail the study device, study procedures, and risks are given 
to the subject and written documentation of informed consent is required before starting 
intervention. The informed consent form is submitted with this protocol. 
 
11.4. 
Subject and Data Confidentiality 
 
Study data will be recorded on an encrypted Excel spreadsheet, and all copies of source 
documents will be locked in a cabinet only accessible to the study investigators. Study ID 
numbers will be assigned to subjects, and the Study ID will be used in lieu of the subject’s 
name on the Case Report Form. 
 
Any publications or presentations resulting from this study will not contain any identifying 
information of subjects enrolled in this study.  
 
Study data may be audited or monitored by the Riverside Medical Center IRB and State and 
Federal agencies that have the right to access the data in order to ensure the study is being 
conducted in accordance with applicable regulations and policies. 
 
12. Data Handling and Record Keeping 
12.1. 
Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the Principal Investigator. The Principal Investigator is 
responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
recorded. All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data. Black ink is required to ensure clarity of reproduced copies. 
When making changes or corrections, cross out the original entry with a single line, and 
initial the date on which the change was made.  
 
Clinical data (including Adverse Events, concomitant medications, and expected adverse 
reactions data) and clinical laboratory data will be entered into an Excel spreadsheet. The 
spreadsheet will include a password and will only be accessible to authorized study 
personnel. 
 

 
 
24 | P a g e  
 
12.2. 
Study Records Retention 
 
Study documents must be retained for a minimum of 3 years after the study has been 
formally closed (e.g., submission of a study closure report to the IRB). 
 
12.3. 
Protocol Deviations 
 
A protocol deviation is any noncompliance with the clinical trial protocol. The 
noncompliance may either be on the part of the participant, the investigator, or the study site 
staff. As a result of deviations, corrective actions are to be developed by the study team, or 
required by the IRB, and implemented promptly to minimize the occurrence of future 
deviations. 
 
It is the responsibility of the PI to use continuous vigilance to identify and report deviations 
within 7 working days of identification of the protocol deviation. All deviations must be 
address in study source documents and reported to the Riverside Medical Center IRB.  
 
13. Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the device 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the 
design, conduct, analysis, publication, or any aspect of this study will be disclosed and reviewed. 
A conflict of interest statement will be submitted to the Riverside Medical Center IRB to review.  
 
14. References 
 
 
1. 
Tzou WS, Russo AM: Luminal esophageal temperature monitoring for the prevention of 
esophageal injury during left atrial ablation: LET it be? J Cardiovasc Electrophysiol 2013, 
24(9):965-967. 
2. 
Nair GM, Nery PB, Redpath CJ, Lam BK, Birnie DH: Atrioesophageal fistula in the era of atrial 
fibrillation ablation: a review. Can J Cardiol 2014, 30(4):388-395. 
3. 
Liu E, Shehata M, Liu T, Amorn A, Cingolani E, Kannarkat V, Chugh SS, Wang X: Prevention of 
esophageal thermal injury during radiofrequency ablation for atrial fibrillation. J Interv Card 
Electrophysiol 2012, 35(1):35-44. 
4. 
Scanavacca M: Current Atrial Fibrillation Ablation: An Alert for the Prevention and Treatment 
of Esophageal Lesions. Arquivos brasileiros de cardiologia 2016, 106(5):354-357. 
5. 
Kumar S, Brown G, Sutherland F, Morgan J, Andrews D, Ling LH, Mc LA, Lee G, Robinson T, Heck 
P et al: The transesophageal echo probe may contribute to esophageal injury after catheter 
ablation for paroxysmal atrial fibrillation under general anesthesia: a preliminary observation. 
J Cardiovasc Electrophysiol 2015, 26(2):119-126. 
6. 
Leite LR, Santos SN, Maia H, Henz BD, Giuseppin F, Oliverira A, Zanatta AR, Peres AK, Novakoski 
C, Barreto JR et al: Luminal esophageal temperature monitoring with a deflectable esophageal 
temperature probe and intracardiac echocardiography may reduce esophageal injury during 
atrial fibrillation ablation procedures: results of a pilot study. Circ Arrhythm Electrophysiol 
2011, 4(2):149-156. 

 
 
25 | P a g e  
 
7. 
Carroll BJ, Contreras-Valdes FM, Heist EK, Barrett CD, Danik SB, Ruskin JN, Mansour M: Multi-
sensor esophageal temperature probe used during radiofrequency ablation for atrial 
fibrillation is associated with increased intraluminal temperature detection and increased risk 
of esophageal injury compared to single-sensor probe. J Cardiovasc Electrophysiol 2013, 
24(9):958-964. 
8. 
Hornero F, Berjano EJ: Atrial ablation and esophageal injury: comments on an experimental 
study. J Thorac Cardiovasc Surg 2006, 132(1):212-213; author reply 213-214. 
9. 
Good E, Oral H, Lemola K, Han J, Tamirisa K, Igic P, Elmouchi D, Tschopp D, Reich S, Chugh A et 
al: Movement of the esophagus during left atrial catheter ablation for atrial fibrillation. J Am 
Coll Cardiol 2005, 46(11):2107-2110. 
10. 
Deneke T, Bunz K, Bastian A, Pasler M, Anders H, Lehmann R, Meuser W, de Groot JR, Horlitz M, 
Haberkorn R et al: Utility of esophageal temperature monitoring during pulmonary vein 
isolation for atrial fibrillation using duty-cycled phased radiofrequency ablation. J Cardiovasc 
Electrophysiol 2011, 22(3):255-261. 
11. 
Aupperle H, Doll N, Walther T, Kornherr P, Ullmann C, Schoon HA, Mohr FW: Ablation of atrial 
fibrillation and esophageal injury: effects of energy source and ablation technique. J Thorac 
Cardiovasc Surg 2005, 130(6):1549-1554. 
12. 
Berjano EJ, Hornero F: A cooled intraesophageal balloon to prevent thermal injury during 
endocardial surgical radiofrequency ablation of the left atrium: a finite element study. Phys 
Med Biol 2005, 50(20):N269-279. 
13. 
Lequerica JL, Berjano EJ, Herrero M, Hornero F: Reliability assessment of a cooled 
intraesophageal balloon to prevent thermal injury during RF cardiac ablation: an agar 
phantom study. J Cardiovasc Electrophysiol 2008, 19(11):1188-1193. 
14. 
Lequerica JL, Berjano EJ, Herrero M, Melecio L, Hornero F: A cooled water-irrigated 
intraesophageal balloon to prevent thermal injury during cardiac ablation: experimental study 
based on an agar phantom. Phys Med Biol 2008, 53(4):N25-34. 
15. 
Arruda MS, Armaganijan L, Di Biase L, Rashidi R, Natale A: Feasibility and safety of using an 
esophageal protective system to eliminate esophageal thermal injury: implications on atrial-
esophageal fistula following AF ablation. J Cardiovasc Electrophysiol 2009, 20(11):1272-1278. 
16. 
Tsuchiya T, Ashikaga K, Nakagawa S, Hayashida K, Kugimiya H: Atrial fibrillation ablation with 
esophageal cooling with a cooled water-irrigated intraesophageal balloon: a pilot study. J 
Cardiovasc Electrophysiol 2007, 18(2):145-150. 
17. 
Scanavacca MI, Pisani CF, Neto S, Tamaki W, Santo sR, Guirao C, Oyama H, Aielo V, Leiner A, 
Sosa E: Cooled intra-esophageal balloon to prevent thermal injury of esophageal wall during 
radiofrequency ablation. In: ESC Congress 2007, 1 - 5 September. vol. 28. Vienna, Austria; 2007: 
156. 
18. 
Kuwahara T, Takahashi A, Okubo K, Takagi K, Yamao K, Nakashima E, Kawaguchi N, Takigawa M, 
Watari Y, Sugiyama T et al: Oesophageal cooling with ice water does not reduce the incidence 
of oesophageal lesions complicating catheter ablation of atrial fibrillation: randomized 
controlled study. Europace : European pacing, arrhythmias, and cardiac electrophysiology : 
journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular 
electrophysiology of the European Society of Cardiology 2014, 16(6):834-839. 
19. 
Sohara H, Satake S, Takeda H, Yamaguchi Y, Nagasu N: Prevalence of esophageal ulceration 
after atrial fibrillation ablation with the hot balloon ablation catheter: what is the value of 
esophageal cooling? J Cardiovasc Electrophysiol 2014, 25(7):686-692. 
 
 
 

 
 
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