Evaluate the Efficiency Impact of Conducting Active Temperature Management During Cardiac Cryoablation Procedures
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Advanced Cooling Therapy, Inc., d/b/a Attune Medical

Clinical Protocol: Evaluating Procedural Efficiency with Active Esophageal Warming during Cardiac Cryoablation Procedures 
 
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Evaluating Procedural Efficiency with Active Esophageal Warming during Cardiac 
Cryoablation Procedures 
 
 
Protocol ID: WMC-Cryo 
Version Number:  1.1 June 12, 2019 
 
 
NCT04087122 
 

Clinical Protocol: Evaluating Procedural Efficiency with Active Esophageal Warming during Cardiac Cryoablation Procedures 
 
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PROTOCOL SYNOPSIS 
 
Sponsor:  
Advanced Cooling Therapy d/b/a Attune Medical, 3440 S. Dearborn St 
#215-S, Chicago, IL, 60616, USA 
Version: 
1.1 June 12, 2019 
Protocol ID 
WMC-Cryo 
PI/Site:  
Objective: 
 
This pilot study will evaluate the efficiency impact of conducting active 
temperature management during cardiac cryoablation procedures. 
Patient Population: 
This study is intended for patients undergoing left atrial cryoablation for 
pulmonary vein isolation for the treatment of atrial fibrillation. 
Study Design: 
Prospective, single center pilot study 
Study Conduct: 
This prospective interventional pilot study will use the FDA cleared Attune 
Medical esophageal heat transfer device (ensoETM) to actively warm the 
esophagus when cryoablations are performed on the posterior atrial wall.  
In consented participants, following induction of anesthesia and 
intubation, the ensoETM will be placed into the esophagus according to 
the device Instructions and maintained at 42°C.  Total procedure time 
from trans-septal puncture to pulmonary vein isolation (PVI) will be 
recorded.   
All patients will be followed up in total for 6 weeks (Long Term FU visit) 
after the procedure to document any clinical complication related to 
thermal esophageal injuries if applicable. 
Study Duration: 
The study duration is projected to be approximately 145 days (estimated 
3-month enrollment and a 6-week long term follow-up window). 
Inclusion Criteria: 
1. Adult patients (age over 18 years) 
2. Undergoing left atrial cryoablation for the treatment of atrial 
fibrillation including pulmonary vein isolation 
3. Patients must be able to understand and critically review the informed 
consent form. 
4. Subjects must understand and agree to study requirements and sign a 
written informed consent 

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Exclusion Criteria: 
1. Patients who are unable to provide informed consent. 
2. Significant co-morbidities that preclude standard ablation procedure. 
3. Patients with <40 kg of body mass 
4. Patients with relevant esophageal pathology (e.g. esophageal cancer, 
esophageal varices) 
Primary Endpoint: 
Total time of active ablation procedure, measured from trans-septal 
puncture to achievement of PVI.   
Sample Size: 
Up to 20 participants will be enrolled in the study.  
 
 
 

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TABLE OF CONTENTS 
 
1 
Protocol Synopsis ........................................................................................................................... 2 
2 
Table of Contents............................................................................................................................ 4 
3 
Introduction ...................................................................................................................................... 6 
3.1 
Background ............................................................................................................................ 6 
3.2 
Study Objective, Hypothesis and Rationale ...................................................................... 7 
3.3 
Primary Endpoint ................................................................................................................... 7 
4 
Study Protocol ................................................................................................................................. 7 
4.1 
Study Design.......................................................................................................................... 7 
4.2 
Study Device Description and Intended Use .................................................................... 7 
4.3 
Installation Use and Storage of the Device ....................................................................... 8 
4.4 
Subject Study Population ..................................................................................................... 9 
4.5 
General Inclusion Criteria .................................................................................................... 9 
4.6 
General Exclusion Criteria ................................................................................................... 9 
5 
Data collection and management ................................................................................................. 9 
5.1 
Confidentiality ........................................................................................................................ 9 
5.2 
Informed Consent................................................................................................................ 10 
5.3 
Data De-Identification ......................................................................................................... 10 
5.4 
Data Management .............................................................................................................. 10 
5.4.1 
Case Report Forms........................................................................................... 10 
5.4.2 
Monitoring Plan .................................................................................................. 11 
5.4.3 
Protocol Deviations and Modifications ........................................................... 11 
5.4.4 
Data Analysis and Acceptance ....................................................................... 11 
6 
Study Procedure and Assessments ........................................................................................... 13 
6.1 
Pre-Procedure Subject Preparation/Baseline ................................................................. 13 
6.2 
Index Procedure .................................................................................................................. 13 
6.3 
Data Collection During AF Ablation Procedure .............................................................. 14 
6.4 
Hospital Discharge .............................................................................................................. 15 
6.5 
Study Duration and Early Termination ............................................................................. 15 
6.6 
Protocol Deviations ............................................................................................................. 15 
6.7 
Adverse Event (AE) Reporting Requirements ................................................................ 15 
7 
Risk Management ......................................................................................................................... 15 
7.1 
Risk Analysis........................................................................................................................ 15 
7.1.1 
Risk Analysis of esophageal damage related to cryoablation .................... 16 
7.1.2 
Risk Benefit Summary ...................................................................................... 16 
8 
Adverse Event Definitions and Classifications ......................................................................... 17 
8.1 
Adverse Events ................................................................................................................... 17 
8.2 
Anticipated Adverse Events and Device Effects ............................................................ 18 
8.3 
Duration of Follow-up Post Adverse Events ................................................................... 18 

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8.4 
Device Failures and Malfunctions..................................................................................... 18 
9 
Device Accountability ................................................................................................................... 19 
10 
ISO 14155 Compliance ................................................................................................................ 19 
11 
Publication Policy .......................................................................................................................... 19 
12 
Acronyms ....................................................................................................................................... 19 
13 
References ..................................................................................................................................... 20 
 
 
 

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INTRODUCTION 
3.1 Background  
 
Left atrial catheter ablation including pulmonary vein isolation  is a standard therapy in the management 
of symptomatic  atrial fibrillation; however thermal esophageal injury is a known potential consequence 
of this procedure.1-4 Delivery of radiofrequency (RF) energy necessary to perform left atrial ablation has 
the potential to cause injury to the nearby esophagus including ulceration, hematoma, spasm, 
esophageal motility disorders, and, in the most extreme case, atrial-esophageal fistula.1,2  Esophageal 
mucosal lesions are the likely precursor to AEF, and esophageal mucosal lesions have been detected on 
post-ablation endoscopy after pulmonary vein isolation with an incidence ranging from 3% to 60%.5-8  
Active esophageal cooling during RF ablation as a means of esophageal injury prevention has been 
investigated through mathematical models, pre-clinical studies, and in clinical trials. Existing data 
support the efficacy of this approach, but the practice has not been widely adopted due to lack of a 
commercially available device. 9-16   
The incidence of esophageal injury after cryoballoon ablation is not as well studied; however, data 
published to date suggest that the incidence is more common than previously assumed.  In a study of 50 
patients with drug-refractory paroxysmal atrial fibrillation or short-standing persistent atrial fibrillation, 
PVI was performed using the second-generation cryoballoon, and esophageal thermal lesions were 
found in 12% to of patients.17  Furnkranz et al., in their study of 94 consecutive patients undergoing PVI 
for paroxysmal or persistent atrial fibrillation found that decreasing the cut-off threshold resulted in a 
decrease in esophageal lesions identified with endoscopy.18    A review of documented cases of atrio-
oesophageal fistula associated with cryoballoon ablation found that it was most commonly related to 
the LIPV.19   Overall mortality rate was 64%, and of survivors, at least 1 patient was left with signiﬁcant 
neurologic deﬁcits.19  AEF has been reported with use of LET monitoring with temperatures remaining 
above 20°C, and even with a cutoff value of 15°C (much lower than current manufacturer 
recommendations), esophageal lesions occur in 1.5% of patients.17-23 
A new esophageal heat transfer device (ensoETM, Attune Medical, Chicago, IL, USA) was recently 
commercialized for a variety of patient temperature management needs.24-29  This device provides a 
closed-circuit water flow through a multi-channel cylindrical silicone tube placed in the esophagus 
analogously to a standard orogastric tube. Warming or cooling a patient is accomplished through 
conductive heat transfer across the esophagus and convective heat transfer through the device.27,30  
Esophageal heat exchange is designed to take advantage of the favorable heat exchange environment 
created by proximity to the heart and great vessels. The device includes an independent lumen to 
decompress the stomach and avoid distention of the esophagus away from the device, which ensures 
good contact with the esophageal mucosa, thus maximizing heat transfer between the device and the 
patient. The esophageal heat transfer device is made of standard medical-grade silicone and is generally 
similar in shape and size to gastric tubes currently used and other devices routinely placed in the 
esophagus (esophagogastroduodenoscopy scopes, transesophageal echocardiography scopes, Ewald 
tubes, etc.).   
Clinical studies in a variety of scenarios have shown strong support for the efficacy and safety of the 
esophageal heat transfer device in critical care and OR settings.27,31-41 Specifically, the device has 
demonstrated effectiveness in the intentional reduction of patient body temperature below normal for 
conditions such as cardiac arrest,26,31,34 the reduction of patient temperature from hyperthermic levels 

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to normal range, 42 the prevention of inadvertent perioperative hypothermia, 29,43 and the reduction of 
elevated intracranial pressure.32 
A number of studies of the device have been completed, or are in progress, evaluating feasibility, safety, 
and effect size of esophageal protection during both RF ablation and cryoablation, including pre-clinical 
models and formal randomized clinical trials.44-49  Because the impact on procedural time has not yet 
been evaluated, the purpose of this study is to determine the impact on procedural efficiency of 
cryoablation procedures performed using esophageal heat transfer with the ensoETM. 
3.2 Study Objective, Hypothesis and Rationale  
The objective of this study is to evaluate the impact on procedural efficiency of ablation procedures 
performed using esophageal heat transfer to warm the esophagus during left atrial cryoablation.  This 
study is designed to measure procedural time of cryoablation to obtain pulmonary vein isolation (PVI) 
and serve as a pilot to compare to historical controls and enable adequate determination of sample size 
requirements for a subsequent larger study.  The hypothesis is that active esophageal warming will show 
a reduced procedural time when compared to standard of care using esophageal temperature 
monitoring.   
3.3 Primary Endpoint 
Procedural time, from trans-septal puncture to attainment of successful PVI.  Ablation will be performed 
as standard procedure with pre-specified ablation technology on the posterior left atrial wall using 
standard cryoablation practice. 
4 
STUDY PROTOCOL 
4.1 Study Design 
This study is a prospective, pilot study using the Attune Medical ensoETM esophageal heat transfer 
device to actively warm the esophagus during cryoablation procedures. This design is appropriate to 
gather the data needed regarding overall procedural time, compare this to historical controls, and 
estimate a sample size for a larger study powered for statistical significance.   
Once patient consent is obtained, the subject will undergo preparation and anesthesia procedures 
following standard practice. Once the patient is intubated, the esophageal heat transfer device will be 
placed into the esophagus according to the IFU. The device will remain in place until the ablation 
procedure is completed and will be removed before extubation. Left atrial cryoablation using the standard 
approach will be performed with the ensoETM set at a temperature of 42°C.  
4.2 Study Device Description and Intended Use 
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. 

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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 (Figure 1). 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 72 hours or less. 
Distilled water circulates inside the ensoETM, water does not come into contact with the patient. 
 
Figure 1. ensoETM System 
Table 1: ensoETM System Components 
Diagram Letter 
Name 
Description 
A 
ensoETM  
ensoETM (ECD-01B or ECD-02B) 
B 
Tube set connector 
Stryker Model 8001-064-035 Insulated Clik-Tite Hose or 
Cincinnati Sub-Zero connector hose (CSZ P/N 286) 
C 
Heat exchanger 
Stryker Altrix Model 8001 Precision Temperature Management 
System or Cincinnati Sub-Zero Blanketrol III Hyper-Hypothermia 
System 
 
The ensoETM has received FDA clearance and its intended use is as a thermal regulating device intended 
to connect to an external heat exchanger in order to modulate and control patient temperature in the 
operating room, recovery room, emergency room, or intensive care unit. 
 
 
4.3 Installation Use and Storage of the Device  
Detailed operation of the system is included in the IFU. The ensoETM device should be stored in a dry 
and clean place and handled according to the IFU. The research team will ensure that the heat exchange 
unit will be operated in accordance with the appropriate IFU. 
Power Supply 

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The Company will provide on-site support for training and operation of the ensoETM according to the 
IFU. As the insertion procedure is similar to placing a standard orogastric tube, it is expected that 
insertion of the probe and operation of the ensoETM will require limited training and ongoing support, 
however, the Company will support cases as requested.  
4.4 Subject Study Population 
Subjects that are indicated for first catheter-based ablation of AF using radiofrequency ablation 
treatment will be eligible for the study.  
4.5 General Inclusion Criteria 
Participants must meet all of the following general inclusion criteria:  
1. 
Adult patients (age over 18 years) 
2. 
Undergoing cryoablation for the treatment of atrial fibrillation, including pulmonary vein 
isolation 
3. 
Patients must be able to understand and critically review the informed consent form. 
4. 
Subjects must understand and agree to study requirements and sign a written informed 
consent. 
4.6 General Exclusion Criteria 
Subjects must meet none of the following general exclusion criteria: 
1. 
Patients who are unable to provide informed consent. 
2. 
Significant co-morbidities that preclude standard ablation procedure. 
3. 
Patients with <40 kg of body mass 
4. 
Patients with relevant esophageal pathology (e.g. esophageal cancer) 
 
5 
DATA COLLECTION AND MANAGEMENT 
5.1 Confidentiality 
All parties involved, at all times throughout the clinical investigation shall observe confidentiality of data. 
All data shall be secured against unauthorized access, and the privacy of each subject and confidentiality 
of his/her information shall be preserved in reports and when publishing any data. Study subject 
identification will remain confidential by the assignment and use of study specific identification 
numbers. All study documentation and/or medical records collected and used for study purposes will be 
pseudonymized so that an individual subject will not identified outside the study. Data safety applies to 
the standard and patient data safety is secured throughout the study. All patients will give informed 
consent on data safety issues. 

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5.2 Informed Consent 
This study will require subjects to have the ensoETM inserted intra-orally prior to the ablation 
procedure. As the ensoETM is not routinely used at this Center, detailed information regarding risks are 
included in the Informed Consent Form presented to subjects enrolling in the study. 
This study will require that the operating physician carry out the standard of care for cryoablation. 
Ultimately, the number and location of ablation lesions and determination of whether to end the 
procedure will be at the discretion of the operating physician and will be based on the Center´s 
standards as used in recent years. Subjects will be required to sign an Informed Consent Form detailing 
the potential risks and benefits of their study participation. A study subject can withdraw consent at any 
time, and for any reason. All patients included will also sign a separate informed consent for 
cryoablation procedure as standard in the Center. 
5.3 Data De-Identification 
Except where required by law, information shared with persons and organizations outside of the 
investigational site will not identify the subject by name, government identification number, address, 
telephone number, or any other direct personal identifier. To ensure that subject identification is kept 
confidential, a subject’s unique identification number will be employed. At the investigational site, a 
confidential file of informed consent forms and anonymization code numbers will be retained, 
accessible to the Principal Investigator and/or designee and other authorized personnel. The subject’s 
unique identification number will be employed on all source documentation that is used for data review 
and analysis.  
5.4 Data Management 
Data entry and development of the primary database of the study will be performed by PI or his 
designee(s). Data inserted into the database will be reviewed after 10 cases, based on original patient 
documentation. In case of data queries, PI will resolve based on original patient documentation.  
The database is password secured and has an audit trail. Changes to the database can only be made by 
the delegated study group. Verification of data will be done after 10 cases based on original patient 
documentation. PI or designee will also be responsible for auditing the database and confirming the 
overall integrity of the database.  
5.4.1 Case Report Forms 
The Center will perform primary data collection based on source-documented hospital chart reviews 
and data transcribed or exported from the mapping and navigation system as well as from the 
cryoablation console, from which temperature data and timing will be transcribed.  

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Deviations from the study protocol or adverse events will be recorded on the appropriate forms 
(Deviation / Adverse Event Report). Deviations will be documented, and patients will be excluded from 
final analysis although deviations will be documented and summarized in final reports. Any deviations 
that concern patient safety and/or the rights of a study subject will be reported to IRB within 24 hours. 
5.4.2 Monitoring Plan 
The investigator and research team will allocate adequate time for monitoring activities and monitoring 
of all data will be performed on a regular basis throughout the study.  For monitoring access to all the 
above noted study-related documents and study related facilities (e.g. clinical EP laboratories) will be 
granted. Monitoring will be performed by a committee not involved in the study conduct. 
5.4.3 Protocol Deviations and Modifications 
Any changes to the approved clinical study must originate from Sponsor in the form of a protocol 
amendment that must be submitted to the relevant IRB contact. Protocol deviations should be avoided 
by the PI and site supporting staff. Any deviation from the protocol should be reported to the Sponsor. 
Any deviation to the clinical study will be reported to the ethical committee in accordance with local 
requirements. In the situation where deviating from the protocol is in order to protect the life or 
physical wellbeing of the subjects, which are considered emergency deviations, these should be 
reported to the Sponsor and Ethical Committee per their local guidelines. 
A deviation is any variance from the Investigational Plan requirements (e.g., failure to obtain informed 
consent, failure to meet inclusion/ exclusion, etc.). 
5.4.4 Data Analysis and Acceptance 
All analyses will be performed using validated statistical software. In general, the study endpoints will be 
assessed relative to the study objectives. Patient data listings and tabular and graphical presentations of 
baseline and operative characteristics and outcome results will be created. After securing 
appropriateness and correctness of data statistical analysis will be performed by a dedicated 
independent statistician. 
5.4.4.1 Sample Size Determination 
 
This study will serve to obtain data from which a formal sample size estimate is made for subsequent 
larger study design.  As a rough estimate prior to obtaining real-world data on which to base a sample 
size estimate, assuming a control patient procedure duration of 110 minutes, and a treatment patient 
duration of 90 minutes, with a standard deviation of 20 minutes, an estimated total of 16 patients in the 
treatment arm, with 16 patients from historical control, will provide 80% power and an alpha of 0.05 for 
identification of a significant difference between groups.   

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5.4.4.2 Analysis Populations 
Safety Population 
All enrolled subjects who underwent a cryoablation of persistent and paroxysmal atrial fibrillation 
procedure will be included in the safety population. 
Evaluable Population 
All enrolled subjects who have received catheter ablation of persistent and paroxysmal atrial fibrillation 
with complete ablation data and procedural timing will be included in the evaluable population.  
Primary Endpoint Analysis 
The primary endpoint of this study will be the total time of active ablation procedure, measured from 
trans-septal puncture to achievement of PVI.   
Secondary Endpoint Analysis 
Secondary endpoints include: 
1. Total procedure time (from patient entry to EP lab until discharge to PACU) 
2. Number of procedural pauses during left atrial instrumentation 
3. Total duration of fluoroscopy use 
 
5.4.4.3 Safety Analysis 
All safety-related issues related to the usage of the device will be recorded and documented as device-
related AEs (ADE). All safety analyses will be performed on the safety population. No imputation of 
missing observations will be performed. The Medical Dictionary for Regulatory Activities (MedDRA) 
version 13.0 or later will be used to code all AEs to a system organ class (SOC) and a preferred term (PT) 
within the SOC.  
The incidence and frequency of AEs will be summarized by system organ class and preferred term for all 
AEs, device-related AEs (with relationship to study devices and/or study-device-related procedure), 
serious device-related AEs and device-related AEs leading to study withdrawal and death. The incidence 
of ADEs will also be tabulated by seriousness, severity, and relationship to study devices and/or 
procedure. 
No AEs will be recorded for study purposes that are not specifically device-related (e.g. arrhythmia 
recurrences) as this is not within the scope of the study.  
 

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6 
STUDY PROCEDURE AND ASSESSMENTS 
 
Table 2: Schedule of Assessments and Procedures 
Assessment/ 
Evaluation 
Baseline 
(-14 days) 
Day 0 
(pre-admission)  
Index Procedure 
Discharge (+1d) 
Pre-screening for Inclusion/ 
Exclusion Criteria 
X 
 
 
 
Medical History 
X 
 
 
 
Demographics 
X 
 
 
 
Informed Consent 
 
X 
 
 
Randomization 
N/A 
 
 
 
Device-related Adverse Events 
 
 
X 
X 
 
 
6.1 Pre-Procedure Subject Preparation/Baseline 
Prior to subject participation the following steps will be completed and documented in the CRF: 
1. Signed informed consent is obtained. 
2. Confirmation that all inclusion criteria are met. 
3. Confirmation that no exclusion criteria are present.  
4. All subjects enrolled into this study will undergo and have documented the following 
evaluations (within two weeks prior to study unless otherwise noted) as standard of care in the 
Center but not related to the study:  
a. Medical history and physical examination  
b. Pregnancy test in female of childbearing potential  
c. Standard of care cryoablation pre-procedure testing if performed (CT or/and TEE)  
Informed consent will be obtained by the study investigators after discussion with the patient. The study 
investigators will provide additional information required and requested by the patient. Any information 
needed for fulfilling the study requirements will be gathered prior to inclusion. Enrollment begins when 
the informed consent form has been executed. 
6.2 Index Procedure 
Cardiac Ablation 
Only participants who are scheduled for a pulmonary vein isolation are eligible for participation in the 
trial. Cardiac ablation will be performed using standard cryoablation technology. Ablation will be 
performed to electrically isolate the pulmonary veins from the left atrial myocardium. The settings for 

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cryoablation are standard protocol at this Center. This is a common and standard of care approach to 
cardiac ablation for atrial fibrillation and has been applied at the Center for the last X years. 
Active Esophageal Warming 
In consented patients, the ensoETM esophageal heat transfer device will be inserted according to 
standard protocol during preparation for the ablation procedure, following intubation. The ensoETM is a 
non-sterile multi-lumen silicone tube placed in the esophagus much like a standard orogastric tube. The 
ensoETM holds FDA clearance and is intended for use as a thermal regulating device intended to 
connect to an external heat exchanger in order to modulate and control patient temperature. The 
device will remain in place until the ablation procedure is completed. Patients will undergo cryoablation 
with the ensoETM device at a temperature of 42°C.  
 
Figure 2: The esophageal heat transfer device is constructed from medical grade silicone with an outer 
diameter of ~12mm (36 Fr), length of 758mm, and circulating water volume of 55mL. The device is 
placed similarly to an orogastric tube. Distilled water circulates inside the tube (never entering the 
patient), directly cooling the esophageal tissue. 
6.3 Data Collection During AF Ablation Procedure 
In this study the study team will collect ablation data from the ablation system.  
 
 

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6.4 Hospital Discharge 
Patients discharged from the hospital following the procedure will follow post procedural standard of 
care for cryoablation procedures.  
6.5 Study Duration and Early Termination 
Study duration is expected to be 3 months to allow for the standard follow-up. The IRB may suspend or 
prematurely terminate the clinical study at the investigation site. If suspension or premature 
termination occurs, the terminating party shall justify its decision in writing and promptly inform the 
other parties involved. If, for any reason, the Sponsor suspends or prematurely terminates the 
investigation the Sponsor shall inform the responsible regulatory authority and Ethics Committee as 
appropriate. 
6.6 Protocol Deviations 
Except for an emergency situation in which proper care for the protection, safety, and well-being of the 
study subjects requires medical treatment, the study will be conducted as described in the approved 
protocol, and in accordance with GCP and regulatory requirements. The investigator will not deviate 
from the protocol for any reason without prior written approval, except in cases of medical 
emergencies, when the deviation is necessary to eliminate an apparent immediate hazard to the 
subject. In that event, the investigator will notify the Sponsor or designee immediately by phone, and 
confirm notification to the Sponsor or designee in writing. 
Any deviation(s) from the protocol will be recorded and presented in the final clinical study report. 
6.7 Adverse Event (AE) Reporting Requirements 
All ADEs will be documented according to institutional standards. All ADEs must be monitored until they 
are adequately resolved or explained.  
SAEs where causal relationship to device and procedure can be excluded will be added to a summary 
table and reported quarterly. At the end of the study an evaluation report of all SAEs will be provided to 
the Ethics Committee if required.  
Definitions regarding adverse events can be found in Section 9. 
7 
RISK MANAGEMENT 
7.1 RISK ANALYSIS 
Risk analysis associated with the ensoETM device has been performed in accordance with ISO 14971: 
Application of Risk Management to Medical Devices. 

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Risk Management activities include 
• 
Identification of intended use 
• 
Identification of Hazards – Biological, Environmental, Radiation 
• 
Estimation of Risk 
• 
Risk Evaluation 
• 
Risk Control 
• 
Evaluation of overall residual risk 
• 
Risk Management Report 
The Attune Medical ensoETM has received CE Marking and FDA 510(k) clearance, and its intended use is 
as a thermal regulating device intended to connect to an external heat exchanger in order to modulate 
and control patient temperature. The ensoETM is constructed from medical grade silicone with an outer 
diameter of 12mm (36 Fr), length of 758mm, and circulating water volume of 55mL. Distilled water 
circulates inside the tube (never entering the patient), directly cooling the esophageal tissue. The device 
is placed similarly to an orogastric tube.  Risks associated with ensoETM use are similar to those of 
standard orogastric tubes.  
The overall risks associated with this study are the same risks associated with standard catheter 
ablation, including standard esophageal temperature monitoring. 
7.1.1 Risk Analysis of esophageal damage related to cryoablation 
Esophageal injury is a well-established risk associated with AF ablation procedures as well as with 
cryoablation procedures. The primary current strategy to minimize injury risk during cryoablation 
includes luminal esophageal temperature (LET) monitoring and cessation of cryoablation below a chosen 
threshold; however, atrio-esophageal fistulas have been reported with use of LET monitoring with 
temperatures remaining above 20°C, and even with a cutoff value of 15°C (much lower than current 
manufacturer recommendations), esophageal lesions occur in 1.5% of patients.17-23 
The ensoETM accommodates high flow rate without causing esophageal deformity. The device has been 
used safely in thousands of critical care patients. We expect there to be no incremental risk associated 
with the use of the ensoETM during cryoablation compared to the existing approach. Unlike 
temperature monitoring strategies that prompt reactive strategies (such as pausing ablation) this 
approach may actively reduce tissue damage while improving procedural efficiency, reducing the time 
under anesthesia, and reducing fluoroscopy usage.  
7.1.2 Risk Benefit Summary 
During this pilot study, the ensoETM will be inserted into the esophagus intra-orally while patients are 
under general anesthesia. The risks to the patient are expected to be similar or the same as those 
associated with the introduction of any standard orogastric tube.  

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Only personnel with knowledge of and experience in placing gastric tubes will be involved in the study. 
Patients will be continuously monitored throughout the procedure. 
All patients will be treated with standard of care technology and ablation settings. All procedures 
performed during the study are part of the standard approach to cryoablation patients at the Center.  
Subjects might not directly benefit from participation in the trial, but the findings of the current study 
will improve the knowledge of esophageal thermal lesion prevention strategies. Information gained in 
the current study will be applied to larger patient cohorts in the future, in an effort to reduce 
esophageal thermal injury and make AF ablation safer and more efficient. 
Cryoablations will be monitored in this study with the safest technology currently available and patients 
will receive optimized treatments using standard of care technology. All patients will be closely 
monitored and receive optimum diagnostic and therapeutic management. 
8 
ADVERSE EVENT DEFINITIONS AND CLASSIFICATIONS 
8.1 ADVERSE EVENTS 
Adverse events are categorized as defined in ISO 14155: 
Adverse event (AE): Any untoward medical occurrence in a subject 
Note: this definition does not imply that there is a relationship between the AE and the device under 
investigation 
Adverse device event (ADE): Any untoward and unintended response to a medical device. 
Note 1: this definition includes any event resulting from insufficiencies or inadequacies in the 
instructions for use or the deployment of the device. 
Note 2: this definition includes any event that is a result of a user error 
Serious adverse event (SAE): Adverse event that: 
1. Lead to a death 
2. Lead to a serious deterioration in the health of the subject: 
• 
resulted in a life-threatening illness or injury 
• 
resulted in a permanent impairment of a body structure or a body function 
• 
required in-patient hospitalization or prolongation of existing hospitalization 
• 
Resulted in medical or surgical intervention to prevent permanent impairment to body 
structure or a body function 
3. Lead to fetal distress, fetal death or a congenital abnormality or birth defect 

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Serious adverse device event (SADE): Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event or that might have led to any of these 
consequences if suitable action had not been taken or intervention had not been made or if 
circumstances had been less opportune. 
Note: The Investigator is responsible for any reporting requirements to the local government or 
Ethics Committee. 
Unanticipated serious adverse device event (USADE): is a serious adverse device effect which by its 
nature, incidence, severity or outcome has not been identified in the current version of the risk analysis 
report 
Note: Anticipated serious device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the risk analysis report. 
Emergency contact details for reporting SAEs and SADEs 24/7 are listed below: 
  
8.2 ANTICIPATED ADVERSE EVENTS AND DEVICE EFFECTS 
Acute Adverse Events that may possibly be caused by or associated with the use of the device or the 
related procedures in this clinical trial are anticipated and characterized in the device insert. 
8.3 DURATION OF FOLLOW-UP POST ADVERSE EVENTS  
All adverse events related to the device procedure (ADE) must be followed until resolution or until 
stable clinical endpoint is reached. All required treatments and outcomes of the adverse events must be 
recorded per reporting requirements defined in Section 5. 
8.4 DEVICE FAILURES AND MALFUNCTIONS  
All device failures and malfunctions will be documented on the CRF and reported to the Company within 
24 hours. Devices that fail or malfunction will be returned to Attune Medical for analysis as soon as 
practicable. Attune Medical will follow its internal procedure (QSP 8.2-1 Customer Inquiries and 
Complaints) to determine the course of testing, further reporting and any corrective action, if required.  
Device Failure:  
A device has failed if it does not perform according to labeling and negatively impacts the treatment 
while used according to the labeling.  
 

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Device Malfunction:  
A device malfunction is an unexpected change to the device that is contradictory to the labeling and 
may or may not affect device performance.  
All malfunctioning devices must be returned to Attune Medical after appropriate decontamination per 
hospital guidelines. Attune Medical will follow its internal procedure (QSP 8.2-1 Customer Inquiries and 
Complaints) to determine the course of testing, Medical Device Reporting and any corrective action, if 
required. 
9 
DEVICE ACCOUNTABILITY 
The Company’s devices will be identified by Lot Number. The site must maintain device accountability 
records documenting study device usage. This form must be maintained and reviewed by the study 
monitor. 
The manufacturer will provide the Center with devices, sufficient to provide the Center with 
approximately 10% additional devices to accommodate demonstration or replacement, to ensure that 
the maximum number of patients may be enrolled in this study. 
10 ISO 14155 COMPLIANCE  
This Clinical Trial has been designed and will be conducted in compliance with the Clinical Investigation 
Plan, ISO 14155:2011, Declaration of Helsinki, ICH Guidelines for Good Clinical Practice (GCP) and 
applicable local and national regulatory requirements. 
11 PUBLICATION POLICY  
Results of this investigation will be published in peer-reviewed scientific journals, and/or presented at 
scientific symposia. Company agrees to review and comment on manuscript/ presentation within sixty 
(60) days of receipt. 
12 ACRONYMS 
AE: Adverse event 
AEF: Atrio-esophageal fistula 
AF: Atrial Fibrillation 
EMR: Electronic Medical Record 
LET:  luminal esophageal temperature 

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RF:  Radiofrequency 
SAE: Serious adverse event 
SOC: Standard of care 
UP:  Unanticipated Problem 
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