Esophageal Deviation in Atrial Fibrillation Ablation
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Massachusetts General Hospital

1 
 
Esophageal Deviation in Atrial Fibrillation Ablation 
A Prospective Single-Arm Study  
 
Principal Investigator: 
Moussa Mansour, MD  
Massachusetts General Hospital  
Tel: (617) 726-5557  
Fax: (617) 724-1241  
Email: mmansour@partners.org  
July 18, 2019 
Version 14.0 
 NCT#: 03261973 
  
 

2 
 
Table of Contents: 
1. 
CONTACT INFORMATION  
1.1. STUDY INVESTIGATORS 
2. 
ABSTRACT 
3. 
STUDY OBJECTIVE 
4. 
INTRODUCTION, RATIONALE, PRELIMINARY DATA  
4.1 FIGURE 1, 2, 3, 4, 5 & 6 
5. 
ENDPOINTS 
5.1. PRIMARY CLINICAL ENDPOINT 
5.2. SECONDARY CLINICAL ENDPOINTS 
6. 
STUDY SUBJECTS 
6.1. INCLUSION CRITERIA 
6.2. EXCLUSION CRITERIA 
7. 
ANALYTICAL PLAN 
7.1 SAMPLE SIZE CALCULATION 
7.2 STOPPING CRITERIA 
8. 
PATIENT ENROLLMENT AND WITHDRAWAL 
9. 
STUDY PROCEDURES 
9.1. PRE- AND ABLATION PROCEDURE 
9.1.1. PRE-PROCEDURE TESTING 
9.1.2. ABLATION PROCEDURAL DETAILS 
9.2. POST-PROCEDURE 
9.2.1. POST-PROCEDURE TESTING 
9.2.2. POST-PROCEDURE FOLLOW-UP 
9.2.3. POST-PROCEDURE MEDICATION MANAGEMENT 
9.2.4 POST-PROCEDURE DATA COLLECTION 

3 
 
9.3. SAFETY 
9.3.1. ADVERSE EVENTS 
9.3.2. SERIOUS ADVERSE EVENTS 
9.3.3. EVENT RECORDING 
9.3.4. CAUSALITY 
9.3.5. REPORTING OF SERIOUS ADVERSE EVENTS 
9.4. RISKS 
9.5. DATA HANDLING 
 
REFERENCES 
Appendix 1: Swallowing impairment score 
Appendix 2: Summary Flow Sheet and Workflow 
  
 
 

4 
 
1 CONTACT INFORMATION 
1.1 STUDY INVESTIGATORS 
 
Project Title: Esophageal Deviation in Atrial Fibrillation Ablation:  
A prospective study 
  
  
• 
Principal Investigator: Moussa Mansour, M.D. 
Cardiac Arrhythmia Service 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-5557 
Fax: 617-724-1241 
E-Mail: mmansour@partners.org  
 
• 
Co-investigator: Kevin Heist, MD, PhD 
Cardiac Arrhythmia Service 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-4959 
E-Mail: kheist@partners.org  
 
• 
Co-investigator: Nathan Van Houzen, MD 
Cardiac Arrhythmia Service 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 978-744-3499 
E-Mail: nvanhouzen@partners.org 
 
 
 
 

5 
 
• 
Co-investigator: Michael Fitzsimons, MD  
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-3318  
Fax: 617-726-5985  
E-Mail: Mfitzsimons@partners.org 
 
• 
Co-investigator: Michael Andrawes, MD  
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-3055  
Fax: 617-726-5985 
E-Mail: Mandrawes@partners.org 
 
 
 
• 
Co-investigator: Agnieszka Lesicka, MD 
  
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-643-7252 
E-Mail: Agnieszka.lesicka@partners.org 
 
• 
Co-investigator: Abraham Sonny, MD  
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-9379 
Fax: 617-724-8500 
E-Mail: Asonny@mgh.harvard.edu 

6 
 
 
• 
Co-investigator: Adam Dalia, MD 
  
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-3030  
E-Mail: Aadalia@mgh.harvard.edu 
 
 
• 
Co-investigator: Alexander Kuo, MD 
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-643-4065 
Fax: 617-726-5985 
E-Mail: Askuo@partners.org 
 
• 
Co-investigator: Kathryn Slattery, CRNA 
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-8995 
E-Mail: Kaslattery@partners.org 
 
• 
Co-investigator: Kenneth Shelton, MD 
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-0917 
Fax: 617-726-5985 
E-Mail: Kshelton2@partners.org 

7 
 
 
• 
Co-investigator: Molly Campbell, CRNA 
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-3030  
E-Mail: Mnelson20@mgh.harvard.edu 
 
• 
Co-investigator: Susan Maher, CRNA 
Cardiac Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Telephone: 617-726-1883 
Fax: 617-726-7536 
E-Mail: Smaher1@partners.org 
 
• 
Co-investigator: Stephen Matson, CRNA 
Anesthesia 
Massachusetts General Hospital, 55 Fruit Street, Boston 02114 
Email: sematson@mgh.harvard.edu 
 
 
2 ABSTRACT 
Catheter ablation with pulmonary vein (PV) isolation is a commonly performed strategy 
employed for the treatment of atrial fibrillation (AF). However, ablation in the posterior wall of the 
left atrium can cause thermal injury to the esophagus. Thermal injury is very common and 
occurs in up to 40% of AF ablations per some studies. When significant thermal injury to the 
esophagus occurs, two significant complications can arise: 1) the formation of an atrio-
esophageal fistula, and 2) gastrointestinal dysmotility. While the occurrence of fistula is rare, it is 
a very important complication since it is often fatal. Currently luminal esophageal temperature 
monitoring is the most commonly employed modality to prevent such injury. However, there are 

8 
 
limitations to its use, and atrio-esophageal fistulas continue to be a major problem in AF ablation 
even when using esophageal temperature monitoring. Esophageal deviation using either a 
Transesophageal echocardiogram (TEE) or Esophagogastroduodenoscopy (EGD) probe has 
been described in the literature, but the effectiveness and practicality of these techniques are 
suboptimal, and have therefore precluded their use in routine clinical practice. Recently, 
esophageal deviation using off-the-shelf equipment (a soft thoracic tube and endotracheal 
stylet) was tested in the randomized double-blind multicenter study “Deviating the Esophagus in 
Atrial Fibrillation Ablation (DEVIATE-AF)”. In that study the standard practice (i.e., use of luminal 
esophageal temperature monitoring) was compared to esophageal deviation using off-the-shelf 
equipment. The results were very encouraging showing that esophageal deviation allowed for 
significant reductions in esophageal temperature and proportion of premature ablation 
terminations. Importantly, esophageal deviation allowed the isolation all PVs in the treatment 
group, which was not the case in the control group. One major limitation in the DEVIATE-AF trial 
was that off-the-shelf equipment tool was challenging to use. The aim of the Esophageal 
Deviation in Atrial Fibrillation Ablation study is to test the feasibility and safety of moving the 
esophagus using a specialized esophageal deviation tool (DV8, Manual Surgical Sciences, 
Minneapolis, MN). 
  
 
  
 
 

9 
 
3. STUDY OBJECTIVE 
  
Catheter ablation is a commonly performed procedure employed for the treatment of drug 
resistant atrial fibrillation (AF). For paroxysmal AF, the ablation typically involves pulmonary vein 
(PV) isolation, and in cases of persistent AF often involves additional linear ablation lesions, 
ablation of sites of complex fractionated atrial electrograms (CFE), and ablation of drivers of AF. 
However, when ablation lesions are placed in the posterior left atrial (LA) wall during the above-
mentioned steps, these lesions can cause thermal injury to the adjacent esophagus. This can 
result in 1) esophageal erosions and/or ulcers – which can culminate in fatal atrio-esophageal 
fistula formation, and 2) gastrointestinal dysmotility such as gastroparesis as a result of damage 
to the peri-esophageal vagal plexus.  
To minimize the chance of these complications, electrophysiologists employ different strategies 
to minimize esophageal injury. A widely accepted and recommended strategy is to deploy a 
transnasal or transoral temperature sensing probe into the esophagus to detect esophageal 
heating during ablation; this allows the physician to either modulate the level of energy used or 
to terminate any individual ablation lesion that results is inappropriate heating of the esophagus. 
While this approach has been shown to reduce esophageal injury, it is clear that this is an 
imperfect tool as evidenced by the reporting of both ulcerations and fistula formation in patients 
with no detectable temperature rise. In addition, even if the detection of esophageal temperature 
rise is identifiable in all cases, this still necessitates that the operator stop ablation and wait for 
the temperature to passively cool before applying another ablation lesion. This adversely 
impacts procedure time, and (by allowing time for tissue edema to form between lesion 
applications) might even impact on the long-term durability of the PV isolating lesion set. 
Recently, the randomized double-blind multicenter study “Deviating the Esophagus in Atrial 
Fibrillation Ablation (DEVIATE-AF) demonstrated that the esophagus can be successfully 
displaced in patients undergoing AF ablation using off-the-shelf equipment (a soft thoracic tube 
and endotracheal stylet. One major limitation in the DEVIATE-AF trial was that off-the-shelf 
equipment tool was challenging to use. The aim of the Esophageal Deviation in Atrial Fibrillation 
Ablation study is to test the feasibility and safety of moving the esophagus using a specialized 
esophageal deviation tool (DV8, Manual Surgical Sciences, Minneapolis, MN).  

10 
 
4 
INTRODUCTION, RATIONALE, PRELIMINARY DATA 
Introduction and Rationale: 
Role of catheter ablation: Atrial fibrillation (AF) is a disorder affecting more than 3 million 
Americans. The likelihood of developing AF increases with age. Three to five percent of people 
over 65 have AF. Given the aging population, it is important that effective therapeutic strategies 
are available. Non-pharmacologic approaches to maintaining sinus rhythm with catheter 
ablation offer an alternative approach for control of AF and avoid the toxicity of anti-arrhythmic 
drugs. Several randomized controlled trials have demonstrated the superiority of catheter 
ablation over medical treatment for AF, in terms of maintenance of sinus rhythm and improved 
symptoms (1,2,3,4,5). PV isolation is a procedure that involves placing circumferential and 
importantly transmural lesions around all the PVs to electrically isolate the veins from the rest of 
the left atrium (LA). This procedure alone is successful for 70–90% of patients with paroxysmal 
AF (6), the effectiveness largely depending on the contiguity and transmurality of these 
circumferential lesions around the PV. Catheter ablation of persistent AF on the other hand 
usually involves a hybrid strategy, incorporating PV isolation with further ablation, typically in the 
form of linear lesions, complex fractionated electrogram ablation, and/or ablation of drivers of 
AF that need to be performed in various locations in the LA including the posterior wall of the LA 
(7,8) which lies in close proximity to the esophagus.  
Gastro-esophageal injury: While the overall complication rates of catheter ablation of AF have 
decreased (major complication rates in large centers are in the 2-3% range) with advancements 
in technique and technology of catheter ablation, the threat of gastro-esophageal damage due 
to thermal injury from ablation remains. In fact, the risk of atrio-esophageal fistula formation 
remains one of the most dreaded complications of catheter based AF ablation today.  
Thermal injury during AF ablation can occur in the form of esophageal erythema, hemorrhage, 
erosions, ulceration, gastro-esophageal motility disorders or rarely atrio-esophageal fistulas. 
These occur consequent to the use of thermal based ablation applied to the posterior wall that 
often lies immediately adjacent to the esophagus (9,10). It is thought that this thermal energy 
extends beyond the posterior LA wall and reaches the adjacent esophagus causing damage 
that manifests as described above. In patients undergoing radiofrequency (the most common 
thermal based energy source) catheter ablation of AF, the reported incidence of any esophageal 
injury varies from 2.2% - 48%. The incidence of the often catastrophic atrio-esophageal fistula 
however, is much lower at around 0.04% (11). Typically, the clinical presentation of such fistulae 
occurs late after the procedure (usually within the first 2 weeks) (9,10). The symptoms are 
usually nonspecific, including fever, neurological abnormalities, gastrointestinal bleeding, and 
sepsis. This condition is often fatal. The mechanism of esophageal injury is thought to be to 
thermal injury (9,10,12,13). The degree of variation in the reported incidence of esophageal 
damage (2.2- 48%) is likely accounted for by differences in the frequency of use of esophageal 
protection (e.g. - temperature monitoring probe), use of general anesthesia versus conscious 
sedation, magnitude of power, duration and contract force during ablation and finally the method 
of assessment of esophageal injury. An effective strategy to reduce gastro-esophageal injury is 
therefore of significant clinical importance.  

11 
 
Esophageal protection strategies: Several strategies have been described to help prevent or 
reduce gastro-esophageal injury during AF ablation. These include luminal esophageal 
temperature (LET) monitoring (14), determination of the anatomical relationship of the 
esophagus to the posterior LA with pre-procedural or real time imaging (15,16,17) and 
modulation of power and duration of radiofrequency lesions (18). The effectiveness of the above 
approaches, even when applied in combination, has failed to prevent atrio-esophageal fistula 
formation (17). Moreover, these strategies do not address the need for reduction of other forms 
of injury, such as gastroesophageal motility disorders that originate from injury of vagal nerves 
that surround the esophagus. In addition, LET monitoring focuses on the early detection of 
thermal injury, and both 1) invariably results in a pause in ablation while waiting for passive 
tissue cooling, and 2) often results in modification of the lesion sets, i.e., by directing the 
encircling lesions to be either more ostial or further midline in order to avoid temperature rises. 
Such modifications increase the risk of vein stenosis and the formation of ‘gaps’ that may 
reduce the long-term clinical success of the ablation procedure. Frequent premature lesion 
terminations and power reductions may also compromise chronic PV isolation rates, an 
endpoint critical to the long-term outcomes of AF ablation. 
Autopsy studies (19) have shown that there is loose areolar tissue between the anterior wall of 
the esophagus and the parietal pericardium of the posterior left atrium. A post-mortem study 
(19) demonstrated that the esophagus relative to the posterior left atrium could be displaced up 
to 7 cm. Both these studies indicate that lateral esophageal displacement is a feasible strategy 
from an anatomic basis. Lateral mechanical displacement of the esophagus along the posterior 
LA as an esophageal protective strategy has been previously described using either an 
endoscope (20) or a TEE (21). Both these strategies had significant limitations. In the strategy 
using the endoscope, i) the actual deviation of the esophagus was unclear since concomitant 
contrast was not employed to differentiate esophageal deviation from esophageal tenting, ii) the 
esophagus could not be deviated in 2/12 patients, and most importantly, iii) the deviation could 
not be maintained in 7 patients to allow uninterrupted lesion delivery. This approach required 
the active participation of a gastroenterologist and the true extent of deviation achieved was 
unclear given the lack of barium contrast. On the other hand, in the strategy using the TEE 
probe, all 3 patients underwent successful displacement that was maintained during ablation, 
but this was not studied in a systematic fashion. Although thought-provoking, widespread 
application of these two techniques has not been realized in clinical practice due to attendant 
limitations. Over the past 2 years the randomized double-blind multicenter study “Deviating the 
Esophagus in Atrial Fibrillation Ablation (DEVIATE-AF) demonstrated that the esophagus can 
be successfully displaced in patients undergoing AF ablation using off-the-shelf equipment (a 
soft thoracic tube and endotracheal stylet) (Figure-1). The study randomized 69 patients and is 
still ongoing. Interim analysis revealed that esophageal deviation allowed for significant 
reductions in maximum esophageal temperature rises {1.1±0.7ºC vs 0.26±0.2 ºC, p<0.0001} 
and proportion of premature ablation terminations {38.8±0.3% vs 5.7%±0.1, p<0.0001}.  
Importantly, all PVs were not isolated in 2 controls due to temperature rises. In the deviation 
arm, total time and RF time for PV isolation was shorter, but did not reach statistical 
significance. There were challenges however related to the ease of deviation using the off-the-
shelf tool, and it was concluded that the technique requires improvement. 

12 
 
Figure-1: Off-the-shelf tapered tip (solid arrows) thoracic catheter used for esophageal 
deviation. Adjacent to that is an endotracheal stylet with a distal curve (dashed arrows) 
 
 
Because of the logistical difficulties attendant with the off-the-shelf tools and the obvious need 
that remains in terms of esophageal protection during AF ablation, we sought to evaluate the 
feasibility and safety of a strategy of mechanical esophageal deviation during AF ablation using 
specialized equipment (DV8 specialized esophageal retraction tool made by Manual Surgical 
Sciences, Minneapolis, MN) (Figure-2). The device is commercially available in the US and 
is 510(k) exempt. (Regulation Number 878.4800, Registered Establishment Number is 
3011596926) Figure-2: DV 8 esophageal retractor. 
 
The DV8 Retractor™ Esophageal Balloon (DV8 Retractor) is a non-sterile, single-use, 
disposable esophageal balloon retractor. It is deployed orally and inflated inside the esophagus. 
The retractor gently and effectively retracts the esophagus to create a stable operating field. 
The DV8 Retractor has a marker band located at the proximal waist and double marker bands 
located at the distal waist of the balloon, which are distinguishable from each other under 
fluoroscopic visualization. When the procedure is completed, the device is deflated and 
removed. Each balloon inflates to its stated diameter and length at 4-8ATM of pressure. The 
balloon diameter is ± 10% at the nominal pressure. The Rated Burst Pressure (RBP) is 16 

13 
 
atmospheres (ATM). The DV8 Retractor is designed with a silicone sleeve and balloon coupled 
to a fitting that can attach to a syringe with a pressure gauge. The DV8 Retractor also has a 
fitting that allows attachment of a syringe to inject contrast medium directly into the esophagus. 
The device is 61 cm in length and the balloon is 15 cm balloon length. When inflated, the 
balloon diameter is 14mm. The detailed steps for deployment are as follows: 
Insertion and Inflation:  
• 
The DV8 Retractor Esophageal Balloon is removed from its package. The Inflation 
Syringe is filled with pressure gauge with an appropriately diluted (25-50%) contrast 
medium (Gastrografin).  
• 
The Luer-tip Inflation Syringe is attached with pressure gauge into the DV8 Retractor 
balloon inflation stopcock. 
• 
Lubricant is applied to the balloon and device shaft. The DV8 Retractor is directed into 
the esophagus using fluoroscopic guidance. 
• 
The balloon is positioned in the appropriate location with the distal marker band at the 
level of the lower esophageal sphincter. 
• 
The balloon is inflated with contrast medium with 4-8 ATM of pressure as indicated on 
the Inflation Syringe (Figure-3).  
Deflation and Withdrawal: 
• 
The balloon is deflated prior to withdrawing from the esophagus. 
• 
The deflated DV8 Retractor Balloon is withdrawn from the esophagus using a smooth, 
gentle, steady motion.  
Figure-3: X ray images of the DV8 retractor before and after inflation. 
 
 

14 
 
Preliminary data:  
The esophagus was successfully displaced using the DV8 retractor in over 200 patients 
worldwide. Eleven cases have been performed at MGH. No complications have been reported 
with its use. In a cohort study at Mt. Sinai Medical Center in New York, 47 patients underwent 
esophageal deviation using the DV8 tool and were compared with 114 patients who underwent 
deviation using the off-the shelf stylet. All procedures were performed under general anesthesia. 
The extent of deviation, as measured by the distance between the trailing edge of the 
esophagus and the ablation points, was significantly larger with the DV8 tool (Figure-4). 
Moreover, the incidence of esophageal temperature rises was higher with the off-the-shelf 
technique compared to the DV8 retractor (Figure-5). Another preliminary study was conducted 
by the Mt-Sinai group in order to assess the optimal distance for esophageal movement that 
eliminates the chance of heating. It showed that if the esophagus is moved by an average of 2 
cm from the ablation site, no significant heating occurs (Figure-6)  
Figure-4: Comparison of the extent of deviation between the DV8 retractor and off-the-shelf 
stylet. 
 
Figure-5: Comparison of the incidence of esophageal temperature rise between the DV8 
retractor and the off-the-shelf stylet. 

15 
 
 
 
 
 
Figure-6: Incidence of esophageal temperature rise at different distances from the area of 
ablation.    
 
 
 

16 
 
 
These data demonstrate the feasibility and safety of the novel technique of esophageal 
deviation that facilitates uninterrupted energy delivery to the posterior wall during AF. It also 
demonstrated that the esophagus needs to be moved by an average of 2 cm in order for heating 
not to occur. Although the results have been very encouraging with respect to safety and 
efficacy, we believe that there is value in an additional study to prove the reproducibility of the 
findings.   
We propose a prospective single-arm study to confirm the safety and feasibility of this novel 
deviation tool. 
 
 
 

17 
 
5 
ENDPOINTS 
 
5.1 PRIMARY CLINICAL ENDPOINT 
The following primary endpoint will be assessed: 
1) The extent of esophageal deviation as measured by the incidence of successfully 
moving the esophagus to achieve a minimum distance of 1 cm between the ablation line 
for the ipsilateral PV pairs and the trailing edge of the esophagus. 
 
5.2 SECONDARY CLINICAL ENDPOINTS 
The following secondary endpoints will be assessed: 
1. 
The extent of esophageal deviation as measured by the incidence of successfully 
moving the esophagus by an average of 2 cm from the ablation line for the ipsilateral PV 
pairs. 
2. 
The incidence of esophageal laceration as assessed by a Barium swallow study 
performed within 1-3 days of the procedure. 
3. 
Incidence of PV reconnection at 30 min post-ablation 
4. 
Fluoroscopy time 
5. 
Procedure duration 
6. 
Time from start of ablation to last ablation lesion for pulmonary vein isolation 
The deviation distance was based on the preliminary study mentioned above, showing that if the 
esophagus is moved by an average of 2 cm, no significant heating occurs.  
 
 

18 
 
6 
STUDY SUBJECTS 
 
6.1 
INCLUSION CRITERIA 
A maximum of up to 64 patients will be enrolled in this prospective single-center single-
arm study. Patients undergoing AF ablation (including paroxysmal and persistent AF) will 
be included in this study. Consistent with the current definitions, paroxysmal AF are 
episodes that will self-terminate in less than 24 hours. Persistent AF, is defined as ≥1 
documented AF lasting >1week in duration or lasting less than 7 days but requiring 
electrical or pharmacological cardioversion to sinus rhythm. 
 
• 
Age >18 - Age < 80 yr 
• 
Documentation of atrial fibrillation (AF) 
• 
General anesthesia 
• 
All patients must understand and adhere to the requirements of the study and be 
willing to comply with the post study follow-up requirements. 
 
6.2 
EXCLUSION CRITERIA 
• 
Any reversible cause of AF (post-surgery, thyroid disorder, etc.) 
• 
INR > 4.0 at the time of the procedure 
• 
H/o of severe esophageal ulcers, strictures, varices, bleeding, laceration or 
perforation, esophagitis 
• 
Severe GERD 
• 
H/o esophageal surgery or any esophageal banding or cautery 
• 
History of chest radiation 
• 
Significant abnormality on Swallowing Impairment Score 
• 
Mental impairment precluding signing consent or completing follow up 
• 
Patients with any other significant uncontrolled or unstable medical condition 
• 
Women who are known to be pregnant or have had a positive β-HCG test within 
7 days prior to procedure 
• 
Presence of left atrial thrombus 
 
 

19 
 
7 ANALYTICAL PLAN 
7.1 
SAMPLE SIZE CALCULATION 
A single arm design is proposed. The primary endpoint will be the incidence of 
successfully moving the esophagus by a minimum of 1 cm from the ablation line for the 
ipsilateral PV pairs. We believe that 64 patients need to be enrolled in this single-arm 
study to achieve this endpoint. With 64 enrolled patients in this single-arm trial, if the true 
success rate is at least 90% then the statistical power will be 83% to detect such a 
performance by ruling out a poor success rate of <=75% using exact Binomial test at a 
two-sided 5% type-1 error rate. The test will reject the null hypothesis H0: Success Rate 
<=75% in favor of the alternative hypothesis H1: Success Rate>=95% if there are seven 
or fewer failures among 64 patients. 
                   Proportion  Proportion 
 
      Given H0     Given H1 
Target 
Actual 
Reject H0 If 
Power     N 
(P0) 
(P1) 
Alpha 
Alpha 
Beta 
≤ R | ≥ R 
0.8321   64    0.7500      0.9000     0.0500      0.0410       0.01679   33 I 47 
 
  
7.2 
STOPPING CRITERIA 
STOPPING CRITERIA 
We propose as a stopping criterion the occurrence of 1 case or more of esophageal 
laceration based on the finding of the Barium Swallow.  
 
 

20 
 
8 PATIENT ENROLLMENT AND WITHDRAWAL 
Patients meeting the study inclusion criteria will be identified in the outpatient setting by 
one of the study staff.  
The study will typically be described (including the risks and benefits) during the clinic 
visit. Consent will typically be obtained at the time of the initial assessment if it is clear 
that the patient truly understands the nature of the study. Alternatively, the patient will be 
allowed to take a copy of the consent form home to contemplate whether they would like 
to be enrolled in the study. Only patients who voluntarily provide consent will be included 
in this study. Consent will be obtained prior to undergoing the ablation procedure. 
Patients will be able to withdraw from the study at any point without compromising their 
medical care. 
Since there is minimal additional follow-up beyond routine clinical care in this study, we 
expect to achieve > 95% rate of follow-up. 
 
 

21 
 
9 
STUDY PROCEDURES 
All aspects of the study (including pre- and post- care) are currently undertaken during 
the care of patients undergoing traditional catheter ablation procedures for AF. 
9.1 
PRE- AND ABLATION PROCEDURE 
9.1.1 PRE-PROCEDURE TESTING 
The following tests and procedures will occur before the ablation: 
• 
Baseline swallowing impairment score 
• 
Collect any pre-procedural imaging of left atrium (if performed): MRI/CT 
within 6 months of procedure 
• 
Baseline CBC-Platelets, PTT/PT-INR 
9.1.2 ABLATION PROCEDURAL DETAILS 
• 
Patients will be brought to the electrophysiology laboratory in a fasting state. 
• 
General anesthesia will be used for all cases, which is routine practice for all 
AF ablations at MGH.  
• 
Venous ± arterial access, number of transseptal punctures performed, and 
catheter selection (coronary sinus catheter, right atrial catheter, intra-cardiac 
echocardiography (ICE), and ablation catheter) will be left to the discretion of 
the operator. 
• 
Any 3D Mapping system can be used 
• 
Any thermal based ablation system can be used for the procedure. 
• 
Insertion of the DV8 tool will be performed at the beginning of the procedure. 
The esophagus will be then moved with a goal of deviation of 2 cm from the 
ablation sites.  
• 
Circumferential pulmonary vein (PV) isolation will be performed next. 
• 
Bidirectional block in and out of the PV must be demonstrated after PV 
isolation (again, this is usual clinical practice). 
• 
Use of adenosine to assess for dormant conduction is required. 
• 
Per usual practice of the clinical site, Isoproterenol may be used at the end of 
the study protocol to assess for PV reconnection 
• 
After performance of PV isolation on both sides additional LA ablation is left 
to the discretion of the electrophysiologist 
9.2 
POST-PROCEDURE 
9.2.1 POST-PROCEDURE TESTING 
• 
Swallowing impairment score: next morning 
 

22 
 
• 
Preferably the next day but up to 3 days after the procedure: Barium swallow 
to be performed on all patients. 
9.2.2 POST-PROCEDURE FOLLOW UP 
• 
2 week and 3-month phone follow up: Repeat swallowing impairment score 
(to be obtained trans-telephonically) 
9.2.3 POST-PROCEDURE MEDICATION MANAGEMENT 
• 
All medications are left up to the discretion of the investigator. 
• 
Visualization of any esophageal injury should prompt proton pump inhibitors 
for 2 weeks (per usual practice of the clinical site), CT scan of the chest, and 
referral to the gastroenterology service.  
• 
Therapeutic anticoagulation (example warfarin or equivalent agent) is at the 
discretion of the patient’s electrophysiologist. 
 
9.2.4 POST-PROCEDURE DATA COLLECTION 
• 
At the end of the case a copy of the Barium swallow (coded) will be obtained 
on CD/DVD and stored.  
• 
Coded fluoroscopy/CINE images from the procedure. 
• 
Coded electroanatomical mapping data. 
 
9.3 
SAFETY 
With the data from the preliminary study, and the 200 cases performed worldwide 
including MGH, we anticipate no significant injury to the esophagus. Instrumental to the 
safety, is a prerequisite for proctoring and education of each study staff with regards to 
the appropriate and safe use of the esophageal deviation procedure. In this regard, each 
study staff should have completed training on the use of the device. All documentation 
for the training will be kept in the regulatory binder.  
The swallowing impairment scores performed the day after the procedure and over the 
phone in 2 weeks will assess for symptoms including dysphagia that can potentially 
occur as a result of esophageal manipulation. 
Patients will report symptoms to the study coordinator and investigators during the 
follow-up period. 
The Principal Investigator will oversee the safety of the study. 
Adverse events and Serious adverse events will be monitored and reported to the IRB.  
 

23 
 
9.3.1 ADVERSE EVENTS 
The incidence of serious adverse events over the course of the study will be recorded. 
An adverse event is any undesirable clinical occurrence in a study patient, whether or 
not it is related to the study intervention. Any condition that was recorded as pre-existing 
is not an AE unless there is a change in the nature, severity or degree of the condition. 
 
9.3.2 SERIOUS ADVERSE EVENTS 
Serious adverse events are defined as any experience that results in a fatality or is life 
threatening; results in significant or persistent disability; or represents other significant 
hazards or potentially serious harm to research subjects or others, in the opinion of the 
investigators. 
 
9.3.3 EVENT RECORDING 
Protocol-defined adverse events will be captured throughout the period of trial 
participation. 
 
9.3.4 CAUSALITY 
The investigator will assess the relationship of an adverse event to the intervention. The 
investigator should distinguish the relationship between the event and (a) ablation 
procedure (i.e. AF ablation procedure or other concomitant procedures), and (b) the 
esophageal deviation. Causality will be defined as follows: 
 
Probable 
Adverse events that, after careful medical evaluation, are considered with a high degree 
of certainty to be related to the intervention (AF ablation ± esophageal deviation). The 
following characteristics will apply: 
• 
A reasonable temporal relationship exists between the event and the 
intervention, and 
• 
The event is a known reaction to the intervention, and cannot be explained by 
an alternative etiology commonly occurring in the population/individual. 
Possible 

24 
 
Adverse events that, after careful medical evaluation, do not meet the criteria for a 
probable relationship to the intervention, but for which a connection cannot be ruled out 
with certainty. The following characteristics will apply: 
• 
The event occurs after intervention, and 
• 
The event is not a known reaction to intervention, but cannot be explained by 
a commonly occurring alternative etiology 
 
Unlikely 
Adverse events that, after careful medical evaluation, do not meet the criteria for a 
possible or probable relationship to intervention and for which a connection is unlikely. 
The following characteristics will apply: 
• 
The event does not follow a reasonable temporal sequence from 
administration of the intervention, or 
• 
May have been produced by environmental factors, and there is no apparent 
pattern of response to the intervention. 
 
9.3.5 REPORTING OF SERIOUS ADVERSE EVENTS 
All investigators must report unanticipated problems involving risks to subjects or others 
including adverse events within 5 working days/7 calendar days of the date the 
investigator first becomes aware of the problem, as dictated by the specific IRB policy. 
 
9.4 
RISKS 
As the protocol described is standard to an AF ablation procedure, the risks of the 
procedure include that of a standard AF procedure, which are: 
Common:   
• 
Discomfort at the site of venous access 
• 
Groin hematoma 
Uncommon:   
• 
Discomfort in the throat region 
• 
Cardiac Perforation requiring drainage or surgery 
• 
Pulmonary venous stenosis / occlusion 
• 
Thrombus formation / stroke 
• 
Injury to adjacent structures (phrenic nerve, esophagus, lung, cardiac valves) 
• 
Bleeding 

25 
 
• 
Congestive heart failure 
• 
Renal dysfunction 
• 
Vascular complications (including pseudoaneurysm, AV fistula requiring 
surgical intervention) 
• 
Myocardial infarction 
• 
Esophageal deviation risks include dental injury and esophageal injury similar 
to that of TEE 
• 
Radiation burns 
• 
Ventricular arrhythmias or QT prolongation 
• 
Pneumonia and/or sepsis 
• 
Anaphylaxis 
• 
Death 
 
Additional risks unique to the protocol are 
• 
Sore throat 
• 
Aspiration pneumonia from barium sulfate or Gastrografin. 
• 
Difficulty or painful swallowing 
• 
Bleeding from the mouth area or from the food pipe 
• 
Perforation—a tear or hole in the esophagus (the “tube” that connects your 
mouth to your stomach”) or heart 
• 
Infection 
• 
Failure to protect the esophagus from heat related injury. 
• 
Nausea 
• 
Abdominal pain 
• 
Atrio-esophageal fistula- An abnormal connection between the atria of the 
heart and the esophagus in which they fuse together 
 
 
9.5 
DATA HANDLING 
Information about patients will be kept confidential and managed according to the 
requirements of the United States of American Health Insurance Portability and 
Accountability Act of 1996 (HIPAA). Those regulations require a signed patient 
authorization informing the patient of the following: 
1. 
What protected health information (PHI) will be collected from patients. 
2. 
Who will have access to that information and why. 
3. 
Who will use or disclose that information. 
4. 
The rights of a research patient to revoke their authorization for use of their PHI. 

26 
 
In the event that a patient revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of 
patient authorization. For patients that have revoked authorization to collect or use PHI, 
attempts should be made to obtain permission to collect at least vital status (i.e. that the 
patient is alive) at the end of their time in the study. 
In order to ensure patient confidentiality, all case report forms and patient information 
(CT / MRI, if reviewed, 3Dmapping study DVDs, fluoroscopic and endoscopic images) 
will be coded with a unique three-digit patient identifier. Information will be stored in the 
office of the local study coordinator, which will be locked when he/she is not in the office. 
The research study coordinators, principal investigator and co-investigators will be the 
only people with access to this data. All data will be stored coded with the unique three-
digit patient identifier. There will be a code sheet that will link the coded data back to the 
subjects. This will be encrypted and password-protected. One copy will be stored in the 
primary investigator’s computer, and another in the research coordinator’s computer. 
 
 

27 
 
REFERENCES 
1) Pappone C,Augello G, Sala S, et al. A randomized trial of circumferential pulmonary 
vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the 
APAF Study. J Am Coll Cardiol 2006;48:2340–7 
2) Jais P, Cauchemez B, MacLe L, et al. Catheter ablation versus antiarrhythmic drugs 
for atrial fibrillation: the A4 study. Circulation 2008;118:2498–505. 
3) Oral H, Pappone C, Chugh A, et al. Circumferential pulmonary-vein ablation for 
chronic atrial fibrillation. N Engl J Med 2006;354:934–41. 
4) Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency ablation vs 
antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a 
randomized trial. JAMA 2005;293:2634–40. 
5) Wilber DJ, Pappone C, Neuzil P, et al. Comparison of antiarrhythmic drug therapy 
and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a 
randomized controlled trial. JAMA 2010;303:333–40. 
6) Oral H, Scharf C, Chugh A, et al. Catheter ablation for paroxysmal atrial fibrillation: 
segmental pulmonary vein ostial ablation versus left atrial ablation. Circulation 
2003;108:2355–60 
7) Hunter RJ, Berriman T, Diab I, et al. Long term efficacy of catheter ablation for AF: 
impact of additional targeting of fractionated electrograms. Heart. 2010: 
Aug;96(16):1259-63 
8) O'Neill MD, Wright M, Knecht S, et al. Long-term follow-up of persistent atrial 
fibrillation ablation using termination as a procedural endpoint. Eur Heart J 
2009;30:1105–12. 
9) Pappone C, Oral H, Santinelli V, Vicedomini G, Lang CC, Manguso F, Torracca L, 
Benussi S, Alfieri O, Hong R, Lau W, Hirata K, Shikuma N, Hall B, Morady F. Atrio-
esophageal fistula as a complication of percutaneous transcatheter ablation of atrial 
fibrillation. Circulation. 2004; 109: 2724–2726 
10) Cummings JE, Schweikert RA, Saliba WI, Burkhardt JD, Kilikaslan F, Saad E, Natale 
A Brief communication: atrial-esophageal fistulas after radiofrequency ablation. Ann 
Intern Med. 2006 Apr 18; 144: 572–574 
11) Doll N, Borger MA, Fabricius A, Stephan S, Gummert J, Mohr FW, Hauss J, 
Kottkamp H, Hindricks G. Esophageal perforation during left atrial radiofrequency 
ablation: Is the risk too high? J Thorac Cardiovasc Surg. 2003; 125: 836–842 
12) Singh SM, d'Avila A, Doshi SK, Brugge WR, Bedford RA, Mela T, Ruskin JN, Reddy 
VY. Esophageal injury and temperature monitoring during atrial fibrillation ablation. 
Circ Arrhythm Electrophysiol. 2008 Aug;1(3):162-8. 
13) Kennedy R, Good E, Oral H, Huether E, Bogun F, Pelosi F, Morady F, Chugh A. 
Temporal stability of the location of the esophagus in patients undergoing a repeat 
left atrial ablation procedure for atrial fibrillation or flutter. J Cardiovasc 
Electrophysiol. 2008 Apr;19(4):351-5. 
14) Good E, Oral H, Lemola K, Han J, Tamirisa K, Igic P, Elmouchi D, Tschopp D, Reich 
S, Chugh A, Bogun F, Pelosi F Jr, Morady F Movement of the esophagus during left 

28 
 
atrial catheter ablation for atrial fibrillation. J Am Coll Cardiol. 2005 Dec 
6;46(11):2107-10. 
15) Daoud EG, Hummel JD, Houmsse M, Hart DT, Weiss R, Liu Z, Augostini R, 
Kalbfleisch S, Smith MC, Mehta R, Gangasani A, Raman SV.Comparison of 
computed tomography imaging with intraprocedural contrast esophagram: 
implications for catheter ablation of atrial fibrillation.Heart Rhythm. 2008 Jul;5(7):975-
80. 
16) Martinek M, Meyer C, Hassanein S, Aichinger J, Bencsik G, Schoefl R, Boehm G, 
Nesser HJ, Purerfellner H. Identification of a high-risk population for esophageal 
injury during radiofrequency catheter ablation of atrial fibrillation: procedural and 
anatomical considerations.Heart Rhythm. 2010 Sep;7(9):1224-30. 
17) Vijayaraman P, Netrebko P, Geyfman V, et al. Esophageal fistula formation despite 
esophageal monitoring and low-power radiofrequency catheter ablation for atrial 
fibrillation. Circ Arrhythm Electrophysiol 2009; 2:e31–e33. 
18) Sommer P, Hindricks G. Prevention of oesophageal injury during catheter ablation of 
atrial fibrillation: is monitoring of oesophageal temperature the solution? Europace 
2010; 12:911–912. 
19) Krishnan SC, Salazar M, Narula N. Anatomical basis for the mobility of the 
esophagus: implications for catheter ablation of atrial fibrillation.Indian Pacing 
Electrophysiol J. 2008 Feb 1;8(1):66-8. 
20) Chugh A, Rubenstein J, Good E, Ebinger M, Jongnarangsin K, Fortino J, Bogun F, 
Pelosi F Jr, Oral H, Nostrant T, Morady F.Mechanical displacement of the esophagus 
in patients undergoing left atrial ablation of atrial fibrillation. Heart Rhythm. 
2009;6(3):319-22. 
21) Herweg B, Johnson N, Postler G, Curtis AB, Barold SS, Ilercil A. Mechanical 
esophageal deflection during ablation of atrial fibrillation. Pacing Clin Electrophysiol. 
2006;29(9):957-61. 
 
 

29 
 
Appendix 1:  
 
Swallowing Impairment Score  
COMMENT  
SYMPTOMS 
Min/ None  
Mild  
Mod  
Severe  
Throat 
pain/discomfort  
  
  
  
  
Effort required to 
swallow  
  
  
  
  
Pain during 
swallowing  
  
  
  
  
SYMPTOMS  
Never  
Some-times  
Often  
Always  
Coughing while 
swallowing  
  
  
  
  
Sensation of 
foreign-body  
in my throat  
  
  
  
  
I notice a change 
in my voice  
  
  
  
  
Bleeding  
  
  
  
  
Vomiting  
  
  
  
  
Nausea  
  
  
  
  
Abdominal Pain  
  
  
  
  
Other, specify:_________________________________________ 
 
 
 

30 
 
Appendix 2: Summary Flow Sheet 
  
Esophageal Deviation in Atrial Fibrillation Ablation 
A single-arm study 
 
Moussa Mansour, MD  
Massachusetts General Hospital 
Cardiac Arrhythmia Service 
55 Fruit Street, Boston MA 02114 
Tel: (617) 726-5557  
Fax: (617) 724-1241  
Email: mmansour@partners.org  
  
 
INCLUSION CRITERIA 
A maximum of up to 64 patients will be enrolled in this prospective single-center single-
arm study. Patients undergoing AF ablation (including paroxysmal and persistent AF) will 
be included in this study. Consistent with the current definitions, paroxysmal AF are 
episodes that will self-terminate in less than 24 hours. Persistent AF, is defined as ≥1 
documented AF lasting >1week in duration or lasting less than 7 days but requiring 
electrical or pharmacological cardioversion to sinus rhythm. 
• 
Age >18 - Age < 80 yr 
• 
Documentation of atrial fibrillation (AF) 
• 
General anesthesia 
• 
All patients must understand and adhere to the requirements of the study and 
be willing to comply with the post study follow-up requirements. 
 
EXCLUSION CRITERIA 
• 
Any reversible cause of AF (post-surgery, thyroid disorder, etc.) 
• 
INR > 4.0 at the time of the procedure 
• 
H/o of severe esophageal ulcers, strictures, varices, bleeding, laceration or 
perforation, esophagitis  
• 
Severe GERD 
• 
H/o esophageal surgery or any esophageal banding or cautery 

31 
 
• 
H/o chest radiation 
• 
Significant abnormality on Swallowing Impairment Score 
• 
Mental impairment precluding signing consent or completing follow up 
• 
Patients with any other significant uncontrolled or unstable medical condition 
• 
Women who are known to be pregnant or have had a positive β-HCG test 
within 7 days prior to procedure 
• 
Presence of left atrial thrombus 
 
PRIMARY CLINICAL ENDPOINT 
The following primary endpoint will be assessed: 
1) The extent of esophageal deviation as measured by the incidence of successfully 
moving the esophagus to achieve a minimum distance of 1 cm between the 
ablation line for the ipsilateral PV pairs and the trailing edge of the esophagus. 
 
SECONDARY CLINICAL ENDPOINTS 
The following secondary endpoints will be assessed: 
1) The extent of esophageal deviation as measured by the incidence of successfully 
moving the esophagus by an average of 2 cm from the ablation line for the 
ipsilateral PV pairs. 
2) The incidence of esophageal laceration as assessed by a Barium swallow study 
performed within 1-3 days of the procedure. 
3) Incidence of PV reconnection at 30 min post-ablation 
4) Fluoroscopy time 
5) Procedure duration 
6) Time from start of ablation to last ablation lesion for pulmonary vein isolation 
  
Pre-procedure testing 
• 
Baseline swallowing impairment score 
• 
Collect any pre-procedural imaging of Left atrium (if performed): MRI/CT 
within 6 months of procedure 
• 
Baseline CBC-Platelets, PTT/PT-INR 
 
AF ablation procedure: 
• 
Patients will be brought to the electrophysiology laboratory in a fasting state. 
• 
General anesthesia will be used for all cases 

32 
 
• 
Venous ± arterial access, number of transseptal punctures performed, and 
catheter selection (coronary sinus catheter, right atrial catheter, intra-cardiac 
echocardiography (ICE), and ablation catheter) will be left to the discretion of 
the operator. 
• 
Any 3D Mapping system can be used 
• 
Any thermal based ablation system can be used for the procedure. 
• 
Insertion of the DV8 tool will be performed at the beginning of the procedure. 
• 
The esophagus will be then moved with a goal of deviation of 2 cm from the 
ablation sites.  
• 
Circumferential pulmonary vein (PV) isolation will be performed next. 
Bidirectional block in and out of the PV must be demonstrated after PV 
isolation (again, this is usual clinical practice). 
• 
Use of adenosine to assess for dormant conduction. 
• 
Per usual practice of the clinical site, Isoproterenol may be used at the end of 
the study protocol to assess for PV reconnection 
• 
After performance of PV isolation on both sides additional LA ablation is left 
to the discretion of the electrophysiologist 
 
POST-PROCEDURE TESTING 
• 
Swallowing impairment score: next morning 
• 
Preferably the next day, but up to 3 days after the procedure: Barium swallow to 
be performed on all patients. 
 
POST-PROCEDURE FOLLOW UP 
• 
2 week and 3-month phone follow up: Repeat swallowing impairment score (to 
be obtained trans-telephonically) 
 
POST-PROCEDURE MEDICATION MANAGEMENT 
• 
All medications are left up to the discretion of the investigator. 
• 
Visualization of any esophageal injury should prompt proton pump inhibitors 
for 2 weeks (per usual practice of the clinical site), CT scan of the chest, and 
referral to the gastroenterology service.  
• 
Therapeutic anticoagulation (example warfarin or equivalent agent) is at the 
discretion of the patient’s electrophysiologist. 
 
POST-PROCEDURE DATA COLLECTION 

33 
 
• 
At the end of the case a copy of the endoscopy (Coded) will be obtained on 
CD/DVD. 
• 
Coded fluoroscopy/CINE images. 
• 
Coded electroanatomical mapping data. 
Work Flow 
• 
Ensure all consents are signed and patient meets inclusion/exclusion criteria 
• 
Baseline Swallowing impairment score 
• 
After induction of general anesthesia, the DV8 tool will be inserted. 
• 
PV isolation will be performed after the deviation of the esophagus.  
• 
Baseline esophageal position (record (cine) straight AP view) to be identified 
with contrast in the esophagus. Exclude from deviation if esophageal 
diverticulum is identified. 
• 
After maximum possible deviation is performed, cine fluoroscopic view is to 
be acquired for both left sided and right-sided ablation. 
• 
Care must be taken to ensure fluoroscopic images are acquired at the same 
level of magnification. Care must also be taken to ensure that the esophagus 
has sufficient barium at all times. 
• 
Esophageal LET probe must be manipulated to approximate catheter tip at all 
times during any posterior wall ablation: Note: All posterior wall lesions are to 
be recorded: 
▪ 
Duration of lesion 
▪ 
Power delivered for all lesion 
 
 
Esophageal deviation and data collection: 
• 
Extent of esophageal deviation measured on the electroanatomic mapping 
system as the distance between the ablation line and the trailing edge of the 
esophagus. The trailing edge of the esophagus will be delineated on the EAM 
system guided by fluoroscopy.  
• 
Time from first ablation to last ablation for PV isolation for all four veins. 
• 
From start of deviation maneuver to last ablation for PV isolation. 
• 
Total procedure duration 
• 
Total Fluoroscopy time 
• 
Confirm PV isolation at 30 minutes, record if vein reconnects. 
• 
All non-PV ablation should be performed after PV isolation only. Above 
parameters should be recorded if additional deviation is performed for non-PV 
ablation such as CFE or atrial tachycardia ablation. 
• 
Obtain all Fluoro/cine images and electroanatomic mapping data. 
 

34 
 
Post-procedural care 
• 
Next morning; Administer SIS symptom scale and record score 
• 
Barium swallow. 
 
Outpatient follow- up 
• 
2 weeks/ 3 months – Telephonic assessment of Swallowing Impairment Score 
• 
Any further follow up that may be relevant to complications during the procedure