Cryterion Cardiac Cryoablation System CE Mark Study
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Boston Scientific Corporation

Cryterion Cardiac Cryoablation System CE Mark Study 
 
Study ID: CEM-A02-02 
ClinicalTrials.gov ID: NCT03723070 
 
This document includes 
• 
CEM-A02-02 Protocol (PR-004382 Rev 3) 
o Date: 04 September 2019 
o Page 3-5 includes the revision history of previous versions 
 

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Cryterion Cardiac Cryoablation System 
CE Mark Study 
 
Protocol: CE Mark Study (CEM-A02-02) 
Version: Amendment 03 
Date:  04 September 2019 
 
Sponsor: 
Cryterion Medical, Inc. 
1949 Palomar Oaks Way 
Suite 100 
Carlsbad, CA  92011 
Tel: +1(760) 206-7910 
 
 
Boston Scientific Corporation 
4100 Hamline Avenue N 
Arden Hills, 
MN 55112-5798, USA 
 
Boston Scientific International S.A. 
Le Val Saint-Quentin, 
2 rue René Caudron, 
78960 Voisins le Bretonneux, France 
 
Boston Scientific Pty. Ltd. 
Level 5 
247 Coward St. 
Mascot 
NSW 
Australia 2020 
 
This study is to be performed in accordance with Good Clinical Practice (GCP), the Declaration of Helsinki, and the International 
Conference on Harmonization E6 and ISO standards 14155:2011 
CONFIDENTIALITY STATEMENT 
This document contains proprietary information that is privileged or confidential and subject to terms of the Non-
Disclosure Agreement.  No portion of this work may be reproduced in whole or in part without the express written 

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permission of Cryterion Medical Persons to whom the information is disclosed must be informed that this and future 
information is privileged or confidential. 
Protocol Signature Page 
 
Protocol: Cryterion Cardiac Cryoablation System 
CE Mark Study (CEM-A02-02) 
Amendment 03 
The signature below constitutes the approval the approval of this Clinical Investigational Plan 
(CIP) and provides assurances that this clinical study will be conducted in accordance with all 
stipulation of the CIP including all statements regarding patient confidentiality. The CIP will be 
followed according to all national and local legal and regulatory requirements. 
 
 
 
             _________________________________ 
                     Site investigator Printed Name 
 
 
 
           ____________________________________                    _________________ 
                    Site investigator Signature                                                      Date 
 

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CEM-A02-02 
Amendment 
02 
 
004927 
Updated Sponsor(s) to include supporting Sponsor(s) associated 
with Boston Scientific OUS Offices. 
Primary Effectiveness Endpoint:  removed the wait period for 
confirming PVI. 
Secondary Endpoint:  removed the wait period for confirming PVI. 
Removed references to the Circular Mapping Catheter (25mm), 
not supported in the study. 
Follow Up Schedule:  Allowed for any additional visit and any 
additional procedure (> Day 0). 
Proposed Indication for Use – inclusive of paroxysmal patient 
population. 
Definition of phrenic nerve paralysis clarified. 
Clarified the definitions of enrolled subjects. 
Clarified baseline visit assessments. 
Revised anticoagulation parameters. 
Revised device return process. 
Clarified Adverse Event definitions. 
Clarified device deficiencies. 
Appendix B:  Informed Consent Form (ICF) revised to reflect BSC 
requirements. 

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CEM-A02-02 
Amendment 
03 
005791 
• Update Revision table: 
o in the ‘revision’ column, the version (Amendment #) of 
the previous protocols was added 
• Update sponsor names in section “Summary of the Cryterion 
CE Mark study” to align with the page 1 content 
• Update Table 1 to add POLARx CM-CATH-03 and CM-CATH-04 
device 
• Update of Table 2 to align with text in section 3.3.1 
• Update of section 2.4.1.1 Study Endpoint to align with the 
endpoints as described in section “Summary of the Cryterion 
CE Mark study” 
• Update of the term ‘Cryterion Medical’ throughout the 
document to ‘the sponsor’ 
• Update wording of definitions of a serious adverse event in 
section 5  
• Update death notification timelines in Table 3 and section 5.3 
to be consistent. 
• Addition of device experience reporting timelines in section 
5.4 to match Table 3 
 
 
 

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Table of Contents 
SUMMARY OF CRYTERION CE MARK STUDY ............................................................................... 10 
1 
Introduction ................................................................................................................ 18 
1.1 
Background ................................................................................................................... 18 
2 
The Cryterion Cardiac Cryoablation System (System). ................................................ 23 
2.1 
General Device Description .......................................................................................... 23 
2.2 
Proposed Indication for Use Statement ......................................................................... 23 
2.3 
Clinical Study Objective ............................................................................................... 23 
2.4 
Clinical Study Design ................................................................................................... 23 
2.4.1 
Study Endpoints ...................................................................................................... 24 
2.5 
Clinical Study Design Justification ............................................................................... 27 
2.6 
Clinical Study Scale and Duration ................................................................................ 28 
2.7 
Clinical Study Population ............................................................................................. 28 
2.7.1 
Inclusion Criteria .................................................................................................... 28 
2.7.2 
Exclusion Criteria ................................................................................................... 29 
2.8 
Clinical Study Enrollment Definitions.......................................................................... 30 
2.9 
Subject Withdrawal ....................................................................................................... 31 
3 
Clinical Study Treatments and Follow-up Visits ........................................................... 32 
3.1 
Informed Consent.......................................................................................................... 32 
3.2 
Subject Enrollment and Baseline .................................................................................. 32 
3.3 
Ablation Procedure ....................................................................................................... 33 
3.3.1 
Determination of Left Atrial Thrombus .................................................................. 33 
3.3.2 
Anticoagulation ....................................................................................................... 33 
3.3.3 
Antiarrhythmic Medications (AADs) ..................................................................... 34 
3.3.4 
Venous Access and Trans Septal Puncture ............................................................. 34 
3.3.5 
Pulmonary Vein Mapping with the PolarMap Circular Mapping Catheter ............ 34 
3.3.6 
Steerable Sheath Preparation and Placement .......................................................... 34 
3.3.7 
Cryoablation Balloon Catheter Preparation ............................................................ 35 

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3.3.8 
Mapping and Ablation ............................................................................................ 35 
3.3.9 
Procedure Data Collection ...................................................................................... 39 
3.3.10 Device Returns ........................................................................................................ 40 
3.4 
Follow-Up Procedures .................................................................................................. 40 
3.4.1 
Hospital Discharge .................................................................................................. 41 
3.4.2 
Visits at One Month (30 +/- 7 days) after the Start (Procedure) Date .................... 41 
3.4.3 
Three Month (90 +/- 14 days) after the Start (Procedure) Date (designation in days 
required by Blanked Follow-Up Period and outcome measures) ......................................... 41 
3.4.4 
Six Month Visits (180 +/- 30 days) after the Start (Procedure) Date ..................... 42 
3.4.5 
Twelve Month Visits (360 +/- 30 days) after the Start (Procedure) Date ............... 42 
3.4.6 
Unscheduled (additional) Visits .............................................................................. 42 
4 
Statistical Methods ...................................................................................................... 46 
4.1 
Analysis Population ...................................................................................................... 46 
4.2 
Statistical Analysis for the Study Outcome Measure ................................................... 46 
4.3 
Study Size Justification ................................................................................................. 47 
5 
Adverse Events ............................................................................................................ 47 
5.1 
Adverse Event Reporting requirements ........................................................................ 49 
5.2 
Event Relationship to the Device .................................................................................. 51 
5.3 
Death Notice ................................................................................................................. 52 
5.4 
Device deficiencies. ...................................................................................................... 52 
5.5 
Clinical Events Committee (CEC) ................................................................................ 53 
6 
Risk-Benefit Analysis.................................................................................................... 53 
6.1 
Risks .............................................................................................................................. 53 
6.2 
Benefits ......................................................................................................................... 54 
6.3 
Mitigation of Risks ....................................................................................................... 54 
7 
Data Quality Assurance ............................................................................................... 55 
7.1 
Data Management ......................................................................................................... 55 
7.2 
Subject Identification .................................................................................................... 56 
7.3 
Screen Failure Subjects ................................................................................................. 56 

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7.4 
Subject Study Completion and Withdrawal .................................................................. 56 
7.5 
Subjects Lost-to-Follow-Up.......................................................................................... 56 
7.6 
Confidentiality of Data ................................................................................................. 56 
7.7 
Source Documents ........................................................................................................ 57 
7.8 
Electronic Case Report Forms (eCRFs) ........................................................................ 58 
7.9 
Records Retention ......................................................................................................... 58 
7.10 
Clinical Monitor ............................................................................................................ 59 
7.11 
Clinical Data Monitoring Procedures ........................................................................... 59 
7.12 
Investigator Responsibilities ......................................................................................... 60 
7.13 
Deviations from the Clinical Investigational Plan ........................................................ 60 
7.13.1 Maintaining Records ............................................................................................... 61 
7.13.2 Submitting Reports ................................................................................................. 62 
7.14 
Sponsor’s Responsibilities ............................................................................................ 62 
7.14.1 General Duties ........................................................................................................ 62 
7.14.2 Selection of Investigators ........................................................................................ 63 
7.14.3 Training ................................................................................................................... 64 
7.14.4 Changes in the Clinical Investigational Plan .......................................................... 65 
7.14.5 Withdrawal of Regulatory Approval ...................................................................... 65 
8 
Ethics and Regulatory Compliance .............................................................................. 66 
8.1 
Conduct of the Clinical Study ....................................................................................... 66 
8.2 
Ethics Committee Approval .......................................................................................... 66 
8.3 
Clinical Study Informed Consent Approval ................................................................. 66 
8.4 
Identification and Confidentiality ................................................................................. 66 
8.5 
Site Qualification Visits ................................................................................................ 67 
8.6 
Site Initiation Visits ...................................................................................................... 67 
8.7 
Insurance ....................................................................................................................... 68 
8.8 
Site Audit Plan .............................................................................................................. 68 
8.8.1 
Site Data Audits by Sponsor ................................................................................... 68 
8.8.2 
External Audits ....................................................................................................... 68 

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8.9 
Device Traceability ....................................................................................................... 68 
8.10 
Public Domain Access to the Clinical Study ................................................................ 69 
8.11 
Required Reports .......................................................................................................... 69 
9 
General Considerations ............................................................................................... 69 
9.1 
Discontinuation of the Clinical Study ........................................................................... 69 
9.2 
Use of Information and Publications ............................................................................ 69 
10 
Bibliography ................................................................................................................ 71 
 
 
 

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SUMMARY OF CRYTERION CE MARK STUDY  
 
Study Title 
Cryterion Cardiac Cryoablation CE Mark Study Amendment 
Device Name 
The Cryterion Cardiac Cryoablation System 
Study  
Device 
Components 
The Cryterion Cardiac Cryoablation System consists of: 
The Cryterion Cryoablation Balloon Catheter (PolarX) 
The Cryterion Circular Mapping Catheter (PolarMap) 
The Cryterion Steerable Sheath (PolarSheath) 
The Cryterion SmartFreeze Cryoablation Console 
Cryterion Accessories (connection cables, mechanical & electrical) 
Cryterion Optional Accessories (foot pedal switch, tablet 
interface) 
{Model Numbers are in Table 1 below} 
Indication for 
Use (Proposed) 
The Cryterion Cardiac Cryoablation System is intended for 
cryoablation and electrical mapping of the pulmonary veins for 
pulmonary vein isolation (PVI) in the ablation treatment of atrial 
fibrillation. 
Sponsors 
Cryterion 
Medical, Inc. 
 
 
 
1949 Palomar Oaks 
Way 
Suite 100 
Carlsbad, CA. 92011 
USA 
Boston Scientific 
Corporation 
 
 
4100 Hamline  
Avenue N 
Arden Hills, 
MN 55112-5798, USA 
Boston 
Scientific 
International 
S.A. 
 
Le Val Saint-Quentin, 
2 rue René Caudron, 
78960 Voisins le 
Bretonneux, France   
Boston 
Scientific Pty. 
Ltd. 
 
 
 
Level 5 
247 Coward St. 
Mascot 
NSW 
Australia 2020 
Study  
Objective 
The clinical study objective is to demonstrate the acute and 12 
months safety and performance of the Cryterion Cardiac Cryoablation 
System when used as intended. 
Study  
Design 
Multi-center, open label, prospective, open enrollment study to 
document the safety and performance of the Cryterion Cardiac 
Cryoablation System. 

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Primary 
Effectiveness 
Endpoint 
Acute Procedural Success (APS) 
Acute procedural success is defined as the documentation of 
pulmonary vein isolation for each of the targeted veins at the end of 
the first protocol-defined (index) cryoablation procedure. 
Documentation will be completed with the Cryterion Circular Mapping 
Catheter to confirm PVI. The physician should confirm and document 
entrance and exit block by standard of care pacing maneuvers during 
the index procedure. 
 
Additional 
Effectiveness 
Endpoint 
Treatment Success 
Treatment success at 12 months will be determined by evaluating the 
proportion of subjects free from symptomatic atrial arrhythmias. A 
treatment failure is defined as a subject being an acute procedural 
failure, having more than one repeat procedure during the 90-day 
blanking period or having a documented, symptomatic episode(s) of 
atrial fibrillation or atrial tachycardia, between 91 and 365 days post 
index procedure. Occurrence or recurrence of a right atrial arrhythmia 
is not considered a treatment failure post the 90-day blanking period. 
Assessments will be made via 12-lead electrocardiogram 
measurements at 3, 6 and 12-month visits (including unscheduled 
visits for symptomatic atrial arrhythmias). In addition, a 24-hour 
Holter (wearable arrhythmia monitor/ patch) will be assessed at the 3, 
6 and 12-month visits (including unscheduled visits for symptomatic 
atrial arrhythmias). 
Primary safety 
endpoint 
Safety endpoint is assessed by freedom from device or procedure 
related serious adverse events (referred to as Major Adverse Events, 
MAE) occurring up to 12 months post index procedure. MAEs include 
the following: 
• Death 
• Myocardial infarction 
• Cardiac perforation/ pericardial tamponade 
• Cerebral infarct or systemic embolism 
• Major bleeding requiring transfusion of blood products 
• Mitral or tricuspid valvular damage 
• Phrenic nerve palsy causing persistent diaphragmatic paralysis 
• Symptomatic pulmonary vein stenosis 
• Atrio-esophageal fistula 
• Air embolism leading to a life-threatening event such as a 
ventricular arrhythmia, stroke or myocardial infarction 
• Any other serious or non-serious adverse device effects (SADEs 
or ADEs)  

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Sample  
Size 
Up to 100 treated subjects 
Study locations 
Up to 10 clinical sites in the EU and NZ 
Study 
Duration 
Enrollment is expected to take 7 - 9 months. Follow-up will occur at 
discharge, and 1, 3, 6 and 12 months. 
Secondary 
Endpoints  
Secondary endpoints include: 
• All Procedure and device related adverse events 
• Documentation of all PVs that demonstrate isolation 
immediately post ablation and then show reconnection during 
entrance/exit block testing 
• Operator’s assessment of handling characteristics (through a 
System Performance Questionnaire) compared to 
commercially available sheaths circular mapping catheters and 
balloon ablation technologies 
Inclusion  
Criteria 
Subjects  
must: 
 
• 
Male or female between the ages of 18 and 80 years  
• 
Currently scheduled for a de novo ablation of paroxysmal 
atrial (PAF) defined as AF with self-terminating episodes 
lasting no longer than 7 continuous days. 
• 
Willingness, ability and commitment to participate in baseline 
and follow-up evaluations for the full duration of the clinical 
study. 
• 
Willing and able to give informed consent 

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Exclusion  
Criteria 
Subjects  
must not: 
 
Exclusion Criteria 
EC 1 In the opinion of the Investigator, any known 
contraindication to an AF ablation, TEE, or anticoagulation 
EC 2 Any duration of continuous AF lasting longer than 7 days  
EC 3 History of previous left atrial ablation or surgical treatment 
for AF/AFL/AT  
EC 4 Atrial fibrillation secondary to electrolyte imbalance, 
thyroid disease, or any other reversible or non-cardiac 
cause 
EC 5 More than four (4) electrical cardioversions in the year 
prior to enrollment excluding cardioversions performed 
within 24 hours of arrhythmia onset. 
EC 6 Structural heart disease or implanted devices as described 
below: 
a. Left ventricular ejection fraction (LVEF) < 40% based on 
the most recent TTE (≤ 6 months) 
b. Left atrial diameter > 50 mm or a left atrial volume 
index >50 ml/m2 based on the most recent TTE (≤ 6 
months, one measurement of the two being sufficient) 
c. An implanted pacemaker or ICD 
d. Previous cardiac surgery: ventriculotomy, or atriotomy 
(excluding atriotomy for CABG) 
e. Previous cardiac valvular surgical or percutaneous 
procedure, or prosthetic valve 
f. Interatrial baffle, closure device, patch, or PFO occluder 
g. Presence of a left atrial appendage occlusion device 
h. Presence of any pulmonary vein stents 
i. Coronary artery bypass graft (CABG) or PTCA procedure 
within the last 90 days. 
j. Unstable angina or ongoing myocardial ischemia 
k. Previous myocardial infarction (≤ 6 months) 
l. Moderate or severe mitral insufficiency noted on the 
most recent TTE (≤ 6 months) 
EC 7 Any previous history of cryoglobulinemia 
EC 8 History of blood clotting or bleeding disease 
EC 9 ANY prior history of documented cerebral infarct, TIA or 
systemic embolism (excluding a post-operative DVT) 
EC 10 Pregnant or lactating (current or anticipated during study 
follow up) 
EC 11 Current enrollment in any other study protocol where 
testing or results from that study may interfere with the 
procedure or outcome measurements for this study 
EC 12 Any other condition that, in the judgment of the 

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investigator, makes the subject a poor candidate for this 
procedure, the study or compliance with the protocol 
(includes vulnerable subject population, mental illness, 
addictive disease, terminal illness with a life expectancy of 
less than two years, extensive travel away from the 
research center) 
 
Secondary Screening: subject or conducted per physician 
discretion according to institution’s SOC 
 
EC 13 Any pulmonary vein diameter >30 mm as evidenced by CT 
scan, LA venogram or intracardiac echo (ICE) 
EC 14 A common left pulmonary vein ostium as evidenced by CT 
scan, LA venogram or intracardiac echo that in the 
judgment of the investigator makes the subject a poor 
candidate for this study 
Data  
Collection at 
Follow-up 
 
See Table 2 below for follow-up schedule 
 
 
 
 

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2All subsequent visits are counted in days from the index procedure

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1 INTRODUCTION 
1.1 
Background  
Supraventricular tachycardias (SVTs) are a collective group of arrhythmias that 
originate superior to the ventricles and most notably in the upper chambers 
(atria) of the heart. SVTs can cause the heart to beat very rapidly or erratically 
with rates more than 100 beats per minute (bpm). The arrhythmia is generally 
well tolerated but may produce clinical symptoms such as light-headedness, 
chest palpitations, shortness of breath, fatigue, and/ or exercise intolerance. In 
more serious SVTs, the heart may beat less efficiently, leading to potentially 
inadequate blood supply to vital organs and formation of thrombus in the heart, 
thus increasing the risk of systemic embolic events, including stroke.  
The most common forms of SVTs include atrial fibrillation (AF), and a variety of 
non-AF rhythms, including atrial flutter (AFL), atrial tachycardia (AT), and 
atrioventricular (AV) nodal reentrant tachycardia (AVNRT). 
Atrial Fibrillation 
Atrial fibrillation (AF) is among the most prevalent arrhythmias in the world today 
affecting approximately 33.5 million subjects worldwide.1 The age of subjects 
with AF is steadily rising and now averages between 75 and 85 years of age. AF is 
associated with a five-fold risk of stroke, a three-fold incidence of congestive 
heart failure, and higher mortality.2 
Symptoms arise from the rapid, irregular rhythm as well as cardiac hemodynamic 
changes related to uncoordinated atrial contractions. These uncoordinated 
contractions also allow blood to pool in the atria and may ultimately lead to 
thromboembolism and stroke. 
AF is characterized by a chaotic contraction of the atrium in which an 
electrocardiogram (ECG) recording is necessary to diagnose the arrhythmia. Any 
arrhythmia that has the ECG characteristics of AF and lasts sufficiently long 
 
1  Chugh S, Havmoeller R, Narayanan K, et al. Worldwide Epidemiology of Atrial Fibrillation: A Global 
Burden of Disease 2010 Study.  CIRC. 2014;129(8):837-847. 
2  Camm AJ, et al. 2012 focused update of the ESC Guidelines for the management of atrial 
fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation--developed 
with the special contribution of the European Heart Rhythm Association. Europace, 2012 Oct; 
14(10):1385-413 

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enough for a 12-lead ECG to be recorded, or at least 30 seconds on a rhythm strip, 
should be considered an AF episode.3,4 
The diagnosis requires an ECG or rhythm strip demonstrating: (1) irregular RR 
intervals (in the absence of complete AV block), (2) no distinct P waves on the 
surface ECG, and (3) an atrial cycle length (when visible) that is usually variable 
and less than 200 milliseconds.3 
AF can be characterized into four classifications: 
1. Paroxysmal AF (PAF) is defined as recurrent AF (≥ two episodes) that 
terminates spontaneously or with intervention within seven days of onset.3  
2. Early Persistent AF is defined as AF that is sustained for seven days but is less 
than 3 months in duration.3   
3. Persistent AF is defined as continuous AF that is sustained beyond seven 
days.  Long-standing persistent AF is defined as continuous AF of greater 
than one year’s duration.3  
4. Permanent AF is defined as AF in which the presence of the AF is accepted by 
the subject (and physician). Within the context of any rhythm control 
strategy, including catheter ablation, the term permanent AF is not 
meaningful. The term permanent AF represents a joint decision by the 
subject and a physician to cease further attempts to restore and/ or maintain 
sinus rhythm at a point in time.3 
For many years, three major schools of thought competed to explain the 
mechanism(s) of AF: multiple random propagating wavelets, focal electrical 
 
3  Calkins H, Hindricks, G, Cappato, R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert 
consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. Vol. 10, 
October 2017 
4 Camm AJ, Kirchhof P, Lip GY et al. Guidelines for the management of atrial fibrillation: the Task 
Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur 
Heart J. Oct 2010;31(19):2369–2429 
 

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discharges, and localized reentrant activity with fibrillatory conduction.5,6,7,8,9  
Significant progress has been made in defining the mechanisms of initiation and 
perpetuation of AF. One of the most important breakthroughs was the 
recognition that, in a subset of subjects, AF was triggered by a rapidly firing focus 
and could be “cured” with a localized catheter ablation procedure.10,11 This 
landmark observation caused the electrophysiology (EP) community to refocus 
its attention on the pulmonary veins (PVs) and the posterior wall of the left atrium 
(LA), as well as the autonomic innervation in that region. It also reinforced the 
concept that the development of AF requires a “trigger” and an anatomic or 
functional substrate capable of both initiation and perpetuation of AF. 
Sustained high rates in the atrium and/ or the presence of heart disease are 
associated with structural and electrophysiological remodeling of the atria and 
can alter the substrate even further, helping to perpetuate AF.12 Atrial fibrillation 
can also be the result of preexisting atrial disease.  Although much has been 
learned about the mechanisms of AF, they are not completely understood.  
Because of this, in the great majority of AF subjects, it is not yet possible to 
precisely tailor an ablation strategy to an AF mechanism. 
3D Electroanatomic Mapping 
In the interventional treatment of arrhythmias (ablation), the electrical circuits or 
pathways may be “mapped” by moving heart catheters to various locations 
 
5 Jalife J, Berenfeld O, Mansour M. Mother rotors and fibrillatory conduction: a mechanism of atrial 
fibrillation. Cardiovasc Res. May 2002;54(2):204–216. 
6 Nattel S. New ideas about atrial fibrillation 50 years on. Nature. Jan 10 2002; 415(6868):219–226. 
7 Dobrev D, Voigt N,Wehrens XH. The ryanodine receptor channel as a molecular motif in atrial 
fibrillation: pathophysiological and therapeutic implications. Cardiovasc Res. Mar 1 2011;89(4):734–
743. 
8 Schotten U, Verheule S, Kirchhof P, Goette A. Pathophysiological mechanisms of atrial fibrillation: a 
translational appraisal. Physiol Rev. Jan 2011;91(1):265–325. 
9 Wakili R, Voigt N, Kaab S, Dobrev D, Nattel S. Recent advances in the molecular pathophysiology 
of atrial fibrillation. J Clinical Invest. Aug 1 2011;121(8):2955–2968 
10 Jais P, Haissaguerre M, Shah DC et al. A focal source of atrial fibrillation treated by discrete 
radiofrequency ablation. Circulation. Feb 4 1997;95(3):572–576. 
11 Haissaguerre M, Jais P, Shah DC et al. Spontaneous initiation of atrial fibrillation by ectopic beats 
originating in the pulmonary veins. N Engl J Med. Sep 3 1998; 339(10):659–666. 
12 Everett TH 4th, Wilson EE, Verheule S, Guerra JM, Foreman S, Olgin JE. Structural atrial 
remodeling alters the substrate and spatiotemporal organization of atrial fibrillation: a comparison in 
canine models of structural and electrical atrial remodeling. Am J Physiol Heart Circ Physiol. Dec 
2006;291(6):H2911–2923 

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within the presumed pathway and measuring the timing of the conduction. In the 
past twenty years, more intricate mapping systems have been developed to 
provide electrical as well as geometrical representation of the chambers of the 
heart. Referred to as three dimensional (3D) electroanatomic mapping systems, 
the development of these systems has progressed rapidly and now include both 
contact and noncontact mapping systems. During an ablation procedure, these 
devices can provide better diagnostic value and guide ablation strategies.13 
Additionally, electromagnetic navigation systems have been shown to 
substantially reduce the fluoroscopy time required for AF ablation.14,15,16 In a 
recent worldwide survey of AF ablation methods, nearly 50% of procedures 
included the navigation means.17 
RF Ablation Catheters 
Radiofrequency (RF) ablation remains the energy source of choice for ablation. In 
the worldwide survey of AF ablation methods, 98% of ablations were completed 
with RF energy while < 2% completed a thermal injury to the endocardium with 
cryoablation.17 This included both irrigated and non-irrigated RF ablation 
catheters. 
Force Sensing RF Ablation Catheters 
To improve on ablation lesion characteristics and durability, two new catheters 
have recently been developed. Described as “contact-force sensing” catheters, 
these new designs remove much of the operator dependence on the force 
applied to the endocardial surface during an ablation. Recent publications have 
 
13 Hindricks G, Willems S, Kautzner J, De Chillou C, Wiedemann M, Schepel S, Piorkowski C, Risius 
T, Kottkamp H; EuroFlutter Investigators. Effect of electroanatomically guided versus conventional 
catheter ablation of typical atrial flutter on the fluoroscopy time and resource use: a prospective 
randomized. J Cardiovasc Electrophysiol. 2009 Jul;20(7):734-40.  
14 Sporton SC, Earley MJ, Nathan AW, Schilling RJ. Electroanatomic versus fluoroscopic mapping for 
catheter ablation procedures: a prospective randomized study. J Cardiovasc Electrophysiol. 2004 
Mar;15(3):310-5.  
15 Kottkamp H, Hügl B, Krauss B, Wetzel U, Fleck A, Schuler G, Hindricks G. Electromagnetic versus 
fluoroscopic mapping of the inferior isthmus for ablation of typical atrial flutter: A prospective 
randomized study. Circulation. 2000 Oct 24;102(17):2082-6.  
16 Smeets JL, Ben-Haim SA, Rodriguez LM, Timmermans C, Wellens HJ. New method for 
nonfluoroscopic endocardial mapping in humans: accuracy assessment and first clinical results. 
Circulation. 1998 Jun 23;97(24):2426-32.  
17 Cappato R, Calkins H, Chen SA, et al. Updated Worldwide Survey on the Methods, Efficacy, and 
Safety of Catheter Ablation for Human Atrial Fibrillation. Circ Arrhythmia Electrophysiology. 
2010;3:32-38. 

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demonstrated improvement in PV isolation and longer-term outcomes for 
ablation when the percentage of time the ablation catheter is in stable contact is 
increased.18,19,20,21 
Cryoablation 
Cryoablation has gained significant popularity and utilization worldwide. With the 
understanding the pulmonary veins may be the “cornerstone” of ablation 
strategies, a cryo balloon has been developed to provide a “single shot” therapy 
for isolation of the pulmonary veins. By navigating the balloon to the ostium of 
the PV and occluding flow, a PV may be isolated with a single cryoablation of 3 - 
4 minutes. The currently approved technology (Artic Front™/ Arctic Front 
Advance™ Cryoablation Balloon, Medtronic®) has completed two landmark 
studies demonstrating efficacy for PAF management of approximately 70% and 
65% respectively.22,23 
Complications arising from cryoablation are consistent with those of heat-based 
therapies. Additionally, as the balloon is placed in the right-sided PVs and near 
the phrenic nerve, diaphragm paralysis, (both transient and permanent), has 
been reported. To mitigate this risk, pacing maneuvers and continuous analysis 
of diaphragmatic movement has been used. 
 
 
18  Sohn C, Williams S, Chubb H, et al.  Catheter Contact Force: A Review of Emerging Techniques 
and Technologies in AF Ablation. 
19 Natale A, Reddy V, Monir G, et al. Paroxysmal AF Ablation with a Contact Force Sensing 
Catheter.  Journal American College of Cardiology 2014;64:647-56. 
20 Reddy V, Dukkipati S, Neuzil P, et al. Randomized, Controlled Trial of the Safety and 
Effectiveness of a Contact Force-Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial 
Fibrillation. Circulation. 2015;132:907-915. 
21 Barnett A, Bahnson T, Piccini J.  Recent Advances in Lesion Formation for Catheter Ablation of 
Atrial Fibrillation. Circ Arrhythmia Electrophysiology, June 2016;9 e003299. 
22 Packer D, Kowal R, Wheelan K, Irwin J, et al.  Cryoballoon Ablation of Pulmonary Veins for 
paroxysmal Atrial Fibrillation. JACC.2013;61:1713-23. 
23 Kuck KH, Brugada J, Fu¨ rnkranz A, Metzner A, Ouyang F, Chun KR, Elvan A, Arentz T, 
Bestehorn K, Pocock SJ, Albeneque JP, Tondo C, for the FIRE AND ICE Investigators. 
Cryoballoon or radiofrequency ablation for paroxysmal atrial fibrillation. N Engl J Med 
2016;374:2235–2245. 

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2 THE CRYTERION CARDIAC CRYOABLATION SYSTEM (SYSTEM).  
2.1 
General Device Description 
The Cryterion Cardiac Cryoablation System is designed to thermally ablate cardiac 
tissue in the management of atrial fibrillation. The components and accessories 
for the system are listed in Table 1. A detailed device description is provided in 
Appendix A.   
2.2 
Proposed Indication for Use Statement  
The Cryterion Cardiac Cryoablation System is indicated for cryoablation and 
electrical mapping of the pulmonary veins for pulmonary vein isolation (PVI) in 
the ablation treatment of Paroxysmal Atrial Fibrillation (PAF). 
2.3 
Clinical Study Objective 
The clinical study objective is to demonstrate the acute and 12 months safety and 
performance of the Cryterion Cardiac Cryoablation System when used as 
intended.  
2.4 
Clinical Study Design 
The study is a non-randomized, open label, prospective multi-center, clinical 
study designed to collect long-term (1 year), system-related, clinical and subject 
reported outcome data from subjects indicated for a de novo ablation of 
paroxysmal atrial fibrillation and treated with the Cryterion Cardiac Cryoablation 
System and components including the SmartFreeze Cryo-console, the 
Cryoablation Balloon Catheter, and the Circular Mapping catheter.  
This protocol is an amendment of the original version initiated in May 2018 
designed for the purpose of obtaining CE mark and is intended to prolong the 
follow-up period to 12 months and extend the number of enrolled subjects from 
30 to 100.   
Subjects will be followed for 12 months by each clinical center with specific 
scheduled visits to detect recurrent AF (Detectable AF) and adverse events (AEs). 

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Safety endpoint is assessed by freedom from device or procedure related serious 
adverse events (referred to as Major Adverse Events, MAE) at 12 months post-
procedure.  
MAEs include the following:   
• Death 
• Myocardial infarction 
• Cardiac perforation/ pericardial tamponade 
• Cerebral infarct or systemic embolism 
• Major bleeding requiring transfusion of blood products 
• Mitral or tricuspid valvular damage 
• Phrenic nerve damage causing persistent diaphragmatic 
paralysis* 
• Symptomatic pulmonary vein stenosis 
• Atrio-esophageal fistula 
• Air embolism leading to a life-threatening event such as a 
ventricular arrhythmia, stroke or myocardial infarction 
• Any other serious or non-serious adverse device effects 
(SADEs or ADEs)  
*Note: according to the consensus document definition3: Phrenic nerve paralysis is 
defined as absent phrenic nerve function as assessed by a sniff test. A phrenic nerve 
paralysis in this study is considered to be permanent when it is documented to be 
present at 12 months following ablation. 
2.4.1.2 Primary effectiveness endpoint: acute procedural success. 
 
The Primary Effectiveness Endpoint is the rate of successful pulmonary vein 
electrical isolation with confirmation of entrance and exit block achieved with the 
Cardiac Cryoablation System (Acute procedural success).  
Acute procedural success is defined as the documentation of pulmonary vein 
isolation following the last cryo application for each of the targeted veins. 
Demonstration of electrical isolation in ≥ 3 PVs or their anomalous equivalents at 
the end of the first protocol-defined cryoablation procedure Documentation will 
be completed with the Cryterion Circular Mapping Catheter to confirm PVI. The 
physician should confirm and document entrance and exit block by standard of-
care pacing maneuvers during the index procedure. 
 
 

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2.4.1.3 Additional effectiveness endpoint: 12 months treatment success 
 
Treatment success is defined as the proportion of subjects free from symptomatic 
atrial arrhythmias at 12 months. A treatment failure is defined as a subject being 
an acute procedural failure, having more than one repeat procedure during the 
90-day blanking period or having a documented, symptomatic episode(s) of atrial 
fibrillation or atrial tachycardia, between 91 and 365 days post index procedure 
(windows allowed per protocol as shown in Table 2 included). Occurrence or 
recurrence of a right atrial arrhythmia is not considered a treatment failure post 
the 90-day blanking period. 
 
 
2.4.1.4 Secondary endpoints 
 
Secondary Endpoint Measurements will include: 
•  All Procedure and device related adverse events*  
• Documentation of all targeted PVs that demonstrate 
isolation immediately post ablation and then show 
reconnection during entrance/exit block testing 
• Recording of time to demonstration of PVI using the 
Circular Mapping catheter following the initiation of a 
freeze cycle 
• 
Operator’s assessment of handling characteristics with a System 
Performance Questionnaire**  
 * be accessed directly from the clinical database (eCRFs hosted on IBM Clinical platform) 
** The System Performance Questionnaire is included in the study clinical database and 
includes questions to the operator to assess quality characteristics of the products, alone 
and compared to commercially available cryoballoon ablation technologies and circular 
mapping catheters. The system performance questionnaire will be used with all new 
clinical users for the first five (5) cases performed with the Cryterion System. After the 
first 5 cases, users can use the questionnaire to provide specific product feedback related 
to user experience(s) on an as needed basis (for example: the ability of the cryoablation 
system to deal with tortuous anatomy of the LA/PVs).  In case the investigator reports 

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quality issues in the questionnaire, he should consider if needed, to enter a device 
deficiency (See section 5.4) 
 
 
 
2.5 
Clinical Study Design Justification  
PAF is a recurring arrhythmia that predisposes subjects to embolic phenomena 
such as stroke. Available treatments include medication, various RF ablation 
procedures in the atria and PVs, atrioventricular (AV) nodal ablation with 
pacemaker implantation, and open-heart ablation and surgery (e.g. maze 
procedure). All these treatments have significant failure rates as well as the 
potential for significant morbidity. 
Cryoablation offers potential advantages. It may have a lower risk of creating 
endocardial thrombus, PV stenosis and permanent nerve damage than heat-based 
ablation. Tissue cooling during cryoablation can be rapidly reversed, allowing 
minimization of unwanted damage while monitoring for adverse effects to 
conduction tissue and adjacent nerves. 
The study is designed as a non-randomized, multicenter study to further evaluate 
the System in the cryoablation of paroxysmal atrial fibrillation. The subject 
population has been chosen based on the ability to assess both the cryoablation 
balloon and the mapping catheter in typical left atrial anatomy.   This study was 
originally designed as a protocol for acute safety and effectiveness evaluation in 
30 subjects with a follow up of one month, to support submission for obtaining CE 
mark. In agreement with the Notifying Body, in order to generate evidence of 
chronic safety and effectiveness   the protocol was amended to increase the 
sample size to 100 subjects and extend the follow up to 12 months. 
De novo subjects are selected as most representative of the population where a 
cryoballoon may first be used for PVI. To determine the performance of the 
Cryoablation Balloon Catheter, an analysis of the ability to electrically isolate a 
targeted PV acutely will be completed. PVI measurements will be taken post cryo 
application  to assess entrance and exit block. 
 
Chronic effectiveness data will be analyzed through 12 months to determine the 
long-term performance of the System. In addition, adverse events will be collected 
through the follow-up period. Adverse events rates collected in the study maybe 

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compared to rates from current market approved AF ablation systems and 
available from literature. 
The Cryterion Cardiac Cryoablation System is a new alternative to the existing 
Medtronic® Cryoablation Balloon Arctic Front Advance™ technology for the 
ablation treatment of atrial fibrillation. Descriptive statistics will be utilized to 
analyze all long-term safety and performance data from this study.  
The potential benefits of this study are that cryoablation will reduce or eliminate 
targeted arrhythmias while minimizing adverse events such as thromboembolism, 
cardiac perforation, PV stenosis or phrenic nerve damage. 
The study protocol and procedures have been designed to minimize risks for study 
subjects, including the selection and training of qualified Investigators and 
investigational sites and careful clinical monitoring of study subjects. 
2.6 
Clinical Study Scale and Duration 
The present study plans to enroll up to 100 subjects. Enrollment of the first 30 
subjects (for the CE study) has concluded in October 2018. Enrollment of the 
additional 70 subjects is expected to take an additional 7-9 months. Follow-up for 
all 100 subjects will occur at discharge and 1, 3, 6 and 12 months resulting in an 
approximate total study duration of 23-30 months.   
2.7 
Clinical Study Population 
The subject population will consist of men and women between the ages of 18 - 
80 years of age scheduled for a de novo percutaneous procedure to ablate atrial 
fibrillation (AF). 
A potential study subject will meet all the following inclusion criteria and none of 
the exclusion criteria. 
2.7.1 
Inclusion Criteria 
IC 1 
Male or female between the ages of 18 - 80 years old. 
IC 2 
Currently scheduled for a de novo ablation of atrial 
fibrillation (AF) defined as AF with self-terminating episodes 
lasting no longer than 7 continuous days (PAF).  
IC 3 
Willingness, ability, and commitment to participate in 
baseline and follow-up evaluations for the full duration of 
the clinical study. 

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IC 4 
Willing and able to give informed consent. 
2.7.2 
Exclusion Criteria 
EC 1 In the opinion of the Investigator, any known contraindication 
to an AF ablation, TEE, or anticoagulation 
EC 2 Any duration of continuous AF lasting longer than 7 days  
EC 3 History of previous left atrial ablation or surgical treatment 
for AF/AFL/AT  
EC 4 Atrial fibrillation secondary to electrolyte imbalance, thyroid 
disease, or any other reversible or non-cardiac cause 
EC 5 More than four (4) electrical cardioversions in the year prior 
to enrollment excluding cardioversions performed within 24 
hours of arrhythmia onset. 
EC 6 Structural heart disease or implanted devices as described 
below:  
a. 
Left ventricular ejection fraction (LVEF) < 40% based 
on TTE based on most recent TTE (≤ 6 months) 
b. 
Left atrial size > 50mm or left atrial volume index >50 
ml/m2 based on most recent TTE (≤ 6 months, one 
measurement of the two being sufficient) 
c. 
An implanted pacemaker or ICD 
d. 
Previous 
cardiac 
surgery: 
ventriculotomy, 
or 
atriotomy (excluding atriotomy for CABG)  
e. 
Previous cardiac valvular surgical or percutaneous 
procedure, or prosthetic valve 
f. 
Interatrial baffle, closure device, patch, or PFO 
occluder 
g. 
Presence of a left atrial appendage occlusion device 
h. 
Presence of any pulmonary vein stents 
i. 
Coronary artery bypass graft (CABG) or PTCA 
procedure within the last 30 days 
j. 
Unstable angina or ongoing myocardial ischemia 
k. 
Previous myocardial infarction (≤ 6 months) 
l. 
Moderate or severe mitral insufficiency noted on 
baseline TTE (≤ 6 months) 
EC 7 
Any previous history of cryoglobulinemia 
EC 8 
History of blood clotting or bleeding disease 

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EC 9 
ANY prior history of documented cerebral infarct, TIA or 
systemic embolism (excluding a post-operative DVT) 
EC 10 Pregnant or lactating (current or anticipated during study 
follow up) 
EC 11 Current enrollment in any other study protocol where 
testing or results from that study may interfere with the 
procedure or outcome measurements for this study 
EC 12 Any other condition that, in the judgment of the 
investigator, makes the subject a poor candidate for this 
procedure, the study or compliance with the protocol 
(includes vulnerable subject population, mental illness, 
addictive disease, terminal illness with a life expectancy of 
less than two years, extensive travel away from the research 
center) 
 
Secondary Screening: subject or conducted per physician discretion according to 
institution’s SOC 
  
EC 1 
Any pulmonary vein diameter >30 mm as evidenced by CT scan, LA 
venogram or intracardiac echo (ICE) 
EC 2 
A common long left pulmonary vein ostium as evidenced by 
CT scan, LA venogram or ICE that in the judgment of the 
investigator makes the subject a poor candidate for this 
study  
2.8 
Clinical Study Enrollment Definitions 
For the purposes of this clinical study, the following definitions regarding the 
status of a subject will apply: 
Enrolled Subject - Any subject who has signed an informed consent form (ICF) 
Consent Ineligible Subject – Any subject who has signed the informed consent but 
is found not to meet all the inclusion/exclusion criteria. This includes a subject 
who has signed an informed consent form but may be excluded based on the 
results of the pre-procedure TEE or intracardiac echocardiogram (ICE) evaluation 
of the left atrial appendage (LAA) and/or PV anatomy. In the event these Subjects 
completed a trans-septal puncture, they will be followed through discharge for 

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the recording of any procedure related adverse events.  These patients will not 
count towards the enrollment ceiling and will not be considered for the primary 
endpoints analysis. 
Intent Subject – Any subject who has signed an informed consent form (ICF) and 
is deemed study eligible by meeting all the inclusion and none of the exclusion 
criteria but does not undergo the ablation procedure. This patient will be 
withdrawn from the study. Data will be collected up to the point of withdrawal, 
will not count towards the enrollment ceiling and will not be considered for 
primary endpoints analysis. 
Attempt Subject - Any subject who has signed an informed consent form (ICF) and 
is deemed study eligible by meeting all the inclusion and none of the 
exclusion/criteria and undergoes the ablation procedure with any of the 
investigational device entered in the patients' body but no energy is delivered to 
the PVs. This patient will be followed through the 30 days follow up then 
withdrawn from the study. Data will be collected up to the point of withdrawal, 
will not count towards the enrollment ceiling and will not be considered for 
primary endpoints analysis. 
Treated Subject – Any screened subject who completes the ablation procedure 
to the point that any of the investigational products are introduced into the body 
and Cryo-energy is delivered. Enrolled subjects will be followed for all study 
outcome measures for the full duration of the clinical study.  
2.9 
Subject Withdrawal 
Individual subjects may withdraw their consent to participate in the study at any 
time. Also, an Investigator may discontinue a subject’s participation in the study 
at any time to protect the safety, rights, or welfare of the subjects.   
Subjects missing follow-up visits will not be considered lost to follow-up until 
adequate attempts to contact the subject have been made by telephone, e-mail, 
and/ or certified/ registered letter. “Adequate attempts” is defined as at least 
three documented communication attempts (phone or email) with at least two 
attempts by phone. 
If a subject withdraws from the clinical investigation, the reason(s) shall be 
reported. All open reportable Adverse Events should be closed or documented as 
chronic. If withdrawal is due to problems related to investigational device safety 

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or performance, the investigator shall ask for the subject’s permission to follow 
his/her status/condition outside of the clinical study. 
All subject withdrawals must be documented on the CRF Exit form and in subject’s 
medical record including the reason for study withdrawal. No more data will be 
captured after point of withdrawal. 
3 CLINICAL STUDY TREATMENTS AND FOLLOW-UP VISITS 
3.1 
Informed Consent 
Informed consent shall be obtained in writing from the subject following the 
process described in ISO 14155:2011. It is the responsibility of the Investigator to 
give each subject full and adequate verbal and written information regarding all 
aspects of the study procedure, device, and associated risks. A signed, informed 
consent form (ICF) must be obtained from the subject before any study-related 
procedures or data collection. The subject must sign and date the informed 
consent form prior to enrollment.  Failure to provide informed consent renders 
the subject ineligible for the study. This form or a modification of it must have 
prior approval of the study site’s Investigational Review Board or Ethics 
Committee prior to obtaining subject consent. The ICF must be signed by the 
subjects (or they legally authorized representative). The Investigator (or 
designee) must also sign the ICF as evidence the proper information regarding 
the study was provided. The original signed ICF is filed in the subject’s study 
records with one copy placed in the subject’s medical notes and one copy 
provided to the subject. 
3.2 
Subject Enrollment and Baseline  
For enrolled subjects, demographic data and medical history data will be 
collected, including: 
• History of AF and other arrhythmias, including date of first 
AF diagnosis and number of cardioversions in the last 12 
months. 
• Medication history including AADs and anticoagulation 
• available 12 Lead EGC  
• DC Electro-cardioversion (DCCV) history 
• Information supportive of determining a CHADS2 score 

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• Most recent (≤ 6 months) transthoracic echocardiogram 
(TTE) will be reviewed to document: 
• Left atrial size or volume 
• Left ventricular ejection fraction 
• Severity of any valvular heart disease 
The subject will undergo a baseline visit that will include Physical assessment 
and ECG.   
CT Scan, TEE, ICE or pulmonary venogram will be used to assess pulmonary 
vein anatomy and diameters and evidence of left-atrial thrombus according 
to table 2 Follow up schedule.  
Additional testing: 
• Pregnancy test (if applicable) 
• Routine standard of care laboratory and x-ray tests for 
pre-ablation work-up 
3.3 
Ablation Procedure 
3.3.1 
Determination of Left Atrial Thrombus 
Determination of any left atrial or left atrial appendage thrombus requires the 
use of either a TEE/CT scan performed within seventy-two (72) hours prior to the 
ablation procedure or an ICE performed during the procedure once vascular 
access is obtained. Proper placement of the ICE catheter for LAA visualization 
should follow the Investigator’s standard of care. If any evidence of atrial 
thrombus is discovered, the procedure will not be performed at that time. The 
subject will be considered a screen failure and exited from the study.  
3.3.2 
Anticoagulation 
Use of anticoagulation leading up to the procedure should be dictated by 
standard of care for the institution. During the ablation procedure, an Activated 
Clotted Time (ACT) > 300 seconds should be achieved before the trans septal 
puncture is performed and immediately followed by an intravenous (IV) heparin 
bolus with repeat heparin administration, administered as necessary, to achieve 
an ACT greater than 350 seconds prior to ablation. Once a therapeutic ACT has 
been achieved, the activated clotting time (ACT) shall be monitored and recorded 
every thirty (30) minutes throughout the procedure to maintain the required 

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level. If the ACT value decreases below 350 seconds, additional heparin should be 
given, and the procedure may continue at the discretion of the investigator.   
Upon removal of the catheters and the trans septal sheath from the left atrium, 
IV heparin may be discontinued. The vascular access sheaths will be removed 
when the ACT reaches a clinically acceptable level. The use of protamine to 
reverse heparin effects is at the discretion of the Investigator. Continuation of all 
oral anticoagulation should follow the standard-of-care for the institution. 
Anticoagulation medications shall be documented on the Concomitant 
Medication eCRFs. 
3.3.3 
Antiarrhythmic Medications (AADs) 
The use of oral antiarrhythmic medications (AADs) leading up to an ablation 
procedure is at the discretion of the Investigator.   
3.3.4 
Venous Access and Trans Septal Puncture 
The placement of venous introducer sheaths should follow the institution’s 
standard-of-care for an AF ablation procedure.   
A single or double trans-septal (TS) puncture is performed. One left atrial sheath 
compatible with the Cryoablation Balloon is required. Methods to perform the TS 
puncture shall follow the institution’s standard-of-care. It is recommended the 
initial sheath placement into the left atrium is appropriately sized to 
accommodate the mapping catheter. Sizing up to the Cryterion sheath should 
occur following the initial PV mapping. 
Since the protocol requires a large bore sheath and catheter exchanges in the left 
atrium, there is an increased risk of air emboli. Left atrial sheath management of 
flushing and fluid infusion shall meticulously follow the lab’s standard-of-care and 
applicable Instructions for use (IFU).   
3.3.5 
Pulmonary Vein Mapping with the PolarMap Circular Mapping 
Catheter 
Prior to the introduction of the Cryterion PolarX Cryoablation Balloon Catheter, 
baseline mapping of the pulmonary veins must occur using the PolarMap 
Mapping Catheter. Each targeted vein must have a recording. Tracings generated 
by the EP recording system are required as a procedure source document. 
3.3.6 
Steerable Sheath Preparation and Placement 
Preparation and deployment of the Steerable Sheath should follow the 
Instructions for Use and any training provided prior to the ablation procedure. 

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Use caution with any sheath advancement to ensure no air emboli is introduced 
into the left atrium. 
3.3.7 
Cryoablation Balloon Catheter Preparation 
Preparation and deployment of the Cryoablation Balloon Catheter should follow 
the Instructions for Use and any training provided prior to the ablation procedure. 
3.3.8 
Mapping and Ablation 
The objective of this clinical study is to evaluate the long-term safety and 
performance of the Cryterion Cardiac Cryoablation System.   
The following is a stepwise approach to the AF ablation procedure that is 
recommended, and a flow diagram is provided in Figure 1:  
Navigation and Placement of the Cryoablation Balloon Catheter  
To use the Cryterion Cryoablation Catheter for a cryoablation procedure, follow 
these steps. (For more detailed instructions on the use of the Cryterion 
Cryoablation Console, refer to the Operator’s Manual.) 
1. Under fluoroscopic guidance, advance the circular mapping catheter/ 
balloon to the proximity of the target pulmonary vein. 
 
2. Inflate the Balloon while remaining outside the target pulmonary vein. 
 
3. To occlude blood flow, advance the balloon as necessary to occlude 
flow but remain outside the tubular portion of the vein.   
 
4. Verify balloon position for complete PV occlusion with fluoroscopy and 
contrast injection diluted as a 50% to 50% solution. 
Apply Cryo Energy until Isolation is Achieved and Documented with the Circular 
Mapping Catheter 
1. Perform the cryoablation. A freezing cycle of ≥ 120 seconds is required. 
If PVI occurs in ≤60s, then an ablation cycle of 180s is performed; if PVI 
occurs in ≥60s, then an ablation cycle of 240s is performed. 
i. If the esophageal temperature falls below 25oC during an 
ablation cycle, the clinician can immediately abort the 
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ii. If there is loss of phrenic nerve capture, the clinician can 
immediately abort the cryoablation. 
 
2. Record the point in time and temperature achieved when the PV 
appears isolated as evidenced by loss of PV signal on the Circular 
mapping catheter. 
 
3. At the completion of the cryo application, wait for the thawing phase 
to complete before any balloon manipulation.   
 
4. During the Thawing Phase, observe the console temperature indicator 
and activate the “push button” on the handle once the temperature 
has reached +20O C to deflate the balloon. When the temperature 
exceeds +10O C, advance the blue button on the catheter handle. 
Maintain pressure on the push button until the balloon deflates. The 
balloon deflates automatically when the temperature reaches 20O C. 
 
5. As needed, reposition the cryo balloon and re-apply cryo energy in the 
same vein. 
 
6. Position the cryo balloon into the next targeted vein ostium and repeat 
the same steps for positioning, cryo application and thawing.  
 
7. After treatments of all targeted veins have been completed and when 
the balloon is completely deflated, retract the catheter/ circular 
catheter/ guidewire into the sheath. 
 
8. Final confirmation of all PVIs must occur before the end of the index 
procedure following the last cryo application for each targeted vein. 
 
9. In the event, a vein is not considered isolated during the index ablation 
procedure or during the 90-day blanking period, additional cryo 
applications may be completed or the investigator may elect to use a 
market-approved device (RF or Cryo focal catheter) to complete the 
isolation of the target vein.   
 

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10. Following confirmation of PVI, the Cryoablation Balloon Catheter and 
Circular mapping catheter may be removed from the left atrium, but 
the sheath should be adequately flushed and left in place. 
Reconfirm Isolation with the Circular Mapping Catheter  
Reconfirmation of the PVI with the PolarMap Mapping Catheter should be 
completed by placing the catheter in each targeted PV and demonstrating 
electrical isolation. Pacing maneuvers to aid in the documentation of isolation 
(block) should follow the institution’s standard-of-care. If IV medications are used 
in the confirmation process, the drug and dose should be documented on the 
eCRF. Final documentation for each targeted PV isolation shall be recorded on 
the EP recording system. Final tracings from the EP recording system shall be 
printed and used as procedure source documents. 
 
 

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AF Reinduction 
Use of IV medications or pacing maneuvers attempting to re-induce the atrial 
fibrillation is at the discretion of the investigator. Drugs and dosages used shall 
be recorded on the eCRF. 
 
 
Figure 1:  Atrial Fibrillation Ablation Procedure Flow Diagram 
 

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3.3.9 
Procedure Data Collection 
Collection of data generated during the procedure shall include (original 
document source to be kept at the site): 
• Any change in health or cardiac medications prior to the ablation 
procedure 
• EP system recording of 12-lead ECG at procedure start 
• EP system recording of 12-lead ECG at procedure completion  
• Total procedure time (from first venous access to time of last 
catheter removal from the left atrium) 
• Total fluoroscopy time  
• Recording of ablation summary data (including all cryo 
applications parameters per vein) 
• Recording of all DCCVs delivered during the procedure 
• Recording of all AADs administered during the procedure 
• Recording of ACT values and Heparin administration 
• Recording of any medications administered for anticoagulation 
reversal 
• Ablation time to complete PVI using the Cryoablation System  
• Baseline and final tracings using a PolarMap Mapping Catheter 
from the EP recording system documenting PV isolation 
(Submitted as procedure source notes) 
• EP recording confirming PV isolation of all treated veins using an 
approved mapping catheter  
• Documentation of System performance as described by the 
operator(s) using the System Performance Questionnaire. The 
system performance questionnaire will be used with all new 
clinical users for the first five (5) cases performed with the 
Cryterion System. After the first 5 cases, users can use the 
questionnaire to provide specific product feedback related to user 
experience(s) on an as needed basis (for example: the ability of 

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the cryoablation system to deal with tortuous anatomy of the 
LA/PVs). 
Documentation of Cryoablation Balloon and Circular Mapping Catheter performance 
including: 
• Catheter Preparation 
• Catheter Access to Cardiac Locations 
• Catheter Visualization 
• Catheter Performance 
 Maneuverability 
 Torque-ability 
 Trackability 
 Durability 
Additional data from the Cryoablation System may be transferred to the sponsor, 
stored and evaluated by sponsor personnel (including research engineers) for use in 
the continued development of the devices. All information and data sent to the 
Sponsor concerning subjects or their participation in this study will be considered 
confidential by the sponsor and all usage will be in full compliance of Cryterion Quality 
Assurance Procedures (QSPs) for protection of human subject and consistent with ISO 
14155:2011, Section 6.5. 
3.3.10 Device Returns 
Any product failures will be reported to the Sponsor and the product will be 
returned to the sponsor for further analysis. 
3.4 
Follow-Up Procedures 
All subjects will be followed for 12 months after their index ablation procedure. 
Each subject will undergo repeated assessments at 1, 3, 6 and 12 months. During 
the 90-day blanking period, subjects can undergo one repeat cryoablation 
procedure with the recommendation that all repeated ablations use the same 
cryoablation method or the investigator may elect to use a market-approved 
device (RF or Cryo focal catheter) without penalty regarding the primary 
effectiveness endpoint. 

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3.4.1 
Hospital Discharge 
The discharge visit will occur 7 days after index procedure or at the patient’s 
discharge date, whichever comes first. 
The subjects may be monitored with telemetry prior to hospital discharge for the 
documentation of recurrence of any atrial tachyarrhythmias and according to 
center practice. 
The following evaluations shall be completed prior to discharge: 
• Physical exam  
• Medication changes 
• Evaluation of Adverse Events 
• 12-lead electrocardiogram 
Careful attention shall be placed in the identification of potential cardiac 
effusions and post-procedure cardiac tamponade. Unexplained reduction in 
blood pressure, chest pain or shortness of breath may require a post-procedure 
TTE with further evaluation and management as per site’s standard of care. 
3.4.2 
Visits at One Month (30 +/- 7 days) after the Start (Procedure) Date 
The following evaluations will be performed during the one-month clinic follow-
up visit. Data will be recorded on the Follow-Up eCRF. 
• Physical exam  
• Medication changes 
• Arrhythmia Recurrence and treatment if any 
• Adverse events assessment 
• 12-lead electrocardiogram 
3.4.3 
Three Month (90 +/- 14 days) after the Start (Procedure) Date 
(designation in days required by Blanked Follow-Up Period and outcome 
measures) 
The following evaluations will be performed during the 3-month clinic follow-up 
visit. Data will be recorded on the Follow-Up eCRF. 
• Physical exam  
• Medication changes 

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• Arrhythmia Recurrence and treatment if any 
• Adverse events assessment 
• 12-lead electrocardiogram 
• 24 Hour Holter/ Cardiac Monitor Patch 
3.4.4 
Six Month Visits (180 +/- 30 days) after the Start (Procedure) Date 
The following evaluations will be performed during the 6-month clinic follow-up 
visit. Data will be recorded on the Follow-Up eCRF. 
• Physical exam  
• Medication changes 
• Arrhythmia Recurrence and treatment if any 
• Adverse events assessment 
• 12-lead electrocardiogram 
• 24 Hour Holter/ Cardiac Monitor Patch 
 
3.4.5 
Twelve Month Visits (360 +/- 30 days) after the Start (Procedure) Date 
The following evaluations will be performed during the 12-month clinic follow-up 
visit. Data will be recorded on the Follow-Up eCRF. 
• Physical exam  
• Medication changes 
• Arrhythmia Recurrence and treatment if any 
• Adverse events assessment 
• 12-lead electrocardiogram 
• 24 Hour Holter/ Cardiac Monitor Patch 
 
3.4.6 
Unscheduled (additional) Visits  
Any visit outside of the scheduled follow-up visits will be considered an 
Unscheduled Visit. These visits will include “return to clinic visits” for analysis of 
any clinical complications or preparation for a DCCV. All pertinent data will be 
recorded on an unscheduled visit eCRF.  

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this should include: 
• Physical exam  
• Medication changes 
• Arrhythmia Recurrence and treatment if any 
• Adverse events assessment 
• 12-lead electrocardiogram

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2All subsequent visits are counted in days from the index procedure 

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4 STATISTICAL METHODS  
4.1 
Analysis Population 
The analysis of the endpoints of the study will be based on the Enrolled Subject 
Population. 
4.2 
Statistical Analysis for the Study Outcome Measure 
Analysis of the primary endpoints will be performed on an intent-to-treat basis. All partial 
data that is available on subjects who drop out during the course of the study will be 
included. 
Descriptive analysis will be used to present the study. Continuous variables will be 
reported as median and range, mean ± standard deviation; categorical variables will be 
reported as n/N (%). 
The primary safety endpoint outcome is freedom from a composite MAE comprised of 
the device or procedure related adverse events as listed in the Primary Endpoints section 
of the protocol.  The primary safety endpoint will be assessed in all screened subjects 
who undertake the ablation procedure to the point that the Cryoablation Balloon is 
inserted into the subject. 
Additionally, the study will compare the study device safety outcome rate to a rate 
derived from available literature data. The study outcome rate will be presented along 
with rates from previous studies on market approved devices and a descriptive 
comparison will be made. 
The primary performance endpoint is acute success defined as rate of successful pulmonary 
vein electrical isolation with confirmation of entrance/exit block.  Any screened subject who 
undertakes the ablation procedure to the point that the Cryoablation Balloon is used to 
deliver at least one cryo application will be used to assess  the primary and the additional  
effectiveness endpoint. 
All study results will be analyzed using widely accepted statistical or graphical software. 
Subject data listings and tabular and graphical presentations of baseline and operative 
characteristics and outcome results will be provided. Additionally, all adverse events will 
be summarized by type of event, severity, relationship to the device and/or procedure, 
and timing of event relative to the procedure date. 
The following will be included in the Clinical Study Report:  

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• Summary of complications will be completed and included in the interim report.  
• Design, methods, procedure, sample size 
• Criteria for the termination of the clinical investigation on statistical grounds, 
• Analysis of endpoints 
• Analysis of Adverse Events and Outcomes 
4.3 
Study Size Justification 
 
 
 
 
 
 
 
 
   
5 ADVERSE EVENTS 
Any adverse event (AE) that occurs in a subject once they are enrolled in the study is 
considered a reportable event.  
Any medical conditions, problems, signs, symptoms, and findings occurring prior to 
treatment are to be reported as pre-existing conditions on the Medical History eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity or 
frequency during the course of the investigation 
Adverse events are categorized as defined in ISO 14155: 2011 and MEDDEV 2.7/3. 
Adverse event (AE): Any untoward medical occurrence unintended disease or injury, or 
any untoward clinical signs (including an abnormal laboratory finding) in subjects, users 
or other persons, whether or not related to the investigational medical device. 
NOTE 1: This includes events related to the investigational medical device or comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events related to the investigational 
medical device. 
 

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Adverse device effect (ADE): Adverse event related to the use of an investigational 
medical device. 
Note 1: this definition includes any event resulting from insufficiencies or inadequacies 
in the instructions for use, the deployment, the implantation, the installation, the 
operation, or any malfunction of the investigational medical device. 
Note 2: this definition includes any event that is a result of a user error or intentional 
abnormal use of the investigational medical device. 
 
Serious adverse event (SAE): Adverse event that: 
1. Led to a death 
2. Led to a serious deterioration in the health of the subject as defined by either: 
a. a life-threatening illness or injury 
b. a permanent impairment of a body structure or a body function 
c. in-patient hospitalization or prolongation of existing hospitalization, 
d. medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to body structure or a body function. 
3. Led to fetal distress, fetal death or a congenital abnormality or birth defect 
 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the clinical 
investigational plan, without a serious deterioration in health, is not considered a serious adverse 
event. 
 
Serious adverse device effect (SADE): Adverse device effect that has resulted in any of 
the consequences characteristic of a serious adverse event.  
 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or 
safety 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 application (including a supplementary 
plan or application), or any other unanticipated serious problem associated with a device 
that relates to the rights, safety, or welfare of subjects.   
 
Unanticipated Serious Adverse Device Effect (USADE): Serious adverse device effect 
which by its nature, incidence, severity, or outcome has not been identified in the current 
version of the risk analysis report. 
 
NOTE: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk analysis report. 
 

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The Principal Investigator is responsible for informing the IRB/EC/REB, and regulatory 
authorities of USADEs and SAEs as required by local/regional regulations. 
 
 
With any procedure or treatment, there are known possible risks and complications. A 
list of known or anticipated adverse events for the Cryoablation System is found in the 
Investigator Brochure.   
Unanticipated Serious Adverse Device Effects (USADEs) 
Investigators are required to submit a report to the Sponsor as soon as possible of any 
suspected Unanticipated Serious Adverse Device Effect (USADE) occurring during an 
investigation on the Adverse Event eCRF, but in no event later than one (1) business days 
after the Investigator first learns of the effect.  
When an Investigator suspects that an event meets the definition for a USADE, the event, 
date of onset, seriousness, severity, duration, treatment, outcome and relationship to 
device will be recorded on the Adverse Event eCRF.   
The Sponsor/ manufacturer must then conduct an evaluation of the suspected USADE 
and maintain records of the evaluation.  
5.1 
Adverse Event Reporting requirements 
The Investigator is responsible for reporting all adverse events that occur during the 
study.  Initial reporting will be with the Adverse Event eCRF; however, additional 
information may be required by the Sponsor, the independent medical monitor,   the 
Ethics Committee, or any other regulatory authority. The Investigator shall report any 
serious adverse events (SAEs), serious adverse device effects, (SADEs), or unanticipated 
serious adverse device effects (USADEs) to the Sponsor as soon as possible after 
becoming aware of the event, but not later than reporting timelines listed in table 3 
below. All SAEs, SADEs, and USADEs will be documented on the Adverse Event eCRF along 
with an explanation of any medical treatment administered. Documentation shall include 
the time of onset, complete description of the event, severity, duration, actions taken 
and outcome. Recurrence of atrial fibrillation (or other atrial tachyarrhythmias) is not 
considered an adverse event as there is a known recurrence rate associated with AF 
ablation, unless associated with worsening subject's conditions. This would include 
scheduled hospitalizations to treat these arrhythmias (e.g., pharmacologic and/or 
electrical cardioversion or re-ablation after blanking period). All recurrences will be 

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reported on the follow-up eCRF. In the event an arrhythmia recurrence resulted in 
hospitalization for other clinical symptoms, an adverse event shall be recorded and 
reported. In the event that an alternative method of reporting is necessary (i.e. the eCRF 
system is unavailable), please report the adverse event or device experience to the 
sponsor by sending the notification form to the following email address:  
 
 
 
Table 3: Investigator reporting requirements:  
Event Classification 
Communication Method  
Communication Timeline pre-market studies 
(MEDDEV 2.7/3: CLINICAL INVESTIGATIONS: 
SERIOUS ADVERSE EVENT REPORTING UNDER 
DIRECTIVES 90/385/EEC AND 93/42/EEC) 
Subject death during the study 
 
Complete information in 
EDC page with all available 
new and updated 
information.  
 
• 
Within 3 calendar days of first becoming aware 
of the event. 
 
Unanticipated Adverse Device 
Effect / Unanticipated Serious 
Adverse Device Effect  
 
Complete information in 
EDC page with all available 
new and updated 
information.  
 
• 
Within 1 business day of first becoming aware 
of the event. 
• 
Reporting required through the end of the 
study 
Serious Adverse Event  
Complete information in 
EDC with all available new 
and updated information.  
• 
Within 3 calendar days of first becoming aware 
of the event or as per local/regional 
regulations.  
• 
Reporting required through the end of the 
study 
Serious Adverse Device Effects 
 
Complete information in 
EDC with all available new 
and updated information. 
• 
Within 3 calendar days of first becoming 
aware of the event or as per local/regional 
regulations.  
• 
Reporting required through the end of the 
study 
Adverse Event including 
Adverse Device Effects 
Complete information in 
EDC with all available new 
and updated information. 
• 
In a timely manner (e.g. Recommend within 10 
business days) after becoming aware of the 
information 
• 
Reporting required through the end of the 
study  
Device Deficiencies (including 
but not limited to failures, 
malfunctions, and product 
nonconformities) 
Complete EDC with all 
available new and updated 
information.  
• 
Within 3 calendar days of first becoming aware 
of the event.  

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Event Classification 
Communication Method  
Communication Timeline pre-market studies 
(MEDDEV 2.7/3: CLINICAL INVESTIGATIONS: 
SERIOUS ADVERSE EVENT REPORTING UNDER 
DIRECTIVES 90/385/EEC AND 93/42/EEC) 
Note:  Any Investigational 
Device Deficiency that might 
have led to a serious adverse 
event 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 a reportable event. 
• 
Reporting required through the end of the 
study 
 
5.2 
Event Relationship to the Device 
The Investigator shall provide information regarding the relationship of the event to the 
Cryoablation System and the AF ablation procedure. The AE relationships are defined in 
Table 4 below: 
 
Table 4:  AE Relationships 
Not Related 
The cause of the AE is known and is not related to any aspect of the 
ablation portion of the AF procedure. 
Unlikely related 
The relationship with the use of the device seems not relevant 
and/or the event can be reasonably explained by another cause, but 
additional information may be obtained. 
Possibly Related 
There is a reasonable possibility that the event may be related to the 
ablation portion of the AF procedure. The AE has a timely 
relationship to the study procedure; however, it follows no known 
pattern of response and an alternative cause seems more likely or 
there is significant uncertainty. 
Probably Related 
It is probable that the event was related to the ablation portion of 
the AF procedure. The AE has a timely relationship to the study 

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procedure and follows a known pattern of response, but a potential 
alternative cause may be present. 
Causal Related 
The event was definitely related to the ablation portion of the AF 
procedure. A related event has a strong temporal relationship and an 
alternative cause is unlikely. 
 
5.3 
Death Notice 
When a site becomes aware of a subject’s death, regardless of cause, it should be 
reported to the Sponsor as soon as possible but no later than three (3) calendar days. 
Notification shall be made to the reviewing EC per local requirements.   
The materials to be submitted to the Sponsor for a death include the following:  
Notification of death must include a detailed narrative (death letter) that provides 
detailed information describing the circumstances surrounding the death: 
• Date and time of death  
• Place death occurred  
• Immediate cause of death  
• Whether or not the death was witnessed 
• An assessment by the Investigator as to whether the death is related to study 
interventions.  
• A copy of the subject’s death certificate If available 
• When applicable, a copy of an autopsy report. If available 
For reported deaths, the Investigator or designee shall supply the Sponsor and the 
presiding EC with any additional requested information, if available (i.e., hospital 
records). 
5.4 
Device deficiencies. 
Device Deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and inadequacy in the information supplied by the 
manufacturer) will be documented on the device experience CRF within 3 calendar days 
of first becoming aware of the event. Device failures and malfunctions should also be 

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documented in the subject’s medical record. Device deficiencies (including but not 
limited to failures, malfunctions, and product nonconformities) are not adverse events. 
However, an adverse event that results from a device failure or malfunction, would be 
recorded as an adverse event on the appropriate eCRF. Any Device Deficiency that might 
have led to a serious adverse event 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 a reportable event.  
Any trends for complaints related to subject adverse events will be assessed by the 
sponsor. 
5.5 
Clinical Events Committee (CEC) 
There is no CEC in place for this study. The Sponsor (or designee) will coordinate the 
convening of meetings to review all safety events reported in the study database. Based 
on this review, the Sponsor may make recommendations regarding all aspects of the 
conduct of the study, including the termination of the study. All recorded minutes of the 
meetings and actions will be kept on file and available for review as requested. The 
Sponsor may consider seeking the input of a Clinical Event Monitor (CEM, independent 
physician expert in the electrophysiology space) for additional recommendations 
regarding specific aspects of the conduct of the study. Additional source documentation 
will be requested as needed to the site.  
 
6 RISK-BENEFIT ANALYSIS 
6.1 
Risks 
The following adverse events are associated with AF mapping and ablation procedures 
using cryo energy: 
• Air embolism/N2O embolism 
• Myocardial infarction 
• Anemia 
• Obstruction, perforation or damage to 
the vascular system 
• Anesthesia reaction 
• Pericardial effusion 
• Arrhythmias 
• Pericarditis 
• Arteriovenous (AV) fistula 
• Phrenic nerve damage 
• Atrial esophageal fistula 
• Pleural effusion 

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• Cardiac perforation/tamponade 
• Pneumonia 
• Cardiac thromboembolism 
• Pneumothorax 
• Cerebral infarct (hemorrhagic or 
thromboembolic) 
• Pseudoaneurysm 
• Chest pain/discomfort 
• Pulmonary edema 
• Complete heart block (transient or 
permanent 
• Pulmonary embolism 
• Congestive heart failure 
• Pulmonary hypertension 
• Coronary artery spasm/dissection 
• Pulmonary vein dissection 
• Coronary artery thrombosis/occlusion 
• Pulmonary vein stenosis 
• Death 
• Pulmonary vein thrombosis 
• Diaphragmatic paralysis 
• Radiation injury 
• Elevated cardiac enzymes 
• Respiratory depression 
• Endocarditis 
• Skin burns 
• Fever 
• ST segment elevation 
• Heart failure/pump failure 
• Temporary complete heart block 
• Hemothorax 
• Thromboembolism 
• Infection/sepsis 
• Transient ischemic attack (TIA) 
• Local hematomas/ecchymosis 
• Valvular damage/insufficiency 
• Major bleeding, requiring surgery or 
transfusion 
• Vasovagal reaction 
6.2 
Benefits 
The Cryterion Cardiac Cryoablation System provides the benefit of creating endocardial 
necrosis using cryo energy delivered to targeted pulmonary veins in the management of 
atrial fibrillation. Unique System design changes including those to the Cryoablation 
Balloon Catheter, may increase the likelihood of safely applying the energy, increasing 
the durability of the PVI, and aiding in more accurate determination of electrical isolation 
of the vein(s).  
6.3 
Mitigation of Risks 
Subject risk will be minimized through the investigator selection process, investigator 
training and subject selection procedures.   

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Benchtop studies and pre-clinical research have demonstrated that the System is safe for 
human use. All potential risks have been evaluated and mitigation strategies have been 
implemented to reduce potential risks to acceptable levels. The sponsor believes that the 
potential benefits of the system outweigh the potential risks. The current amendment to 
the CE Mark Study is designed to follow the investigator’s standard of care for AF ablation 
subjects and evaluate the long-term effectiveness and safety of the System.  The subject 
data from the amended CE Mark Study will be retrospectively included in a subsequent 
Post Market Clinical Follow-Up study to collect long-term system-related, clinical and 
subject reported outcome data for the Cryterion Cardiac Cryoablation System.   
Additionally, study risks shall be minimized by:  
• The use of standard medical grade materials that have been thoroughly characterized 
and tested to assure biocompatibility 
• Extensive pre-clinical evaluation including in vitro bench testing and animal study 
• The well-established, standard nature of the intra-cardiac procedures and techniques 
to be used 
7 DATA QUALITY ASSURANCE  
The sponsor will oversee the database for this study in accordance with regulatory data 
integrity requirements, the Data Management Plan (DMP), and corporate QSPs. Data will 
be collected and entered on the eCRFs in the database. Data will be reviewed for accuracy 
and completeness by the sponsor (or designees) during all onsite and remote monitoring 
visits, and throughout the data management process. Any discrepancies will be resolved 
with the Investigator or designees, as appropriate. To preserve data integrity and security 
of the database, access to the database will be controlled by the sponsor (or designees) 
and shall be limited to appropriately trained personnel with assigned log-on credentials.   
7.1 Data Management 
The standard procedures for handling and processing records will follow the sponsor (or 
designee) QSPs for data management. All data collection will be in compliance with Good 
Clinical Practice (GCP). A comprehensive Data Management Plan (DMP) will be developed 
for the clinical study.   
For the duration of the study, the Investigator and their designees will maintain complete 
and accurate documentation, including, but not limited to, medical records, study 
progress notes, laboratory reports, signed subject informed consent forms, device 

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accountability logs for the investigational product (i.e., Cryoablation System 
components), correspondence with the reviewing EC, correspondence with the sponsor 
(or designees) and study monitors, adverse event reports, and information regarding 
subject discontinuation/withdrawal or completion of the study. 
The Investigator/ Institution will permit direct access to source data and documents to 
complete study-related monitoring, audits, EC reviews, adverse event adjudication and 
regulatory inspections that may be performed. The Investigator will obtain, as part of the 
informed consent process, permission for authorized Sponsor employees, study monitors 
or regulatory authorities to review, in confidence, any records that identify subjects in 
this study. 
7.2 
Subject Identification  
Subjects will be identified on all eCRFs and source documents by a unique identification 
reference, which will be issued once the Informed Consent has been signed and date of 
signature has been entered in the database. An identification reference shall not be 
reused for any reason.   
7.3 
Screen Failure Subjects 
Subjects who are screened for the study but are not enrolled for any reason will not be 
followed and their data will not be used for any outcomes analysis.  
7.4 
Subject Study Completion and Withdrawal 
A subject will be considered to have completed their participation in the study when the 
12-month visit data collection is complete and submitted. Subjects who withdraw for any 
reason will have all available data entered into the database. Reasons for withdrawal will 
be entered on the Study Exit eCRF. 
7.5 
Subjects Lost-to-Follow-Up 
A subject will be considered lost-to-follow-up if any of the follow-up visits through 12 
months is missed and all reasonable efforts have been made to contact the subject to 
request their return for the study visit. All attempts to contact the subject will be 
documented on the Study Exit eCRF.   
7.6 Confidentiality of Data 
Information regarding study subjects will be kept confidential and managed according to 
the requirements and regulations of local and national governing bodies, ISO 14155: 

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2011, Section 6.5, EU 536/2014 and QSPs of Cryterion Medical or participating Contract 
Research Organizations (CROs). 
All data and information collected during this study will be considered confidential by the 
sponsor and their delegates. All data used in the analysis and summary of this study will 
be anonymous and without reference to specific subject names. Access to subject files 
will be limited to authorized personnel of the sponsor (including core labs), their 
designees, the Investigator, Clinical Site research staff and authorized Regulatory 
Authorities. Authorized regulatory personnel have the right to inspect and copy all 
records pertinent to this study. 
7.7 
Source Documents 
Source data encompasses all information, original records of clinical findings, 
observations, or other activities, which are required in a clinical study for the 
reconstruction and evaluation of the study. Examples of these original documents, and 
data records include, but are not limited to, hospital records, clinic and office charts, 
laboratory notes, memoranda, subject diaries or evaluation checklists, recorded data 
from automated instruments, copies or transcriptions certified after verification as being 
accurate and complete, copies of clinic and procedural site coding and billing records, 
microfiches, photographic negatives, microfilm or magnetic media, X-rays, subject files, 
and records kept at the pharmacy, and at the laboratories involved in the clinical trial. 
Regulations require that the Investigator maintain information in the subject’s medical 
records that corroborate data collected for the study.  To comply with these regulatory 
requirements, the following is a list of information that shall be maintained, at a 
minimum:  
Medical history/ general physical condition of the subject before involvement in the 
study, which will be of a sufficient nature to verify the protocol eligibility criteria. 
Study/ progress notes, including the date of entry into the study, documenting the 
following: 
• The general health of the subject. 
• The discussion of the study risks and benefits with the subject. 
• Completion of the informed consent process. 
• A statement that the subject reviewed and signed the subject informed 
consent form. 

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• Dated notes from each subject visit to support all data recorded on the 
eCRFs. 
• Adverse Events reported and their continuation or resolution at each 
visit, including supporting documentation, such as discharge summaries, 
lab results, non-invasive testing reports, etc. 
• Notes regarding protocol-required and prescription medications taken 
during the study (including start and stop dates, dosage, and routes of 
administration, if known). 
• Subjects general health and medical condition upon completion of or 
withdrawal from the study. 
7.8 
Electronic Case Report Forms (eCRFs) 
This study will use Case Report Form worksheets and an electronic Case Report Form 
(eCRF) as the primary data collection instruments and will record data by electronic 
capture. All data requested on the eCRF must be entered in a timely manner. If a data 
entry error has been made, the corrected information will be entered on the eCRF. All 
such changes are recorded in the audit and queries report.   
Additional device/ procedure data related to the performance during a cryoablation 
procedure is collected within the Cryo Console. These data may be downloaded on a per-
subject basis and printed for use as a supporting source document to the procedure eCRF. 
Specific guidelines to complete the eCRFs will be provided to the Investigator and other 
site personnel, as appropriate. The Investigators (and designees) are responsible for 
reporting clinical study-requested information in the eCRFs.   
7.9 
Records Retention 
The Investigator will retain study-essential documents for ten (10) years after formal 
closure or discontinuation of the trial. These documents must be retained for a longer 
period if required by an agreement with the sponsor or defined by local or national 
regulations. The sponsor will inform the Investigator/ Institution as to the date of formal 
closure or discontinuation of the trial and when these documents no longer need to be 
retained. 

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7.10 
   
Clinical Monitor 
A Clinical Trial Monitor (or designee) will be assigned as the clinical monitor for this study. 
The personnel will be qualified by training and experience to oversee the conduct of the 
study. The Clinical Monitor's responsibilities include maintaining regular contact with 
each investigational site through telephone contact and on-site visits to ensure that:  
• The CIP and the defined visit schedule is followed,  
• Complete, timely, and accurate data are submitted,  
• Issues with inconsistent and incomplete data are addressed;  
• All Device Experiences, AEs, SAEs and UADEs are reported to the Sponsor,  
• The site facilities continue to be adequate. 
Any questions regarding these matters should be addressed to the Clinical Affairs 
department of the sponsor. Monitoring of the conduct and data produced from the 
clinical study will be assigned to the Clinical Trial Monitor (or designee). 
7.11 
Clinical Data Monitoring Procedures 
Clinical Trial Monitors (or designees) will conduct site visits at the study facilities to 
monitor the study, which will be compliant with the CIP, QSPs, and the Clinical Monitoring 
Plan (CMP) and applicable regulations. Monitoring visits will occur as defined in the CMP. 
The Investigational site agrees to allow these monitors and other authorized sponsor 
personnel access to information and clinical supplies related to the study. The Cryterion 
Medical monitors (or designees) will review source data and verify data entered into the 
eCRFs against hospital/ clinic records and/or other source documents, to ensure accuracy 
and completeness of the eCRFs for each subject. Clinical Investigators and their staff 
agree to assist the monitors in their activities. Requests may be made to review subject 
charts by sponsor personnel and/ or designee(s) so that protocol adherence and source 
documentation can be verified.   
Monitoring visits will be performed at regular intervals throughout the course of the 
study to ensure compliance with the protocol. Monitoring activities may include, but are 
not limited to:  
• Evaluation of subject screening and selection methods 
• Verification of signed ICF for each subject 

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• Verification of source documentation against completed eCRFs and 
worksheets for each subject 
• Source data review to ensure proper reporting of all reportable events 
• Assurance that required study reports, including reports to the applicable 
EC, are generated in a timely manner 
• Monitoring of Safety Events, including device deficiencies that may have 
led to an SAE 
• Monitoring of device experiences, irrespective of associated safety events 
• Review of device accountability records and device reconciliation 
• Review of protocol deviations 
• Overall study compliance 
• Review of the Investigator Site File (ISF) 
7.12 
Investigator Responsibilities 
The investigator is responsible for ensuring that the clinical study is performed in 
accordance with the protocol, the Declaration of Helsinki, the principles of Good Clinical 
Practice (GCP), ISO 14155: 2011, applicable regulatory requirements, and institutional 
procedures.  
7.13 
Deviations from the Clinical Investigational Plan 
A protocol deviation is defined as an event in which the Investigator or site personnel 
deviates from the study protocol or study procedures. It is the Investigator’s 
responsibility to ensure that there are no deviations from the protocol. On a rare 
occasion, a sponsor-approved deviation to a screening test, exclusion criteria, or 
protocol-specific procedure may be granted in advance by the sponsor and must be 
reported in full compliance with all established procedures and conditions of the 
reviewing EC.   
An Investigator may deviate from the protocol without prior written approval from the 
sponsor in cases of medical emergencies to protect the life or physical well-being of a 
subject. In the event of an emergent deviation, the Investigator is required to notify the 
sponsor and the applicable EC as soon as possible, but in no event later than five (5) 
business days after the occurrence of the deviation from the protocol.  

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Except in such an emergency, prior approval by the sponsor is required for changes in, or 
deviations from, the CIP/ protocol. Additionally, if these changes or deviations affect the 
scientific soundness of the investigational plan or the rights, safety, or welfare of human 
subjects, EC notification is required. 
Prior approval is generally not expected in situations where unforeseen circumstances 
are beyond the Investigator’s control (e.g., the subject was not available for a scheduled 
follow-up office visit or has moved without providing a forwarding address). These 
events, although outside the Investigator’s control, are still required to be reported on 
the appropriate Protocol Deviation eCRF to ensure that all deviations from the standard 
subject population are adequately documented and reported. The Investigator will 
inform the sponsor and the reviewing EC of all protocol deviations as per the EC 
requirements established for this study.   
If the sponsor becomes aware that an Investigator is not complying with the any part of 
the CIP, including the signed Investigator Agreement, the protocol, or any conditions of 
approval imposed by the reviewing EC, the sponsor will first try to secure compliance, 
and may suspend the Investigator’s participation (including enrollment at the site) in case 
of failure to implement remedial actions. The sponsor may terminate an Investigator’s 
participation in the study at its discretion.  
7.13.1 Maintaining Records 
The Investigator will maintain the following accurate, complete, and current records 
related to the Investigator's participation: 
Correspondence with another Investigator, an EC, Cryterion Medical, a Sponsor monitor 
or designee, or any regulatory agency. 
Records of each subject's case history and exposure to the device, including:  
• Source records evidencing each eligibility criterion to enroll in the study 
• Documents evidencing informed consent and for participation in the 
clinical study without informed consent,  
• Any written concurrence of a licensed physician and a brief description of 
the circumstances justifying the failure to obtain informed consent, 
• All relevant observations, including records concerning adverse device 
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• Information and data on the condition of each subject upon entering, and 
during the investigation, including information related to relevant 
previous medical history and the results of all diagnostic tests, 
• A record of the procedure involving treatment with the CryoAblation 
System for each subject, including the date and time of the procedure. 
• The protocol, with documents showing the dates of and reasons for each 
deviation from the protocol. 
 
7.13.2 Submitting Reports 
In compliance with local and national laws, each Investigator may be required to prepare 
and submit complete, accurate, and timely reports to the sponsor and/ or ECs. These 
reports may include: 
• Any unanticipated adverse device effects or SAEs occurring during an 
investigation.  
• Any deviation from the investigational plan emergently made to protect 
the life or physical well-being of a subject.  
• A protocol deviation requiring prior written approval from Cryterion 
Medical (except in emergency situations). If the deviation affects the 
scientific soundness of the plan or the rights, safety, or welfare of subject, 
prior documentation of EC approval may be required. 
• Any further information requested by an EC about any aspect of the 
investigation. 
The Investigator will provide, in writing, any withdrawal of EC approval of the study or an 
Investigator within five (5) business days of such action. 
7.14 Sponsor’s Responsibilities 
7.14.1 General Duties 
The sponsor has the overall responsibility for the conduct of the study, including 
assurance that the study satisfies the regulatory requirements of the appropriate 
regulatory agencies, ensuring EC approvals, selecting Investigators, ensuring proper 
monitoring and that informed consent was obtained by the principal investigator or 
authorized designee. The sponsor will provide all information necessary to conduct the 

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study, including the Clinical Study Protocol, and any reports of prior investigations, as 
appropriate. During the conduct of the clinical study, updates regarding information that 
may impact the clinical study will be made available to all appropriate national and local 
regulatory authorities. 
7.14.2 Selection of Investigators 
The sponsor will select Investigators (including co-Investigators performing the 
procedure) qualified by training and experience. Sites will be selected based on a site 
assessment, appropriate facilities, clinical experience and the qualifications of the 
Principal Investigator. Investigators will be evaluated by the sponsor based on: 
Curriculum vitae, or other statement of Investigator’s relevant training and experience, 
including type of experience with the intended procedure and clinical research, 
specifically,  
Education and experience in the ablation management of arrhythmias, 
Whether the Investigator has an adequate subject population to meet requirements of 
the study enrollment, 
Whether the Investigator has adequate time to be personally involved in the conduct of 
the study, and adequate research staff and resources to support the study, 
Whether the Investigator’s Study Center is associated with an EC that satisfies all 
applicable regulatory requirements, 
Whether an Investigator was involved in an investigation or other research that was 
terminated. This may require an explanation of the circumstances that led to the 
termination.  
Prior to study initiation, each Investigator must also submit a:  
• Certificate of human subject’s protection training (if required by the 
reviewing EC) 
•  Certificate of GCP training, 
• Signed Investigator’s Agreement, indicating an Investigator’s 
commitment to: 
• Conduct the investigation in accordance with the agreement, 
the CIP/protocol, GCP, and any conditions of approval imposed 
by the EC,  

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• Supervise all testing of the device involving human subjects,  
• Ensure that the requirements for informed consent are met,  
• Conduct the study according to the CIP/protocol. 
The Sponsor reserves the right to apply additional criteria to site and/or Investigator 
selection. 
7.14.3 Training 
The Sponsor will provide technical training on all components of the Cryoablation System 
prior to enrolling any subject. Training may consist of a review of the IFU, hands-on 
training on the device and procedure, presentations, literature, etc, and/or providing 
clarifications to site personnel concerning the operation of study equipment/devices. The 
training program will be standardized and will be documented. Additional training will 
include a review of the protocol, the regulations for medical device investigations and 
general study logistics required to complete the study. 
At the request of the investigator and while under investigator supervision, Sponsor 
personnel may support equipment operation during the ablation procedure or additional 
procedures, assist with the conduct of testing specified in the protocol, and interact with 
the subject to accomplish requested activities. 
Typical tasks may include the following: 
• Operating, support preparation and setting the Balloon Catheter system to adjust 
parameters to investigator-requested settings. 
• Clarifying device behavior, operation or diagnostic output as requested by the 
investigator or other health care personnel 
• Entering data on technical source form as long as the responsible investigator 
verifies and signs the completed worksheet. 
• Print out/download programming reports/parameters directly from the EP 
equipment and provide original printouts or electronic data reports to clinical site as 
source documentation. 
• Provide technical expertise/support to subjects during office visits and/or during 
teleconference calls/electronic communications with the principal investigator or 
their delegated site staff and the subject.  
Sponsor personnel will not do the following: 

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• Practice medicine 
• Provide medical diagnosis or treatment to subjects 
• Discuss a subject’s condition or treatment with a subject without the approval and 
presence of the investigator 
• Independently collect study data (defined as primary or secondary endpoint data) 
• Enter data in electronic data capture systems or on paper case report forms 
Training of appropriate clinical study personnel will be the responsibility of the sponsor 
(or designee). To ensure uniform data collection and protocol compliance, the sponsor 
will review the CIP/protocol (including the ICF), techniques for identification of eligible 
subjects, instructions on data collection, methods for scheduling follow-up visits within 
the visit window, etc. Detailed feedback regarding completion of the eCRFs, study 
requirements, and protocol compliance will be provided by the sponsor, its study 
monitors, and/ or designees, functioning in a data management capacity. 
7.14.4 
Changes in the Clinical Investigational Plan 
The sponsor will obtain appropriate regulatory approval for any change to the CIP/ 
protocol that may affect the scientific soundness of the investigation or the rights, safety 
and/ or welfare of the subjects.  
The sponsor will provide approved protocol amendments to the Investigators prior to 
implementing the amendment. The Investigator (or Sponsor designee) will be 
responsible for notifying the reviewing ECs of the protocol amendment (administrative 
changes) or obtaining EC approval of the protocol amendment (changes in subject care 
of safety), according to the instructions provided with the protocol amendment. The EC 
acknowledgement/ approval of the protocol amendment must be documented in writing 
prior to implementation of the protocol amendment. Copies of this documentation must 
be provided to the sponsor and placed in the Trial Master File (TMF). 
7.14.5 
Withdrawal of Regulatory Approval  
The sponsor will notify all reviewing ECs and participating Investigators of any withdrawal 
of regulatory approval to conduct the clinical study and shall do so within five (5) business 
days after receipt of notice of the withdrawal of approval. 

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8 ETHICS AND REGULATORY COMPLIANCE 
8.1 
Conduct of the Clinical Study 
Conduct of the clinical study will follow QSPs from Cryterion Medical, as well as the 
Declaration of Helsinki, Good Clinical Practices, ISO 14155: 2011, and other regional and 
local laws. Each Investigator must sign and date the Investigator Agreement prior to the 
start of this study. With the signature, the Investigator agrees to perform all study 
procedures according to the governing local and national regulations and the Clinical 
Investigational Plan. 
8.2 Ethics Committee Approval 
A properly constituted, valid EC must review and approve the CIP, ICF, and related subject 
information and recruitment materials prior to initiation of the study. It is the 
responsibility of the Investigator (or Sponsor designee) to obtain protocol approval from 
the institution’s EC, and to keep the EC informed of any serious adverse events or serious 
adverse device effects and amendments to the protocol. Additional requirements 
imposed by the EC or other regulatory authority shall be followed as appropriate. All 
correspondence with the EC shall be filed in the ISF and copies sent to the sponsor (or 
designees). 
8.3 Clinical Study Informed Consent Approval 
In accordance with the principles of Informed Consent, the Declaration of Helsinki, Good 
Clinical Practice (GCP), and ISO 14155: 2011, informed consent will be obtained and 
documented in writing before a subject is enrolled in the clinical study.  
It is the responsibility of the Investigator to ensure that a written informed consent is 
obtained from the subject (or legally acceptable representative) before any activity or 
procedure is undertaken that is not part of routine care.  Information obtained during 
the conduct of the clinical study that may impact the subject informed consent may 
require revisions to the informed consent. If so, revisions and approvals of such changes 
by the appropriate regulatory authority is required. Documentation of the current 
versions of the informed consent will be filed in the clinical study TMF. 
8.4 
Identification and Confidentiality 
Subject identification and confidentiality will be ensured in accordance with all applicable 
regulatory and EC governance. This includes, but is not limited to, the following: 

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• Subjects will be identified on all eCRFs and source documents by a unique 
identification reference.  
• eCRFs are confidential documents and will only be made available to 
Cryterion Medical (or designees), the Investigator, the biostatistician, the 
Clinical Events Monitor (CEM), and, if requested, to advisory committees 
and regulatory authorities (including US FDA). 
• Data will be stored and analyzed by computer following national 
regulations for handling of computerized data. 
• Each Study Center will maintain (anonymous to Cryterion Medical) a list 
identifying all subjects entered into the trial. The list will be maintained as 
part of the ISF and monitored for completeness. 
8.5 
Site Qualification Visits 
A site qualification visit (SQV) will be performed to evaluate site facilities, Investigator 
qualifications, and site knowledge of Good Clinical Practice (GCP) guidelines. Cryterion 
Medical’s QSP for SQVs will be followed and a report filed in the Trial Master File (TMF), 
which will be maintained by the sponsor (or designee). If the site has been involved in 
previous sponsor research within the previous 12 months, the SQV may be waived in 
compliance with Cryterion QSPs. 
8.6 
Site Initiation Visits 
All study personnel will be required to participate in a Site Initiation Visit (SIV), following 
Cryterion Medical’s QSPs (or designee’s QSPs).  Components of the SIV may include: 
• Introduction of the study design including the protocol-specific treatment 
and follow-up phase 
• Informed Consent process 
• Product training to all end-users  
• eCRF completion training 
• Safety reporting instructions 
• Training on the regulations governing human research 
• Procedure training on the use of the device 

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8.7 
Insurance 
The sponsor shall maintain insurance coverage for this study. Pertinent information 
regarding the coverage shall be made available to the site upon request. 
8.8 
Site Audit Plan 
Participation as an Investigator in this study implies acceptance of potential inspection 
by government regulatory authorities and applicable compliance and quality assurance 
offices. The Investigator and/ or designee must be available to respond to reasonable 
requests and queries made by authorized regulatory representatives during the audit 
process. The Investigator must provide the sponsor with copies of all correspondence 
that may affect the review of the current study or their qualifications as an Investigator 
in this and future clinical studies conducted by the sponsor. 
8.8.1 Site Data Audits by Sponsor 
In accordance with local and national regulations and Sponsor’s operating procedures, 
an internal audit may be requested to access all study records, including source 
documents, for inspection and duplication. The investigator will ensure the capability for 
inspections of applicable study-related functions. 
Site data quality assurance audits may be conducted at various sites during the clinical 
study. Selection of sites to undergo auditing will be determined by the sponsor as 
needed.  
8.8.2 External Audits 
Participating study sites may receive requests from National regulatory agencies to 
conduct a site audit. The Investigator and/ or designee is required to report to the 
sponsor as soon as possible after receiving a request from a regulatory authority to 
perform an audit. The clinical Investigator agrees to allow inspectors from regulatory 
agencies to review records and to assist the inspectors in their duties, if requested. 
8.9 
Device Traceability 
The Cryoablation System components will be provided for the procedures and will be 
stored at each site or transported for the procedure. All sites will maintain a device 
accountability log for investigational devices used in the study. Commercially available 
products will not be tracked. At the end of the study, all unused study devices will be 
returned to the sponsor. 

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8.10 Public Domain Access to the Clinical Study 
A description of this clinical trial will be available on http//www.Clinicaltrials.gov.  
8.11 Required Reports 
The sponsor will remain in compliance with all required and pre-specified reports during 
the enrollment and follow-up of the clinical study. EC requirements for reports, including 
all clinical study reports will be provided as requested.  
9 GENERAL CONSIDERATIONS 
9.1 
Discontinuation of the Clinical Study 
The Sponsor reserves the right to discontinue the study at any stage, with suitable written 
notice to the Investigator and the appropriate government regulatory agencies. Such 
decisions will be based on advice from the Scientific Advisory Board or Clinical Events 
Monitor. Similarly, Investigators may withdraw from the study, subject to providing 
written notification to the Sponsor, within 30 days of their intent to withdraw. However, 
the Sponsor and Investigators will be bound by their obligation to complete the follow-
up of subjects already enrolled into the study. 
as the sponsor, may terminate Investigator and site participation in the study if there is 
evidence of an Investigator’s failure to maintain adequate clinical standards or evidence 
of an Investigator’s or staff’s failure to comply with the Clinical Investigation Plan/ 
protocol. 
Notification of suspension or termination will occur no later than fifteen (15) business 
days after the sponsor makes the determination. In the event of study suspension or 
termination, the sponsor or designee will send a report to the reviewing EC, the 
appropriate regulatory agencies, and all participating Investigators, outlining the 
circumstances. Any suspension or termination may not be re-initiated without prior 
approval of the EC and the sponsor. 
9.2 
Use of Information and Publications 
All information concerning sponsor’s operations, patent applications, manufacturing 
processes, and basic scientific data supplied by the sponsor to the Investigator and not 
previously published, are considered confidential and remain the sole property of the 
sponsor. This includes all study materials, CRF worksheets, eCRFs and any subject data 
collected during the conduct of this study. 

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All parties shall observe data confidentiality rules during the course of the study.  The 
privacy of each study subject and confidentiality of his/her information shall be preserved 
in reports and publication of any data. 
The information developed in this study may be used by the sponsor as support for future 
regulatory filing(s) and in connection with the continued development of the 
Cryoablation System components. Any publication or other public presentation of the 
data resulting from this study will require prior review and written approval of the 
sponsor. 
At the end of the study, it is expected that the sponsor and the Investigators will promptly 
prepare and submit a multi-center manuscript for publication in a reputable scientific 
journal. The publication of the principal results, including abstracts, from any single-site 
experience within the study is not allowed until the preparation and publication of the 
multi-center results. Exceptions to this rule require the prior written approval of the 
sponsor. 
Further analyses, beyond those presented in the initial multi-center publication may be 
proposed to the sponsor. Many secondary manuscripts are anticipated. For purposes of 
timely abstract presentation and publication, such secondary publications may be 
delegated to the appropriate principal authors; however, final analyses and manuscript 
review for all multi-center data will require the prior written approval of the sponsor. 
None of the results, in whole or part, of the study carried out under this protocol, nor any 
of the information provided by the sponsor for the purposes of performing the study, will 
be published or passed on to any third party without the consent of the sponsor. Any 
Investigator involved with this study is obligated to provide the sponsor with complete 
test results and all data derived from the study. 
 
 

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10 BIBLIOGRAPHY 
1. Chugh S, Havmoeller R, Narayanan K, et al. Worldwide Epidemiology of Atrial 
Fibrillation: A Global Burden of Disease 2010 Study.  CIRC. 2014;129(8):837-847. 
2. Camm AJ, et al. 2012 focused update of the ESC Guidelines for the management of 
atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial 
fibrillation--developed with the special contribution of the European Heart Rhythm 
Association. Europace, 2012 Oct; 14(10):1385-413 
3. Calkins H, Hindricks, G, Cappato, R, et al. 2017HRS/EHRA/ECAS/APHRS/SOLAECE 
expert consensus statement on catheter and surgical ablation of atrial fibrillation. 
Heart Rhythm. Vol. 10, October 2017 
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Cryterion Cardiac Cryoablation System CE Mark Study, Amendment 03  
 
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