A Prospective, Non-Randomized Study to Evaluate the CIRCA Esophageal Temperature Monitoring System in Prevention of Esophageal Lesions Following Atrial Fibrillation Radiofrequency Catheter Ablation
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: University of California, San Diego

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DIVISION OF CARDIOVASCULAR MEDICINE 
            GREGORY K FELD, MD 
PH  858-246-2972 
            PROFESSOR OR MEDICINE 
NIGHTS & WEEKENDS  619-543-6737  
 
 
 
            CARDIAC ELECTROPHYSIOLOGY 
FX  858-246-2958 
            DIRECTOR CCEP PROGRAM 
            9452 MEDICAL CENTER DR  MC 7411 
            ALTMAN BLDG, 3rd FL, RM 3E-313 
 
 
 
 
 
 
 
             LA JOLLA, CALIFORNIA 92037  
 
 
 
 
 
          
           
             gfeld@ucsd.edu 
 
 
 
Date: 5/29/2021 
 
RE: Circa/EGD Study Expansion Protocol 
 
To whom it may concern: 
 
This protocol (attached below) was approved by the IRB on 12/22/2016 (approval letter 
on file). 
 
Sincerely, 
 
Gregory Feld, MD 
 
 

 
UCSD Human Research Protections Program 
New Biomedical Application 
RESEARCH PLAN 
Version date: 9/30/2013 
 
1. 
PROJECT TITLE 
Project Title: A Prospective, Non-Randomized Study to Evaluate the CIRCA Esophageal Temperature 
Monitoring System in Prevention of Esophageal Lesions Following Atrial Fibrillation Radiofrequency Catheter 
Ablation 
 
2. 
PRINCIPAL INVESTIGATOR  
Gregory Feld, M.D 
 
3. 
FACILITIES 
UCSD Medical Center – Sulpizio Cardiovascular Center 
 
4. 
ESTIMATED DURATION OF THE STUDY 
12 months 
 
5. 
LAY LANGUAGE SUMMARY OR SYNOPSIS (no more than one paragraph) 
One rare but potentially fatal complication of radiofrequency catheter ablation (RFCA) with the use of the 
Circa™ monitoring system is the development of atrio-esophageal fistula due to thermal injury of the esophageal 
tissues. The Circa™ temperature monitoring probe and temperature monitoring system are currently used in 
RFCA procedures here at UCSD to monitor thermal output in an effort to reduce the risk of complications due to 
thermal injury. This study is being conducted to determine the short-term effects of radiofrequency AF ablation 
with the use of the Circa™ monitoring system on the esophageal (swallowing tube) lining the day after  AF 
ablation. Patients who choose to participate will receive an esophagoscopy  the day after  the ablation procedure 
to identify the presence or absence of esophageal lesions (number and size) reflecting damage to the lining of the 
esophagus.   
 
6. 
SPECIFIC AIMS 
To evaluate the effects of left atrial endocardial radiofrequency catheter ablation for AF, guided by the newly 
designed Circa ™ esophageal temperature probe and monitoring system, on formation of esophageal thermal 
lesions with post-ablation esophagoscopy. 
 
7. 
BACKGROUND AND SIGNIFICANCE 
Radiofrequency catheter ablation (RFCA) for treatment of AF has been performed for nearly 15 years, but is 
associated with a small percentage of complications, including the rare but potentially fatal atrio-esophageal 
fistula. In patients where the esophagus traverses the left atrium near posterior left atrial endocardial ablation 
sites, it is thought that thermal injury to the atrial and esophageal wall may lead in rare cases to the formation of 
an atrio-esophageal fistula, which can lead to fatal gastrointestinal hemorrhage, or fatal systemic embolization 
causing stroke and/or cardiac arrest. The diagnosis of atrio-esophageal fistula after ablation has unfortunately 
most commonly been after one of these fatal events, but earlier recognition of this rare complication based on 
symptoms, fever, transient bleeding or embolic events, has led to use of esophageal stenting, or emergency 
thoracic surgery, which can be life-saving in some cases. 
 
Due to the rarity of this complication, systematic study of its cause(s) is impossible, but in order to avoid it, it 
has been recommended in guidelines that ablation power and duration on the posterior left atrial wall be 
empirically limited, and in some cases esophageal position is marked by a barium swallow, or esophageal 
temperature and position can be monitored by a naso-gastric tube with an embedded temperature sensor 
(typically a single sensor in the past). 
 
Recently a multi-sensor (12 sensors) temperature monitoring probe (Circa™) has been developed and FDA 
approved, that can be placed in the esophagus (while the patient is under general anesthesia) and positioned 

 
 
Biomedical IRB Application Instructions 
Page 3 
under fluoroscopy directly posterior to the left atrium during RFCA for AF or left atrial flutter (LAAFL). This 
multi-sensor probe has the theoretical advantage of monitoring temperature at multiple locations in the 
esophagus (cranial to caudal temperatures spanning the left atrium are simultaneously displayed on monitor) 
during ablation, warning the operator of impending temperature rises during ablation and allowing ample time 
to terminate ablation and prevent esophageal heating above a target temperature of typically 38-39˚C. Limiting 
esophageal heating to this maximum level of temperature may prevent potentially serious thermal injury to the 
esophagus that could lead to potentially fatal atrio-esophageal fistula. 
 
In the electrophysiology laboratories at UCSD, where we have performed RFCA for AF and LAAFL for nearly 
15 years, in several thousand cases, and to our knowledge have had possibly 1 or 2 atrio-esophageal fistulas 
(presumed but not confirmed) develop in our patients, over a decade ago. These patients were treated at outside 
hospitals for associated comorbidities however, which were fatal, and the diagnosis was thus only suspected 
and not confirmed. Since that time we have always monitored esophageal position and temperature, and then 
for the last several years since its FDA approval, we have used the Circa™ temperature probe in all our patients 
and have had no reported cases of atrio-esophageal fistula. We recently began using a newly designed Circa™ 
probe (see Figure for old and new probe shape) with good results, and plan to evaluate it success in preventing 
esophageal thermal lesions as well. 
 
Previous studies have suggested that even when one reduces power during ablation at the posterior left atrium 
and monitors temperature, approximately 27% of patients will develop some evidence of esophageal thermal 
lesions (including endothelial esophageal ulcers or mediastinal changes). In addition, one center reports an even 
greater number of lesions observed when using the Circa™ probe during RFCA (although in this study power 
delivery and temperature were not modulated based on the temperature monitoring during ablation). 
 
In contrast, we believe that due to its sensitivity and ability to monitor esophageal temperature at multiple 
locations spanning the atrium, use of the Circa™ probe should result in fewer or no esophageal thermal lesions, 
if esophageal temperature measured by the Circa™ probe is used to guide power delivery and duration of 
ablation on the posterior left atrial wall. 
 
8. 
PROGRESS REPORT 
There is a paucity of data in patients on the value of temperature monitoring during RFCA for AF to reduce 
thermal esophageal injury. However, during the routine clinical use of the device in several hundred cases over 
the past few years we have clinically observed a marked reduction in ablation time and power delivery in the 
posterior left atrial wall as compared to prior years before FDA approval of the Circa™ device. 
 
In addition, in some patients we have been unable to ablate critical areas in the left atrium due to such temperature 
rises observed on the Circa™ probe, and have resorted to having the GI service attending/fellow move the 
esophagus with an endoscope to the right or left away from the critical ablation sites, thus allowing normal power 
delivery to achieve transmural atrial ablation and cure AF. 
 
Thus, we believe that by using the Circa™ probe, to guide and limit power delivery and duration of ablation on 
the posterior left atrial wall, to avoid excessive esophageal temperature rises, and yet successfully complete the 
ablation, we will limit the potential for any esophageal thermal injury that might lead to an atrio-esophageal 
fistula. 
 
We have recently completed a non-randomized esophagoscopy study in 20 patients, in whom AF ablation was 
performed while using the Circa™ probe to monitor and limit luminal esophageal temperature (LET), and thus 
prevent esophageal thermal lesions. We observed a single possible esophageal thermal lesion in only one patient 

 
 
Biomedical IRB Application Instructions 
Page 4 
undergoing ablation (see progress report Table). This is significantly less than that typically observed in such 
patients according to previously published studies. 
 
9. 
RESEARCH DESIGN AND METHODS 
Study Design: 
 
This will be a non-randomized, prospective, single-centered clinical trial.  Twenty-five consecutive patients 
who agree to enroll in the study will undergo their clinically indicated AF ablation, during which all patients 
will be monitored using the newly designed Circa™ esophageal temperature probe, to prevent luminal 
esophageal temperature  (LET) from rising above 39°C. The day following ablation, patients will undergo 
esophagoscopy before being discharged from the post-operative recovery area (PTU), in order to determine if 
there is any evidence of esophageal lesions that might be due to thermal injury. 
 
The gastroenterologist performing esophagoscopy will be blinded to any intra-procedural data during the atrial 
fibrillation ablation, specifically any data relating to esophageal position during the ablation procedure, any 
observed temperature rises, and the power and duration of radiofrequency energy delivery during the ablation. 
 
Following endoscopy, all patients will remain in the PTU until recovered from sedation, and when standard 
criteria are met they will be discharged directly to home and followed up in the outpatient arrhythmia clinic in 
the same manner as all other patients undergoing AF ablation at UCSD. This routine follow-up process is 
described to the patient prior to ablation as part of his/her clinical consent for the procedure, and does not 
involve any research procedures related to this study.  
 
Methods: 
 
The only research component of this study is the post-ablation esophagoscopy which is not standard of care for 
patients receiving RFCA for atrial fibrillation. The day following the patient’s AF ablation, provided there have 
been no complications and vital signs are stable, he/she will undergo esophagoscopy under sedation, as is 
standard of care.   During this procedure all vital signs will be monitored in a standard manner as they had been 
during the AF ablation, and the esophagus inspected in a standard manner for any evidence of lesions that 
might be due to thermal injury. Photographic evidence will be obtained and stored on disk of any lesions 
observed.  A written description of the findings will also be provided by the gastroenterologist in his report of 
the procedure. Following esophagoscopy the patient will be monitored for the appropriate time to ensure 
stability of vital signs, and then patient will be discharged home when appropriate criteria are met. 
 
The patient will be provided written instructions, as to allowed and disallowed activities following ablation and 
endoscopy, as they would normally be provided for any clinically indicated procedure. 
 
There will be no other research related procedures or follow-up required for this study. 
 
10. 
HUMAN SUBJECTS 
A total of 25 patients will be recruited from the Cardiology Electrophysiology clinics and PTU, in order to 
account for any withdrawal. There will be no discrimination in enrollment based on gender or ethnic 
background. We expect the population of enrolled subjects to reflect similar percentages for gender and 
ethnicity as the overall population of patients receiving CIED procedures at UCSD.  Patients will be 
approached and consented for the post-ablation esophagoscopy prior to AF ablation. If the eligibility of the 
subject changes between the time the subject is consented and the procedure, the subject will be considered a 
screen failure and the subject’s participation will not be counted towards accrual for the study. It is the patient’s 

 
 
Biomedical IRB Application Instructions 
Page 5 
choice to withdraw from this study at any time before the esophagoscopy, or prior to ablation, without effect on 
his/her usual clinical care. 
 
Inclusion Criteria: (all must be met) 
1. Must have atrial fibrillation and be schedule for AF ablation. 
2. Must agree to esophagoscopy under sedation the next day in order to determine if there is any 
evidence of esophageal thermal injury. 
3. Must give written informed consent. 
4. Must be at least 18 years old 
 
 
Exclusion Criteria: (presence of any one or more) 
1. Patient’s refusal to participate in the study. 
2. Any known esophageal disease or prior injury that would preclude esophagoscopy. 
3. Any complications occurring during or after AF ablation that would result in esophagoscopy being 
an added significant risk to the patient beyond the known potential risks from the esophagoscopy 
itself.  
4. Prior AF ablation  
 
2 
Patients seen in the UCSD cardiac arrhythmia clinic or hospital inpatients, who are referred for consideration of 
AF ablation, will be evaluated to see if they meet enrollment criteria by Dr. Feld and/or the co-investigators. 
Medical records of potential patients will be screened prior to enrollment to ensure eligibility. If eligible, they will 
be asked if they would like to participate in the study. All patients will be under the care of the cardiac 
electrophysiology group at UCSD Medical Center. 
 
A partial waiver of HIPAA and waiver of consent will be needed to screen medical records of patients of 
Sulpizio Cardiovascular Center to determine study eligibility. The partial waiver of HIPAA and waiver of 
consent for recruitment are necessary to ensure that patients who are approached for the study meet all 
inclusion and exclusion criteria in addition to reaching the enrollment goal for the study. The medical records 
of patients in UCSD cardiac arrhythmia clinic will be screened to assess eligibility for the study. Patients who 
have been determined to be eligible will be recruited in clinic or PTU by Dr. Feld or his research staff. The 
privacy risk to patients is minimal as all PHI collected for screening purposes will be stored in a password 
protected document in a limited access drive on the UCSD secured computer system. The waiver of consent 
and partial waiver of HIPAA will not adversely affect the rights and welfare of the potential subjects as only the 
minimal PHI necessary to determine eligibility will be collected for screening. This would include name, age, 
procedure type, procedure dates, medical record number, and medical information indicating satisfaction of the 
inclusion and exclusion criteria for the study. This will also benefit patients by reducing the likelihood of 
ineligible patients being consented to participate in the study or that patients are approached more than once to 
participate. Only Dr. Feld and his research staff will have access to the PHI and will be involved in the 
screening process. As soon as recruitment for the study is complete, identifiers for all screened patients who did 
not enroll in the study will be destroyed or deleted from our system. The only information that will be retained 
from screened patients will be information necessary for publication, including reason for study exclusion and 
date the patient was screened. If at any point during the study, there is a change in the risk to benefits ratio 
affecting a patient’ safety or willingness to participate, those enrolled or screened (as applicable) will be 
notified. There will be no advertising (brochures, flyers, posters, etc.) used in recruitment for this study. 
 
12. 
INFORMED CONSENT 
Patients must sign the most current IRB approved informed consent form prior to any study related procedures. 
Only the principal investigator, sub-investigators, or research coordinators will obtain informed consent, after 

 
 
Biomedical IRB Application Instructions 
Page 6 
complete explanation of the nature and purpose of this study. The consent for this study will be signed by the 
subject and the individual obtaining informed consent.  
 
13. 
ALTERNATIVES TO STUDY PARTICIPATION 
The alternatives to participation in this study are to not participate in the study and to continue to receive 
standard care AF ablation. Standard of care for RFCA ablation for atrial fibrillation would not include post-
ablation esophagoscopy.  
 
14. 
POTENTIAL RISKS 
The published literature indicates that there are known risks during routine esophageal endoscopic procedures 
including: 
 
Minor irritation leading to a sore throat, and major complications including esophageal perforation leading to 
potential mediastinal infection and death, the potential need for surgery to repair a perforation, and major 
traumatic injury leading to bleeding.  
 
Although every effort will be undertaken to maintain confidentiality, there is a risk of possible loss of 
participant’s confidentiality. 
 
Radiation Exposure: 
Fluoroscopy is used as standard of care throughout the ablation including placement of the CIRCA monitoring 
system and is not affected by the research study (as the endoscopy does not require radiation). Each patient will 
only undergo the RFCA procedure once. The RFCA can take up 4-8 hours, average fluoroscopy time for Dr. 
Feld’s ablations are 40 minutes and can run up to about 60 minutes. This will be the same regardless of study 
participating. The estimated radiation exposure for this procedure is 70.4mSv.  
 
15. RISK MANAGEMENT PROCEDURES AND ADEQUACY OF RESOURCES 
After AF ablation and endoscopy, patients will be monitored in the PTU, including vital signs, until all criteria 
are met for patient discharge.  The PTU is a fully staffed, licensed facility where all recovery from AF ablation 
is currently routinely clinically performed during a patient’s overnight stay, and where all trans-esophageal 
echocardiograms (similar procedure to esophagoscopy) and cardioversions are also currently performed safely 
and effectively. 
 
The cardiac arrhythmia clinic is staffed by nurse practitioners, attendings and fellows, for procedural related 
issues. The clinic number (858) 657-8530 is answered daily from 8 AM to 5 PM, and the nurse practitioners are 
always available during this time period. The nurse practitioners discuss all phone calls with the primary 
cardiac electrophysiologist and make notes into the EPIC electronic medical record.  After business hours, the 
answering machine provides the number for the electrophysiology fellow and attending on call, who are 
available 24 hours daily for urgent issues. Or the patients can call the page operator to reach a fellow or 
attending with questions at (619) 543-6737.  
 
The research staff, also, will be monitoring patients during the study procedure and prior to discharge for 
adverse events. All adverse events will be reported according to current IRB requirements.  
 
The Research Coordinator in the cardiac electrophysiology division who can assist with the reporting of any 
adverse events to the Human Studies Committee.   
 
16. PRIVACY AND CONFIDENTIALITY CONSIDERATIONS INCLUDING DATA ACCESS AND MANAGEMENT 

 
 
Biomedical IRB Application Instructions 
Page 7 
Every effort will be made to protect subject confidentiality. Only the Principal Investigator, the Sub-
Investigators, and the research coordinators will have access to the patient’s identifying information. All 
collected participant information will be stored in locked cabinets and maintained in a password protected 
database in UCSD system. Subjects will be assigned a non-identifiable study number based on order of 
enrollment. The master-log linking subject PHI with study ID number will be kept separate from other study 
information, in a password protected document on a limited access drive on UCSD secured computer system, 
accessible only by Dr. Feld and his research staff. Data reported to Circa Scientific, LLC will not contain any 
PHI. If the results of this study are published, the subject’s identity will remain confidential. Records may be 
viewed by the Sponsor, or their representatives, the FDA, or the UCSD HRPP. However, no personal 
information about the study subject will be recorded at these times.  
 
Patients who may have any questions or concerns can contact the research team at 858-657-5323 or the HRPP. 
 
17. POTENTIAL BENEFITS 
The patient may or may not benefit directly from participation in this study. If significant thermal lesions are 
observed in the esophagus as determined by the gastroenterologist performing the esophagoscopy, the patient 
will receive the directed to appropriate clinical treatment or follow-up care. It is possible that observation of 
few or no esophageal lesions will confirm the utility and benefit of the routine use of the Circa™ temperature 
monitoring probe, and that publication of this data would results in it being disseminated worldwide to benefit 
other patients undergoing atrial fibrillation, and further reduce the risk of atrio-esophageal fistula formation, a 
rare, but known and potentially fatal complication of AF ablation.   
 
18. RISK/BENEFIT RATIO 
It is possible that identification of few or no esophageal thermal lesions will lead to more widespread use of the 
Circa ™ temperature monitoring probe, and thus reduce the risk of atrio-esophageal fistula, as we believe it has in 
our laboratory. Furthermore, early identification of any thermal lesions in an individual patient would lead to 
directed treatment in such an individual subject’s case, in this study, possibly preventing progression to a more 
serious condition. However, the current subjects may derive no direct benefit from this study. The risk of 
esophagoscopy is low, although there are finite risks, including those noted above in section 14. However, in the 
assessment of the principal investigator, the benefits outweigh the small risks to the subjects in this study.   
 
19. EXPENSE TO PARTICIPANT 
There will be no additional expense to patient for participation in this research study. The cost associated with the 
esophagoscopy procedure will be paid for by the sponsor, Circa Scientific, LLC. As the ablation and any expenses 
related to the procedure are standard of care, those costs will be covered by the patient and/or the patient’s 
insurance.  
 
20. COMPENSATION FOR PARTICIPATION 
On completion research activities, each participant will be provided $25 for the inconvenience associated with the 
research-related procedures. No other compensation will be provided for participation in this study.  
 
21. PRIVILEGES/CERTIFICATIONS/LICENSES AND RESEARCH TEAM RESPONSIBILITIES 
Only physicians and the clinical research coordinator will be involved in performing this study. All procedures 
will take place at UCSD Medical Center PTU. 
1. Dr. Gregory Feld, M.D., Dr. Jonathan Hsu, Dr. Kurt Hoffmayer, Dr. Farshad Raissi, Dr. David 
Krummen, and Dr. Amir Schricker, EP Faculty in the Division of Cardioloy, licensed in California with 
full privileges at UCSD, will implement the protocol, perform ablations, screen and consent patients, as 
well as perform data analysis and review images.  

 
 
Biomedical IRB Application Instructions 
Page 8 
2. Dr. Thomas Savides, MD or his delegated attending physicians and fellows in the Division of 
Gastroenterology, licensed in California with full privileges at UCSD will be performing the 
esophagoscopy component of the protocol. 
3. Jessica Hunter, BHS, Maylene Alegre, and Carole Marks : Clinical research coordinators assisting with 
screening, consenting, data collection, data analysis, adverse event reporting, and serve as the liaison 
between the PI and the IRB. Jessica Hunter will be the lead study coordinator and primary contact for 
this study. Carole Marks will be the secondary contact. 
 
22. BIBLIOGRAPHY 
1. Martinek M, Bencsik G, Aichinger J, Hassanein S, Schoefl R, Kuchinka P, Nesser HJ, Purerfellner H. 
Esophageal damage during radiofrequency ablation of atrial fibrillation: impact of energy settings, 
lesion sets, and esophageal visualization.J Cardiovasc Electrophysiol. 2009;20:726-33. 
2. Dagres N, Anastasiou-Nana M. Prevention of atrial-esophageal fistula after catheter ablation of atrial 
fibrillation. Curr Opin Cardiol. 2011;26:1-5.  
3. Halm U(1), Gaspar T, Zachäus M, Sack S, Arya A, Piorkowski C, Knigge I, Hindricks G, Husser D. 
Thermal esophageal lesions after radiofrequency catheter ablation of left atrial  arrhythmias. Am J 
Gastroenterol. 2010;105:551-6. 
4. Sause A, Tutdibi O, Pomsel K, Dinh W, Füth R, Lankisch M, Glosemeyer-Allhoff T, Janssen J, Müller 
M. Limiting esophageal temperature in radiofrequency ablation of left atrial tachyarrhythmias results in 
low incidence of thermal esophageal lesions. BMC Cardiovasc Disord. 2010;10:52. 
5. Zellerhoff S, Ullerich H, Lenze F, Meister T, Wasmer K, Mönnig G, Köbe J, Milberg P, Bittner A, 
Domschke W, Breithardt G, Eckardt L. Damage to the esophagus after atrial fibrillation ablation: Just 
the tip of the iceberg? High prevalence of mediastinal changes diagnosed by endosonography. Circ 
6. 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. 201;24:958-64. 
7. Feld GK, Tate C, Hsu J.  Esophageal temperature monitoring during AF ablation: multi-sensor or 
single-sensor probe? J Cardiovasc Electrophysiol. 2013;24(12):E24. 
8. Ben-Menachem T, et.al. for the ASGE Standards of Practice Committee. Gastrointestinal Endoscopy 
2012:76;707-718 
 
23. FUNDING SUPPORT FOR THIS STUDY 
This is a single-center, PI initiated study, however the necessary research procedures, including esophagoscopy, 
are to be funded by the sponsor of this study, Circa Systems, LLC through an OCGA contract. 
 
24. BIOLOGICAL MATERIALS TRANSFER AGREEMENT 
Not applicable. 
 
25. INVESTIGATIONAL DRUG FACT SHEET AND IND/IDE HOLDER 
Not applicable. 
 
26. IMPACT ON STAFF 
Most of the research-related procedures will be performed by the research team (PI, Sub-I’s, or study 
coordinators). However, the Gastroenterology department will be required for the research post-ablation 
esophagoscopy. 
 
27. CONFLICT OF INTEREST 

 
 
Biomedical IRB Application Instructions 
Page 9 
There is no conflict of interest between the sponsor of this study and the investigators. The Circa™ esophageal 
temperature probe is already routinely used in all cases during atrial fibrillation ablation at UCSD Medical Center, 
and the investigators have no ownership interest in the company sponsoring this study, nor have they received in 
the past or will receive in the future any payments, honoraria, or equivalent from the sponsor. 
 
28. SUPPLEMENTAL INSTRUCTIONS FOR CANCER-RELATED STUDIES 
Not applicable. 
 
29. OTHER APPROVALS/REGULATED MATERIALS 
Not needed at this time. 
 
30. PROCEDURES FOR SURROGATE CONSENT AND/OR DECISIONAL CAPACITY ASSESSMENT 
Not applicable.