A Randomized Controlled Clinical Evaluation of the DiamondTemp™ Ablation System for the Treatment of Paroxysmal Atrial Fibrillation
Phase: NA
Conditions: Paroxysmal Atrial Fibrillation, Atrial Fibrillation
Sponsor: Medtronic Cardiac Ablation Solutions

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DIAMOND-AF STUDY 
Study Title: A Randomized Controlled Clinical Evaluation of the DiamondTemp™ Ablation 
System for the Treatment of Paroxysmal Atrial Fibrillation 
 
Sponsor: 
  
 
Epix Therapeutics (EPIX) 
 
 
 
 
945 Stewart Drive, Suite 100 
 
 
 
 
Sunnyvale, CA 94085 USA 
 
 
 
 
+1 (408) 755-1500 
Protocol No:  
 
TP00599 
Investigational Device: 
DiamondTemp Ablation System  
(Inclusive of the DiamondTemp Ablation Catheters, DiamondTemp 
Catheter-to-RFG Cable, DiamondTemp GenConnect Cable, 
DiamondTemp RF Generator, DiamondTemp Irrigation Pump and 
DiamondTemp Irrigation Tubing Set) 
Revision Number: 
 
I 
Effective Date: 
 
 01 APR 2020 
 
 
 
 
 

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1. STUDY CONTACT INFORMATION 
Sponsor 
Katie Flor  
Principal Clinical Research Specialist/Global Study Manager 
 
Email: katie.j.flor@medtronic.com  
 
 
 
Coordinating Principal 
Investigators, US 
Tom McElderry, MD, FACC, FHRS 
Section Chief, Cardiac Electrophysiology 
 
 
 
William Maddox, M.D., FACC, FHRS 
Assistant Professor, Electrophysiology 
 
 
 
University of Alabama Birmingham (UAB) 
930B Faculty Office Tower 
510 20th Street South 
Birmingham, AL 35294 
 
Coordinating Principal 
Investigator, OUS 
Josef Kautzner, M.D., PhD, FESC 
Director, Electrophysiology 
Institut klinické a experimentální medicíny (IKEM) 
Vitebsk 1958/9 
140 21 Prague 4 
 
 
 
 
 

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Steering Committee 
Including Coordinating 
Principal Investigators 
Andrea Natale, M.D., FACC, FHRS  
Director, Electrophysiology 
Texas Cardiac Arrhythmia Institute at St. David’s Medical Center 
 
 
Frank Cuoco, M.D., MBA 
Director, Arrhythmia Research Center 
Trident Medical Center 
  
 
OUS Contract Research 
Organizations (CRO) 
High Tech Med Consult 
Firmlova 1322/4e 
15500 Prague 5, Czech Republic 
Phone: +402 777 671 069 
 
 
 
MERC srl 
Via Elia Capriolo, 41 
25122 Brescia, Italy 
Phone: +39 030 2754021 
 
 
 
 
Data Management / 
Biostatistics 
Advanced Research Associates 
Data Management / Biostatistics 
2350 Mission College Blvd., Suite 825 
Santa Clara, CA 94054 
Sr. Director, Biostatistics: Jennifer Nezzer 
Phone: +1 (650) 817-7062  
 
 
Electronic Data 
Capture (EDC) 
Medrio 
345 California Street, Suite 325 
San Francisco, CA 94104 
Phone:  +1 (415) 963-3700 
 
ECG Core Lab 
HeartcoR Solutions, LLC 
Event Monitor, ECG Core Lab 
2403 Harnish Drive #201 
Algonquin, IL 60102  
Project Manager: Madalina Andreescu, BS, CRA, CCT 
Phone: +1 (224) 333-3318 
 
 

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Investigator Protocol Signature Page and Agreement 
I have read this Investigational Plan and agree to adhere to the requirements.  I will share 
this Investigational Plan and all pertinent information to all site personnel involved in this 
study.  I will discuss this material with them and ensure they are fully informed regarding 
the study products and the conduct of the study. 
I agree to conduct the study as outlined in the Investigational Plan, in accordance with the 
signed clinical study agreement and to the ethical principles stated in the latest version of 
the Declaration of Helsinki (2013), the applicable guidelines for good clinical practices, 
MEDDEV 2.7/4 (Guidelines on Clinical investigations: A Guide for Manufacturers and 
Notified Bodies) and 2.7/3 (Clinical investigations: Serious Adverse Event reporting), ISO 
14155:2011 (Clinical Investigation of Medical Devices for Human Subjects – Good 
Clinical Practice) or the applicable local and international regulations, whichever provide 
the greater protection of the individual.   
I agree to provide all the information requested in the Case Report Forms presented to me 
by the Sponsor in a manner to assure completeness, legibility and accuracy.  I agree to 
actively enroll subjects into this study. 
I also agree that all information provided to me by the Sponsor, including pre-clinical data, 
protocols, Case Report Forms, and any verbal and written information, will be kept strictly 
confidential and confined to the clinical personnel involved in conducting the study. It is 
recognized that this information may be relayed in confidence to the Institutional Review 
Board / Ethics Committee.   
In addition, no reports or information about the study or its progress will be provided to 
anyone not involved in the study other than the Sponsor, the Institutional Review Board / 
Ethics Committee, the core labs, or the Data Safety Monitoring Board.  Any such 
submission will indicate that the material is confidential. 
 
 
 
 
 
Investigator Signature 
 
Date 
 
 
 
 
Investigator Printed Name 
 
 
 
 
 
 
 
 
 
Sponsor Signature 
 
Date 
 
 
 
 
Sponsor Printed Name 
 
 
 
 

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2. REVISION HISTORY 
Revision 
Level 
DCO 
Description of Change 
Reason for Change 
Effective 
Date 
A 
0426 
Initial Release 
N/A 
08/25/2017 
B 
0429 
a. Update section 7.1, Proposed 
Intended Use of the Investigational 
Device to include: accessories 
(DiamondTemp Cable-to-RFG 
Cable, DiamondTemp GenConnect 
Cable, DiamondTemp Irrigation 
Pump/Tubing Set); removed 
ablation, RF, and three dimensional 
descriptors.  
b. Update SAE rates for 7 and 30 day 
follow up 
a. Clarification of 
statement; no change 
to intent. 
b. Reflects updated 
results. 
08/29/2017 
C 
0438 
Updated Table 4, Summary of 
Procedural Data, in Section 5. 
Reflects updated results.  
08/31/2017 
D 
0608 
a.  Updated planned subject sample 
size from 350 to 480. 
b.  Revised primary safety endpoint 
from 7 days to 30 days and 
included clinically symptomatic PV 
stenosis through 6 months. 
c. Added atrial flutter and atrial 
tachycardia to primary 
effectiveness endpoint.  Revised 
effectiveness failure definition to 
remove time period and add 
inability to isolate all accessible 
targeted PV; use of non-study 
device for AF targets; restricted 
repeat ablation to 1 procedure 
during blanking period. 
d. Defined single procedure success 
and study success. 
e. Revised inclusion criteria for PAF 
history from 12 to 6 months from 
index procedure and requirement 
for physician documentation for 
recurrent, self-terminating AF. 
a. Revised statistical 
calculations in 
G170227 A001 and 
A002; FDA approval 
letter dated February 
7 2018. 
b-g. Feedback from FDA 
in G170227 
amendment 
responses. 
h.    Supports request 
from FDA to add PV 
stenosis to primary 
safety endpoint. 
i-o.  Feedback from FDA 
in G170227 
amendment 
responses. 
 
 
02/20/2018 

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Revision 
Level 
DCO 
Description of Change 
Reason for Change 
Effective 
Date 
f.  Revised randomization 
stratification to include failure of 
AADs. 
g. Added requirement for bi-monthly 
periodic event monitoring from 3 to 
12 month follow up. 
h. Added definition of PV stenosis. 
i. Revised stroke definition. 
j. Revised sample size justification, 
modifying estimated attrition rate 
to 7% and composite safety rate to 
6.5%. 
h. Revised enrolled patient criteria to 
be the point at which subject is 
randomized to a treatment arm. 
i. Revised baseline tests to include 
TEE and ICE diagnostics and 
criteria to assess subjects for 
thrombus. 
j. Clarified that continuation of AADs 
should be at the physician 
discretion and at the failed dose. 
k. Added instructions for placement 
of esophageal temp probe and 
guidance for temperature increase 
that should terminate energy 
delivery. 
l.  Clarified that EGM will be used to 
guide termination of RF delivery 
within 3-5 seconds after EGM 
amplitude is achieved. 
m. Added anticoagulation guidelines 
based on 2017 HRS Expert 
Consensus Standard on Catheter 
and Surgical Ablation of AF. 
n. Revised physical exam from 
limited to full. 
o. Added questionnaire for subjects to 
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Revision 
Level 
DCO 
Description of Change 
Reason for Change 
Effective 
Date 
they received (investigational, control 
or unknown). 
E 
0676 
a. Updated address for steering 
committee member. 
b. Added DiamondTemp 
Bidirectional Catheter to section 3 
(Protocol Summary), section 7.3 
(Investigational Device 
Description), section 7.4 
(DiamondTemp Ablation Catheter) 
c. Clarification that clinical subjects 
from US sites will be 
approximately 50% (from a 
minimum of 50%). 
d. Clarification that inclusion criteria 
of at least one episode of PAF, 
documented by 
electrocardiographic data, is 
sufficient (versus requiring 
documented duration of a minimum 
of 30 seconds) in section 3 
(Protocol Summary) and section 
9.2 (Study Inclusion Criteria). 
e. Revision of regularly prescribed 
amiodarone as an exclusion criteria 
from within 3 months of enrollment 
to 2 months of enrollment in 
section 3 (Protocol Summary), 
section 8.2 (Study Design) and 
section 9.3 (Study Exclusion 
Criteria). 
f. Clarification of randomization 
stratification in section 8.2 as 
blocked randomization stratified by 
site followed by stratification by 
failure of Class I/III or Class II/IV 
AADs. 
a. Updated hospital 
association 
b. Five day notice 
submitted to FDA on 
3/22/2018 as 
G170227 S002. 
c. Enrollment rate in 
Europe at multiple 
centers is ongoing; a 
hard stop at exactly 
50% of total study 
subjects (total 
subjects = 480) may 
not be possible. 
Subjects slightly in 
excess of 50% will 
not impact overall 
study conclusions. 
d. Steering committee 
feedback that 
requiring a 30 second 
recording is 
impractical.  Per the 
committee, a 
recording of any 
duration, with 
objective 
electrocardiographic 
evidence, is sufficient 
to document PAF. 
e. Based on steering 
committee feedback 
and the 
pharmacokinetic 
profile of 
amiodarone, reducing 
the exclusion criteria 
to 60 days still allows 
for subjects to be 
amirodarone-free 
04/18/2018 

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Revision 
Level 
DCO 
Description of Change 
Reason for Change 
Effective 
Date 
g. Clarification in Table 6 and section 
12.7 (Adverse Event Reporting) of 
extended hospitalization events that 
are and are not included in safety 
endpoints. 
h. Clarification of AADs during the 
effectiveness evaluation period as 
acceptable to discontinue an AAD 
but not acceptable to add a new 
class of AAD or to substitute an 
AAD in Section 11.5 (Post 
Procedure). 
i. Clarified early recurrences of atrial 
arrhythmias within the blanking 
period  (section 11.9,  Repeat 
Ablation Procedure) as AF, AT and 
AFL, not solely AF. 
during the blanking 
period. 
f. Change reflects 
intended stratification 
protocol and matches 
actual stratification 
being done. 
g. Not all extended 
hospitalizations meet 
the intent of the 
safety endpoints. 
h. Provides clarification 
of what constitutes a 
change in AAD 
regimen. 
i. Clarifies the original 
intent of the 
statement. 
F 
0928 
a. Added generator models to 
sections 7.3, 7.5. 
b. Clarified secondary endpoints for 
ablation time in protocol summary 
and section 8.5. 
c. Added analysis for catheter model 
evaluation in section 8.7. 
d. Added Per Protocol analysis to 
Section 8.7, Statistical Analysis. 
Clarified the Safety Analysis Set 
population in Section 8.7. 
a. Study includes 
generator models 
CEDTG100 and 
CEDTG200. 
b. Assists in secondary 
endpoint data 
analysis. 
c. Provides for analysis 
by model of catheter 
used. 
11/15/2018 
G 
1026 
Updated company name to Epix 
Therapeutics or EPIX.   
Updated company address to reflect 
new headquarters 
Updated Company logo in the header 
of document 
Updated Sponsor email addresses to 
reflect @epixthx.com 
Epix Therapeutics 
officially changed names 
and updated logo and 
email addresses to reflect 
name change 
EPIX moved company 
headquarters 
2/27/2019 
H 
1036 
Updated Section 5, 5.5, 5.6, Table 2 
and Table 4 and Table 5. 
Changed contact info on page 3 
Updated final TRAC-AF 
study data results     
Project Manager changed 
03/18/2019 

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Revision 
Level 
DCO 
Description of Change 
Reason for Change 
Effective 
Date 
I 
1595 
• Updated study contact 
information 
• Primary effectiveness endpoint 
definition updated to remove 
“symptomatic” from the 
definition (Section 3 and 8.4). 
• Secondary endpoint bullet number 
4 updated to remove 
“symptomatic and asymptomatic” 
from the definition (Section 3 and 
8.5).  
• Secondary endpoint bullet number 
5 removed altogether (Section 3 
and 8.5). 
• Clarified definition of secondary 
endpoint bullet number 7- single 
procedure success, in alignment 
with revised primary effectiveness 
endpoint definition (Section 3 and 
8.5). 
• Added new secondary endpoint 
for single procedure success, in 
alignment with the composite 
primary effectiveness endpoint 
failure criteria (Section 3 and 8.5) 
• Changed to reflect 
primary Sponsor 
study contact and 
current Advance 
Research Associates 
Contact 
• Primary effectiveness 
endpoint definition 
updated to align with 
endpoint failure 
definition and in 
accordance with 
study data collection 
(i.e. symptoms data 
associated with ECG 
transmissions not 
submitted to ECG 
Core Lab). 
• Secondary endpoint 
bullet 4 updated to 
align with primary 
effectiveness 
endpoint definition 
and in accordance 
with study data 
collection. 
• Secondary endpoint 
bullet 5 removed as it 
cannot be reliably 
analyzed. 
• Secondary endpoint 
bullet 7- single 
procedure success 
definition updated to 
clarify scope of 
analysis.  
• New secondary 
endpoint added per 
FDA feedback. 
04/01/2020 
 
 

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3. PROTOCOL SUMMARY 
Objective 
The objective of this study is to demonstrate the safety and effectiveness 
of the DiamondTemp Ablation System for the treatment of drug 
refractory, recurrent, symptomatic paroxysmal atrial fibrillation. 
Test Device 
DiamondTemp Ablation System consists of: 
• DiamondTemp Ablation Catheter  
o Unidirectional and Bidirectional models  
• DiamondTemp Catheter-to RFG Cable  
• DiamondTemp GenConnect Cable  
• DiamondTemp Generator with Footswitch  
• DiamondTemp Irrigation Pump  
• DiamondTemp Irrigation Tubing Set  
The investigational device will be used with commonly available: 
• EP recording systems 
• Cardiac stimulators 
• EnSite™ Velocity™ or Precision™ Cardiac Mapping System  
Control Device 
 
St. Jude Medical (Abbott) Ablation System 
o TactiCath™ Quartz Contact Force Ablation Catheter   
o AMPERE™ RF Ablation Generator and Cables or equivalent 
o COOL POINT™ Irrigation Pump and Tubing or equivalent 
The control device will be used with commonly available: 
• EP Recording Systems 
• Cardiac Stimulators 
• EnSite™ Velocity™ or Precision™ Cardiac Mapping System 
Study Design 
The DIAMOND-AF study is a prospective, single-blind, 1:1 
randomized, controlled trial being performed at multiple centers in the 
United States, Canada and Europe. 
Planned Subject 
Sample Size 
A maximum of 480 subjects will be enrolled and randomized in this 
study. 
Planned Number of 
Global 
Investigational Sites 
Subjects will be enrolled at up to 30 investigational sites in the United 
States (US) and outside of the US (OUS). 
Approximately 50% of the data will be generated from sites within the 
US. 
Ablation Procedure 
The primary focus of the ablation procedure is to create a series of point-
by-point radiofrequency (RF) lesions encircling the left and right PVs to 

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achieve electrical pulmonary vein isolation (PVI) from the rest of the 
left atrium (LA).  
Investigators may use their preferred approach to obtain PVI, such as 
antral or wide area circumferential ablation (WACA) targeting PVs 
individually or PV pairs ipsilaterally.   
PVI must be confirmed by entrance block at least 20 minutes following 
the last ablation around the respective PV.   Targeting non-PV foci and 
complex fractionated electrograms (CFAE) is not recommended in this 
investigation.  If the investigator identifies additional focal or macro-
reentrant atrial sites to be clinically relevant to AF and requiring 
ablation, the ablation location will be documented. 
Primary Safety 
Endpoint 
The primary safety endpoint is defined as freedom from a composite of 
serious adverse events (SAE) occurring within 30-days and clinically 
symptomatic pulmonary vein stenosis through 6-months post-index 
ablation procedure, as adjudicated by an independent Clinical Events 
Committee (CEC) for relatedness to the procedure or device.  
The primary safety device- or procedure-related SAE composite will be 
the combined rate of the following events:     
• Atrioesophageal fistula  
• Bleeding complication  
• Cardiac tamponade / perforation  
• Death 
• Extended hospitalization 
• Myocardial infarction  
• Pericarditis  
• Phrenic nerve paralysis 
• Pulmonary edema 
• Pulmonary vein stenosis 
• Stroke post-ablation    
• Thromboembolism 
• Transient ischemic attack (TIA) post-ablation 
• Vagal nerve injury  
• Vascular access complications 

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Primary 
Effectiveness 
Endpoint 
The primary effectiveness endpoint is defined as freedom from 
documented atrial fibrillation (AF), atrial flutter* (AFL) and atrial 
tachycardia (AT) episodes following the blanking period (3-month 
follow-up post-ablation procedure) through the end of the effectiveness 
evaluation period (12-month follow-up post-ablation procedure).  
An effectiveness failure is defined by any of the following events: 
• Inability to electrically isolate all accessible targeted pulmonary 
veins during the ablation procedure 
• Documented episodes of AF, AFL or AT lasting ≥ 30 seconds in 
duration as evidenced by electrocardiographic data during the 
effectiveness evaluation period 
• DC cardioversion for AF, AFL or AT during the effectiveness 
evaluation period 
• A repeat ablation procedure to treat AF, AFL or AT during the 
effectiveness evaluation period 
• Use of a new or modification to existing Class I-IV anti-
arrhythmic drug (AAD) regimen to treat AF, AFL or AT 
recurrence during the effectiveness evaluation period 
• Use of a non-study device for ablation of any AF targets during 
the index or repeat ablation procedure during the blanking period 
• More than one (1) repeat ablation procedure during the blanking 
period 
*  Occurrence and/or ablation of cavotricuspid isthmus (CTI)-dependent AFL, 
as confirmed by entrainment maneuvers during EP testing at any time 
during this study is not a primary effectiveness failure because it is not 
considered an iatrogenic arrhythmia following a left atrial ablation 
procedure for AF.    
Secondary Endpoints 
Secondary endpoints to characterize the performance of the 
DiamondTemp Ablation System, relative to the control device, will 
include: 
• Mean duration of individual RF ablations (seconds). 
• Mean cumulative RF time per procedure (minutes).     
• Freedom from a composite of SAE occurring within 7-days post-
index ablation procedure as adjudicated by an independent CEC 
for relatedness to the procedure or device.  
• Freedom from documented AF, AT and AFL* episodes 
following the blanking period through 12-month follow-up post-
ablation procedure in the absence of class I and III anti-
arrhythmic drug therapy. 

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• Rate of acute procedural success, defined as confirmation of 
electrical isolation of PVs via assessment of entrance block at 
least 20 minutes following the last ablation around the respective 
PV.    
• Rate of single procedure success defined as the rate of subjects 
treated with one single ablation procedure during study 
participation and with freedom from documented AF, AT and 
AFL* at 12 months.  
• Rate of single procedure success defined as the rate of subjects 
treated with one single ablation procedure during study 
participation and with freedom from ALL primary effectiveness 
endpoint failure criteria.  
• Rate of occurrence of electrically reconnected PVs following a 
20-minute waiting period assessed by entrance block at index 
procedure.  
• Accumulated changes in QOL using the AF QOL Survey 
(AFEQT Questionnaire) from baseline through 6 and 12 months 
following ablation procedure. 
• Neurological changes measured using the NIH stroke scale 
between baseline and post-ablation (pre-discharge visit) and at 
12 months post-ablation procedure. 
• Total procedure time (minutes), defined as time of first assigned 
ablation catheter insertion into the vasculature to time of last 
procedural ablation catheter removed. 
• Time to achieve initial PVI at index procedure (minutes), defined 
as time of delivery of first RF ablation with the assigned ablation 
catheter until confirmation of PVI. 
• Total treatment device time (minutes), defined as time of 
delivery of first RF ablation with the assigned ablation treatment 
catheter to removal of the treatment catheter. 
• Total number of RF ablations per procedure.  
• Total fluid infused through the assigned ablation catheter (mL). 
• Total fluoroscopy time (minutes). 
• Number of re-hospitalizations due to atrial fibrillation recurrence 
after blanking period. 
*Occurrence and/or ablation of cavotricuspid isthmus (CTI)-dependent AFL, 
as confirmed by entrainment maneuvers during EP testing at any time during 
this study is not a primary effectiveness failure because it is not considered an 
iatrogenic arrhythmia following a left atrial ablation procedure for AF.    

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Inclusion Criteria 
1. Above eighteen (18) years of age or of legal age to give 
informed consent specific to state and national law.   
2. Subjects with a history of symptomatic, paroxysmal atrial 
fibrillation (PAF) who have had ≥ 2 episodes of PAF reported 
within the 6 months prior to index ablation procedure with a 
physician note indicating recurrent, self-terminating AF. 
3. At least one episode of PAF documented by electrocardiographic 
data within 12 months prior to index ablation procedure.  
4. Refractory to at least one Class I-IV anti-arrhythmic AAD for 
treatment of PAF.  
5. Suitable candidate for intra-cardiac mapping and ablation of 
arrhythmia. 
6. Subject agrees to comply with study procedures and be available 
(geographically stable) for follow-up visits for at least 12 months 
after enrollment. 
7. Subject is willing and able to provide written consent.  
Exclusion Criteria 
At time of enrollment and/or prior to procedure: 
1. AF secondary to electrolyte imbalance, thyroid disease or 
reversible or non-cardiac cause. 
2. LA diameter > 5.5 cm. 
3. Left ventricular ejection fraction (LVEF) < 35%. 
4. Currently NYHA Class III or IV or exhibits uncontrolled heart 
failure. 
5. Body Mass Index (BMI) > 40 kg/m2. 
6. LA ablation, septal closure device or mitral valve surgical 
procedure at any time prior to enrollment. 
7. Presence of intramural thrombus, tumor or abnormality that 
precludes vascular access, catheter introduction or manipulation. 
8. Coagulopathy, bleeding diathesis or suspected procoagulant state 
9. Sepsis, active systemic infection or fever (>100.5 oF / 38 oC) 
within a week prior to the ablation procedure. 
10. Significant restrictive or obstructive pulmonary disease or 
chronic respiratory condition. 
11. Renal failure requiring dialysis or renal compromise that in the 
investigator’s judgement would increase risk to the subject or 
deem the subject inappropriate to participate in the study. 
12. Known allergies or intolerance to anticoagulant and antiplatelet 
therapies to be used in conjunction with the study or contrast 

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sensitivity that cannot be adequately pre-treated prior to the 
ablation procedure. 
13. Positive pregnancy test results for female subjects of 
childbearing potential or breast feeding. 
14. Enrollment in a concurrent clinical study that in the judgement of 
the investigator would impact study outcomes. 
15. Acute or chronic medical condition that in the judgment of the 
investigator would increase risk to the subject or deem the 
subject inappropriate to participate in the study. 
16. Life expectancy < 12 months based on medical history or the 
medical judgement of the investigator. 
Within 1 month of enrollment or just prior to procedure: 
17. Documented LA thrombus upon imaging. 
18. Creatinine >2.5mg/dl or creatinine clearance <30mL/min.     
Within 2 months of enrollment: 
19. Regularly (uninterrupted) prescribed amiodarone. 
Within 3 months of enrollment: 
20. Significant gastrointestinal (GI) bleed. 
21. Myocardial infarction (MI), unstable angina, cardiac surgery or 
coronary intervention. 
Within 6 months of enrollment: 
22. Coronary artery bypass graft (CABG) procedure.   
23. ICD, CRT leads or pacemaker implant procedure. 
24. Documented stroke, CVA, TIA or suspected neurological event. 
Within 12 months of enrollment: 
25. An episode of AF lasting >7 days in duration.  
Follow-up Visit 
Schedule 
Subject Visit Description 
Timeframe / Visit Window 
Enrollment and Screening 
Visit(s) 
Within 60 days of ablation procedure 
Ablation Procedure (Index) 
Day 0; follow-up visit windows 
determined by ablation procedure 
completion date 
Pre-Discharge  
Prior to discharge from hospital 
following ablation procedure 
7 days Follow-Up (Phone) 
7 ± 3 days 

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1 Month Follow-Up  
30 ± 14 days 
3 Month Follow-Up 
90 ± 21 days 
6 Month Follow-Up 
180 ± 28 days 
12 Month Follow-up 
365 ± 45 days 
Unscheduled Visits 
As needed/necessary 
Repeat Ablation Procedure 
Within 90 days of ablation procedure 
(follow-up visit schedule does not 
restart) 
 
 
 

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TABLE OF CONTENTS 
1. 
STUDY CONTACT INFORMATION ............................................................... 2 
2. 
REVISION HISTORY ......................................................................................... 5 
3. 
PROTOCOL SUMMARY ................................................................................. 10 
4. 
INTRODUCTION............................................................................................... 20 
4.1. 
ATRIAL FIBRILLATION (AF) AND CLINICAL NEED ..................................... 20 
4.2. 
PRIOR CLINICAL EVIDENCE FOR RF ABLATION TO TREAT PAF ................. 21 
5.  
SUMMARY OF FIRST-IN-HUMAN CLINICAL STUDY (TRAC-AF) ...... 22 
5.1. 
TRAC-AF STUDY DESIGN ......................................................................... 22 
5.2 
INVESTIGATIONAL DEVICE ......................................................................... 22 
5.3.  
TRAC-AF CLINICAL ENDPOINTS .............................................................. 23 
5.4.  
STUDY ELIGIBILITY CRITERIA .................................................................... 23 
5.5 
STUDY RESULTS ........................................................................................ 24 
5.6.  
CONCLUSION FROM CLINICAL STUDY ........................................................ 28 
6. 
TACTICATH CONTROL DEVICE................................................................. 28 
6.1. 
INDICATIONS FOR USE................................................................................ 28 
6.2.  
PRODUCT CLASSIFICATION, CODE, REGULATION....................................... 29 
6.3. 
CONTROL DEVICE DESCRIPTION ................................................................ 29 
6.4.  
TACTICATH QUARTZ CONTACT FORCE ABLATION CATHETER .................. 29 
6.5.  
TACTISYS QUARTZ EQUIPMENT ................................................................. 30 
6.6. 
ADDITIONAL REQUIRED EQUIPMENT ......................................................... 30 
7. 
DIAMONDTEMP INVESTIGATIONAL DEVICE ....................................... 30 
7.1.  
PROPOSED INTENDED USE OF THE INVESTIGATIONAL DEVICE ................... 30 
7.2. 
PRODUCT CLASSIFICATION, CODE, REGULATION....................................... 30 
7.3. 
INVESTIGATIONAL DEVICE DESCRIPTION ................................................... 31 
7.4. 
DIAMONDTEMP ABLATION CATHETER ...................................................... 32 
7.5.  
DIAMONDTEMP RF GENERATOR ............................................................... 33 
7.6. 
DIAMONDTEMP IRRIGATION PUMP ............................................................ 33 
7.7  
DIAMONDTEMP TUBING SET...................................................................... 34 
7.8. 
DIAMONDTEMP FOOTSWITCH .................................................................... 34 
7.9.  
DIAMOND TEMP CABLES ........................................................................... 34 
7.10. MAPPING SYSTEM AND EP RECORDING SYSTEM COMPATIBILITY ............. 36 

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8. 
STUDY PROTOCOL AND METHODS .......................................................... 36 
8.1. 
 STUDY OBJECTIVE .................................................................................... 36 
8.2. 
 STUDY DESIGN .......................................................................................... 36 
8.3.  
 PRIMARY SAFETY ENDPOINTS ................................................................... 38 
8.4. 
 PRIMARY EFFECTIVENESS ENDPOINTS ...................................................... 40 
8.5.  
SECONDARY ENDPOINTS ............................................................................ 41 
8.6. 
 SAMPLE SIZE JUSTIFICATION ..................................................................... 42 
8.7. 
 STATISTICAL ANALYSIS ............................................................................ 42 
8.8. 
 SITE TRAINING .......................................................................................... 43 
9. 
SUBJECT SELECTION .................................................................................... 44 
9.1.  
CRITERIA FOR ELIGIBILITY ........................................................................ 44 
9.2. 
 STUDY INCLUSION CRITERIA ..................................................................... 44 
9.3.  
STUDY EXCLUSION CRITERIA .................................................................... 44 
10.  
SUBJECT ACCOUNTABILITY ...................................................................... 45 
10.1.  POINT OF ENROLLMENT ............................................................................. 45 
10.2.  SUBJECT STATUS AND CLASSIFICATION ..................................................... 46 
10.3.  SUBJECT WITHDRAWAL ............................................................................. 46 
11.  
STUDY METHODS............................................................................................ 46 
11.1.  ENROLLMENT AND VISIT SCHEDULE .......................................................... 46 
11.2. SCREENING EVALUATION .............................................................................. 48 
11.3. BASELINE EVALUATION ............................................................................. 48 
11.4.  PRE-ABLATION TESTING AND REQUIREMENTS .......................................... 49 
11.5.  ABLATION PROCEDURE .............................................................................. 49 
11.6  
PRE-DISCHARGE FOLLOW-UP VISIT .......................................................... 55 
11.7  
SEVEN DAY FOLLOW-UP PHONE CALL ...................................................... 56 
11.8 
 ONE MONTH FOLLOW-UP VISIT ................................................................ 56 
11.9      REPEAT ABLATION PROCEDURE (IF APPLICABLE) ...................................... 56 
11.10   THREE MONTH FOLLOW-UP VISIT ............................................................. 57 
11.11   SIX MONTH FOLLOW-UP VISIT................................................................... 57 
11.12   TWELVE MONTH FOLLOW-UP VISIT ........................................................... 58 
11.13   UNSCHEDULED VISITS ................................................................................ 58 
11.14   SUBJECT LOST TO FOLLOW-UP ................................................................... 58 
11.15   EXTENDED FOLLOW-UP PERIOD (IF APPLICABLE) ....................................... 59 
11.16   STUDY COMPLETION .................................................................................. 59 
12.  
STUDY CONDUCT ............................................................................................ 59 
12.1.  STATEMENT OF COMPLIANCE .................................................................... 59 
12.2.  REGULATORY CONSIDERATIONS ................................................................ 59 

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12.3.  INVESTIGATOR RESPONSIBILITIES .............................................................. 59 
12.4.  CONFIDENTIALITY AND DATA PROTECTION ............................................... 60 
12.5.  INSURANCE ................................................................................................ 60 
12.6.  PROTOCOL AMENDMENTS .......................................................................... 60 
12.7.  ADVERSE EVENT REPORTING..................................................................... 61 
12.8.   DEVICE DEFICIENCY REPORTING ............................................................... 63 
12.9.  PROTOCOL DEVIATIONS ............................................................................. 63 
12.10  INVESTIGATIONAL DEVICE ACCOUNTABILITY ........................................... 64 
12.11.  DOCUMENTATION ...................................................................................... 64 
12.12.  RECORD RETENTION .................................................................................. 65 
13.  
POTENTIAL RISKS AND BENEFITS............................................................ 65 
13.1.  ANTICIPATED ADVERSE EVENTS ................................................................ 65 
13.2.  RISK MINIMIZATION .................................................................................. 67 
13.3.  BENEFITS ................................................................................................... 68 
14.  MONITORING ........................................................................................................ 69 
14.1.  STUDY MONITOR ....................................................................................... 69 
14.2.  MONITORING PROCEDURES ........................................................................ 69 
14.3.  ECG CORE LAB ......................................................................................... 70 
14.4.  DATA SAFETY MONITORING BOARD.......................................................... 70 
14.5.  CLINICAL EVENTS COMMITTEE .................................................................. 71 
14.6.  STEERING COMMITTEE ............................................................................... 71 
15.  
SUSPENSION OR TERMINATION ................................................................ 71 
15.1. PREMATURE TERMINATION OF THE STUDY ................................................ 71 
15.2.  TERMINATION OF PARTICIPATION .............................................................. 72 
16.  
PUBLICATION AND REPORTING POLICY ............................................... 72 
17.  
REIMBURSEMENT AND COMPENSATION FOR SUBJECTS ................ 73 
18. ABBREVIATIONS AND DEFINITIONS .............................................................. 73 
18.1.  TABLE OF DEFINITIONS .............................................................................. 73 
18.2.  TABLE OF ABBREVIATIONS ........................................................................ 78 
19.  
BIBLIOGRAPHY ............................................................................................... 80 
 

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4. INTRODUCTION 
4.1. Atrial Fibrillation (AF) and Clinical Need 
Atrial fibrillation (AF) is the most common clinically-significant cardiac arrhythmia. It is a 
major public health concern in the United States, affecting an estimated 2.3 million people in 
North America and 4.5 million people in Europe[1]. It has been projected that the prevalence 
of AF will increase 2.5 fold during the next 50 years in the United States [2]. AF is associated 
with increased cardiovascular morbidity and mortality and the prevalence increases over time 
due to the aging population and an increase in age-specific occurrence of AF [3-5].  
Symptoms of AF vary with the ventricular rate, underlying functional status, duration of AF, 
presence and degree of structural heart disease, and individual patient perception; however, 
most patients with AF complain of palpitations, angina, dyspnea, fatigue, or dizziness. AF 
also significantly impairs quality of life, with up to two-thirds of patients reporting it is 
disruptive and debilitating to their lives [6-8]. AF is an abnormal heart rhythm that has been 
classified as recurrent when two or more episodes are detected. If these episodes of AF last 
less than seven days and terminate spontaneously, then it is classified as paroxysmal AF 
(PAF).  PAF accounts for approximately 40 to 45 percent of AF cases. [4, 9]  
AF is a sustained arrhythmia characterized by rapid and disorganized atrial activation leading 
to impaired atrial function, which can be diagnosed on an ECG by lack of a P-wave and 
irregular QRS complexes. The disorganized atrial activation appears as “fibrillatory” waves 
activating the atria at a rate generally between 350 and 600 beats/min and the syncytial 
contraction of the atria is replaced by irregular atrial twitches. While AF can occur in 
isolation, it may also be associated with other arrhythmias such as atrial flutter or atrial 
tachycardia. 
The electrophysiological mechanisms responsible for AF may include rapid focal 
tachyarrhythmia in the pulmonary veins (PVs) and/or other atrial regions with fibrillatory 
conduction, multiple reentrant wavelet conduction initiated by premature atrial complexes 
(PACs) and/or atrial tachyarrhythmia, and/or formation of stable or unstable reentrant circuits 
of very short cycle lengths that generate fibrillatory conduction [10, 11].  
Of all electrophysiological mechanisms responsible for AF, of significant interest are the PVs 
which have been identified to play a critical role in triggering and maintaining AF. 
Haissaguerre and colleagues have demonstrated that in most AF patients, the focus is in one 
of the PVs [12].  
The choice of therapy for AF is influenced by patient preference, associated structural heart 
disease, severity of symptoms and whether the AF is classified as recurrent paroxysmal, 
recurrent persistent or permanent. Although AF can be problematic to manage medically due 
to its progressive nature, there are multiple therapies in current use for the treatment of AF, 
and many of these therapies are sub-optimal for most patients. Treatment options include 
medical management, pacing, cardioversion, implantable devices, surgery and ablation 
therapy to eliminate the arrhythmia [4, 13].  
Of all therapeutic strategies for AF one of interest is radiofrequency catheter ablation 
(RFCA) as a potential curative treatment.  RFCA for the treatment of AF is a commonly 
performed procedure for symptomatic patients in whom medications are either ineffective or 

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not tolerated [4, 9, 14]. RFCA restores normal sinus rhythm by delivering RF energy through a 
catheter at targeted focal sites to disrupt abnormal electrical activity. The most common 
catheter ablation approach to treat AF is to electrically isolate the PVs (PVI).  Other 
approaches used include WACA and CFAE ablation. Additional focal or macro-reentrant 
atrial sites may be ablated but the approach varies from center to center.   
Despite significant improvements in catheter ablation strategies to treat AF in recent years, 
Neuzil and colleagues report that refractory recurrence of arrhythmia remains a continuing 
concern with recurrence rates of AF after RFCA still remaining relatively high (20-55%) [15] 
and perhaps attributed to lack of transmural lesions during PVI[16]. Technological innovations 
in RFCA include multi-electrode ablation catheters, high resolution ablation catheters, force-
sensing technologies and navigation technologies. 
4.2. Prior Clinical Evidence for RF Ablation to Treat PAF   
Ablation has become the standard of care in many centers due to the superiority of catheter 
ablation to AADs.  The first two classes of devices to seek and achieve FDA approval for 
ablation of PAF were an irrigated RF catheter (ThermoCool, Biosense Webster) and a 
cryoballoon ablation catheter (ArticFront, Medtronic).  The prospective randomized studies 
for these devices demonstrated the safety and efficacy and the superiority of catheter ablation 
over drug therapy in drug refractory patients.[17, 18] 
 
Subsequent approval studies of new ablation technologies have been either compared with a 
previously-approved device with the same indications for use in a randomized, controlled 
non-inferiority study or, in the case of a second-generation RF ablation catheter, compared 
with predefined performance goals in a single-arm study.   
Recently, two catheters have been developed to measure real-time contact force during 
ablation, a concept where force is one of the primary factors determining lesion size. One 
catheter uses three optical fibers to measure the micro-deformation of a deformable body in 
the catheter tip (TactiCath, St Jude Medical, Incorporated), which correlates with tip force [19-
21]. The second catheter uses a small spring between the ablation tip electrode and the 
catheter shaft, with a tiny magnetic transmitter in the tip and magnetic sensors to measure 
microdeflection of the spring (ThermoCool SmartTouch, Biosense Webster, Inc.), 
corresponding to tip force[22-24]. 
The TactiCath catheter was evaluated in the FDA investigational study, TOCCASTAR 
clinical trial[25]. In this prospective, randomized clinical trial, 300 patients with PAF were 
randomized to ablation with the TactiCath catheter or to the non-contact force sensing 
ThermoCool ablation catheter. No difference in efficacy was observed, with success rates of 
67.8% and 69.4% in the contact force (CF) and control arms, respectively. When the CF arm 
was stratified into optimal CF and non-optimal CF groups, effectiveness was 75.9% vs 
58.1%, respectively. There was no difference in the rate of complications in the two groups. 
Cardiac tamponade occurred in one subject in each group. 
The ThermoCool SmartTouch catheter was evaluated in a multicenter, prospective, 
randomized clinical trial performed for FDA approval[24]. The outcomes were compared with 
the ThermoCool IDE trial[18], in which 170 subjects were enrolled. The 12-month freedom 
from AF/AT/AFL in SMART-AF was 72.5% at 1-year follow-up, compared with 66% 

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efficacy for the ThermoCool non-contact force catheter. The average CF per procedure was 
18 grams. Four subjects experienced cardiac tamponade. A post hoc analysis revealed that 
when the CF was between investigator-selected working ranges >80% of the time, outcomes 
were 4.25 times more likely to be successful.  
5.  SUMMARY OF FIRST-IN-HUMAN CLINICAL STUDY (TRAC-AF) 
EPIX conducted a multi-center First-In-Human clinical study, TRAC-AF, across four European 
centers to establish evidence of clinical safety and effectiveness of the DiamondTemp Ablation 
System to treat patients with drug refractory, recurrent, symptomatic paroxysmal atrial 
fibrillation (PAF).  
TRAC-AF (DiamondTemp TempeRAture-Controlled and Contact Sensing RF Ablation Clinical 
Trial for Atrial Fibrillation, NCT02821351) study was a prospective, multi-center, single-arm 
feasibility study initiated in 2016 and conducted at four European investigational sites.   
Enrollment was performed in two phases.  Phase 1 included enrollment of 38 subjects from 
January through March of 2016 and Phase 2 included enrollment of an additional 34 subjects 
from June through July 2017.  A total of 72 subjects were enrolled in the study and 70 subjects 
were treated with the study device and analyzed.  Enrollment is now closed and all subjects in 
both phases have completed their 12-month follow-up visits and are now exited from the study.   
Primary safety and long-term primary safety endpoints were met through 7-days and 30-days 
post-procedure, with SAEs reported in two subjects (2.9%) and three subjects (4.3%) 
respectively, for a total of three subjects experiencing an SAE up to 30 days post-procedure. The 
primary effectiveness endpoint of acute procedural success was achieved in all 70 subjects 
(100%) through the demonstration of clinically-relevant pulmonary vein isolation and 
confirmation 20 minutes after the last delivery of radiofrequency energy. Freedom from AF at 12 
months post-procedure was 72.5%.  
5.1. TRAC-AF Study Design 
Subjects with symptomatic PAF who were refractory or intolerant to at least 1 anti-
arrhythmic drug (AAD; class I-IV) were screened for enrollment. Subjects that met the study 
eligibility criteria and signed the informed consent form (ICF) were enrolled and treated in 
accordance with the protocol and the HRS/EHRA/ECAS Expert Consensus Statement on 
Catheter and Surgical Ablation of Atrial Fibrillation [14, 26].  Subjects received ablation using 
the investigational device which required electrical isolation of all clinically relevant 
pulmonary veins.  
5.2  Investigational Device 
The investigational device in this clinical study is the DiamondTemp Ablation System.  The 
investigational device was used with a commonly available EP recording system, cardiac 
stimulator and mapping device, the EnSite™ Velocity™ or Precision™ Cardiac Mapping 
System (St. Jude Medical).  There were no control devices in this study. 
 

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5.3.  TRAC-AF Clinical Endpoints 
The primary endpoint events for this trial used to assess the safety and effectiveness of the 
DiamondTemp Ablation System for the treatment of drug refractory, recurrent, symptomatic 
PAF are as follows: 
Primary Safety Endpoint  
The safety of the DiamondTemp Ablation System was assessed by evaluating the nature and 
frequency of serious adverse events (SAEs) and serious adverse device effects (SADEs) 
during the time of the ablation procedure and within 7 days afterwards. 
Long Term Primary Safety 
The long-term safety of the DiamondTemp System was assessed by evaluating the nature and 
frequency of serious adverse events (SAE) and SADEs at 30 days post-procedure. 
Primary Effectiveness Endpoint 
The effectiveness of the DiamondTemp System was evaluated post-ablation by 
demonstration of acute procedural success, defined as isolation of clinically relevant 
pulmonary veins by demonstration of block or isolation of signals confirmed after delivery of 
the ablation treatment.  
Secondary Endpoints 
The chronic safety of the DiamondTemp System was assessed by evaluating the nature and 
frequency of adverse events (AE) and adverse device effects (ADE) at 90 days, 6 months and 
12 months post-procedure.  
5.4.  Study Eligibility Criteria 
Subjects presenting with drug refractory, paroxysmal atrial fibrillation requiring treatment 
and clinically indicated for standard of care pulmonary vein isolation ablation treatment were 
eligible for screening and potential enrollment in the study.  Enrollment was confirmed once 
the subject signed informed consent, had echocardiographic assessment to confirm final 
eligibility and the study device was introduced into the subject’s vasculature. 
Subjects had to meet all of the defined inclusion and none of the defined exclusion criteria to 
be eligible for enrollment in this study. 
Inclusion Criteria 
1. Suitable candidate for intra-cardiac mapping and ablation for arrhythmias 
2. History of recurrent symptomatic PAF with ≥2 episodes reported within the 365 days 
(12) months prior to enrollment 
3. At least 1 episode of AF documented by Holter monitor, rhythm strip, trans-telephonic 
monitor (TTM), or 12-lead ECG prior to enrollment 
4. Refractory to at least one Class I-IV anti-arrhythmic drug (AAD) 
5. Eighteen (18) years of age or above 
 
 
 

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Exclusion Criteria 
1. Previous left atrial ablation procedure  
2. Intracardiac thrombus, tumor or other abnormality that precludes catheter introduction 
and placement 
3. Known severe cerebrovascular disease or history of cerebrovascular event (within 1 
month) 
4. Subjects with severely impaired kidney function as measured by a Cockcroft-Gault 
Glomerular Filtration Rate (GFR)3 with a GFR ≤ 29. Active gastrointestinal bleeding 
5. Active infection or fever (>100.5 F/38 ◦C)  
6. Sepsis 
7. Cardiac surgery within the past two months. 
8. Short life expectancy (<1 yr.) due to other illnesses, such as cancer or pulmonary, 
hepatic, or renal disease Significant anemia (hemoglobin < 8.0 mg/dL) 
9. Severe uncontrolled systemic hypertension (systolic pressure > 240 mm Hg within the 
last 30 days) 
10. Documented anaphylaxis during previous exposure to angiographic contrast media 
11. Uncontrolled congestive heart failure (NYHA1 Class III or IV) 
12. Unstable angina or acute myocardial infarction within the past three months 
13. Bleeding, clotting disorders, or known thrombosis 
14. Severe Peripheral vascular disease 
15. Uncontrolled diabetes 
16. Heart valve replacement 
17. Mitral clip (E-valve)  
18. Women who are of childbearing potential who are currently pregnant or not willing to 
use contraception for the duration of the study 
19. Active participation in another investigational protocol currently or the last 30 days 
20. Unable or unwilling to take anti-coagulants 
21. Unwilling or unable to comply with any protocol or follow up requirements 
5.5 Study Results 
Study Accountability and Disposition 
Study enrollment is closed and all subjects in both phases have completed their 12-month 
follow-up visits and are now exited from the study. Subjects were followed for 7 and 30 days 
after the index ablation procedure to assess primary safety and effectiveness endpoints. The 
last subject’s 30-day visit was completed on 17 August 2017. Table 1 provides a summary of 
the subject disposition for the study. Although a total of seventy-two (72) subjects met the 
definition for enrollment, analysis of the study results was conducted on seventy (70 
subjects).  
 
 

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Table 1. Subject Accountability and Disposition 
Subject Accountability 
Number 
Subjects enrolled in study 
72 
Subjects who did not have PVI attempted with study device 
(excluded from the analysis) 
2 
Analyzable Population 
70 
Baseline subject demographics for the analyzable subjects are described in Table 2. The 
mean age for subjects in this cohort was 60.5 ± 9.8 years, with a higher incidence of subjects 
being of males (N=42) vs. females (N=28).  Overall the characteristics of the subjects 
enrolled in the study were representative of the patient population usually undergoing RF 
ablation for the treatment of paroxysmal atrial fibrillation. 
Study Population Demographics   
Table 2.  Subject Demographics (n=70) 
Characteristic   
Measurement 
Results 
Age at Ablation Procedure (years) 
Mean ± SD 
60.5 
± 
9.8 
Range 
35 
- 
76 
Gender [N] (%) 
Female 
28 
 
(40%) 
Male 
42 
 
(60%) 
Height (cm) 
Mean ± SD 
173.8 
± 
11.7 
Range 
115.0 
- 
194.0 
Weight (kg) 
Mean ± SD 
91.3 
± 
17.5 
Range 
59.0 
- 
140.0 
Resting Heart Rate (bpm) 
Mean ± SD 
72.2 
± 
17.6 
Range 
47.0 
- 
135.0 
Resting Systolic BP (mmHg) 
Mean ± SD 
142.5 
± 
17.6 
Range 
110.0 
- 
135.0 
Resting Diastolic BP (mmHg) 
Mean ± SD 
82.6 
± 
10.1 
Range 
60.0 
- 
110.0 
Hemoglobin (g/l) 
Mean ± SD 
140.0 
± 
33.5 
Range 
13.1 
- 
176.0 
Creatinine (umol/l) 
Mean ± SD 
88.5 
± 
17.8 
Range 
54.0 
- 
140.1 
GFR (ml/min/1.73m2) 
Mean ± SD 
77.1 
± 
19.0 
Range 
34.0 
- 
128.0 
LVEF %i 
Mean ± SD 
61.2% 
± 
7.2% 
Range 
25.0% 
- 
72.0% 
LA diameter, cmii 
Mean ± SD 
4.4 
± 
0.7 
Range 
2.9 
- 
6.5 
i  LVEF not recorded on four subjects 
ii  LA diameter not recorded on 14 subjects 

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The medical history of each subject was assessed including history of atrial fibrillation, 
cardiovascular disease, non-cardiovascular disease and cardiac surgery at time of the 
screening visit. Table 3 lists the pre-existing conditions recorded during the screening visits. 
 
Table 3.  Medical History, (N=70) 
PAF History 
N (%) 
History of Prior Ablation Treatment 
0 (0) 
Refractory to Anti-Arrhythmic Drugs  
70 (100) 
Duration of AF (Mean±SD, years)1 
2.6 ± 2.4 
 
Medical History 
 
History of Smoking 
21 (30) 
Diabetes Mellitus Type II 
8 (11.4) 
Previous Stroke or TIA 
6 (8.6) 
Previous Myocardial Infarction  
3 (4.3) 
Coronary Artery Bypass Grafting (CABG) 
0 (0) 
Concurrent Medical Conditions 
 
Hepatic Disease 
9 (12.9) 
Pulmonary disease 
17 (24.3) 
Other Relevant Cardiac Diseases 
 
Hypertension 
38 (54.3) 
Hypertrophic Cardiomyopathy 
0 (0) 
Coronary Artery Disease 
0 (0) 
1 Onset date of PAF not collected in first phase subjects; data only 
available on 30 subjects. 
Study Procedural Results  
Pulmonary vein isolation (PVI) was achieved by point-by-point, wide antral ablation 
encircling each pair of ipsilateral PV’s supported by the EnSite Velocity or Precision to 
collect electrical map of the atrium and assist the navigation of the DiamondTemp to each 
ablation site. The investigational device was used with the market-approved EnSite 
Velocity/Precision in 70/70 (100%) of the subjects. A summary of procedural data is listed in 
Table 4. 
 
 
 

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Table 4.  Summary of Procedural Data, (N=70) 
Procedure Data (n=70) 
Measurement 
Results 
Mode of Operation 
Temperature Control 
Programmed Infusion Rate (ml/min) 
Standby Flow Rate – 2 ml/min 
Therapeutic Flow Rate – 8 ml/min 
No. of RF Applications¥ 
                       4662  
Ablation Duration† (sec) 
Mean ± SD 
17.5 ± 2.4 
Range 
10.2 - 
22.4 
Average Power† (W) 
Mean ± SD 
36.2 ± 2.7 
Range 
31.7 - 
41.9 
Max Power* (W) 
Mean ± SD 
50.8 ± 0.5 
Range 
50.2 - 
53.1 
Temperature Set-Point† (°C) 
Mean ± SD 
58.1 ± 1.6 
Range 
51.5 - 
60 
Max Temperature† (°C) 
Mean ± SD 
65.0 ± 3.5 
Range 
56.8 - 
73.8 
Average Temperature† (°C) 
Mean ± SD 
48.2 ± 1.9 
Range 
43.3 - 
52.5 
Max Impedance† (Ω) 
Mean ± SD 
134.7 ± 31.2 
Range 
94 - 
239 
Average Impedance† (Ω) 
Mean ± SD 
95.5 ± 8.9 
Range 
74.9 - 
118.9 
Total RF Ablation Time† (min) 
Mean ± SD 
19.8 ± 8.6 
Range 
8.5 - 
41.8 
Total Procedure Time (mean)   
Mean ± SD 
2:35 ± 0:47 
Range 
1:25 - 
4:35 
Total Fluoroscopy Time‡ (mins) 
Mean ± SD 
9:38 ± 6:38 
Range 
0:03 - 
18:00 
Total fluid vol.§ (ablation procedure) 
Mean ± SD 
322.6 ± 99 
Range 
152 - 
531 
¥RF application count includes all ablations (PVI + atrial tachycardia, etc.) 
† These values were generated from the generator, not the database.   
‡ Fluoroscopic time not recorded on two subjects. 
§ Fluid volume not collected on one subject. 
Once electrical isolation was achieved, ablation in the targeted veins was considered 
complete. Documentation of entrance block into the PVs (PVI) was required for each vein 
ablated. PVI was confirmed by either testing with an adenosine bolus (n=36 or 51% of 
subjects) or confirming PVI after a minimum of 20 minutes (n=34 or 49% of subjects) after 
the last RF application. 
Primary Endpoint Results 
All primary study endpoints have been met through 30 days.  Assessments of primary safety 
events resulted in a total of two (2) SAEs (2.9%) through the 7-day safety endpoint and three 
(3) SAEs (4.%) through the 30-day safety endpoint, as adjudicated by an independent CEC 
(Table 5).   The primary effectiveness endpoint of acute procedural success was achieved in 
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 Table 5.  Summary of Primary Safety Endpoint (Analyzable Population) 
Event 
DiamondTemp 
N=70 
Timing 
Subjects (%) 
Pericardial Effusion 
1 (1.4%) 
Prior to 7 days 
Hospitalization for AF recurrence 
1 (1.4%) 
Prior to 7 days 
Supraventricular Tachycardia 
1 (1.4%) 
Prior to 30 days 
Total SAEs through 7 days 
2 (2.9%) 
Total SAEs through 30 days 
3 (4.3%) 
  
Long Term Interim Safety Analysis 
The chronic safety of the DiamondTemp System is assessed in TRAC-AF by evaluating the 
nature and frequency of all serious adverse events at 90 days, 6 months and 12 months post 
procedure, as adjudicated by the CEC.     
  
5.6.  Conclusion from Clinical Study   
The objective of this First-In-Human study was to substantiate the safety and effectiveness of 
the DiamondTemp Ablation System use to ablate cardiac tissue in patients with paroxysmal 
atrial fibrillation. The study endpoints achieved the efficacy performance goal demonstrating 
100% effectiveness by confirming PVI isolation in all subjects treated as intended under this 
study protocol.  Freedom from AF 12 months post-procedure was 72.5%.  The safety profile 
demonstrated in this study indicates the DiamondTemp System can be used safely in cardiac 
ablation procedures in this patient population, with no incidences of acute serious adverse 
device-related events (SADEs) and a 2.9% to 4.3% safety endpoint rate through 7 and 30 
days, respectively.   
The safety results observed in these seventy (70) subjects treated with the DiamondTemp 
System up to 30 days are well within the recommendations of the published literature and 
documented safety and efficacy rates of catheter ablation for PAF[26]. 
 
6. TACTICATH CONTROL DEVICE 
6.1. Indications for Use 
The TactiCath Quartz Contact Force Ablation Catheter is indicated for use in cardiac 
electrophysiological mapping and for the treatment of drug refractory recurrent symptomatic 
paroxysmal atrial fibrillation, when used in conjunction with a compatible radiofrequency 
generator and three-dimensional mapping system.  
TactiSys Quartz Equipment and accessories are indicated for use in conjunction with a 
TactiCath Quartz Contact Force Ablation Catheter. TactiSys Quartz Equipment allows the 
visualization of the force information coming from the catheter tip. 

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6.2.  Product Classification, Code, Regulation 
Device Name: 
TactiCath Quartz Contact Force Ablation Catheter  
Classification: 
Catheter, Percutaneous, Cardiac Ablation, for Treatment of Atrial 
Fibrillation 
Product Code: 
OAE 
Device Class: 
3 
Submission Type: PMA (P130026, Approved) 
6.3. Control Device Description 
The TactiCath Quartz Contact Force Ablation System is comprised of the following 
components:  
• TactiCath Quartz Contact Force Ablation Catheter 
• TactiSys Quartz CF Equipment hardware inclusive of: 
o TactiSys Quartz Unit 
o TactiSoft Software 
o TactiSys Quartz RF Cable 
o TactiSys Quartz Ethernet Cable 
o Equipotential Cable 
o Mains Cord and Adapter 
• Optional Accessories: 
o TactiSys Quartz Mount 
o TactiSys Analog Output Cable 
o TactiSys Quartz Integration Module 
6.4.  TactiCath Quartz Contact Force Ablation Catheter 
TactiCath Quartz Contact Force Ablation Catheter (TactiCath) is a sterile, 7F steerable, open-
irrigated, multi-electrode RF ablation catheter with a deflectable tip incorporating a force 
sensor and a thermocouple temperature sensor. The catheter is designed to facilitate 
electrophysiology mapping of the heart chambers and to transmit RF current to the catheter 
tip electrode for intracardial ablation. The deflectable distal section of the catheter shaft 
includes four platinum-iridium electrodes (three ring electrodes and one tip electrode) and is 
available in 65 mm or 75 mm length, with a total usable length of 115 cm. At the proximal 
end of the catheter, a saline port is used to deliver isotonic saline solution to irrigate and cool 
the tip electrode and ablation site, through a 0.7 mm diameter catheter lumen and six small 
holes on the distal electrode tip. The catheter features a tri-axial optical force sensor 
embedded in the tip section which transmits contact force information to the TactiSys Quartz 
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6.5.  TactiSys Quartz Equipment 
The contact force visualization equipment associated with TactiCath is comprised of the 
TactiSys Quartz (TactiSys) unit (hardware and associated cables) and TactiSoft (stand-alone 
software). The TactiSys unit is a non-sterile active signal and data processing unit that 
interconnects the TactiCath catheter to an external RF generator and collects data from the 
catheter to compute contact force and related information transmitted from the catheter. The 
optical measurement system, which is compatible with the force sensing technology 
incorporated in the TactiCath catheter, is comprised of three optical sensor analyzer modules. 
The TactiSoft software displays the contact force information transmitted from the catheter 
through an Ethernet connection on a dedicated, properly configured computer.  
6.6. Additional Required Equipment 
The following devices are required in addition to the TactiCath Quartz System to perform 
catheter ablation procedures:  
• AMPERE Generator (St. Jude Medical) or Stockert Generator (Biosense Webster) 
• Cool Point Irrigation Pump (St. Jude Medical) or CoolFlow Irrigation Pump 
(Biosense Webster) 
• Electrophysiology recording system and cardiac stimulators 
• Dedicated Personal Computer with display screen to run TactiSoft software  
• St. Jude EnSite Velocity or Precision Cardiac Mapping System 
Optional accessories include choice of RF cable, Ethernet cables available in different 
lengths, an analog output cable, a mount and an integration module (Ethernet - switch) that 
will allow the integration of contact force information with third party equipment (e.g. 
integration in the screen of 3D mapping system for enhanced electrophysiology laboratory 
set-up).  
7. DIAMONDTEMP INVESTIGATIONAL DEVICE 
7.1.  Proposed Intended Use of the Investigational Device 
The DiamondTemp Catheter is indicated for use in cardiac electrophysiological mapping 
(stimulation and recording) and for treatment of drug refractory, recurrent, symptomatic 
paroxysmal atrial fibrillation when used in conjunction with the DiamondTemp Generator and 
accessories (DiamondTemp Cable-to-RFG Cable, DiamondTemp GenConnect Cable, 
DiamondTemp Irrigation Pump/Tubing Set) and compatible mapping system. 
7.2. Product Classification, Code, Regulation 
Device Name: 
DiamondTemp Ablation Catheter 
Classification: 
Catheter, Percutaneous, Cardiac Ablation, for Treatment of Atrial 
Fibrillation 
Product Code: 
OAE 
Device Class: 
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Submission Type: PMA 
7.3. Investigational Device Description 
The EPIX DiamondTemp Ablation System investigational device includes: 
• DiamondTemp Catheter  
o Unidirectional and Bidirectional models 
• DiamondTemp Catheter-to RFG Cable  
• DiamondTemp GenConnect Cable  
• DiamondTemp RF Generator  
o Model CEDTG100 
o Model CEDTG200 
• DiamondTemp Irrigation Pump  
• DiamondTemp Irrigation Tubing Set 
• DiamondTemp Footswitch (optional) 
The DiamondTemp Ablation System can be used with the St. Jude EnSite Velocity or 
Precision Cardiac Mapping System and commonly available EP recording systems and 
cardiac stimulators. 
A representative DiamondTemp Ablation System is illustrated in Figure 1. 
 
Figure 1. DiamondTemp Ablation System 
Key features of the DiamondTemp System: 
EGM Cable  
(not supplied) 

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• The DiamondTemp System allows for cardiac mapping, pacing and ablation when 
connected to the St. Jude EnSite Velocity or Precision Mapping System and 
commercially-available cardiac stimulators and recording systems.   
• The DiamondTemp Catheter design, materials and composite tip geometry allow 
for the recording of local electrograms at the ablation site. 
• Six thermocouples at the DiamondTemp Catheter tip provide surface temperature 
feedback. 
• The DiamondTemp Generator modulates power to maintain catheter-tissue 
interface temperature at a set point optimal for creating an effective lesion without 
char or thrombus formation.  
• The DiamondTemp Generator displays the ablation parameters and the composite 
temperature recorded from the thermocouples. 
All investigational devices for use in the clinical study are identified with model, lot or serial 
number and will be tracked for dispositioning throughout the study. For the DiamondTemp 
Ablation Catheter and DiamondTemp Catheter-to-RFG Cable, in addition to the model and 
lot number, a unique serial number will be used. System Accessories used in the clinical 
study will be identified by lot and/or serial number. 
7.4. DiamondTemp Ablation Catheter 
The DiamondTemp Ablation Catheter (DiamondTemp Catheter) is a sterile, single use, 
externally-irrigated cardiac ablation catheter, 110 cm in length, designed to deliver RF 
energy at the catheter tip electrode for mapping and cardiac ablation. The DiamondTemp 
Ablation Catheter is a 7.5F externally-irrigated catheter, with either unidirectional (Figure 
2a) or bidirectional (Figure 2b) steering, designed to deliver RF energy to the composite tip 
electrode of the catheter for mapping and cardiac ablation.  The unidirectional catheter is 
deflected in one direction using an actuation piston; the bidirectional catheter has a steering 
knob to actuate the curve in either direction and a tension knob to lock the curve.  The distal 
tip and ring electrodes are designed to record electrocardiogram (EGM) signals for mapping 
and deliver stimulus for pacing. RF emission from the composite tip is similar to 
commercially-available, externally-irrigated catheters.   
 
Figure 2a.  DiamondTemp Ablation Catheter, Unidirectional 
 
 

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Figure 2b.  DiamondTemp Ablation Catheter, Bidirectional 
7.5.  DiamondTemp RF Generator 
The DiamondTemp RF Generator (Figure 3) is a temperature-controlled RF generator and 
provides power to the DiamondTemp Catheter at approximately 460 kHz.  It has a universal 
AC power supply and provides isolated communication ports to the DiamondTemp Irrigation 
Pump and serial output to an external monitor which can mirror the RF Generator front panel 
information (Figure 3b) such as temperature, power and impedance curves resulting during 
RF delivery. 
There are two generator models for use in this investigation: model CEDTG100 and 
model CEDTG200.  The DiamondTemp Generator model CEDTG100, upon initiation of 
RF energy and contact with the target tissue, reaches the user-selected temperature set 
point in approximately five (5) seconds. The DiamondTemp Generator model 
CEDTG200, under the same conditions, reaches the user-selected temperature set point 
in approximately one (1) second.  All other control features, feedback and safety features 
are the same between the two models.  It is the discretion of the investigator to select 
which generator model is used. 
 
 
Figure 3.  DiamondTemp RF Generator (a) and Front Panel Display (b) 
7.6. DiamondTemp Irrigation Pump 
The DiamondTemp Irrigation Pump (Figure 4) is a peristaltic pump designed to deliver 
normal saline (0.9%, with heparin 1 IU/ml) when used in conjunction with the 
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prescribed therapeutic flow rate of 8 ml/min at all power levels up to 50 Watts. The 
DiamondTemp Irrigation Pump can also be controlled using the touch-screen display on the 
front panel of the DiamondTemp RF Generator or Irrigation Pump.  
 
Figure 4.  DiamondTemp Irrigation Pump 
7.7  DiamondTemp Tubing Set 
The DiamondTemp Tubing Set is a disposable, one-time use, one-piece tubing that connects 
the DiamondTemp Ablation Catheter to the DiamondTemp Irrigation Pump.  
7.8. DiamondTemp Footswitch 
The DiamondTemp Footswitch (Figure 5) is an optional accessory used for On/Off control 
of RF power delivery. Pressing the footswitch turns RF energy ON. Releasing the footswitch 
terminates delivery of RF energy.  
 
Figure 5.  DiamondTemp Footswitch 
7.9.  Diamond Temp Cables 
DiamondTemp Catheter-to-RFG Cable  
The DiamondTemp Catheter-to-RFG Cable (Figure 6) is 2.4 meters in length, supplied 
sterile, and contains no latex. The cable distal end has a 19-pin connector that connects 
to the DiamondTemp Catheter. The cable proximal end, identified by a green band, has 

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a 26-pin connector that connects to either the DiamondTemp RF Generator or to the 
DiamondTemp GenConnect Cable when a mapping system is used.  
 
Figure 6.  DiamondTemp Catheter-to-RFG Cable 
 
 

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DiamondTemp GenConnect Cable  
The DiamondTemp GenConnect Cable (Figure 7) is 2 meters in length and has 4 
connectors. The cable connects the DiamondTemp Catheter-to-RFG Cable to a 
commercially-available mapping system (e.g. St. Jude EnSite Velocity or Precision) 
GenConnect Box (Maestro/EPT) and to the DiamondTemp RF Generator. The cable is 
supplied non-sterile and contains no latex.  
 
Figure 7.  DiamondTemp GenConnect Cable 
7.10. Mapping System and EP Recording System Compatibility 
The DiamondTemp System is used with the St. Jude EnSite Velocity and Precision Cardiac 
Mapping Systems and commonly available EP recording systems and cardiac stimulators. 
8. STUDY PROTOCOL AND METHODS 
8.1.  Study Objective 
The objective of this study is to demonstrate the safety and effectiveness of the 
DiamondTemp Ablation System for the treatment of drug refractory, recurrent, symptomatic 
paroxysmal atrial fibrillation (PAF).  The study will be considered successful if the 
investigative device is considered non-inferior to the control device for the primary safety 
and effectiveness endpoints. 
8.2.  Study Design 
The DIAMOND-AF study is a prospective, single-blind, 1:1 randomized, controlled trial 
being performed at multiple centers in the United States, Canada and Europe to evaluate the 
safety and effectiveness of the DiamondTemp Ablation System for the treatment of drug 
refractory, recurrent, symptomatic paroxysmal atrial fibrillation compared to the TactiCath 
Quartz Contact Force Ablation Catheter and compatible ablation system. 
This study will enroll up to 480 subjects diagnosed with PAF at up to 30 investigational sites 
in the US, Canada and Europe.  Investigational sites will have a principal investigator (PI) 
that is responsible for the conduct of a research study as well as sub-investigators.  It is 
anticipated that approximately 50% of the randomized subjects will be enrolled at centers 
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After providing consent, subjects will undergo screening and baseline tests. Subjects that 
meet the eligibility criteria will be randomly assigned to either treatment with the 
investigational or control device only after completion of all screening and eligibility 
procedures. A randomization module within the Electronic Data Capture (EDC) system will 
be used to randomize subjects 1:1 to one of two treatment groups using a blocked 
randomization stratified by site followed by stratification by failure of Class I/III or Class 
II/IV AADs.  Since full eligibility for the study may not be confirmable until pre-ablation 
procedure tests are performed, subjects will only count towards the enrollment ceiling once 
final eligibility is confirmed and they are randomized.  Once randomized, a subject will be 
considered enrolled in the study. 
The primary focus of the left atrial ablation procedure is to create a series of point-by-point 
RF lesions encircling the left and right PVs to achieve electrical PVI from the rest of the left 
atrium (LA). Investigators may use their preferred approach to obtain PVI, such as antral or 
WACA ablation targeting PVs segmentally or PV pairs ipsilaterally.  PVI must be confirmed 
by entrance block at least 20 minutes following the last ablation around the respective PV.   
Targeting non-PV foci and complex fractionated electrograms is not recommended in this 
investigation.  If the investigator identifies additional focal or macro-reentrant atrial sites to 
be clinically relevant to AF and requiring ablation, the ablation location will be documented. 
All subjects will be followed per protocol in relation to the date of the index ablation 
procedure. Follow up will be required prior to hospital discharge and at 7 days, 1 month, 3 
months, 6 months and 12 months post-ablation.   
Subjects will be given a cardiac event monitor (Sentinel Wireless ECG Recorder System or 
equivalent, HeartcoR Solutions, LLC.) at the hospital pre-discharge visit to be used 
throughout the duration of the study. If subject exhibits symptoms (e.g. palpitations, 
dizziness, tiredness, lightheadedness, shortness of breath, chest pain, fatigue, syncope) 
associated with AF recurrence at any time after the ablation procedure, they will be 
instructed to record their heart rhythm using their cardiac event monitor and to contact the 
site investigator.  This data will be transmitted to and read at an ECG core lab.  If a subject 
has an arrhythmia recurrence within the first 90 days after the ablation procedure (blanking 
period), one repeat ablation procedure is allowed per protocol.  Investigators should make 
every attempt to schedule a repeat ablation procedure on or before day 90.  The repeat 
ablation procedure must be performed with the assigned investigational or control catheter.  
Repeat ablation procedures performed with a catheter different than originally assigned will 
be a protocol deviation.  Subjects will also be required to perform bi-monthly periodic event 
recording from the 3-month follow up visit to the 12-month follow-up visit to detect possible 
asymptomatic atrial tachycardias. The event recordings, Holter recordings and 12-lead ECG 
data collected between the 3 and 12 month post ablation procedure timepoints will be 
reviewed, analyzed and reported on by an ECG core lab to determine the study effectiveness.  
To evaluate the success of subject blinding to treatment assignment, all subjects will be asked 
whether they think they were in the investigational group, control group or if they don’t 
know at the 12-month follow-up visit. 
The duration of the study is projected to span approximately 36 months.  The duration 
accounts for:  

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• Approximately 12-15 months to enroll all subjects in the trial; 
• Approximately 12 -15 months subject participation from consent to end of 12-month 
follow-up visit window;  
• Approximately 3-6 months to analyze, report on study results and close the study. 
8.3.   Primary Safety Endpoints 
The primary safety endpoint is defined as freedom from a composite of serious adverse 
events (SAE) occurring within 30-days and clinically symptomatic pulmonary vein stenosis 
through 6 months post-index ablation procedure, as adjudicated by an independent Clinical 
Events Committee (CEC) for relatedness to the procedure or device. 
The primary safety device- or procedure-related SAE composite will be the combined rate of 
the following events in Table 6. 
 
 

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Table 6.  Primary SAE, Classification and Definition 
Primary SAE 
Severity Classification / Definition[26] 
Atrioesophageal 
fistula  
Creation of direct communication between the left atrium and esophagus 
as documented by esophageal erosion combined with evidence of a 
fistulous connection to the atrium (e.g. air emboli, an embolic event or 
direct observation at the time of surgical repair). A CT or MRI scan is 
recommended to document event.   
Bleeding 
complication 
Major bleed that requires a transfusion or results in a ≥ 20% fall in 
hematocrit  
Cardiac tamponade / 
perforation 
Significant pericardial effusion with hemodynamic compromise that 
requires elective or urgent pericardiocentesis or results in a 1-cm or 
more pericardial effusion as documented by echocardiography. 
Death 
Cardiovascular-related death post ablation that is related to the 
procedure or device 
Extended 
hospitalization 
Extended hospital stay or re-hospitalization that is related to the 
procedure or device.* 
Myocardial 
infarction  
MI as it relates to AF ablation resulting in the presence of any one of the 
following criteria: 
• ECG changes indicative of new ischemia that persist for > 1 hour 
• development of new pathological Q waves on an ECG 
• imaging evidence of new loss of viable myocardium or new 
regional wall motion abnormality 
Pericarditis 
Pericarditis resulting in an effusion that leads to hemodynamic 
compromise, requires pericardiocentesis, prolongs hospitalization > 48 
hours or persists for more than 30 days following procedure. 
Phrenic nerve 
paralysis 
Absence of phrenic nerve function assessed by a sniff test that persists > 
7 days.  A phrenic nerve paralysis is considered to be permanent when it 
is documented to be present ≥ 12 months following ablation. 
Pulmonary edema 
Pulmonary alveolar fluid accumulation accompanied by typical 
symptoms (dyspnea), physical findings (rales, hypoxemia), radiologic 
findings, and response to diuretic therapy and requiring or prolonging 
hospitalization. 
Pulmonary vein 
stenosis 
A severe or clinically symptomatic PV stenosis verified by a chest CT or 
MRI will be classified as a SAE.  PV stenosis symptoms are shortness of 
breath, cough and hemoptysis.  Pulmonary vein stenosis is defined as a 
reduction of the diameter of a PV or PV branch. PV stenosis will be 
categorized as mild <50%, moderate 50%–70%, and severe >70% 
reduction in the diameter of the PV or PV branch when compared to the 
proximal reference diameter.  
Stroke post-ablation 
Stroke Diagnostic Criteria: 
• 
Rapid onset of a focal or global neurological deficit with at least one 
of the following: change in level of consciousness, hemiplegia, 
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body, dysphasia or aphasia, hemianopia, amaurosis fugax or other 
neurological signs or symptoms consistent with stroke 
• 
Duration of a focal or global neurological deficit ≥24 hours; or <24 
hours if therapeutic intervention(s) were performed (e.g., 
thrombolytic therapy or intracranial angioplasty); or available 
neuroimaging documents a new hemorrhage or infarct; or the 
neurological deficit results in death  
• 
No other readily identifiable non-stroke cause for the clinical 
presentation (e.g., brain tumor, trauma, infection, hypoglycemia, 
peripheral lesion, pharmacological influences).^ 
• 
Confirmation of the diagnosis by at least one of the following: 
neurology or neurosurgical specialist; neuroimaging procedure (MRI 
or CT scan or cerebral angiography); lumbar puncture (i.e., spinal 
fluid analysis diagnostic of intracranial hemorrhage) 
Stroke will be determined by the consulting neurologist using diagnosis 
criteria above and subsequent neuroimaging procedure (MRI or CT scan 
or cerebral angiography). 
^ Subjects with non-focal global encephalopathy will not be reported as 
a stroke without unequivocal evidence based on neuroimaging studies. 
Thromboembolism 
Occurrence of deep vein thrombosis or pulmonary embolism post 
ablation 
Transient ischemic 
attack (TIA) post-
ablation 
Rapid onset of new focal neurological deficit with immediate symptom 
resolution (usually 1 to 2 hours), always within 24 hours as determined 
by consulting neurologist and neuroimaging without tissue injury. 
Vagal nerve injury 
Esophageal dysmotility or gastroparesis requiring or prolonging 
hospitalization following an ablation procedure 
Vascular access 
complications  
 
Resulting in development of a hematoma, an AV fistula or a 
pseudoaneurysm that requires intervention, such as surgical repair or 
transfusion, prolongs the hospital stay, or requires hospital admission. 
*  Planned hospitalization for a pre-existing condition, or a procedure required by the clinical 
investigational plan (including repeat ablation procedure), without serious deterioration in 
health, will not be included in the primary safety endpoint analysis.   Hospitalizations due to 
recurrent AF/AT/AFL or prolonged hospitalization during the 30 days following procedure 
to adjust anticoagulation regimen or to administer diuretic medication are not considered 
part of the combined primary safety endpoint.   
 
8.4.  Primary Effectiveness Endpoints 
The primary effectiveness endpoint is defined as freedom from documented atrial 
fibrillation (AF), atrial flutter* (AFL) and atrial tachycardia (AT) episodes following the 
blanking period (3-month follow-up post-ablation procedure) through the end of the 
effectiveness evaluation period (12-month follow-up post-ablation procedure).  
An effectiveness failure is defined by any of the following events: 

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• Inability to electrically isolate all accessible targeted pulmonary veins during the 
ablation procedure 
• Documented episodes of AF, AFL or AT lasting ≥30 seconds in duration as 
evidenced by electrocardiographic data during the effectiveness evaluation period 
• DC cardioversion for AF, AFL or AT during the effectiveness evaluation period 
• A repeat ablation procedure to treat AF, AFL or AT during the effectiveness 
evaluation period 
• Use of a new or modification to existing Class I-IV anti-arrhythmic drug (AAD) 
regimen to treat AF, AFL or AT recurrence during the effectiveness evaluation 
period 
• Use of a non-study device for ablation of any AF targets during the index or repeat 
ablation procedure during the blanking period 
• More than one (1) repeat ablation procedure during the blanking period 
*   Occurrence and/or ablation of cavotricuspid isthmus (CTI)-dependent AFL, as confirmed by 
entrainment maneuvers during EP testing at any time during this study is not a primary 
effectiveness failure because it is not considered an iatrogenic arrhythmia following a left 
atrial ablation procedure for AF.    
8.5.  Secondary Endpoints 
Secondary endpoints to characterize the performance of the DiamondTemp Ablation System, 
relative to the control device, will include 
• Mean duration of individual RF ablations (seconds) 
• Mean cumulative RF time per procedure (minutes)     
• Freedom from a composite of SAE occurring within 7-days post-index ablation 
procedure as adjudicated by an independent CEC for relatedness to the procedure or 
device.  
• Freedom from documented AF, AT and AFL episodes following the blanking period 
through 12-month follow-up post-ablation procedure in the absence of class I and III 
anti-arrhythmic drug therapy. 
• Rate of acute procedural success, defined as confirmation of electrical isolation of 
PVs via assessment of entrance block at least 20 minutes following the last ablation 
around the respective PV.    
• Rate of single procedure success defined as the rate of subjects treated with one single 
ablation procedure during study participation and with freedom from documented AF, 
AT and AFL* at 12 months.  
• Rate of single procedure success defined as the rate of subjects treated with one single 
ablation procedure during study participation and with freedom from ALL primary 
effectiveness endpoint failure criteria.  
• Rate of occurrence of electrically reconnected PVs following a 20-minute waiting 
period assessed by entrance block at index procedure.  

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• Accumulated changes in QOL using the AFEQT Questionnaire from baseline through 
6 and 12 months following ablation procedure. 
• Neurological changes measured using the NIH stroke scale between baseline and 
post-ablation (pre-discharge visit) and at 12 months post-ablation procedure. 
• Total procedure time (minutes), defined as time of first assigned ablation catheter 
insertion into the vasculature to time of last procedural ablation catheter removed. 
• Time to achieve initial PVI at index procedure (minutes), defined as time of delivery 
of first RF ablation with the assigned ablation catheter until confirmation of PVI via 
exit block following a 20-minute waiting period. 
• Total treatment device time (minutes), defined as time of delivery of first RF ablation 
with the assigned ablation treatment catheter to removal of the treatment catheter. 
• Total number of RF ablations per procedure.  
• Total fluid infused through the assigned ablation catheter (mL). 
• Total fluoroscopy time (minutes). 
• Number of re-hospitalizations due to atrial fibrillation recurrence after blanking 
period. 
 
*   Occurrence and/or ablation of cavotricuspid isthmus (CTI)-dependent AFL, as confirmed by 
entrainment maneuvers during EP testing at any time during this study is not a primary 
effectiveness failure because it is not considered an iatrogenic arrhythmia following a left atrial 
ablation procedure for AF. 
8.6.  Sample Size Justification 
With a randomization ratio of 1:1 and an estimated attrition rate of 7%, 240 subjects per 
treatment group (total N=480) should yield sufficient power for both the primary safety and 
primary effectiveness endpoints.   
For primary safety, assuming a control composite SAE rate of 6.5%, 226 subjects per group 
yields 80% power to detect a non-inferiority margin of 6.5% between treatment groups at a 
one-sided significance level of 0.025.  Similarly, assuming a control effectiveness rate of 
65%, 229 subjects per group yields 80% power to detect a non-inferiority margin of -12.5% 
between treatment groups at a significance level of 0.025. 
8.7.  Statistical Analysis 
Before database lock, the final SAP for clinical data will be prepared to provide full details of 
all planned analyses. The analyses presented here represent an outline of the intended 
methodology. 
Analysis Populations 
The following analysis populations are defined in this study: 
• ITT Population: The Intention-to-Treat (ITT) population will be comprised of all 
randomized subjects regardless of whether they receive study treatment, with 
analyses conducted according to the randomized treatment assignment. 

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• Per Protocol Analysis Set: The Per Protocol analysis set will be a subset of the ITT 
Set and comprised of all subjects who did not have any major protocol deviations. 
• Safety Analysis Population: In the unlikely case where a subject is randomized but 
the procedure is prematurely halted and no catheter is deployed, said catheter will e 
included in the ITT Set but excluded from the Safety Set since the subject was not 
exposed to the study device.  The Safety Set will be comprised of all randomized 
subject in which treatment was at least attempted (assigned treatment catheter 
inserted into vasculature), with analyses conducted by actual treatment received. 
General Considerations 
Descriptive summary statistics for continuous variables will include the number of 
subjects, mean, standard deviation or standard error, median, minimum and maximum. 
Nominal categorical variables will be summarized using counts and percentages. Ordinal 
variables may be analyzed as if they were continuously scaled. 
The study will be considered successful when the primary safety and effectiveness 
endpoints are met.   
If primary effectiveness success is determined to be less than 52% for either the treatment 
arm or the control arm, the primary effectiveness endpoint will be difficult to interpret, 
and additional analyses will be necessary to explain the poor device performance.  
Subject Disposition 
The number and percentage of subjects who complete and discontinue as well as reasons 
for early discontinuation will be presented. 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics will be summarized descriptively. Treatment 
groups will be compared statistically to confirm that the randomization process generated 
two homogeneous groups prior to treatment. 
Catheter Model Analysis 
The final study data will include evaluations of the DiamondTemp Unidirectional and 
Bidirectional Catheters in aggregate as well as stratified by catheter model. 
There will be a minimum of 30 subjects treated with the DiamondTemp Bidirectional 
Catheter. 
8.8.  Site Training 
Technical training with the DiamondTemp Ablation System will be provided by the Sponsor.  
Training will be documented and will include a review of the investigational plan, study 
procedures, CRF completion, instructions for use (IFU) and all study compliance 
requirements.   

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9. SUBJECT SELECTION 
9.1.  Criteria for Eligibility 
Subjects included in the DIAMOND-AF study should be selected from the general patient 
population indicated for or currently scheduled for catheter ablation of PAF. Investigators are 
responsible for screening all potential subjects and selecting those who meet all inclusion and 
none of the exclusion criteria for the study.  
9.2.  Study Inclusion Criteria 
Candidates must meet ALL the following criteria to be enrolled in the DIAMOND-AF study:  
1. Above eighteen (18) years of age or of legal age to give informed consent specific to 
state and national law.   
2. Subjects with a history of symptomatic, paroxysmal atrial fibrillation (PAF) who have 
had ≥2 episodes of PAF reported within the 6 months prior to index ablation procedure 
with a physician note indicating recurrent, self-terminating AF. 
3. At least one episode of PAF documented by electrocardiographic data within the 12 
months prior to index ablation procedure.  
4. Refractory to at least one Class I-IV AAD for treatment of PAF.  
5. Suitable candidate for intra-cardiac mapping and ablation of arrhythmia. 
6. Subject agrees to comply with study procedures and be available (geographically 
stable) for follow-up visits for at least 12 months after enrollment. 
7. Subject is willing and able to provide written consent. 
9.3.  Study Exclusion Criteria 
Candidates will be excluded from the DIAMOND-AF study if any of the following 
conditions apply within the following timeframes: 
At time of enrollment and/or prior to procedure: 
1. 
AF secondary to electrolyte imbalance, thyroid disease or reversible or non-cardiac 
cause. 
2. 
LA diameter > 5.5 cm. 
3. 
LVEF < 35%. 
4. 
Currently NYHA Class III or IV or exhibits uncontrolled heart failure. 
5. 
BMI > 40 kg/m2. 
6. 
LA ablation, septal closure device or mitral valve surgical procedure at any time 
prior to enrollment. 
7. 
Presence of intramural thrombus, tumor or abnormality that precludes vascular 
access, catheter introduction or manipulation. 
8. 
Coagulopathy, bleeding diathesis or suspected procoagulant state 
9. 
Sepsis, active systemic infection or fever (>100.5oF / 38oC) within a week prior to 
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10. Significant restrictive or obstructive pulmonary disease or chronic respiratory 
condition. 
11. Renal failure requiring dialysis or renal compromise that in the investigator’s 
judgement would increase risk to the subject or deem the subject inappropriate to 
participate in the study. 
12. Known allergies or intolerance to anticoagulant and antiplatelet therapies to be used 
in conjunction with the study or contrast sensitivity that cannot be adequately pre-
treated prior to the ablation procedure. 
13. Positive pregnancy test results for female subjects of childbearing potential or 
breast feeding. 
14. Enrollment in a concurrent clinical study that in the judgement of the investigator 
would impact study outcomes. 
15. Acute or chronic medical condition that in the judgment of the investigator would 
increase risk to the subject or deem the subject inappropriate to participate in the 
study. 
16. Life expectancy < 12 months based on medical history or the medical judgement of 
the investigator. 
Within 1 month of enrollment or just prior to procedure: 
17. Documented LA thrombus upon imaging. 
18. Creatinine >2.5mg/dl or creatinine clearance <30mL/min.     
Within 2 months of enrollment: 
19. Regularly (uninterrupted) prescribed amiodarone. 
Within 3 months of enrollment: 
20. Significant GI bleed. 
21. MI, unstable angina, cardiac surgery or coronary intervention. 
Within 6 months of enrollment: 
22. CABG procedure.   
23. ICD, CRT leads or pacemaker implant procedure. 
24. Documented stroke, CVA, TIA or suspected neurological event. 
Within 12 months of enrollment: 
25. An episode of AF lasting >7 days in duration. 
10.  SUBJECT ACCOUNTABILITY 
10.1.  
Point of Enrollment 
All subjects will be considered enrolled following the assignment to a randomized treatment 
arm.  Since full eligibility for the study may not be confirmed without pre-ablation procedure 
testing (e.g. echocardiography, pregnancy test, creatinine), consented subjects will count 

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towards the maximum enrollment ceiling once final eligibility is confirmed and they are 
randomized.  Once randomized, a subject will be considered enrolled in the study. 
10.2.  
Subject Status and Classification  
The following classifications will be applied to all subjects: 
• Screening Failure: A subject who has consented (signed ICF) but is found to not meet 
eligibility criteria through medical file review and/or screening procedures to confirm 
eligibility. Screening failures do not count against the maximum study enrollment 
ceiling and there are no follow-up requirements.  If screening failure occurs after 
randomization but prior to insertion of the assigned treatment catheter, the screening 
failure will be documented. 
• Intent-to-Treat: Includes all subjects who sign ICF, meet eligibility criteria and are 
randomized into one of the two study groups.  These subjects will count against the 
maximum study enrollment ceiling.  
• Treatment-Per-Protocol: A subject who is successfully treated per the study protocol 
with the assigned randomized treatment catheter. These subjects are followed in 
accordance with the follow-up schedule and are included in all analyses of safety and 
effectiveness.   
The statistical analysis for each classification will be documented in the Statistical Analysis 
Plan (SAP). 
10.3.  
Subject Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study 
or lost to follow-up) will be accounted for and documented.  If a subject withdraws from the 
clinical study, the reason(s) will be documented.  Reasons for withdrawal may include 
physician discretion, subject choice to withdraw consent, loss to follow-up or death.  While 
study withdrawal is discouraged, subjects may withdraw from the study at any time, with or 
without reason, and without prejudice to further treatment.   
All applicable case report forms up to the point of subject withdrawal must be completed.  
For subjects who are “lost-to-follow-up” the investigator/center should have at least three 
documented attempts to contact the subject prior to withdrawal from the study.    No 
additional data may be collected after a subject has been withdrawn from the study or 
withdraws his/her consent, for whatever reason.  All open adverse events should be closed or 
documented as chronic.  Data collected up to the point of subject withdrawal may be used. 
11.  STUDY METHODS 
11.1.  
Enrollment and Visit Schedule 
Enrollment of subjects will occur at the clinical sites only after the appropriate local and 
national study approvals, “Approval to Enroll” documentation from the Sponsor and written 
informed consent from subjects have been obtained. Table 7 summarizes the study follow-up 
and testing schedule: 
 
 

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Table 7.  Follow up and Testing Schedule 
Assessments/ 
Activities 
Baseline 
Evaluation 
Ablation 
Procedure 
Blanking Period 
(Ablation procedure – 3 months post 
procedure) 
Effectiveness Evaluation 
Period 
(3 months -12 months post 
procedure) 
Pre-  
Discharge 
7-Day 
Follow-
Up 
(± 3 
days) 
1-
Month 
Follow-
Up 
(± 14 
days) 
Repeat  
Ablation  
Procedure 
3-
Month 
Follow-
Up 
(±21 
days) 
6-
Month 
Follow-
up 
(± 28 
days) 
12-
Month 
Follow-
up (± 
45 
days) 
Eligibility Screening 
X 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Patient 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Physical Exam  
X 
 
X 
 
X 
XA 
X 
X 
X 
12-lead ECG 
  
X 
X 
 
 X 
XA 
X 
X 
X 
TEE or TTE 
XB 
 
 
 
 
 
 
 
 
TEE or ICEG 
 
XC 
 
 
 
XC 
 
 
 
Chest CT / MRI 
 
 
 
 
 
 
XF 
XF 
XF 
NIH Stroke Scale 
X 
 
X 
 
 
XA 
 
 
X 
Procedural Data 
 
X 
 
 
 
XA 
 
 
 
Event Monitor 
Recording 
 
 
XD 
XD 
XD 
 
XE 
XE 
XE 
24 hr. Holter Monitor 
 
 
 
 
 
 
 
X 
X 
Cardiac Medication 
Changes 
X 
X 
X 
X 
X 
XA 
X 
X 
X 
Protocol Deviations 
X 
X 
X 
X 
X 
XA 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
XA 
X 
X 
X 
AF Quality of Life 
Survey (AFEQT) 
X 
 
 
 
 
XA 
 
X 
X 
A Only required if a repeat ablation procedure performed. 1 repeat ablation procedure is allowed during Blanking Period.  
B TEE or TTE only required if subject does not have imaging data to determine LA diameter, LVEF for eligibility within 180d of ablation 
procedure 
C TEE or ICE required pre-procedure to rule out LA thrombus if any of the following are met:  CHA2DS2-VASc score is ≥ 2, if LA diameter 
≥4.6 or if pre-procedure anticoagulation requirements are not met 
D Event monitor recording only required if subject is experiencing symptoms during blanking period 
E Following the blanking period (3-12 month following ablation), subjects are required to take two 1-minute event monitor recordings per month 
regardless of whether they are experiencing symptoms. 
F Only required if subject presents with symptoms associated with PV stenosis 
G ICE allowed for subjects who cannot undergo TEE 
 
 
 

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11.2. Screening Evaluation 
Investigators and research staff at each site are responsible for conducting screening 
evaluations and obtaining subject medical history to identify subjects that meet eligibility 
requirements per the study inclusion and exclusion criteria.  Sites should maintain a subject 
screening log to document subjects evaluated for enrollment into the study that did not 
consent.  A reason for ineligibility or not providing consent should be provided.  Subjects 
who meet general eligibility for consideration in the study will sign an informed consent and 
undergo a baseline evaluation. 
11.3. Baseline Evaluation 
After eligible subjects have signed an informed consent form and before the scheduled 
interventional procedure, subjects will undergo a baseline evaluation. This evaluation may be 
conducted up to 45 days prior to the interventional procedure or on the same day. The 
evaluation will include but is not limited to the following:  
• Medical History and Physical Exam: 
o Subject Demographics  
o Limited Physical Assessment 
▪ Height and weight 
▪ Resting blood pressure 
▪ Resting heart rate 
o Medical History  
▪ History and documentation of PAF  
▪ NYHA score 
▪ CHA2DS2-VASc score  
▪ Cardiovascular or other medical history as it pertains to eligibility criteria 
o Medication History 
▪ Class I-IV AAD history, current doses and/or failure or intolerance 
▪ Other:  cardiac, diuretic, and anticoagulation medications 
• Baseline Tests 
o Transesophageal or transthoracic echocardiography (TEE or TTE)*  
▪ to determine LA diameter and % LVEF 
o Transesophageal or Intracardiac echocardiography (TEE or ICE for subjects who 
cannot undergo TEE) 
▪ Required within 48 hours of the ablation procedure to rule out LA 
thrombus in subjects that meet any one of the following criteria: 
• CHA2DS2-VASc score is ≥2 
•  LA diameter ≥4.6 cm 
• Pre-procedure anticoagulation requirements are not met 
o Pregnancy test for women of child bearing potential 
• Baseline Assessments 

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o NIH Stroke Scale administration** 
o AF Quality of Life Survey (AFEQT Questionnaire version 1.0) 
*  
Only required if subject does not have imaging data within 180 days of procedure to determine LA 
diameter, LVEF for eligibility 
**  
NIH Stroke Scale must be administered by staff certified to conduct assessment 
11.4.  
Pre-Ablation Testing and Requirements 
• Echocardiogram (TEE or TTE) must be performed prior to ablation in the following 
instances: 
o To confirm LA diameter and LVEF  
▪ if not available within 180 days of the ablation procedure  
• Echocardiogram (TEE) must be performed within 48 hours of the ablation procedure to 
rule out LA thrombus* in subjects that meet the following criteria: 
o Not currently and adequately anticoagulated for 3 weeks or longer 
▪ If subject is on an oral anticoagulant (OAC) they should be taking it 
regularly for 21 days prior to ablation 
▪ If a subject is on warfarin prior to ablation, they should have a therapeutic 
International Normalized Ratio (INR) > 2 
o CHA2DS2-VASc score is ≥2 
o  LA diameter ≥4.6 cm 
*ICE may be considered to rule out LA thrombus in subjects contraindicated for TEE 
If a thrombus is observed on echo, the subject no longer meets eligibility criteria.  The 
subject can be anticoagulated for 30 days until confirmation is received that the clot has 
resolved but if the clot persists, the subject will not meet eligibility for the study. 
• Discontinuation of AADs prior to the procedure is left to the discretion and practice of 
the investigator and investigational site best practices.  AADs should be maintained at 
current failed dose. 
o Regular amiodarone use must be discontinued 2 months prior to the ablation 
procedure and not restarted after the ablation procedure.    
• Performance of the ablation procedure on uninterrupted anti-coagulation therapy (e.g. 
warfarin or OACs) is strongly recommended. 
o For subjects anticoagulated with a OAC prior to AF catheter ablation, it is 
reasonable to hold one to two doses of the OAC prior to AF ablation with re-
initiation post-ablation. 
• Women of child bearing potential will be required to verify entrance criteria prior to 
procedure by providing documentation of a negative pregnancy test conducted within 7 
days prior to enrollment. 
11.5.  
Ablation Procedure 
Pre-procedural Preparation 

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Subjects that meet the eligibility and pre-ablation requirements will be prepped for the 
ablation procedure with the ablation system to which they are randomized.    
The procedures will follow standard hospital practice but should, at a minimum, include the 
following: 
1. Prep and sedate subject per institutional standard practice. 
a. Method of sedation will be recorded (i.e. conscious sedation or general 
anesthesia). 
b. Placement of an esophageal temperature probe to guide energy delivery on the 
posterior wall is strongly recommended.  
i. An esophageal temperature increase of 1 – 2 °C from baseline or a 
recorded temperature of 39 – 40 °C should trigger interruption of RF 
energy delivery.  Care should be taken to ensure that the esophageal 
temperature probe is aligned as close as possible with the position of the 
ablation catheter during ablation to avoid a false impression of safety.  
ii. Deviation of the esophageal temperature probe is allowed if standard 
practice at the institution. 
c. Place Ensite Velocity or Precision patches on subject per IFU. 
d. Place commercially available Dispersive Indifferent Electrode (DIP) patch.  
2. Gain vascular access per lab protocol via the femoral veins and/or right or left internal 
jugular or subclavian veins by insertion of sheaths.  
3. Any commercially available 8.5F, fixed or steerable, sheath may be used. 
a. A steerable sheath is recommended to be used with the DiamondTemp Ablation 
Catheter. 
4. Aspirate and flush sheaths with heparinized saline to remove air prior to introduction 
into the body and catheter insertion. 
a. Sheaths (fixed or steerable) should be continuously infused with heparinized 
saline at 1-2ml/min throughout the procedure. 
5. Complete a single or double transseptal puncture to access the LA. 
6. A heparin loading dose should be administered just prior to transseptal puncture 
(recommended) or immediately following.  A standard heparin infusion through 
catheter and sheaths should be given to maintain anticoagulation and activated clotting 
times (ACT) ≥300 seconds throughout the ablation procedure. 
a. ACT must be ≥300 seconds prior to first ablation. 
b. ACT levels should be checked every 20-30 minutes during the ablation procedure. 
c. If ACT is <300 seconds during ablation procedure, more heparin should be 
administered.  
7. Insert and place multi-electrode diagnostic catheters under fluoroscopic guidance.  

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a. Placement of intracardiac catheters will be per standard lab practice but must 
include a coronary sinus (CS) catheter and a multi-electrode circular catheter for 
PV mapping and verification of PV isolation and entrance block. 
8. Create a 3D anatomical map of the left atrium and location of the PVs with a 
multielectrode catheter using Ensite Velocity or Precision system. 
a. RF applications and location will be added to the map during the procedure. 
9. A pre-ablation EGM/12 lead ECG documenting the subject’s rhythm at the beginning 
of the procedure will be collected. 
10. All peri-procedural AEs must be recorded on the AE CRF and reported to the Sponsor.  
All device issues, malfunction or deficiencies with the investigational or control 
devices must be reported on the Device Deficiency CRF.  The use of a replacement 
(back-up) device should be indicated on the Procedure CRF. 
TactiCath Quartz Contact Force Ablation Catheter Set-up 
The TactiCath Quartz Contact Force Ablation Catheter and TactiSys Quartz Equipment 
hardware should be prepped and deployed following the operator’s manual, IFUs and 
physician training. General recommended ablation parameters taken directly from the 
TactiCath IFU are listed in Table 8.  Please refer to the TactiCath Quartz Catheter IFU for 
more information. 
Table 8.  TactiCath Recommended RF Application Parameters 
 
DiamondTemp Ablation System Set-up 
EPIX DiamondTemp Ablation System and Catheter should be prepped and deployed 
following the respective user manuals, IFUs and physician training.  The recommended 
Generator and Irrigation Pump settings are listed in Table 9. 

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Table 9.   Recommended DiamondTemp RF Generator and Irrigation 
Pump Settings 
RF Generator Settings 
Operational Mode 
Temperature Control 
Maximum Temperature Set Point 
60oCelcius 
Maximum Power Setting 
50 Watts 
Ablation Duration 
45 seconds 
Irrigation Pump Settings 
High Irrigation Flow Rate (during ablation) 
8 mL/min 
Low Irrigation Flow Rate (minimum continuous 
flow rate) 
2 mL/min 
 
When using the DiamondTemp Catheter, the change in the high-resolution EGM will be used 
to guide the termination of the RF delivery.  After EGM amplitude attenuation is reached, RF 
delivery is to be stopped three (3) to five (5) seconds after EGM amplitude attenuation is 
reached.  The point of significant EGM attenuation is defined as the time when there are no 
more changes in the EGM amplitude and/or there is a 75 to 80% reduction in EGM 
amplitude. 
Investigators are recommended to not ablate for greater than 45 seconds without moving the 
tip of the investigational ablation catheter.  
In the event of a generator cutoff (impedance, temperature) or if a steam pop is observed, the 
catheter must be withdrawn and the tip electrode observed for the presence of char or 
coagulum formation. The tip should be cleaned, if necessary, before RF current is reapplied. 
Purge the catheter prior to insertion into the subject. 
Pulmonary Vein Electrical Mapping 
The electrical activity of the PVs must be mapped prior to ablation. The investigator may 
determine the order in which the PVs are mapped and if PV angiography is necessary to 
facilitate vein access.   
To perform the electrical PV mapping, each vein should have a diagnostic catheter inserted 
to document the presence of PV potentials.  Documentation of the PV electrical mapping (PV 
potentials or lack thereof) is required for each vein. If the mapping catheter is successfully 
positioned in the vein but no PV potentials are present, ablation of the PV is not 
recommended.  Pre-ablation mapping determines which veins are clinically relevant for 
appropriate declaration of acute procedural success.  If the investigator determines it is not 
clinically relevant to perform ablation of a PV, the rationale must be noted prior to starting 
the ablation. 
 

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Index Ablation Procedure 
The primary focus of the ablation procedure will be to create a series of point-by-point RF 
lesions encircling the left and right PVs to achieve PVI (electrical isolation of PVs from the 
LA).  
Investigators may use their preferred approach to obtain PVI such as antral or WACA 
targeting PVs segmentally or PV pairs ipsilaterally.  A circumferential approach applying RF 
application 1-2 cm outside of the PV ostium to prevent PV stenosis is recommended.  
Targeting non-PV foci and complex fractionated electrograms is not recommended in this 
investigation.  If the investigator identifies additional focal or macro-reentrant atrial sites to 
be clinically relevant to AF and requires ablation, the ablation location will be documented. 
The order in which PVs are isolated is up to the investigator’s discretion.  While isolating the 
right superior PV, high-voltage pacing may be used before each RF application to check for 
phrenic nerve stimulation.  Ablation should be avoided in areas of phrenic nerve capture as to 
not cause injury to the phrenic nerve.  While ablating on the posterior wall in proximity to the 
esophagus it is highly recommended that investigators use an esophageal temperature probe 
during RF ablation procedures to monitor esophageal temperature and help guide energy 
delivery.  An esophageal temperature increase of 1-2°C from baseline or a recorded 
temperature of 39°C–40°C should trigger interruption of RF energy delivery[26]. Care should 
be taken to ensure that the esophageal temperature probe is aligned as close as possible with 
the position of the ablation catheter during ablation to avoid a false impression of safety. 
Additionally, each ablation on the posterior LA wall needs to consider the duration, power 
and temperature (investigational catheter only) settings while in proximity to other structures 
that could potentially be injured, such as the esophagus.  Moving a catheter after shorter 
durations of RF application, reducing the power (W) and/or temperature set point to 50 or 55 
oC (investigational system only) is encouraged but is left to the discretion of the investigator. 
Procedural recommendations  
• PVI must be confirmed and documented by entrance block of potentials into the 
PV a minimum of 20 minutes following the last RF application in each PV or PV 
pair to monitor for PV reconnection.  
• Adenosine and/or isoproterenol may be administered 20 minutes following PVI to 
detect for the presence of dormant PV conduction. 
o Administration of isoproterenol for the sole purpose to identify non-PV 
triggers is allowed but not recommended.  
• Exit block testing is not required, but if performed, exit block must be 
demonstrated for the PVI to be considered successful. If conduction resumes in 
any of the PVs, additional RF application can be applied until PVI is achieved. If 
additional ablation is performed following reconnection of PV, PVI must be 
reconfirmed at a minimum of 20 minutes following last ablation in the respective 
PV or PV pair. 
• Empiric targeting of complex fractionated electrogram, rotors, ganglionated plexi 
or performing left atrial mitral isthmus or roof lines are not recommended.  

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• Spontaneously-occurring atrial arrhythmias that present during the procedure are 
allowed to be ablated at the investigator’s discretion. 
o CTI-dependent (typical) flutter is also allowed if the subject has a known 
history of typical flutter. 
• Cardioversions do not signify procedural failures and are not adverse events. A 
post-ablation EGM/12 lead ECG documenting the subject’s rhythm at the end of 
the procedure will be collected. 
All procedure logistical data, ablation parameters, procedural outcomes, adverse events, 
fluids administered from both catheter and non-catheter sources (i.e., steerable sheath, etc.) 
and medications administered will be recorded and reported throughout the procedure. 
Prophylactic administration of intravenous diuretics during or after the procedure is allowed 
and will not be considered an adverse event.  All ablation catheters must be removed from 
the subject and inspected for char and coagulum formation if there is a generator cutoff 
(impedance or temperature) as well as each time a steam pop is observed.   
Ablation data collected during the procedure will include but may not be limited to: 
• Catheter lot/serial number(s) used  
• Temperature set point 
• Power set point 
• Total number of RF applications for PVI 
• Total number of RF applications during the procedure 
• Total RF time during the procedure 
• ACT levels and times taken 
• Location of additional ablations performed and number of RF applications per 
location 
• Total fluid infused from the ablation catheter 
• Presence of char or coagulum formation and incidence(s) of steam pops 
• Procedure and fluoroscopy times  
• EP recording system gain and filter settings for the ablation distal recording channel 
and manufacturer 
If at any time during the ablation procedure the investigator is unable to continue the ablation 
with the investigational or control catheter (other than when ablating an RA flutter line), the 
investigator may consider the case a procedural failure and complete the case with a device 
determined best for the subject.  The point at which failure was determined as well as the 
rationale must be documented. 
After removal from the subject, the investigational or control catheter should be inspected, 
and if any abnormalities such as char or coagulum formation are noted on the catheter, it 
must be documented.  All adverse experiences with the investigational device during the 
ablation procedure must be promptly reported to the Sponsor and documented on the CRF. 
 

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Post-Procedure 
All sheaths will be removed immediately after ablation and hemostasis will be achieved 
either by direct pressure or the use of a commercially-available closure device.  Investigators 
may use protamine to reverse the intravenous heparin used during the procedure. 
Subjects must be anticoagulated for a minimum of 60 days post index ablation procedure.  It 
is up to the investigator’s discretion which drug is best suited for the subject.  If 
anticoagulation was discontinued prior to and during the ablation procedure, anticoagulation 
should be resumed within 24 hours post-procedure to achieve a therapeutic anticoagulation 
level.  It is recommended that investigators follow the anticoagulation guidelines set forth in 
the 2017 HRS Expert Consensus Statement on Catheter and Surgical Ablation of AF [26], 
regardless of the apparent success or failure of the AF ablation procedure.  Additionally, the 
Investigator’s decision regarding continuation of systemic anticoagulation more than 60 days 
post ablation should be based on the subject’s stroke risk profile (e.g CHA2DS2-VASc score 
≥2 in men and ≥3 in women, prior stroke or TIA and/or age ≥75 years) and not on the 
perceived success or failure of the ablation procedure. 
If AADs are restarted following the ablation procedure, it is recommended to maintain 
subjects on a drug regimen for a duration of 2 to 4 weeks to address symptoms or early 
recurrences of AF, AFL or AT during the post-ablation healing and stabilization phase.  
If AADs are restarted for clinical reasons during the blanking period but not later than the 3-
month follow-up visit, it is recommended that subjects are maintained under the same AAD 
regimen throughout the effectiveness period (12-month follow-up). During the effectiveness 
evaluation period, physicians may discontinue an AAD, but may not add a new class or 
substitute an AAD.  
11.6  Pre-Discharge Follow-Up Visit 
Prior to being discharged from the hospital, subjects will complete a pre-discharge visit.  The 
evaluation while in the hospital will include but is not limited to the following: 
• Complete Physical Exam to assess for procedure related complications per 
investigational center’s standard of care including but not limited to: 
o Vital signs (blood pressure, heart rate, respiration rate, temperature) will be 
obtained  
o Cardiovascular and pulmonary examination 
o Standard neurological assessment 
o Catheter insertion sites (both groins) will be assessed 
• Assess the subject for any adverse events following ablation procedure 
• Perform a 12-lead ECG  
o Report presence or absence of atrial fibrillation or other supraventricular 
tachycardias 
• NIH Stroke Scale Evaluation follow-up 

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• Provide subjects with cardiac event monitor and operating instructions 
• Record medication changes since ablation procedure 
o Cardiac, AAD, diuretic, or anticoagulation 
Subjects will be discharged from the hospital when stable, per the investigator’s discretion.  
11.7  Seven Day Follow-up Phone Call 
All subjects must be evaluated seven days (7 ± 3 days) post ablation procedure.  The follow-
up will be conducted over the phone and the following evaluation will be completed: 
• Adverse Event Assessment 
o Ask the subject if there have experienced any new adverse events since discharge 
from the hospital and inquire about resolution of any previously reported event(s) 
• Medication changes 
o Ask subject if there have been any changes in their regularly prescribed 
medications (cardiac, AAD, diuretic, or anticoagulation) 
• Review event monitor data for recordings made due to symptomatic episodes of 
arrhythmias since the last follow-up 
11.8  One Month Follow-Up Visit 
All subjects must be evaluated at one month (30 ± 14 days) after the index ablation 
procedure.   During the follow up, the following will be performed: 
• Perform a complete physical exam with vital signs and 12-lead ECG 
• Assess the subject for any new adverse events and inquire about resolution of any 
previously reported events(s). 
• Record any medication changes 
• Review event monitor data for recordings made due to symptomatic episodes of 
arrhythmias since the last follow-up 
o If there has been an early recurrence of AF, investigator should schedule a visit 
so he/she can evaluate subject to determine if a repeat ablation procedure can 
be scheduled before the end of the 90-day blanking period. 
11.9      Repeat Ablation Procedure (if applicable) 
It is expected that some subjects will have early recurrences of atrial arrhythmias (e.g. AF, 
AT, AFL) within the blanking period (90 days following the ablation procedure)[18].  
Investigators may perform one repeat ablation procedure in subjects with highly symptomatic 
or multiple early recurrences of atrial arrhythmias that cannot be controlled with 
antiarrhythmic therapy [26, 28]. Subjects with documented early recurrence during the blanking 
period are not being considered a primary effectiveness failure.  
The repeat ablation procedure must be performed with the originally assigned investigational 
or control catheter.   Prior to the repeat ablation procedure, subjects must meet the pre-
ablation requirements described in Section 11.4 and repeat baseline NIH Stroke Scale and 

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QOL survey.  Investigators must follow all procedural requirements defined in Section 11.5 
for the repeat ablation procedure.  During the repeat procedure, the presence or absence of 
PV electrical reconnection will be recorded.  In addition, the location of reconnection will be 
noted. 
The blanking period and follow-up visit schedule will not restart following the repeat 
ablation procedure.  Subjects that receive a repeat ablation procedure will undergo a repeat 
ablation pre-discharge visit.    
11.10   Three Month Follow-Up Visit 
All subjects must be evaluated three-months (90 ± 21 days) following the index ablation 
procedure. During this follow-up visit, the following will be performed: 
• Perform a limited physical exam (weight, resting heart rate, and blood pressure). 
• Assess the subject for any new adverse events and inquire about resolution of any 
previously reported events(s). 
o Subjects who have experienced symptoms or adverse events suggestive of PV 
stenosis are required to receive a chest CT or MRI scan to rule out PV stenosis. 
• Perform a 12-lead ECG  
o Report the absence or presence of atrial fibrillation or other atrial 
tachyarrhythmia. 
• Record any medication changes 
• Review event monitor data from the 2 required monthly recordings to ensure 
compliance, assess whether or not there has been a recurrence of AF, AT, or AFL 
since last visit or if there were symptoms associated with the episodes of arrhythmias 
since the last follow-up. 
11.11   Six Month Follow-Up Visit 
All subjects must be evaluated six-months (180 ± 28 days) following the index ablation 
procedure. During this follow-up visit, the following will be performed: 
• Perform a limited physical exam (weight, resting heart rate, and blood pressure). 
• Assess the subject for any new adverse events and inquire about resolution of any 
previously reported events(s). 
o Subjects who have experienced symptoms or adverse events suggestive of PV 
stenosis are required to receive a chest CT or MRI scan to rule out PV stenosis. 
• Perform a 12-lead ECG  
o Report the absence or presence of atrial fibrillation or other atrial 
tachyarrhythmia. 
• Record any medication changes 
• Review event monitor data for recordings made due to symptomatic episodes of 
arrhythmias (if applicable) since the last follow-up and the event monitor data 
from the two (2) required monthly recordings. 

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• Subjects will be provided a 24-hour Holter monitor  
o Subjects will be given instructions for set-up and return to the core lab   
• Administer a follow-up AFEQT Questionnaire (QOL) 
11.12   Twelve Month Follow-Up Visit 
All subjects must be evaluated twelve-months (365 ± 45 days) following the index ablation 
procedure. During this follow-up visit, the following will be performed:    
• Perform a limited physical exam (weight, resting heart rate, and blood pressure). 
• Assess the subject for any new adverse events and inquire about resolution of any 
previously reported events(s). 
o Subjects who have experienced symptoms or adverse events suggestive of PV 
stenosis are required to receive a chest CT or MRI scan to rule out PV stenosis. 
• Perform a 12-lead ECG  
o Report the absence or presence of atrial fibrillation or other atrial 
tachyarrhythmia. 
• Record any medication changes 
• Review event monitor data for recordings made due to symptomatic episodes of 
arrhythmias (if applicable) since the last follow-up and the event monitor data 
from the two (2) required monthly recordings. 
• Subjects will be provided a 24-hour Holter monitor  
o Subjects will be given instructions for set-up and return to the core lab  
• Administer a follow-up QOL assessment (AFEQT Questionnaire) 
• Administer a follow-up NIH Stroke Scale assessment 
• To evaluate the success of subject blinding, ask subject if they think they were in the 1. 
Investigational group 2. Control group or 3. Didn’t Know 
11.13   Unscheduled Visits 
Unscheduled visits may occur at any time during the study for the assessment of for example, 
possible adverse events and/or medication changes. Each unscheduled visit will be 
documented in a CRF. 
11.14   Subject Lost to Follow-Up 
The investigator will attempt to contact a subject at least three times prior to designating 
them as lost-to-follow-up subjects; two of these attempts should include attempting to contact 
subject via registered mail.  The investigator will document the date and type of attempted 
communication, and will complete the Study Completion Form when a subject is lost to 
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11.15   Extended Follow-up Period (if applicable) 
Dependent on the safety and efficacy data collected in this study, it is possible that extended 
surveillance of subjects will be requested by a Regulatory Authority, including the FDA 
resulting in an extended follow-up period of up to three (3) years. If extended follow-up is 
requested, subjects would be re-consented and followed per standard of care for their 
Institution with continued adverse event collection and reporting. The information collected 
during these regular follow-up visits would be reported via the EDC system or equivalent and 
the decision to extend follow-up would be documented in a letter communicated at a 
minimum to the Investigators, IRB/EC and regulatory authorities as necessary. CEC review 
of clinical event information and DSMB oversight, if applicable would continue to occur as 
specified in the CEC/DSMB charter.  
11.16   Study Completion  
It is the intent of the protocol that all subjects will be followed for a minimum of 12 months 
post procedure. Documentation of study completion will be required for all subjects, 
independent of the point at which they complete the study (including screening failure, early 
withdrawal or loss to follow-up as applicable). 
12.  STUDY CONDUCT 
12.1.  
Statement of Compliance 
This study will be conducted in accordance with the ethical principles stated in the latest 
Declaration of Helsinki, ISO 14155: 2011 and FDA 21 CFR parts 50, 54, 56, 812. The study 
will not begin until appropriate national and local approvals have been obtained, as 
appropriate. Any additional requirements imposed by the IRB/EC or regulatory authority will 
be followed where appropriate. 
12.2.  
Regulatory Considerations 
The clinical investigational plan, subject informed consent and associated documents will be 
reviewed by the relevant Ethics Committee (EC)/Institutional Review Board (IRB) and 
appropriate agencies prior to any subject enrollment. The study will not start without the 
written approval of the IRB/EC and, where needed, the FDA and/or Competent Authority 
(CA) approval, and after the completion of any other local regulation requirements. 
12.3.  
Investigator Responsibilities 
The Principal Investigator of an investigational center is responsible for ensuring that the 
study is conducted in accordance with all Clinical Study Agreements, the clinical 
investigational plan and applicable regulations in FDA 21 CFR part 812, as well as any 
prevailing local and/or country laws and/or regulations, whichever affords the greater 
protection of the subject’s rights, safety and welfare. In addition, Investigators are 
responsible for: 
• Ensuring that an IRB/EC reviews and approves Clinical Investigational Plan 
• Maintaining adequate and accurate records related to: 
o Subject eligibility 

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o Subject Informed Consent form 
o Study related subject source data as described in clinical investigational plan 
o Case report forms 
o Device accountability log 
o Staff delegation of authority and training logs 
• Ensuring that conducting the study will not give rise to conflicts of interest 
• Informing the Sponsor in writing of the reason(s) for any withdrawal of any IRB/EC 
approval.  
• Ceasing the enrollment of subjects immediately in the event of the withdrawal of any 
IRB/EC approval.  
• Ensuring that no subjects will be enrolled, without prior, written Approval to Enroll 
from the Sponsor.  
• Agreeing to use their best efforts to satisfactorily complete the planned work and 
comply with accepted GCP. 
• Ensuring that informed consent is obtained appropriately and that the conditions of 
informed consent are complied with. 
• Ensuring the appropriate completion of all CRFs (paper and/or EDC) with the 
understanding that certain records and reports may be submitted to regulatory agencies 
by the Sponsor to support regulatory submissions.  
• Supporting a monitor/auditor (as applicable) in their activities. 
• Informing the Sponsor of all adverse events and adverse device effects in a timely 
manner and informing the IRB/EC of any serious adverse device effects as applicable. 
12.4.  
Confidentiality and Data Protection 
Health data will be recorded and forwarded to the sponsor of the study, and where needed, to 
participating IRB/EC and the FDA/CA for evaluation as required.  Information obtained in 
this study that can be identified with the subject’s identification will remain confidential.  
Any data that may be published in scientific journals will not reveal the identity of the study 
participants.   
12.5.  
Insurance 
As the Sponsor of this clinical investigation, EPIX will provide proof and type of insurance 
coverage for subjects in the study, upon request or where required by local/country 
regulations.  
12.6.  
Protocol Amendments 
Changes to this study that affect the safety or welfare of the subject, scope of the 
investigation or scientific integrity of the data will require an amendment to the 
investigational plan.  Amendments to the investigational plan may be initiated by EPIX or at 
the request of an Investigator. A formal amendment cannot be initiated by an Investigator or 
clinical site staff without the approval of EPIX.  
Protocol amendments must be submitted and subsequently approved by the site IRB/EC and 
CA and FDA, if applicable.  

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EPIX may make certain administrative changes to the protocol without prior approval of the 
IRB/EC. EPIX will notify all investigative sites of such changes to ensure the study 
continues to be conducted consistently across all sites. 
12.7.  
Adverse Event Reporting 
All AEs observed by the Investigator or staff during a physical or laboratory examination, 
interventional procedure or mentioned by the subject, either spontaneously or upon 
questioning, will be recorded on an AE case report form. All AEs will be documented with 
the date of occurrence, relatedness to device or procedure, severity, action taken, resolution 
and any pertinent additional information.  Additionally, the Investigator is responsible for 
providing appropriate treatment for the event and for adequately following the event until 
resolution.  
All adverse events (AE) will be monitored from the time of signed ICF through the twelve-
month follow-up visit.  Table 10 details AE classification, definitions and reporting 
timelines. 
Table 10.  Adverse Event Classification, Definitions and Reporting Timelines 
Event 
Classification 
Definition 
Reporting Timeline 
Adverse Event  
(AE) 
Any untoward and unintended medical 
occurrence experienced by a clinical study 
subject. An AE can be any unfavorable and 
unintended sign (including an abnormal 
laboratory finding), symptom or disease 
temporally associated with the use of a 
Sponsor’s investigational system or the control 
system, whether it is related to the product or 
not.  
Study staff must complete an AE 
CRF for each AE that occurs per 
subject throughout the duration of 
the study.  AE CRF will be 
completed in a timely manner. 
 
Adverse 
Device Effect 
(ADE) 
AE related to the use of an investigational 
medical device 
Study staff must complete an AE 
and device deficiency CRF within 
2 business days after the event for 
each subject through the duration 
of the study. 
Serious 
Adverse Event 
(SAE) 
AE that: 
• Led to death, 
• Led to serious deterioration in the health of 
the subject, that either resulted in: 
o a life-threatening illness or injury, or 
o a permanent impairment of a body 
structure or a body function, or 
o in-patient or prolonged hospitalization of 
existing hospitalization, or 
o medical or surgical intervention to 
prevent life-threatening illness or injury 
or permanent impairment to a body 
structure or a body function 
Study staff must complete an AE 
CRF within 2 business days after 
becoming aware of an SAE for 
each subject through the duration 
of the study.   
Study staff must provide all 
relevant / supporting source 
information (de-identified) in a 
timely manner when 
documentation becomes available. 
SAE or SADE will be reported to 
IRB/EC or FDA/CA per 
local/regional regulations. 

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• Led to fetal distress, fetal death, or a 
congenital abnormality or birth defect. 
Serious 
Adverse 
Device Effect 
(SADE) 
 
ADE that has resulted in any of the 
consequences characteristic of the above-
mentioned SAE. 
Study staff must complete an AE 
and device deficiency CRF within 
2 business days after becoming 
aware of an SAE for each subject 
through the duration of the study.   
Unanticipated 
Adverse 
Device Effect 
(UADE) 
 
 
Any SAE or any life-threatening problem or 
death caused by, or associated with, a device, 
if that effect, problem, or death was not 
previously identified in nature, severity, or 
degree of incidence in the investigational plan 
or risk analysis plan, or any other unanticipated 
serious problem associated with a device that 
relates to the rights, safety, or welfare of 
subjects.   
Study staff must complete and AE 
and device deficiency CRF within 
1 business day of becoming aware 
of the event and report to IRB/EC 
or FDA/CA per local/regional 
regulations. 
 
Adverse events will be recorded, reported and followed for all subjects for the duration of their 
participation in the study regardless of whether they are in the investigational or control cohort. 
The Principal Investigator is responsible for informing the IRB/EC, and regulatory authorities of 
UADE(s) and SAE(s) as required by local/regional regulations. 
Planned hospitalization for a pre-existing condition, or a procedure required by the clinical 
investigational plan, without serious deterioration in health, is not considered as part of the 
primary composite safety endpoint.  Additionally, underlying diseases/ pre-existing conditions 
will not be reported as an AE unless there has been a substantial increase in the severity or 
frequency of the problem which has not been attributed to natural history during the 
investigation.  To this extent, hospitalizations due to recurrent AF / AFL or prolonged 
hospitalization following procedure to adjust anticoagulation regimen or to administer diuretic 
medication are not considered AEs for this study. 
Device-Related Adverse Event   
An AE is considered to be device-related (ADE) when, in the opinion of the Investigator, the 
clinical event has an association in time and/or proximity with the use of the investigational 
device such that it is reasonable and likely that the investigational device directly caused or 
contributed to the AE. A device-related adverse event that impacts or potentially impacts a 
primary and/or secondary safety endpoint will be reviewed and adjudicated by the 
independent CEC. ADEs include any AE resulting from insufficient or inadequate IFU, 
deployment, operation, or malfunction of the investigational medical device, as well as, from 
intentional misuse of the device. 
Procedure-Related Adverse Event   
An AE is considered to be procedure-related when, in the opinion of the Investigator, it is 
reasonable to believe that the event is associated with the ablation procedure and is not 
specific to the investigational device used and that other products, surgical techniques, or 

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medications required specifically for the procedure are likely to have caused or contributed to 
the event. A procedure-related adverse event that impacts or potentially impacts a primary 
and/or secondary safety endpoint will be reviewed and adjudicated by the independent CEC. 
12.8.   
Device Deficiency Reporting   
A device deficiency is defined as any inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety or performance. Device deficiencies include 
malfunctions, misuse or use errors and inadequate labeling.  
Device deficiencies related to the investigational ablation systems may occur in the absence 
of any associated AE and must be completely documented on a CRF.  
Device deficiencies related to the DiamondTemp Ablation System and associated accessories 
should be reported to the Sponsor within two (2) business days and returned to the sponsor 
for analysis as expeditiously as possible. Instructions for returning the clinical device(s) will 
be provided to investigational sites by the Sponsor. If it is not possible to return the device, 
the investigator should document why the device was not returned and the final disposition of 
the device. Device failures and malfunctions should also be documented in the subject’s 
medical record. If a device deficiency is associated with an AE that specific event would be 
recorded as an AE. 
Device deficiencies related to the control system will be handled per the hospital standard 
complaint handling procedure.  
Note: Any Device Deficiency that might have led to an SAE if a) suitable action had not been 
taken or b) intervention had not been made or c) if circumstances had been less fortunate is 
considered reportable and should be notified to EPIX. 
12.9.  
Protocol Deviations 
The Investigator is not allowed to deviate from the protocol without prior approval by 
Sponsor and prior review and documented approval from the governing IRB/EC.   
Under emergency circumstances, deviations from the clinical investigation plan to protect the 
rights, safety and well-being of human subjects may proceed without prior approval of the 
sponsor and the IRB/EC. 
Reports of any deviation from the clinical investigational plan as per above emergency 
circumstances will be reported to the Sponsor and to the IRB/EC as soon as possible after 
detection, but no later than twenty-four (24) hours from the time of the deviation. 
Deviations must be documented on the appropriate protocol deviation CRF. 
Any report of withdrawal of IRB/EC approval will be submitted to the Sponsor within five 
(5) working days. 
If a Clinical Monitor becomes aware that an Investigator is not complying with the signed 
Investigator’s Agreement, the Investigational Plan, the requirements of ISO 14155 or other 
applicable regulations, or any conditions of approval imposed by the reviewing IRB/EC 
Committee, Sponsor will immediately either secure compliance or discontinue shipments of 
the device to the Investigator and terminate the Investigator’s participation in the 

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investigation.  The Investigator will be required to return all investigational components to 
Sponsor, unless this action would jeopardize the rights, safety or welfare of a subject. 
Protocol deviations will be analyzed by Sponsor for the impact to the overall integrity of the 
study.  Input from the statistician and/or the Data Safety Monitoring Board (DSMB) may be 
obtained to determine if the deviation warrants disqualifying the Investigator.   
Disqualification is warranted when an investigator has repeatedly or deliberately violated 
governing regulations or has repeatedly or deliberately submitted false information in any 
report.  Where protocol deviations occur, which do not warrant disqualification from a study, 
Sponsor will implement appropriate corrective and preventive actions, including repeat 
training as deemed necessary. 
12.10  
Investigational Device Accountability 
No device supplies will be shipped to the Investigator until IRB/EC and regulatory authority 
(CA and/or FDA) approval has been achieved in writing and each Investigator has supplied 
Sponsor with copies of the IRB/EC approval document and the approved informed consent 
form to be used. 
The investigational devices are to be used only in this clinical investigation and according to 
this protocol and the IFU.  The devices for use in this study must be stored in a secure area.  
The secure area will have restricted access and the study devices will be kept separate from 
other medical devices. The study devices will only be handled by trained personnel and will 
not be supplied to any individual not involved in the investigation.  The study devices will be 
inventoried at regular intervals during the study and all unused or expired devices will be 
returned to the Sponsor when study enrollment is closed. 
The Principal Investigator or his/her authorized representative is responsible to keep records 
documenting the receipt, use, return and disposal of the investigational devices.  A form will 
be provided to the site that will log the device model, lot number or serial number and date 
received by the site.  As the devices are used, the site will record the subject study 
identification number and date of procedure for each device.  A space will be provided for 
recording returned product and the reason for the return. 
12.11.  
Documentation 
Source documents may include a subject’s medical record, hospital charts, clinic charts, the 
Investigator’s study files, questionnaires and the results of diagnostic tests such as laboratory 
tests, electrocardiograms, CT angiograms, MR angiograms, echocardiograms and such.  The 
Investigator’s copy of the CRFs serves as part of the Investigator’s record of a subject’s 
study-related data. 
The following information should be included in the subject’s medical record: 
• Name and contact information 
• The study title (DIAMOND-AF Study), study number, and Sponsor name (Epix 
Therapeutics or EPIX) 
• Date the subject was informed about the study, that he/she had sufficient opportunity 
to ask questions and he/she was informed regarding alternative treatments  

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• The subject was allowed adequate time to consider participation prior to signing the 
consent form 
• A statement that written informed consent was obtained 
• Date of enrolment into the clinical study and the subject ID number 
• Date of procedure, procedural type, and device lot number 
• Visit dates 
• Cardiac medications 
• Occurrence of any adverse events 
• Date subject exited the study, and a notation as to whether the subject completed the 
study or discontinued, with the corresponding reason. 
The Investigator is responsible for ensuring that data are properly recorded in each subject’s 
source data, CRFs and related documents and ensuring timely transfer of data to the CRF. 
The Investigator who signs the Protocol Signature Page should sign the CRFs requiring 
signatures to ensure that the observations and findings are recorded correctly and completely. 
Source data from baseline until 12-month follow-up, respectively, must be transferred to the 
CRF. All CRFs will be reviewed for completeness, accuracy and clarity. Queries for missing 
or unclear data will be made as necessary and must be answered within 10 business days. 
12.12.  
Record Retention 
The Investigator will maintain, at the investigative site, in original format, all essential study 
documents and source documents that support the data collected on the study subjects in 
compliance to ICH/GCP guidelines. Documents will be retained for at least two (2) years 
after the last approval of a marking application or until at least two (2) years have elapsed 
after the formal discontinuation of the clinical trial of the device. Documents may be retained 
longer by agreement with the Sponsor or in compliance with other local regulations. The 
Investigator will take measures to ensure that these essential documents are not accidentally 
damaged or destroyed. Sponsor requires to be notified in writing if the Investigator intends to 
leave the hospital so that both parties can be assured a new responsible person is appointed in 
the hospital responsible for maintaining these essential documents.  
13.  POTENTIAL RISKS AND BENEFITS 
13.1.  
Anticipated Adverse Events  
There are potential or anticipated risks associated with the use of the DiamondTemp Ablation 
System.  The handling characteristics and principles of operation of the DiamondTemp 
System are like conventional RF ablation systems and it is anticipated that the rate of 
catheter/system related complications in this study will be similar to those reported from 
ablation procedures used with commercially approved ablation systems.  
Specific risks are outlined in the system labeling, but in summary the possible risks for 
catheterization and RF ablation are, but are not limited to the following: 
1. Access site complications, including: 
a. Arteriovenous fistula 

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b. Ecchymosis 
c. Hematoma 
d. Hemorrhage or aneurysm 
e. Infection 
f. Pain 
g. Surgical correction involving loss of limb 
h. Thrombosis 
2. Sequelae of fluoroscopic exposure, including: 
a. Possible cancer risk 
b. Risk of birth defect 
c. Harm to fetus 
d. Skin burns 
3. Direct cardiac damage, including: 
a. Cardiac tamponade / perforation resulting in pericardial effusion 
b. Catheter entrapment within heart or blood vessels, leading to damaged heart wall, 
valves, chordae tendineae or blood vessels, possibly requiring surgical correction 
or involving loss of function 
c. Congestive heart failure 
d. Damage to cardiac conduction system 
e. Pulmonary vein stenosis   
f. Endocarditis 
g. Myocardial infarction 
h. Pericarditis resulting in pericardial effusion 
i. Persistence of an atrial septal defect (resulting from the transseptal puncture) 
j. Stiff left atrial syndrome 
k. Valve damage due to catheter entrapment 
4. Other intrathoracic collateral effects, including: 
a. Atrioesophageal fistula  
b. Damage to trachea, bronchi or pulmonary tissue 
c. Damage to great vessels 
d. Esophageal injury 
e. Phrenic nerve injury  
f. Vagal nerve injury 
5. Embolic phenomena including: 
a. Coronary artery embolism with or without myocardial infarction 
b. Gas embolism from procedural error or equipment malfunction with embolic 
phenomenon 
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d. Obstruction of vasculature leading to limbs causing the need for surgical 
interventions, loss of a limb, or loss of organ function 
e. Pulmonary embolism 
f. Paradoxical embolism through patent foramen ovale 
g. Stroke or TIA 
6. Arrhythmias including: 
a. New arrhythmias occur   
b. Worsening of existing arrhythmia 
c. Creation of a partial or complete conduction block, with or without the 
implantation of a temporary or permanent pacemaker 
7. The general sequelae of catheterization including: 
a. Pulmonary edema 
b. Skin burns 
c. Hypotension 
d. Sepsis 
e. Pneumothorax 
f. Myocardial infarction 
g. Cardiac arrest 
h. Death 
8. Medication side effects, especially: 
a. Heparin administration: including bleeding, thrombosis, changes in circulating 
blood elements and skin necrosis 
b. Ionic and nonionic radiopaque contrast medium, major complications: life-
threatening reactions including: cardiovascular collapse, severe respiratory 
difficulty, nervous system dysfunction, convulsions, coma and cardio-respiratory 
arrest 
c. Ionic and nonionic radiopaque contrast medium, minor complications: allergic 
reactions including: nausea, vomiting, facial flush, feeling of body warmth, 
dermal manifestations of urticaria with or without pruritus, erythema and 
maculopapular rash, dry mouth, allergic glossitis, sweating, conjunctival 
symptoms, facial, peripheral and angio-neurotic edema 
d. Anesthetic reactions: including respiratory difficulties, sedation induced apnea, 
pneumonia, low blood pressure, cardiac arrest (death) and nausea and/or 
vomiting. 
13.2.  
Risk Minimization 
A comprehensive functional risk analysis was performed to quantify the risks associated with 
the use of the DiamondTemp Ablation System. This functional risk analysis evaluated the 
potential interfaces of the DiamondTemp Ablation System with the subject and/or user and 
listed the potential harms and potential causes.  The associated probability of each cause was 
estimated and risk control measures were considered and implemented to further reduce the 
potential for all risks.  

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The completed risk analyses of the DiamondTemp Ablation System identified all known 
potential risks to the subject and user.  All risks were categorized in the negligible or 
marginal categories. Since all identified risks were low or moderate, the design is determined 
to be safe for human use. The risk analysis did not result in findings of any risk that would be 
considered intolerable. The potential risks associated with any ablation procedure include 
standard surgical risks for example: infection, electrical shock, perforation, tamponade, skin 
burns and complications associated with use of ancillary devices, drugs, and anesthetic.  The 
DiamondTemp Ablation System does not create new risks nor does it increase procedural 
risks as compared with other ablation systems for electrophysiology procedures. The risks 
associated with the use of the DiamondTemp Ablation System have been identified and 
evaluated, controls have been put in place to adequately mitigate risks, and a system is 
implemented that monitors the effectiveness of the risk controls and provides a process to 
implement corrective and preventive actions 
The DiamondTemp Ablation System is similar in design to existing commercial ablation 
systems and intends to provide an equivalent functionality to existing irrigated 
electrophysiology ablation catheter/systems on the market.  Additionally, technology 
integrated within the catheter allows to measure interface tissue temperature and the RF 
generator can be set to automatically adjust the power to achieve a desired interface tissue 
temperature. The DiamondTemp Ablation System does not introduce any new or additional 
safety risks beyond those associated with similar cardiovascular and ablation procedures. 
Further, the system is also capable of assessing the extent of contact between the ablation 
electrode and the cardiac tissue ensuring good energy to transfer to the therapy location. This 
study is intended to evaluate the safety and performance effectiveness of the DiamondTemp 
Ablation System for the treatment of atrial arrhythmias. 
Risks associated with the DIAMOND-AF Study can be minimized through appropriate 
training of Investigators and research staff, compliance to this protocol, adherence to 
inclusion / exclusion criteria and by promptly supplying Epix Therapeutics with data and 
information required by this protocol.   
Additionally, extensive in vitro bench and in vivo animal studies have been successfully 
performed with the DiamondTemp Ablation System. Verification and lot release testing for 
all components of the system will be completed. The associated risks proposed in this study 
are similar to risks posed by other interventional, electrophysiological cardiac procedures.  
Based upon the risk analysis conducted to assess the DiamondTemp Ablation System, EPIX 
has determined that the benefits of the device can outweigh the risks if used in the 
appropriate patient population by a physician trained in the use of electrophysiology 
procedures.  As a primary treatment for cardiac arrhythmias, the DiamondTemp Ablation 
System is determined to be safe for human use. 
13.3.  
Benefits 
Participants in this research study may or may not receive benefits from participation in this 
study as compared to standard of care treatment of PAF.   

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Based on bench and clinical testing with the DiamondTemp Ablation System it is expected 
that the subjects enrolled in this study will experience similar benefits as those of the 
currently available commercial systems.   
Subjects included in this research study may benefit from closer evaluation of their atrial 
fibrillation via more frequent office follow-ups, cardiac event monitoring and from having 
diagnostic non-invasive and invasive evaluation of their cardiac anatomy in the event of 
previously undiagnosed cardiac abnormalities. There is potential that subjects may have their 
AF eliminated or AF burden reduced resulting in a better quality of life and reduced need for 
medication.   
Additionally, there may be a benefit to the subjects enrolled in this study through improved 
therapy delivery.  The DiamondTemp system was designed to provide investigators with 
additional information to a) monitor real-time tissue interface temperatures b) automatically 
adjust output power to a temperature set point based on the composite temperature c) utilize a 
low irrigation flow rate for all power output up to 50 Watts.   
14.  MONITORING 
Monitoring will be performed during the study to assess continued compliance with the protocol 
and applicable regulations. Monitoring will occur in line with the Study Monitoring Plan. 
14.1.  
Study Monitor 
Study Monitors assigned to the DIAMOND-AF study will be responsible for reviewing the 
device accountability documentation and subject data as collected on CRFs or via an EDC 
system. The monitor will ensure that the clinical protocol has been approved by the IRB/EC 
and will assure ongoing compliance with clinical protocol.   
The Investigator/institution guarantees direct access to original source documents by Sponsor 
personnel, their designees, and appropriate regulatory authorities. 
14.2.  
Monitoring Procedures 
Monitoring visits to the clinical sites will be made periodically to ensure that Investigators 
and their staff understand and accept their defined responsibilities, assess compliance with 
current GCP guidelines, evaluate clinical trial progress, assess the continued acceptability of 
the clinical site facilities, assess compliance with the investigational plan, and verify the 
accuracy of data recorded on CRFs or via an EDC system to source documentation.  
The Sponsor Monitor or its designated representative will be allowed to visit the clinical site 
and have direct access to all study records throughout the duration of the study. The Monitor 
will review all source data and compare them to the data documented in the case report 
forms, in addition to performing a review of the Regulatory Binder and conducting device 
accountability. Subject safety will be ensured by noting that consent was properly 
documented, the investigational plan was followed and that AEs were reported and followed-
up as appropriate. 
The Investigator and/or institution will provide direct access to source data/documents for 
trial-related monitoring, audits, IRB/EC review and regulatory inspection.   

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It is important that the Investigator and relevant study personnel are available during the 
monitoring visits and that sufficient time is devoted to the process. 
Additionally, telephone and/or e-mail contact will be conducted on a regular basis with the 
Investigator and the site staff to ensure that the protocol is being followed and to address any 
issues that may occur during the trial. 
If a deficiency is noted during the trial the Clinical Monitor is required to bring this to the 
attention of EPIX Clinical Affairs Management to discuss the situation and (if required) to 
secure compliance.  
The study Monitor will evaluate and summarize the results of each clinical site visit in 
written reports, identifying any repeated data problems with any Investigator and specifying 
recommendations for resolution of noted deficiencies. 
As required by IDE regulations, the conduct and monitoring of the clinical investigation will 
be conducted in accordance with the Sponsor’s approved monitoring plan.    
14.3.  
ECG Core Lab 
A designated CRO, HeartcoR Solutions, LLC (Algonquin, IL) will provide centers and/or 
subjects with instructions and training on the use of an event monitors that serves as a hand-
held event recorder for short duration recordings and can be worn as a 24 hr. Holter.  
Subjects will be provided with an event monitor prior to discharge from the hospital and 
instructed to collect 1-minute ECG recordings with their event monitor if they experience AF 
symptoms throughout the study.  Additionally, subjects will be required to collect 1-minute 
ECG recordings with their event monitor two times per month starting at the end of the 3-
month blanking period to the 12-month follow up visit.  
The event monitors will be configured to automatically transmit recordings securely and 
wirelessly to the core lab.  All events will be analyzed by the core lab to determine if 
symptoms are associated with arrhythmia recurrence.  The core lab will be blinded to subject 
treatment assignment.  The company will identify the subject’s transmitted rhythm and send 
reports to the investigational center within 72 hours.  If there is discordance between the core 
labs rhythm analysis in the report and the investigator, a third-party cardiologist will be used 
for final rhythm determination.  All event monitors should be returned to the Core Lab after a 
subject completes the study. 
At 6 and 12 months post-ablation procedure, the event monitor will be configured to take a 
24-hr continuous reading (like a Holter monitor) supplied by the core lab.  
The ECG core lab will also review, analyze and report on all event and Holter recordings as 
well as the 12-lead ECGs taken at the 3, 6 and 12-month follow-up visits. 
14.4.  
Data Safety Monitoring Board 
The purpose of the DSMB committee is to complete unbiased review of all safety data in 
comparison to the established criteria in order to determine if the rate of SAEs is acceptable, 
to evaluate interim data analysis results, to provide related advice on study management and 
progress, and to make any recommendations regarding the study protocol. Members of the 
DSMB will be comprised of three (3) voting individuals with relevant expertise for the study 

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and a biostatistician, they will not be employees or shareholders of EPIX and they will not be 
a participating DIAMOND-AF Investigator.      
The DSMB will be responsible to communicate any safety, scientific concerns, or other 
perceived concerns to EPIX or designee as soon as possible. The DSMB will provide, after 
each scheduled meeting, written recommendation regarding the continuation of the trial, 
early stopping, or any suggested changes for the conduct of the trial. EPIX is responsible for 
informing the IRB/EC and regulatory authorities, as applicable, if the DSMB has advised 
them of any major safety concerns and has recommended the study be stopped or if they have 
made any recommendations to alter the study. DSMB decisions are final and non-negotiable 
by the sites. 
14.5.  
Clinical Events Committee 
The purpose of the CEC is to complete unbiased reviews and classification of serious adverse 
events and deaths reported by clinical study investigators. The CEC will consist of physicians 
who are not participating Investigators in the DIAMOND-AF Study and who do not have any 
significant investment in Sponsor’s or any of their entities. The three (3) voting members will 
also serve on the CEC to provide an independent unbiased review and adjudication of clinical 
events throughout the trial will not also be DSMB members. A complete description of CEC 
and DSMB responsibilities, qualifications, members and operating principles will be outlined 
in a combined charter. 
14.6.  
Steering Committee 
The DIAMOND-AF Steering Committee is comprised of senior clinical, medical and 
regulatory members of EPIX, as well as international physician investigator advisors and the 
study statistician. The role of the Steering Committee is to provide oversight of the clinical 
study regarding the design, submission and conduct of the study. Steering Committee 
members may participate in the review and approval of all requests for data analysis, abstract 
and manuscript preparation, and submission; however, EPIX remains responsible for all 
decisions related to any such requests in line with approved study agreements. 
15.  SUSPENSION OR TERMINATION 
15.1. Premature Termination of the Study 
EPIX reserves the right to terminate the study at any stage but intends to exercise this right 
only for valid scientific or administrative reasons and reasons related to protection of 
subjects.  Investigators, associated IRBs/ECs, and regulatory authorities, as applicable, will 
be notified in writing in the event of study termination. 
Possible reasons for premature study termination include, but are not limited to, the 
following. 
• The occurrence of UADEs that present a significant or unreasonable risk to subjects 
enrolled in the study; 
• A decision on the part of Epix Therapeutics to suspend or discontinue development of 
the device. 

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15.2.  
Termination of Participation  
Any investigator or IRB/ EC involved in the DIAMOND-AF study may discontinue 
participation in the study or withdrawal approval of the study, respectively, with suitable 
written notice to Epix Therapeutics Investigators, associated IRBs/ECs, and regulatory 
authorities, as applicable. 
Requirements for Documentation and Subject Follow-up 
In the event of premature study termination by the Sponsor, a written statement as to why the 
premature termination has occurred will be provided to all participating centers by EPIX. The 
IRB/EC and regulatory authorities, as applicable, will be notified. Detailed information on 
how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB or EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by EPIX. 
In the event an investigator terminates participation in the study, study responsibility will be 
transferred to a co-investigator when possible or another authorized clinical Investigator.  In 
the event there are no opportunities to transfer investigator responsibility; detailed 
information on how enrolled subjects will be managed thereafter will be provided by EPIX. 
The investigator must return all documents and investigational product to EPIX, unless this 
action would jeopardize the rights, safety, or welfare of the subjects. 
Criteria for Suspending/Terminating a Study Center 
EPIX reserves the right to stop the inclusion of subjects at a study center at any time if no 
subjects have been enrolled for a period beyond 3 months after the site has been granted 
Approval to Enroll or if the center has multiple or severe protocol violations/noncompliance 
without justification and/or fails to follow remedial actions. 
In the event of termination of investigator participation, all study-related devices and 
equipment, as applicable, will be returned to EPIX unless this action would jeopardize the 
rights, safety or well-being of the subjects. The IRB/EC and regulatory authorities, as 
applicable, will be notified. All subjects enrolled in the study at the center will continue to be 
followed per protocol-defined follow-up.  The Principal Investigator at the center must make 
provision for these follow-up visits unless EPIX notifies the investigational center otherwise. 
16.  PUBLICATION AND REPORTING POLICY 
Epix Therapeutics is committed to the publication and dissemination of clinical study results, 
regardless of study outcomes.  Any publication or presentation relating to the DIAMOND-AF 
Study will require that ACT’s role as a sponsor or financial supporter is included.  
The final clinical study report of the conclusions of this study will be written within six (6) 
months of the closing of the database at the end of the study.  The report will be signed by the 
global study principal investigators and provided to all study investigators.  The study protocol 
will be registered at www.clinicaltrials.gov before the inclusion of any study subjects. 

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17.  REIMBURSEMENT AND COMPENSATION FOR SUBJECTS  
Travel and other expenses incurred by subjects because of participation in the study may be 
reimbursed in accordance with pertinent country laws and regulations and per the study site’s 
regulations.   
18. ABBREVIATIONS AND DEFINITIONS  
18.1.  
Table of Definitions  
Term 
Definition 
ACT 
ACT is a test that is used to monitor the effectiveness of the 
administration of Heparin through measuring activated clotting 
time (ACT) 
Asymptomatic AF, 
AT or AFL 
Also known as silent AF or silent atrial tachycardia (e.g. AT, 
AFL). Defined as an opportune diagnosis of AF, AT, and/or AFL 
with electrocardiographic data; specifically, subject’s event 
monitor, 24 hr. Holter monitor or 12 lead ECG at clinic visit. 
Atrioesophageal 
fistula  
Creation of direct communication between the left atrium and 
esophagus as documented by esophageal erosion combined with 
evidence of a fistulous connection to the atrium (e.g. air emboli, 
an embolic event or direct observation at the time of surgical 
repair). A CT or MRI scan is recommended to document event.   
Attempt Subject 
Refers to a subject who has been enrolled and has treatment 
catheter introduced but does not receive an ablation with the 
treatment or control catheter per protocol. 
Blanking Period 
The ~ 90-day period between ablation procedure and the 3-month 
follow-up visit.  During the blanking period, a repeat ablation can 
be performed with the same treatment catheter subject originally 
randomized to and was treated with.  Subjects can be prescribed 
antiarrhythmic drugs as determined necessary by the investigator 
during blanking period. 
Bleeding 
complication 
Major bleed that requires a transfusion or results in a ≥ 20% fall 
in hematocrit  
Cardiac tamponade / 
perforation 
Significant pericardial effusion with hemodynamic compromise 
that requires elective or urgent pericardiocentesis or results in a 1-
cm or more pericardial effusion as documented by 
echocardiography. 
CHA2DS2-VASc 
score 
Clinical prediction rules for estimating stroke risk in patients with 
non-rheumatic AF.  The rule gives a better risk stratification of 
low-risk patients than CHADS2 score by inclusion of additional 
stroke risk modifier risk factors. 

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Condition 
Points 
C 
Congestive heart failure (or LV systolic 
dysfunction) 
1 
H 
Hypertension (consistently > 140/90mmHg or 
treated) 
1 
A2 
Age ≥ 75 years  
2 
D 
Diabetes Mellitus 
1 
S2 
Prior stroke or TIA or thromboembolism 
2 
V 
Vascular disease (e.g. peripheral artery disease, 
MI, aortic plaque) 
1 
A 
Age 65-74 years 
1 
Sc 
Sex category (i.e. female sex) 
1 
Char 
The remains of solid biomass originating from intracavity blood 
or myocardium that has formed as proteins in the blood are 
denatured by excessive heating that present as friable material 
observed on the catheter after RF ablation.  
Congestive Heart 
Failure 
Heart doesn’t pump properly and fluid builds up in arms, legs, 
ankles, feet, lungs, or an organ. 
Coagulum 
The remains of solid biomass originating from intracavity blood 
or myocardium that has formed as proteins in the blood are 
denatured by excessive heating that present as adherent material 
observed on the catheter after RF ablation.  
Death 
Cardiovascular related death post ablation 
Effectiveness 
Evaluation Period 
The period between subject’s 3-month follow-up visit and 12-
month follow-up visit during which the primary effectiveness 
endpoint will be assessed. 
Enrolled Subject 
All subjects who sign ICF and are randomized to a treatment arm. 
Heart block 
Damage to the heart’s electrical system that controls heart 
rhythm. 
Hemoptysis 
Coughing up blood 
Femoral (groin) 
hematoma 
Bleeding at the catheter insertion site that causes swelling or a 
pocket of blood.  May need to be drained or require additional 
procedure. 

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Long Standing 
Persistent AF 
Long-standing persistent AF is defined as continuous AF of 
greater than 12 months duration. 
Myocardial 
infarction  
MI as it relates to AF ablation resulting in the presence of any 
one of the following criteria: 
• ECG changes indicative of new ischemia that persist for > 1 
hour 
• development of new pathological Q waves on an ECG 
• imaging evidence of new loss of viable myocardium or new 
regional wall motion abnormality 
Paroxysmal Atrial 
Fibrillation (PAF) 
Recurrent atrial fibrillation that last ≥ 30 seconds and terminates 
spontaneously within 7 days.  
Pericardial effusion 
Accumulation of blood between heart and lining of the heart 
(pericardium).  It is not uncommon to observe “trace” pericardial 
effusion following AF ablation.  Trace effusion that does not 
need intervention is not considered a serious AE. 
Persistent Atrial 
Fibrillation   
Recurrent atrial fibrillation that lasts ≥ 7 days and does not 
terminate spontaneously   
Self-Limiting 
Pericarditis 
Pleuritic chest discomfort with or without pericardial rub and 
ECG changes and did not require additional hospitalization.  
Generally, not an SAE. 
Serious Pericarditis 
Pericarditis resulting in an effusion that leads to hemodynamic 
compromise, requires pericardiocentesis, prolongs hospitalization 
> 48 hours or persists for more than 30 days following procedure. 
Source Data 
Original records (or certified copies) of clinical findings, 
information, observations, or other activities in an investigation 
necessary for the reconstruction and evaluation of the clinical 
study. 
Source Document 
Printed or electronic document containing source data like 
hospital charts / records, lab notes, device accountability records, 
radiographs, signed procedural worksheets, records kept at the 
investigation site, and at the laboratories involved in the clinical 
study. 
Phrenic nerve 
paralysis 
Absence of phrenic nerve function assessed by a sniff test that 
persists > 7 days.  A phrenic nerve paralysis is considered to be 
permanent when it is documented to be present ≥ 12 months 
following ablation. 
Pulmonary edema 
Pulmonary alveolar fluid accumulation accompanied by typical 
symptoms (dyspnea), physical findings (rales, hypoxemia), 

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radiologic findings, and response to diuretic therapy and 
requiring hospitalization. 
Screen Failure 
A subject who has consented (signed ICF) but is found to not 
meet eligibility criteria through medical file review and/or 
screening procedures to confirm eligibility. 
Steam pop 
Excessive tissue temperatures over ~100°C that may result in an 
audible pop.  The pop is a sudden release or explosion due to the 
vaporization of interstitial fluid in myocardium. This may 
produce biotraumas and tissue disruption that is usually clinically 
benign but may cause rupture of thin-walled structures with 
subsequent pericardial tamponade, usually requiring emergency 
pericardiocentesis, and/or surgical repair.  
Stroke post-ablation 
Rapid onset of a focal or global neurological deficit with at least 
one of the following: change in level of consciousness, 
hemiplegia, hemiparesis, numbness or sensory loss affecting one 
side of the body, dysphasia or aphasia, hemianopia, amaurosis 
fugax that persists for >24 hours as determined by the consulting 
neurologist and subsequent neuroimaging procedure (MRI or CT 
scan or cerebral angiography). 
Symptomatic AF, 
AT or AFL 
Symptoms associated with AF, AT or AFL that were experienced 
by the subject, made them seek medical attention, and were 
concurrent with a documented episode by ECG, event monitor 
and/or Holter monitor. Symptoms may have included 
palpitations, irregular pulse (i.e. rapid, racing, pounding, 
fluttering, bradycardic), dizziness, weakness, chest discomfort, 
and breathlessness. 
Thromboembolism 
Occurrence of deep vein thrombosis or pulmonary embolism post 
ablation 
Thrombus 
An aggregation of blood factors, primarily platelets and fibrin 
with entrapment of cellular elements, frequently causing vascular 
obstruction at the point of its formation.  
Transient ischemic 
attack (TIA) post-
ablation 
Rapid onset of new focal neurological deficit with immediate 
symptom resolution (usually 1 to 2 hours), always within 24 
hours as determined by consulting neurologist and neuroimaging 
without tissue injury. 
Vagal nerve injury 
Esophageal dysmotility or gastroparesis requiring or prolonging 
hospitalization following an ablation procedure 
Vascular access 
complications  
 
Resulting in development of a hematoma, an AV fistula or a 
pseudoaneurysm that requires intervention, such as surgical repair 
or transfusion, prolongs the hospital stay, or requires hospital 
admission. 

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Vasospasm 
Sudden narrowing of artery that usually relaxes with medication 
or by waiting a short period of time (minutes). 
Wide Area 
Circumferential 
Ablation (WACA) 
The location of PVI has moved more proximally, from the PV 
ostium to the antral insertion of the PV, several centimeters 
proximal to the PV ostium. This is called “wide area 
circumferential ablation” or WACA, and is also known as PV 
antral isolation.  Technique has several advantages: 1) decreases 
risk of PV stenosis 2) eliminates proximal antral AF triggers 3) 
modification of nerve bundles that innervate the atria and 
contribute to AF maintenance may also be ablated.  
 
 
 

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18.2.  
Table of Abbreviations  
Abbreviation 
Definition  
AAD 
Anti-arrhythmic drugs 
ACT 
Activated Clotting Time 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AF 
Atrial Fibrillation 
AFEQT 
Atrial Fibrillation Quality of Life Survey 
AFL 
Atrial Flutter 
AT 
Atrial Tachycardia 
BMI 
Body Mass Index 
CA 
Competent Authority 
CABG 
Coronary artery bypass graft 
CEC 
Clinical Events Committee 
CF 
Contact Force 
CFAE 
Complex fractionated atrial electrogram 
CS 
Coronary Sinus 
CT 
Computed Tomography 
CTI 
Cavotricuspid Isthmus 
DIP 
Dispersive Indifferent Patch 
DSMB 
Data Safety Monitoring Board 
EC 
Ethics Committee (see IRB for US) 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture  
EGM 
Electrogram 
EP 
Electrophysiologist 
EPIX 
Epix Therapeutics 
EU 
European Union 
F 
French size 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
ICE 
Intracardiac Echocardiography 
ICF 
Informed Consent Form 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
IU 
International Unit 
IV 
Intra-venous 
LA 
Left Atrium 
LVEF 
Left Ventricular Ejection Fraction 
MACE 
Major Adverse Cardiovascular Event  
MRI 
Magnetic Resonance Imaging 
NYHA 
New York Heart Association 
PAF 
Paroxysmal Atrial Fibrillation 

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PI 
Principal Investigator 
PV 
Pulmonary Vein 
PVI 
Pulmonary Vein Isolation 
QOL 
Quality of Life 
RF 
Radiofrequency 
RFCA 
Radiofrequency catheter ablation 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
TEE 
Transesophageal echocardiography 
TIA 
Transient Ischemic Attack 
TTE 
Transthoracic echocardiography 
TTM 
Trans-telephonic Monitor 
UADE 
Unanticipated Adverse Device Effect 
US 
United States 
W 
Watts 
WACA 
Wide area circumferential ablation 
 
 

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19.  BIBLIOGRAPHY 
1. 
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Friberg, J., et al., Rising rates of hospital admissions for atrial fibrillation. Epidemiology, 
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14. 
Calkins, H., et al., 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and 
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Nakagawa, H., et al., Locations of high contact force during left atrial mapping in atrial 
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Natale, A., et al., Paroxysmal AF catheter ablation with a contact force sensing catheter: 
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Reddy, V.Y., et al., Randomized, Controlled Trial of the Safety and Effectiveness of a 
Contact Force-Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial Fibrillation: 
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(TOCCASTAR) Study. Circulation, 2015. 132(10): p. 907-15. 
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Calkins, H., et al., 2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus 
Statement on Catheter and Surgical Ablation of Atrial Fibrillation. Heart Rhythm, 2017. 

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27. 
Doherty, J.U., et al., 2017 ACC Expert Consensus Decision Pathway for Periprocedural 
Management of Anticoagulation in Patients With Nonvalvular Atrial Fibrillation: A 
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Liang, J., et al., Early recurrence of atrial arrhythmias following pulmonary vein antral 
isolation: Timing and frequency of early recurrences predicts long-term ablation success. 
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