Safety and Feasibility of Atrial Deganglionation as Adjunctive Therapy for Atrial Fibrillation
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Atrian Medical Ltd.

DESCRIPTION: CIP-001 Clinical Investigation Plan for OCED System 
Rev: H 
 
 
Page 1 of 47 
 
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without the expressed written consent of AtriAN Medical Ltd. 
 
Clinical Investigational Plan 
Safety and Feasibility of Atrial Deganglionation as an Adjunctive Therapy for Atrial Fibrillation 
 
 
 
This protocol has been prepared in compliance with current International Standard EN-ISO 14155:2020, Clinical 
Investigations of medical devices for human subjects - Good Clinical Practices; Annex A (normative) Clinical 
Investigation Plan (CIP). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This document contains confidential information for use by the Investigators and their designated personnel 
participating in this clinical investigation. It should be held confidential and maintained in a secure location. 
 
 
Protocol No. 
CIP-001 
Rev 
H 
Date 
31 March 2022 
Sponsor: 
AtriAN Medical Ltd 
Unit 204, NUIG Business Innovation Centre, Galway, Ireland 
Principal 
Investigator: 
Tamaz Shaburishvili, MD (Tbilisi Heart & Vascular Clinic) 
64 Ljubljana Street, Tbilisi, Georgia. 
Tel +995 32 218 15 55 
 
Ivo Skalsky, MD, (Na Homolce Hospital) 
Roentgenova 37/2, Praha 5, Czech Republic. 
Tel +420 257 271 111 
Study Manager: 
Barry O’Brien, AtriAN Medical Ltd 
Unit 204, NUIG Business Innovation Centre, Galway, Ireland 
Tel +353 87 2934292 

DESCRIPTION: CIP-001 Clinical Investigation Plan for OCED System 
Rev: H 
Page 2 of 47 
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Approval by Sponsor 
All persons below agree on the present CIP. The information it contains is consistent with the current risk/benefit 
evaluation of the study preparation as well as with the moral, ethical and scientific principles governing clinical 
research as set out in the current versions of the Declaration of Helsinki and of the guidelines on Good Clinical 
Practice. 
Sponsor 
Name 
Date 
Signature 
Ken Coffey 
(Chief Executive Officer) 
Barry O’Brien 
(Chief Technology Officer/Study Manager) 
Prof. Dr. J.R. (Joris) de Groot,  
(Cardiologist/Electrophysiologist - Medical 
Advisor) 
DocuSign Envelope ID: 999D3633-BC14-4696-94B7-6BBDD12EADE4
31-Mar-2022
31-mrt-2022
31-Mar-2022

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Investigator Signature Page 
I have read this Investigational Plan and agree to adhere to the requirements. I also have read and understand fully 
the Investigator’s Brochure, and I am familiar with the investigational devices and their use according to this 
protocol. I will provide copies of this Investigational Plan and all pertinent information to all site personnel involved 
in this study ensuring they are adequately trained. I will discuss this material with them and ensure they are fully 
informed regarding the study products and the conduct of the study. 
I agree to conduct the study as outlined in the Investigational Plan, in accordance with the signed clinical study 
agreement and to the ethical principles stated in the latest version of the Declaration of Helsinki (2013), the 
applicable guidelines for good clinical practices, MDCG 2020-10/1 ‘Safety reporting in clinical investigations of 
medical devices under the Regulation”, ISO 14155:2020 (Clinical Investigation of Medical Devices for Human 
Subjects - Good Clinical Practice), or the applicable local and international regulations, whichever provide the 
greater protection of the individual. 
In addition, I agree to provide all the information requested in the Case Report Forms presented to me by the 
Sponsor in a manner to assure completeness, legibility and accuracy. 
I also agree that all information provided to me by the Sponsor, including pre-clinical data, protocols, Case Report 
Forms, and any verbal and written information, will be kept strictly confidential and confined to the clinical 
personnel involved in conducting the study. It is recognized that this information may be relayed in confidence to 
the Ethics Committee. 
In addition, no reports or information about the study or its progress will be provided to anyone not involved in the 
study other than the Sponsor, the Ethics Committee, or the Clinical Events Committee. Any such submission will 
indicate that the material is confidential. 
 
 
 
 
 
Investigator Signature 
 
Date 
 
 
 
 
Investigator Printed Name 
 
 
 
 
 
 
Investigator Signature 
 
Date 
 
 
 
 
Investigator Printed Name 
 
 
 
 
 
 
Investigator Signature 
 
Date 
 
 
 
 
Investigator Printed Name 
 
 

DESCRIPTION: CIP-001 Clinical Investigation Plan for OCED System 
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Table of Contents 
 
Table of Contents ................................................................................................................................................... 4 
Study Synopsis ....................................................................................................................................................... 6 
1. 
Background and Justification of the Proposed Trial Design ............................................................................11 
2. 
Device Description ........................................................................................................................................13 
2.1 
Catheters - Finger & Glove .....................................................................................................................13 
2.2 
Dispersive Pad .......................................................................................................................................14 
2.3 
ECG Synchronization Unit ......................................................................................................................14 
2.4 
PEF Generator .......................................................................................................................................15 
3. 
Intended Use .................................................................................................................................................16 
4. 
System Training .............................................................................................................................................16 
5. 
Risk Benefit Analysis ......................................................................................................................................16 
6. 
Study Protocol ...............................................................................................................................................17 
6.1 
Study Objectives ....................................................................................................................................17 
6.2 
Study Design ..........................................................................................................................................17 
6.3 
Study Rationale .....................................................................................................................................18 
6.4 
Sample size ............................................................................................................................................18 
6.5 
Statistical Justification and Analysis of Results .......................................................................................18 
6.6 
Site Selection and Training .....................................................................................................................18 
6.7 
Patient Inclusion Criteria ........................................................................................................................18 
6.8 
Patient Exclusion Criteria .......................................................................................................................19 
7. 
Study Endpoints ............................................................................................................................................20 
7.1 
Primary Safety Endpoint: .......................................................................................................................20 
7.2 
Primary Feasibility Endpoints: ................................................................................................................20 
7.3 
Efficacy Endpoints: ................................................................................................................................20 
8. 
Study Procedure and Data Collection ............................................................................................................21 
8.1 
Informed Consent ..................................................................................................................................25 
8.2 
EDC Data Collection Platform .................................................................................................................26 
8.3 
Study Completion ..................................................................................................................................27 
8.4 
Schedule of Events.................................................................................................................................28 
8.5 
Patient Lost to Follow-Up ......................................................................................................................28 
8.6 
Patient Withdrawals and Discontinuation ..............................................................................................28 
8.7 
Early Termination of Clinical Investigation .............................................................................................29 

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8.8 
Adverse Event Reporting .......................................................................................................................30 
8.9 
Anticipated Adverse Events ...................................................................................................................34 
8.10 
Emergency Contact Details for Reporting Adverse Device Effects ...........................................................36 
8.11 
Device Deficiencies and Malfunctions ....................................................................................................36 
9. 
Study Conduct ...............................................................................................................................................38 
9.1 
Ethics .....................................................................................................................................................38 
9.2 
Regulatory Considerations .....................................................................................................................38 
9.3 
Investigator Responsibilities ..................................................................................................................38 
9.4 
Confidentiality and Data Protection .......................................................................................................38 
10. Insurance ......................................................................................................................................................39 
11. Protocol Deviations .......................................................................................................................................39 
12. Device Accountability ....................................................................................................................................39 
13. Study Management .......................................................................................................................................40 
13.1 
Data Management .................................................................................................................................40 
13.2 
Data Collection ......................................................................................................................................40 
13.3 
Source Documents .................................................................................................................................40 
13.4 
Record Retention ...................................................................................................................................40 
13.5 
Study Summary .....................................................................................................................................40 
13.6 
Amendments to the Protocol .................................................................................................................41 
13.7 
Monitoring ............................................................................................................................................41 
13.8 
Monitor or Designee Names and Addresses ...........................................................................................41 
13.9 
Clinical Events Committee .....................................................................................................................41 
14. Ethics Committee Approval ...........................................................................................................................42 
15. Statement of Compliance ..............................................................................................................................42 
16. Publication Policy ..........................................................................................................................................42 
17. Revision History ............................................................................................................................................43 
18. Bibliography ..................................................................................................................................................46 
 
 

DESCRIPTION: CIP-001 Clinical Investigation Plan for OCED System 
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Study Synopsis 
 
Study Sponsor: 
AtriAN Medical Ltd., 
Unit 204, NUIG Business Innovation Centre, Galway, 
Ireland. 
Contact Person: Barry O’Brien 
Title 
Safety and Feasibility of Atrial Deganglionation as an Adjunctive Therapy for Atrial 
Fibrillation 
Protocol Number 
CIP 001 
Regulatory Status 
For Clinical Investigation Use Only 
Investigational 
Device(s) 
Open Chest Epicardial Deganglionation (OCED) system 
Indications for Use 
Intended to ablate the autonomic ganglionated plexi (GP) structures on the epicardial 
surface of the heart to treat cardiac arrhythmia. 
Study Design  
A prospective, single-arm, multi-centre exploratory study of safety and feasibility in the 
treatment of patients undergoing cardiothoracic surgery. 
Study Objectives 
To assess the safety and feasibility of electroporation/Pulsed Electric Field (PEF) as a 
technology to achieve selective GP ablation. 
The primary hypothesis is that selective GP ablation (i.e. with minimal myocardial 
ablation) will lead to an extension in the atrial effective refractory period. 
Study Duration 
The study duration is expected to be 24 months including study close out. Patients will 
begin enrolment and undergo screening and surgical procedures 
Study Monitoring 
Study monitoring will be conducted by AtriAN designee as per the Monitoring Plan. 
Subject Assessments 
Screening, baseline evaluations & pre-procedural assessments will be used to 
determine subject eligibility for GP ablation. 
Sample Size 
Up to 30 subjects will be enrolled in the study. 
Investigational Sites 
• 
Tbilisi Heart & Vascular Clinic, Tbilisi, Georgia. 
• 
Na Homolce Hospital, Prague, Czech Republic. 
Patient Population 
Patients undergoing coronary artery bypass grafting (CABG). 
Inclusion Criteria 
To be eligible for this trial, subjects must meet all the following inclusion criteria: 
1. 
Age is between 18 and 70 years. 
2. 
Scheduled for open-chest cardiothoracic surgery, for coronary artery bypass 
grafting. 
3. 
Legally competent and willing to sign the informed consent. 
4. 
Life expectancy of at least 2 years. 

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Exclusion Criteria 
To be eligible for this trial, subjects must NOT meet any the following exclusion 
criteria: 
1. 
Previous cardiac surgery 
2. 
Prior pericardial interventions 
3. 
Prior pulmonary vein isolation (PVI) 
4. 
Previous or existing pericarditis 
5. 
Persistent or long-standing persistent atrial fibrillation 
6. 
Indication for surgical ablation or PVI for atrial fibrillation 
7. 
Indication for concomitant surgical valve repair or replacement 
8. 
Indication for concomitant left atrial appendage (LAA) ligation or excision 
9. 
History of previous radiation therapy on the thorax 
10. History of previous thoracotomy. 
11. Prior electrical or mechanical isolation of the Left Atrial Appendage (LAA) 
12. The presence of LAA occlusion devices, coronary stents, prosthetic heart valves, 
pacemakers or implantable cardioverter defibrillators (ICDs) 
13. Myocardial infarction within the previous 2 months 
14. New York Heart Association (NYHA) Class IV heart failure symptoms 
15. Left Ventricular Ejection Fraction (LVEF) < 40%, measured by transthoracic 
echocardiography (TTE) 
16. Left atrial diameter > 5.0 cm, measured by transthoracic echocardiography (TTE) 
17. The presence of left atrial thrombus when examined by transesophageal 
echocardiography (TEE) 
18. The presence of atrial fibrillation (AF) attributable to non-cardiovascular causes 
such as thyroid disease, electrolyte imbalance/dehydration or other reversible 
causes 
19. Active infection or sepsis as evidenced by increased white blood cell count, 
elevated C-reactive protein (CRP) or temperature > 38.5°C 
20. Known or documented carotid stenosis > 80% 
21. Stroke or transient ischemic attack within the previous 6 months  
22. Known or documented epilepsy 
23. Pregnancy or child-bearing potential without adequate contraception  
24. Circumstances that prevent follow-ups 
25. Drug abuse 
26. Patients cannot be enrolled in another clinical study 
Primary Safety 
Endpoint 
Rate of device related Primary Safety Adverse Events within 30 days of the procedure. 
Primary Safety Adverse Events include: 
1. 
Atrial perforation or excessive bleeding (excessive bleeding is defined as 
bleeding which requires any blood transfusion). 
2. 
Pericarditis 
3. 
Pericardial effusion 
4. 
Cardiac tamponade (if either surgical or percutaneous drainage is required). 
5. 
Constrictive pericarditis, requiring re-operation. 
6. 
Newly developed sinus node dysfunction 
7. 
Newly developed first, second or third degree atrioventricular (AV) block 
8. 
Vasovagal reactions during hospital stay 
9. 
Ventricular fibrillation 

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Primary Feasibility 
Endpoints 
The primary feasibility endpoint includes confirmation of access and delivery of Pulsed 
Electric Field energy to targeted ablation sites. 
Efficacy Endpoints 
The clinical effectiveness endpoints are defined as the following: 
• 
A primary efficacy end point will be confirmation of an extension in the atrial 
effective refractory period (AERP) through the Pulsed Electric Field ablation of 
the GPs. Experimental and clinical data indicates that GP ablation extends 
AERPs. 
• 
A secondary efficacy endpoint will be the incidence of post-operative atrial 
fibrillation (POAF) up to the point of patient discharge. Ablation of GPs is a 
potential prophylactic treatment for post-operative atrial fibrillation. Data will 
be collected to quantify duration (from ICU arrival) to first incidence of POAF, 
duration of first POAF episode and standard of care method used to treat the 
POAF. POAF is defined as any AF of 30 seconds or longer duration. 
Clinical Study 
Requirements 
Baseline: (* Standard of Care) 
• 
Inclusion/Exclusion criteria 
• 
Signed Informed Consent 
• 
Frequency of reported episodes of atrial fibrillation * 
• 
Medical History including NYHA class * 
• 
Documentation of Smoking and Substance abuse * 
• 
Medication History, review of current and past Medications* 
• 
General Physical Exam* 
• 
ECG (12 Lead)* 
• 
24Hr Holter recording documentation of AF, frequency and severity of AF and 
presence of asymptomatic episodes if relevant  
• 
TTE for LVEF and LA diameter* 
• 
Blood sample for laboratory investigation comprising Hgb, WBC, Platelet, Na, K, 
Creatinine, NT-proBnP, Troponin, C-reactive protein, TSH, INR * 
• 
Short form-36 (SF-36) QOL 
• 
TEE to assess for LA thrombus per elective procedure* 
 
Procedure & Post-procedure 
• 
GP ablation 
• 
AERP 
• 
Device Performance 
• 
Adverse event assessment 
• 
Protocol Deviation assessment 
• 
Cardiac Telemetry through to discharge (Post-Operative AF Detection) 
 
Discharge 
• 
Physical exam 
• 
ECG (12 Lead) 
• 
Medications 
• 
Adverse event assessment 
• 
Protocol Deviation assessment 
 

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Follow-Up Intervals at 30 Days (±7days), 3M (±30days),  
6M (±45days) and 12M (±60days) 
• 
Physical exam 
• 
Blood tests (6M only) 
• 
Short form-36 (SF-36) QOL  (12M only) 
• 
Medications 
• 
ECG (12 Lead) 
• 
24HR Holter  (30 Days, 3M, 6M, 12M) 
• 
Adverse event assessment  
• 
Protocol Deviation assessment 
Statistical Analysis 
The study is not powered for any formal hypotheses testing or inference. Therefore, 
the statistical analyses conducted will be descriptive in nature. The primary safety, 
feasibility and efficacy endpoints will be summarized with descriptive statistics. 
 

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Schedule of Assessments (* Standard of Care) 
NYHA – New York Heart Association; TTE – transthoracic echocardiography; LVEF – left ventricular ejection fraction; LA – left 
atrium; SF-36 – Short Form 36; AAD-ATT – antiarrhythmic drugs and antithrombotic therapy; ECG – electrocardiogram; TEE – 
transesophageal echocardiography; AERP – atrial effective refractory period.
Schedule of Tests: 
Baseline 
Procedure  
Post-
Procedure 
to 
Discharge 
Discharge 
30 Days 
±7 days 
3 Mo 
±30 
Days 
6 Mo 
±45 
Days 
12 Mo 
±60  
Days 
Subject Eligibility/ 
Informed Consent 
X 
 
 
 
 
 
 
 
Medical history & 
Demographics* 
X 
 
 
 
 
 
 
 
NYHA Score*  
X 
 
 
 
 
 
 
X 
Physical Exam* 
X 
 
 
X 
X 
X 
X 
X 
TTE for LVEF and LA 
diameter* 
X 
 
 
 
 
 
 
 
Blood tests* 
X 
 
 
 
 
 
X 
 
SF-36 QOL 
X 
 
 
 
 
 
 
X 
Medication Log* 
(AAD-ATT) 
X 
 
 
X 
X 
X 
X 
X 
ECG (12 Lead) * 
X 
 
 
X 
X 
X 
X 
X 
TEE to exclude 
thrombus* 
X 
 
 
 
 
 
 
 
24HR Holter * 
X 
 
 
 
X 
X 
X 
X 
Cardiac Telemetry 
 
 
X 
 
 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
X 
Device Performance 
 
X 
 
 
 
 
 
 
AERP 
 
X 
 
 
 
 
 
 

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1. Background and Justification of the Proposed Trial Design 
Atrial fibrillation (AF) is the most common chronic arrhythmia in man. In the European Union, its prevalence is 1.5-
2% in the total population, and this number is expected to increase in the forthcoming decades1. AF is associated 
with a five-fold increased risk of stroke, a doubled risk of mortality and an increased risk of heart failure and 
cognitive impairment. Whether AF causes these detrimental concomitant diseases or is merely a marker of a bad 
vascular prognosis is debated. Similarly, prospective evidence that AF ablation improves prognosis is not yet 
available. However, a recent propensity matched study from Sweden demonstrated that AF ablation was associated 
with less stroke and a lower mortality rate2. 
In patients with symptomatic paroxysmal AF refractory for antiarrhythmic drugs (AAD), catheter ablation, 
pulmonary vein isolation in particular, is a successful treatment strategy3. A large proportion of AF patients have 
more advanced forms of AF, which is persistent (not spontaneously terminating or requiring electrical 
cardioversion), with enlarged left atria or after previously failed catheter ablations. In those patients, isolation of 
the pulmonary veins may be insufficient to achieve an acceptable procedural success4. The HRS/EHRA/ECAS 
consensus statement suggests that additional ablation may be warranted in those patients5.  
Therefore, a plethora of additional ablation approaches have been attempted over the last decade, among which 
the ablation of additional left atrial lines6, the ablation of continuous fractionated atrial electrograms (CFAE)7, 
ablation of rotors8 and modulation of the autonomic nervous system9,10. Interestingly, the recent STAR-AF II trial 
randomized patients with persistent AF to pulmonary vein isolation (PVI) alone, PVI+CFAE ablation or PVI+ 
additional left atrial lines and found no difference in AF recurrence among these groups11. Basically, all these 
additional ablation strategies rely in some way on extended ablation of the atrial myocardium, which, in itself, may 
create channels for conduction and iatrogenic AF recurrences. This could (at least in part) explain the limited efficacy 
of those additional ablation strategies. If, however, additional ablation strategies could be performed without 
increasing the risk of iatrogenic AF, this could importantly improve the results of invasive therapy for advanced 
atrial fibrillation. 
 
Role of the autonomic nervous system 
The autonomic nervous system has been demonstrated to play an important role in initiation and perpetuation of 
AF. Injection of cholinergic agents into the ganglionated plexi (GPs), electrical stimulation of nerves, and pacing 
induced AF induces proarrhythmic autonomic hyperactivity12 13, leading to shortening of the atrial and PV APD 
(parasympathetic effect), and increase of intracellular [Ca2+] (sympathetic effect), resulting in triggered firing and 
induction of AF. Indeed, injection of botulinum toxin into the epicardial fat pads containing the GPs results in 
reduction of postoperative AF in patients undergoing coronary artery bypass grafting (CABG) surgery14, but in 
addition appears to have a beneficial long-term effect on freedom of AF in this population15. However, in patients 
without pre-existent AF the beneficial effects of botulinum injection into the GPs are less clear16,17. Though 
radiofrequency (RF) ablation of GPs in CABG patients without AF has also shown potential for post-operative AF 
reduction18. The development of post-operative AF is associated with a higher risk of atrial fibrillation and stroke in 
the long term19. 
GP stimulation also directly affects atrial myocardial electrophysiology in a proarrhythmic manner and consistent 
with a predominantly parasympathetic action20. Disconnecting the extrinsic from the intrinsic cardiac innervation 
results in shortened regional refractory periods in dogs, and an increased burden of atrial fibrillation and atrial 
tachycardia (AF/AT) starting after 4-5 weeks21. Thus, removing the inhibitory effect of the extrinsic on the intrinsic 
autonomous cardiac innervation causes proarrhythmogenic hyperactivity of the GPs, which provides the rationale 
for GP ablation. Indeed, Katritsis et al. demonstrated fewer recurrences in paroxysmal AF patients randomized to 
catheter ablation of 4 major GPs areas and Marshall’s ligament in addition to PVI versus either treatment in 
isolation. An anatomical approach toward GP ablation conferred less AF recurrence than an evoked vagal response 
based localization22. These were catheter ablation studies in patients with only paroxysmal AF, and it cannot be 

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discerned whether these effects are caused by GP ablation or by more atrial myocardial ablation, resulting in more 
rigorous and longer lasting PVI. The AFACT trial attempted to overcome these issues by randomizing patients 
undergoing thoracoscopic ablation of AF between additional epicardial radiofrequency ablation of the 4 major GPs 
versus no additional GP ablation. The study showed no benefit in absence of AF after one and two years, but 
significantly more surgical complications, mainly major bleedings23. Also, more sinus node dysfunction was noted 
in the GP group, and more pacemaker implantations. A sub-analysis of recurrences in AFACT showed that atrial 
tachycardias were more frequently noted in the GP ablation group, at least suggesting that the myocardial substrate 
was modified by GP ablation to facilitate atrial tachycardias. Therefore, it is very well possible that epicardial 
radiofrequency GP ablation in AFACT was not tissue selective, and additional myocardial ablation took place, 
resulting in the adverse effect of more atrial tachycardias.  
Hence, radiofrequency ablation appears not selective for the GPs, and inadvertent myocardial ablation seems to 
occur both with endocardial as with epicardial approaches. An ablation approach selective for nervous system tissue 
may overcome this and may combine the potential benefits of GP ablation with the absence of iatrogenic atrial 
tachycardias. 
 
Electroporation to cause selective irreversible cell damage within the GP - with minimum myocardium ablation. 
Electroporation refers to the principle that cell membranes become permeable when subjected to high voltage, 
which results in apoptosis and cell death. Typically, very short episodes (microseconds) of high voltage are applied 
to the tissue to ablate. This technology has been used successfully in the treatment of various types of cancer24,25. 
One of the attractive features of the technology is the relative tissue selectivity, allowing ablation of the tissue of 
choice while sparing the surrounding structures, such as for example vessels26 Particularly larger cells, such as 
neurons appear vulnerable for electroporation27,28. Therefore, in this instance, the electroporation enables 
irreversible damage to the GP, while sparing the myocardium and other adjacent tissues. 
Electroporation - also known as Pulsed Electric Field (PEF) - now has also successfully been applied to isolate the 
pulmonary veins during catheter ablation for AF, making use of specificity for myocardial tissue when adjusting the 
characteristics of the electroporation pulse. The early reports on this strategy indicate that the technology is 
effective on acute and short-term outcomes, and safe as there were no cases of injury of the oesophagus or phrenic 
nerves29,30, supporting the premise that this technology (using adjusted pulse characteristics) is tissue specific. 
 
Electroporation [PEF] - Acute animal experiments 
Madhavan et al. have described the effects of GP ablation with DC electroporation in 6 dogs, in which the heart was 
approached via subxiphoid access31. The authors demonstrate that with specially designed catheters, 
electroporation can be applied to abolish the GP response, with only a limited effect on atrial bipolar voltage, 
indicating no or limited myocardial ablation. In one animal ventricular fibrillation was induced, as a consequence of 
inadvertent movement of the catheter over the ventricle. Subsequent work utilized ECG gating of the electrical 
pulses to ensure that energy is delivered only during the ventricular refractory period; this showed that a much 
higher voltage than that used for GP ablation was required to cause ventricular fibrillation (VF) (3/3 animals had VF 
with 3000V, 1/4 with 2500V and none with ≤2000V) when the catheter was positioned on the ventricle. This work 
showed that GP ablation can be accomplished by applying ten 1000V pulses of 100 µs duration. Atrial effective 
refractory periods (AERP) consequently prolonged after GP ablation, indicating ceasing of vagal AERP shortening, 
and AF inducibility decreased. Pathological examination after the ablation procedure showed no pericardial lesions 
or adhesions, no damage to vessels or to the phrenic nerve, and no injuries to the transverse sinus, oblique sinus 
or left atrial posterior wall. These data support the acute tissue selectivity of DC electroporation for nervous tissue, 
sparing the myocardium and surrounding tissues. 
 
 

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Electroporation [PEF] - Chronic animal experiments 
In another set of experiments, Padmanabhan et al. used a scoring system from grade 0 to III (from no damage, 
modified damage, >50% damage and >90% damage) for myocardial damage following GP electroporation32. They 
demonstrated in 6 dogs that after approximately 4 months, there was no myocardial damage following GP ablation 
in 15/21 ablated GP sites, with only minimal myocardial damage at 5/21 sites and myocardial damage greater than 
grade I at 1/21 site. All GP lesions were grade III or higher, with documentation of spill over ganglionic lesions at 
distant, non-ablated GPs. There were no signs of esophageal damage. These data demonstrate that also in the 
intermediate term, there is no evidence of concomitant damage, supporting the selectivity of the DC 
electroporation for ablation of nervous tissue with minimal ablation of the surrounding myocardium. 
 
 
2. Device Description 
AtriAN Medical’s treatment involves ablation of ganglionated plexi structures on the epicardial surface of the heart. 
Using a Pulsed Electric Field (PEF) energy source and specialty catheters, the AtriAN System ablates these structures 
selectively with no or minimal myocardial injury. The system is known as the Open Chest Epicardial Deganglionation 
(OCED) system and is intended to ablate the autonomic ganglionated plexi structures on the epicardial surface of 
the heart. Treatment using this ‘OCED’ System is delivered as a concomitant procedure during open heart surgery 
with the intended purpose of eliminating autonomic drivers of atrial fibrillation, including post-operative atrial 
fibrillation. The system consists of the following components: 
 
2.1 Catheters - Finger & Glove 
The Glove catheter is used to ablate the oblique sinus ganglia (inferior right and inferior left ganglia). The 
Finger catheter is used to ablate the superior left, right superior, Vein of Marshall and transverse sinus 
ganglia. The Glove and Finger catheters are used separately, and both will be used during the procedure. 
The main body of the catheter consists of a flexible braided sheath. The distal end of each catheter is 
steerable via a wire pulling system on the catheter handle. Each electrode has an irrigation hole for 
infusion of saline to aid with procedure outcomes. On both catheters the back of the electrodes are 
insulated. Selective GP ablation is performed using monopolar direct current supplied by the PEF 
Generator. 
 

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Figure 1: Drawing of the Finger Catheter 
 
 
 
 
Figure 2: Drawing of the Glove Catheter  
 
 
2.2 Dispersive Pad 
This electrode/pad allows the return of the electrical path from the patient to the generator during the 
procedure. It has a large surface area and is attached to the patient's body typically in the shoulder or 
lumbar region. AtriAN will include a commercially available single-use adult dispersive pad as part of the 
OCED system. 
 
2.3 ECG Synchronization Unit 
The purpose of this unit is to trigger the correct timing of the 1000 V DC, 100 µs pulses to the treatment 
site. This timing is critical and must occur during the ventricular refractory period so as not to induce 
ventricular fibrillation. AtriAN is using a commercially available synchronization unit; system testing has 
been performed with this unit integrated with the generator. 
 

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2.4 PEF Generator 
The PEF generator, with footswitch, provides 1000 V DC, 100 µs pulses to the connected catheter and 
dispersive pad circuit. The generator includes a user interface for input of treatment parameters which 
operates on a Linux system. The generator (Model PEFG01) and user interface has been developed 
specifically by AtriAN for this cardiac treatment. 
 
 
Figure 3: AtriAN Pulsed Electric Field Generator 
 
 
 

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3. Intended Use 
The Open Chest Epicardial Deganglionation (OCED) system is intended to ablate the autonomic ganglionated plexi 
structures on the epicardial surface of the heart to treat cardiac arrhythmia. 
 
4. System Training 
Training will be provided by AtriAN to site investigation staff on all aspects of the AtriAN system, including selection 
and input of treatment parameters, connection of system parts, operation of catheters and delivery of ablation 
pulses. While the targeted anatomical locations are readily identified, training and instruction will be provided in 
terms of accessing and identifying these in the open-chest setting. 
The investigation team will need to be qualified and experienced in both cardiac surgery and cardiac 
electrophysiology. Specifically, the device will be used during a concomitant median sternotomy and in addition to 
applying the ablative treatments to the epicardial surface, cardiac pacing and measurements will be required to 
assess treatment. 
 
5. Risk Benefit Analysis 
A comprehensive risk analysis has been performed by AtriAN Medical Ltd in accordance with EN ISO 14971. Use of 
Failure Modes and Effects Analysis (FMEA) and Hazard Analysis techniques have identified potential device 
malfunctions and potential user errors along with clinical procedure risks. Mitigation steps to address each of the 
potential device malfunctions and potential user error risks along with clinical procedure risks have been 
implemented to reduce the risks as low as possible. These mitigation actions include extensive performance and 
safety testing, pre-clinical studies, development of Instructions for Use and User Manuals as well as development 
of user training materials. None of the remaining residual risks are higher than the risks associated with the use of 
currently available surgical and ablation tools. Section 8.9 of this document presents a list of the anticipated adverse 
events associated with GP ablation (deganglionation) in the planned concomitant open-chest surgical setting - these 
represent the risks associated with participation in this trial. 
 
Of the risks directly associated with GP ablation, using the AtriAN system, that of ventricular fibrillation is noted as 
potentially having the highest severity. However, central to the mitigations here is the use of ECG-gated delivery of 
pulse energy which ensures that the ablation pulse is delivered during the refractory period of the cardiac cycle. 
This risk mitigation approach has been demonstrated during AtriAN’s pre-clinical (animal) studies. Ventricular 
arrhythmia was also not observed in clinical studies that utilized voltages and pulse energies higher than AtriAN is 
using 29, 30. Ventricular arrhythmia is not an uncommon occurrence during cardiac surgery and is dealt with using 
standard defibrillation techniques. Therefore, induction of ventricular fibrillation during GP ablation is not expected 
to harm study subjects. 
 
The anticipated benefit of GP ablation is the reduced likelihood of experiencing post-operative atrial fibrillation in 
the days after the cardiac surgery 14, 18 - thus reducing the associated risk of stroke and the possibility of extended 
durations in hospital. The development of post-operative atrial fibrillation is also associated with a higher risk of 
atrial fibrillation and stroke in the long term (Ref 19) - thus the GP ablation may also reduce the probability of 
developing these longer-term complications. For patients that may already have paroxysmal atrial fibrillation there 
is also a potential benefit in that the GP ablation may reduce or eliminate the incidence of this condition 10, 15. 
In summary, based on a review of the potential benefits along with the residual risks identified through the 
completion of risk management activities to date, the overall residual risk is considered appropriate for the clinical 
benefits. Additionally risk management principles with relating risk control measures are implemented to both the 
planning and the conduct of clinical investigation, in order to ensure the reliability of the clinical data generated 
and the safety of subjects. 

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6. Study Protocol 
6.1 Study Objectives 
The objective of this first-in-human study is to assess the safety and feasibility of electroporation/PEF as 
a technology to achieve selective GP ablation. 
The primary hypothesis is that selective GP ablation (i.e. with minimal myocardial ablation) will lead to an 
extension in the atrial effective refractory period. 
 
6.2 Study Design 
This is a prospective, single arm, exploratory study of safety and feasibility in the treatment of up to 30 
patients undergoing cardiothoracic surgery; as such no control or comparator group is required. The study 
will be performed at two sites; 
• 
Tbilisi Heart & Vascular Clinic, Tbilisi, Georgia. 
• 
Na Homolce Hospital, Prague, Czech Republic. 
 
The primary feasibility endpoint will be demonstration of ability to access and deliver Pulsed Electric Field 
energy to all of the targeted ablation sites. 
A primary efficacy end point will be to achieve an extension in the atrial effective refractory period (AERP) 
through the Pulsed Electric Field ablation of the GPs. Experimental and clinical data indicates that GP 
ablation extends AERPs. 
 
A secondary efficacy endpoint will be the incidence of post-operative atrial fibrillation up to the point of 
patient discharge. Ablation of GPs is a potential prophylactic treatment for post-operative atrial 
fibrillation. Data will be collected to quantify duration (from ICU arrival) to first incidence of POAF, 
duration of first POAF episode and standard of care method used to treat the POAF. POAF is defined as 
any AF of 30 seconds or longer duration. 
 
This exploratory treatment will be performed on patients undergoing elective open-chest cardiothoracic 
surgery. Once the heart is exposed, the treatment is performed before the elected procedure; the 
exploratory treatment and measurements will take 35-40 minutes to complete. 
 
The sponsor will supply the ablation catheters, the pulsed electric field generator, the ECG synchronization 
unit and the patient dispersive pad. The investigation site will be expected to supply the stimulator and 
recording system for measurement of AERP, including the necessary temporary epicardial pacing wires. 
In addition, a conventional irrigation pump and tube set is required on-site for delivery of physiological 
saline through the ablation catheter during the pulse delivery. 
 
 

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6.3 Study Rationale 
This study is intended to evaluate the safety and feasibility of the OCED system to ablate autonomic 
ganglionated plexi structures on the epicardial surface of the heart. The patient population will be those 
undergoing coronary artery bypass grafting (CABG). 
 
6.4 Sample size 
The study will include up to 30 patients with completed GP ablations. The justification for the number of 
test subjects is described in the Statistical Justification section below. 
A subject is considered enrolled once he/she signs the informed consent form. All enrolled subjects will 
then proceed to complete the screening and any applicable baseline tests. If they do not meet the study 
criteria they will be withdrawn from the study and will not count towards the treated study population.  
If a subject meets all inclusion criteria and none of the exclusion criteria and are deemed eligible for this 
study, they will be treated with the study device and system. Patients will be followed for approximately 
12 months post-procedure. 
 
6.5 Statistical Justification and Analysis of Results 
This trial is intended to demonstrate safety and feasibility and is not designed to be a statistically 
significant study. As a result, no formal statistical hypothesis is planned to derive the appropriate sample 
size. 
For all primary safety and performance endpoints, the 95% 2-sided exact binomial confidence intervals 
will be presented. 
For the secondary end-point of AERP extension, it is anticipated that a 10% extension may be obtained. 
This will be assessed using Paired t-testing from the pre-treatment and post-treatment AERP values from 
all patients. 
 
6.6 Site Selection and Training 
All operators included in this clinical trial will be trained by the Sponsor in the use of investigational device.  
Study training will be documented and will include a review of the following:  
• 
the investigational plan,  
• 
ISO 14155, Declaration of Helsinki (2013),  
• 
SAE reporting,  
• 
Good Clinical Practices (GCPs)  
• 
and all study procedures. 
 
Each site will have a site qualification visit to assure the Investigator clearly understands and accepts the 
obligations incurred in undertaking the study and that the facilities and systems for conducting the study 
are acceptable. Each site must have equipment for conducting cardiac ablation procedures including 
equipment for cardiac pacing and recording and should have permission according to local law to perform 
cardiac ablations. 
 
6.7 Patient Inclusion Criteria 
• 
Age is between 18 and 70 years. 
• 
Scheduled for open-chest cardiothoracic surgery, for coronary artery bypass grafting. 
• 
Legally competent and willing to sign the informed consent. 
• 
Life expectancy of at least 2 years. 
 

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6.8 Patient Exclusion Criteria 
A potential subject who meets any of the following criteria will be excluded from participation in this 
study: 
• 
Previous cardiac surgery. 
• 
Prior pericardial interventions. 
• 
Prior pulmonary vein isolation (PVI). 
• 
Previous or existing pericarditis. 
• 
Persistent or long-standing persistent atrial fibrillation. 
• 
Indication for surgical ablation or PVI for atrial fibrillation. 
• 
Indication for concomitant surgical valve repair or replacement. 
• 
Indication for concomitant left atrial appendage (LAA) ligation or excision. 
• 
History of previous radiation therapy on the thorax. 
• 
History of previous thoracotomy.  
• 
Prior electrical or mechanical isolation of the Left Atrial Appendage (LAA). 
• 
The presence of LAA occlusion devices, coronary stents, prosthetic heart valves, pacemakers or 
implantable cardioverter defibrillators (ICDs). 
• 
Myocardial infarction within the previous 2 months. 
• 
NYHA Class IV heart failure symptoms.  
• 
Left ventricular ejection fraction (LVEF) < 40%, measured by transthoracic echocardiography (TTE). 
• 
Left atrial (LA) diameter > 5.0 cm, measured by transthoracic echocardiography (TTE). 
• 
The presence of left atrial thrombus when examined by transoesophageal echocardiography (TEE).  
• 
The presence of AF attributable to non-cardiovascular causes such as thyroid disease, electrolyte 
imbalance/dehydration or other reversible causes. 
• 
Active infection or sepsis as evidenced by increased white blood cell count, elevated CRP or 
temperature > 38.5°C. 
• 
Known or documented carotid stenosis > 80% 
• 
Stroke or transient ischemic attack within the previous 6 months.  
• 
Known or documented epilepsy. 
• 
Pregnancy or child-bearing potential without adequate contraception.  
• 
Circumstances that prevent follow-ups. 
• 
Drug abuse. 
• 
Patients cannot be enrolled in another clinical study 
 
The study will involve up to 30 patients with completed GP ablations. Recruitment is anticipated to be 
completed within 9 months. 
 
Subjects may withdraw from the study at any time for any reason if they wish to do so without any 
consequences. The investigator can decide to withdraw a subject from the study for urgent medical 
reasons. Patient recruitment will be terminated prematurely at any time if the risk of serious adverse events 
exceeds the expected benefit of the trial. 
 
 

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7. Study Endpoints 
7.1 Primary Safety Endpoint: 
Rate of device related Primary Safety Adverse Events within 30 days of the procedure. 
Primary Safety Adverse Events include: 
1. 
Atrial perforation or excessive bleeding (excessive bleeding is defined as bleeding which requires 
any blood transfusion). 
2. 
Pericarditis 
3. 
Pericardial effusion 
4. 
Cardiac tamponade (if either surgical or percutaneous drainage is required). 
5. 
Constrictive pericarditis, requiring re-operation. 
6. 
Newly developed sinus node dysfunction. 
7. 
Newly developed first, second or third degree atrioventricular (AV) block 
8. 
Vasovagal reactions during hospital stay 
9. 
Ventricular fibrillation 
 
7.2 Primary Feasibility Endpoints: 
The primary feasibility endpoint includes confirmation of access and delivery of Pulsed Electric Field 
energy to targeted ablation sites. 
 
7.3 Efficacy Endpoints: 
The clinical effectiveness endpoints are defined as the following: 
• 
A primary efficacy end point will be confirmation of an extension in the atrial effective refractory 
period (AERP) through the Pulsed Electric Field ablation of the GPs. Experimental and clinical data 
indicates that GP ablation extends AERPs. 
• 
A secondary efficacy endpoint will be the incidence of post-operative atrial fibrillation up to the 
point of patient discharge. Ablation of GPs is a potential prophylactic treatment for post-operative 
atrial fibrillation. Data will be collected to quantify duration (from intensive care unit (ICU) arrival) 
to first incidence of POAF, duration of first POAF episode and standard of care method used to treat 
the POAF. POAF is defined as any AF of 30 seconds or longer duration33. 
 
 

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8. Study Procedure and Data Collection 
The following baseline data must be collected prior to the procedure for all subjects meeting the inclusion criteria 
(*Assumed to be standard of care): 
• 
Baseline: 
o 
Inclusion/Exclusion criteria 
o 
Signed Informed Consent 
o 
Frequency of reported episodes of atrial fibrillation * 
o 
Medical History including NYHA class * 
o 
Documentation of Smoking and Substance abuse * 
o 
Medication History, review of current and past Medications* 
o 
General Physical Exam* 
o 
12 Lead ECG* 
o 
24Hr Holter recording documentation of AF, frequency and severity of AF and presence of 
asymptomatic episodes if relevant  
o 
TTE for LVEF and LA diameter* 
o 
Blood sample for laboratory investigation comprising Hgb, WBC, Platelet, Na, K, Creatinine, NT-
proBnP, Troponin, C-reactive protein, TSH, INR * 
o 
Short form-36 (SF-36) QOL 
o 
TEE to assess for LA thrombus per elective procedure* 
 
The procedures required for screening and baseline may be conducted during more than one visit, provided that all 
procedures are conducted within 90 days prior to the index procedure. 
• 
123I-mIBG Scintigraphy and SPECT - UMC Amsterdam only 
 
• 
Study Procedure: 
After opening of the chest (and after cannulation at the discretion of the operator), but before 
cardiopulmonary bypass and cardioplegia, baseline atrial effective refractory period (AERP) will be 
determined. The atrial GPs will then be ablated, with AERP measurements performed at intermediate 
timepoints and after all GP ablations. 
 
Paralytic Agent 
In addition to standard of care general anaesthesia, a paralytic agent or nerve block needs to be 
administered to suppress skeletal muscle stimulation. Vecuronium or Rocuronium are the preferred drug 
options as these have minimal impact on AERP values; however, the baseline AERP reading should be taken 
with paralytic already administered, just before the first ablation. 
 
Measurement of AERP 
AERP will be measured at any one, or more, of the following sites: left atrial appendage, left atrium or right 
atrium, depending on clinician preference. Measurements will be performed using temporary epicardial 
pacing wires; one wire connected to the measurement site (-ve) and one wire positioned subcutaneously 
(+ve); the wires are connected to the stimulator unit of an EP system. A standard diagnostic quadripolar EP 
catheter will be positioned behind the atrium and connected to the EP system for recording atrial activation 
and sensing of capture. Check that the temperature of the heart is 36˚C -1/+2˚C just before, during or just 
after AERP measurement. 
AERP will be determined with standard premature pacing protocols. Pace the measurement site (i.e. left 
atrial appendage, left atrium or right atrium) with a train of 8 S1 cycles at Basic Cycle Length 500 ms, output 

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in range 10-20 mA, pulse width 2-3 ms, followed by an S2 of 400 ms. Once capture of S2 is confirmed 
immediately continue with the next pacing train. Progressively shorten S2 by 50 ms per cycle, until loss of 
capture is observed. Then retry at the last S2 coupling interval that captured and reduce coupling interval 
of S2 by 10 ms per cycle until loss of capture is observed on 2 consecutive occasions. The longest S2 coupling 
interval that does not capture is the AERP. 
If attempts to measure AERP result in atrial fibrillation or atrial flutter, a cardioversion should be attempted, 
after which a waiting time of 10 minutes is needed before new attempts to measure AERP are undertaken. 
If more than one cardioversion is needed, removing that patient from the study analysis should be 
considered. 
 
Ablation of GPs 
The GPs to be ablated in this study are illustrated in Figure 4. The sequence of the ablations will be as 
follows: 
1) 
Oblique Sinus GP (OSGP) 
These are the retro-atrial GPs located on the posterior left atrium, close to the junction of the 
pulmonary veins and the left atrium. They are sometimes separately identified as the inferior left GP 
(ILGP) and inferior right GP (IRGP). 
2) 
Right Superior GP (RSGP) 
This is located on the anterosuperior surface of the right atrium, medial to the superior vena 
cava/right atrium junction and lateral to the aortic root. 
3) 
Transverse Sinus GP (TSGP) 
This is located at the base of the aorta and pulmonary artery within the transverse sinus. 
4) 
Left Superior GP (LSGP) 
The superior left GP is located at the junction of the left superior pulmonary vein with the posterior 
left atrium, in the left superolateral area. 
5) 
Ligament of Marshall GP (LMGP) 
This is located between the anterior aspect of the left pulmonary veins and the posterior left atrial 
appendage. 
 
 
 
Figure 4: Targeted ablation locations; OSGP, RSGP, TSGP, LSGP and LMGP. 
 

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AERP will be determined at baseline (before ablations) and after all ablations are completed. In addition, at 
the discretion of the operator, intermediate AERP measurements may be made after ablation of the OSGP 
and after TSGP ablation. The sequence of ablations and measurements is therefore as shown in Figure 5. 
The OSGP is ablated with the Glove catheter while all other sites are ablated with the Finger catheter. Each 
ablation sequence consists of 10 sequential ECG-gated pulses; each pulse at 1000 V and of 100 µs duration. 
Each GP location is ablated with between three and six of these sequences; in some instances a pull-back 
of a few millimetres or catheter repositioning is allowable between sequences in order to ensure good 
coverage of the target area. Optionally, the OSGP may be treated using separate approaches from the left 
and right sides i.e. individually treating the inferior left and inferior right GPs with up to three sequences 
each, rather than treating them as a single entity. A 0.9% normal saline solution is irrigated through the 
catheter at a flow rate of 2 ml/min, during ablation only. 
 
 
 
 
 
Figure 5: Sequence of ablations and AERP measurements 
 
Document electrical cardioversion or defibrillation during the procedure in the study records. The record 
should indicate when this was performed i.e. before ablations/measurements, between specific 
ablations/measurements or after final AERP measurement (during the index procedure). 
 
 

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• 
Index Cardiac Surgery Procedure 
Upon completion of GP ablations and AERP measurements, the elected cardiothoracic surgery will progress 
as planned. 
• 
Post-Operative Care and Discharge: 
o 
Adverse Events and Concomitant AAD-ATT Medication 
o 
Cardiac telemetry through to discharge. 
o 
ECG 
o 
Physical Exam 
• 
Follow-Up at 30 Days: 
o 
24 Hr. Holter for Frequency and Duration of atrial arrhythmias 
o 
Adverse Events and Concomitant AAD-ATT Medication 
o 
ECG 
o 
Physical Exam 
• 
3 months: 
o 
24 Hr. Holter for Frequency and Duration of atrial arrhythmias  
o 
Adverse Events and Concomitant AAD-ATT Medication 
o 
ECG 
o 
Physical Exam 
• 
6 months: 
o 
24 Hr. Holter for Frequency and Duration of atrial arrhythmias 
o 
Adverse Events and Concomitant AAD-ATT Medication 
o 
ECG 
o 
Physical Exam 
o 
Blood sample for laboratory investigation comprising Hgb, WBC, Platelet, Na, K, Creatinine, NT-
proBnP, Troponin, C-reactive protein, TSH, INR 
• 
12 months: 
o 
24 Hr. Holter for Frequency and Duration of atrial arrhythmias 
o 
Short Form-36 (SF-36) QOL 
o 
Adverse Events and Concomitant AAD-ATT Medication 
o 
ECG 
o 
Physical Exam 
o 
NYHA score 
 
8.1 Informed Consent 
Patients will be asked to sign informed consent after an explanation of the risks and potential benefits has 
been provided. Informed consent must be obtained from each patient prior to conducting any study-
related procedures including screening procedures that are not part of the standard of care at the 
institution.  Patients with a planned cardiothoracic surgical procedure will receive written information 
about the study prior to their scheduled procedure date to give sufficient time to carefully read the patient 
information letter. During the pre-procedural outpatient clinic visit the investigator or his staff will provide 
information about the study in case any questions remain. The information is intended to give each 
participant a thorough understanding of the purpose and the nature of the trial, the cooperation required, 
anticipated benefits, and potential hazards of the study. The investigator also explains that the subject is 
completely free to refuse or to withdraw from the study and that if he/she does so then he/she receives 
standard treatment with the same degree of care. It is the responsibility of the treating physician or his 
staff to obtain written informed consent (according to local legal requirements and regulations). A consent 

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form (in the native language) will be made available. The consent form will be signed and dated by both 
the investigator or his staff and the subject. The subject is obliged to date the informed consent 
him/herself. The fact that informed consent was obtained is recorded in the Case Report Form (CRF). 
Screening failures will not be followed further and will not be counted toward the maximum possible 
patients who receive treatment. 
The Investigator will retain an original of the signed informed consent document in each patient’s record, 
and also provide an original to the patient. The Investigator shall not request the written informed consent 
of any patient and shall not allow any patient to participate in the investigation, before obtaining Ethics 
Committee (EC) and or Competent Authority approval. 
Prior to starting the study, the Investigator will provide the Sponsor with a copy of the Informed Consent 
Document approved by the EC with documented evidence that the EC has approved the protocol. 
 
8.2 EDC Data Collection Platform 
Study data will be recorded in a limited-access, secure electronic data capture (EDC) system with data 
entry into electronic case report forms (eCRFs) that capture the data for each enrolled Subject, as required 
by the clinical study protocol.  Data reported on the CRF, which are derived from Source Documents, must 
be consistent with the Source Documents or the discrepancies must be explained. 
Investigators are responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported to the Sponsor in the eCRF. eCRFs must be completed by Investigators or their authorized 
personnel. 
An audit trail must be maintained for any changes or corrections to an eCRF. 
Paper CRF changes or corrections must be dated, initialled, and explained (if necessary) and must not 
obscure the original entry. Changes and corrections to eCRFs should be made by the data originator, 
Investigator or their authorized personnel. If it is necessary for Sponsor personnel to make changes to the 
eCRF, a justification for the necessity should be documented and any such changes must be endorsed by 
the Investigator. 
By default, users of the EDC system should have view-only permissions, unless the user’s specific role 
requires entering or changing data. A list of all individuals with authorized access the EDC will be 
maintained. The list of authorized users will reflect the permissions assigned for each user and the dates 
that access was granted and terminated.  Access will be terminated as soon as possible for users that are 
no longer working on the study (e.g., terminated employees, site closures, Investigator disqualification, 
etc.) and for users that have demonstrated intentional misuse. 
The EDC system will be designed with computer-generated, time-stamped electronic audit trails. Audit 
trails must apply to the creation, modification or deletion of any data elements and must capture the user 
that is creating, modifying or deleting data. The reason for modifications and deletion of data should also 
be captured. 
Data will be backed up and archived in a manner that protects against catastrophic loss and ensures the 
quality and integrity of the data. 
Signed electronic records must contain the following information associated with the signing that clearly 
indicates: 
• 
Printed name of the signer; 
• 
Date and time when the signature is executed; and 
• 
Meaning (such as review, approval, responsibility or authorship) associated with the signature. 
 
An electronic signature must be linked to the respective electronic record to ensure that signatures cannot 
be excised, copied, or otherwise transferred to falsify and electronic record by ordinary means. Each 

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electronic signature must be unique to one individual and may not be reused or reassigned to anyone 
else. 
The system facilitating electronic signatures will be designed so that the attempted use of an electronic 
signature by anyone other than the genuine user requires collaboration by two or more individuals. 
 
8.3 Study Completion 
The date of study completion for study subjects who complete all follow-ups is recorded on the STUDY 
COMPLETION Case Report Form. 
 
 

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8.4 Schedule of Events 
The tests and measurements to be conducted at baseline, during the treatment procedure, and during 
follow-up visits are illustrated in the following chart. (*Considered as Standard of Care) 
NYHA – New York Heart Association; TTE – transthoracic echocardiography; LVEF – left ventricular ejection fraction; LA – left atrium; SF-36 
– Short Form 36; AAD-ATT – antiarrhythmic drugs and antithrombotic therapy; ECG – electrocardiogram; TEE – transesophageal 
echocardiography; AERP – atrial effective refractory period. 
 
8.5 Patient Lost to Follow-Up 
The investigator will attempt to contact a subject at least three times prior to designating them as lost-to-
follow-up subjects; two of these attempts should include attempting to contact subject via registered mail.  
The investigator will document the date and type of attempted communication and will complete the 
STUDY COMPLETION Form when a patient is lost to follow-up. 
 
8.6 Patient Withdrawals and Discontinuation 
Subjects have the right to withdraw from the clinical investigation at any time and for any reason without 
prejudice to their future medical care by the investigation team or investigation site. The investigator will 
ask for the reason for their withdrawal and will record all information regarding the patient 
Schedule of Tests: 
Baseline 
Procedure  
Post-
Procedure 
to 
Discharge  
Discharge 
30 Days 
±7 days 
3 Mo 
±30 
Days 
6 Mo 
±45 
Days 
12 Mo 
±60  
Days 
Subject Eligibility/ Informed 
Consent 
X 
 
 
 
 
 
 
 
Medical history & 
Demographics* 
X 
 
 
 
 
 
 
 
NYHA Score*  
X 
 
 
 
 
 
 
X 
Physical Exam* 
X 
 
 
X 
X 
X 
X 
X 
TTE for LVEF and LA 
diameter* 
X 
 
 
 
 
 
 
 
Blood tests* 
X 
 
 
 
 
 
X 
 
SF-36 QOL 
X 
 
 
 
 
 
 
X 
Medication Log (AAD-ATT)* 
X 
 
 
X 
X 
X 
X 
X 
ECG (12 Lead) * 
X 
 
 
X 
X 
X 
X 
X 
TEE to exclude thrombus* 
X 
 
 
 
 
 
 
 
24HR Holter * 
X 
 
 
 
X 
X 
X 
X 
Cardiac Telemetry 
 
 
X 
 
 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
Protocol Deviation 
X 
X 
X 
X 
X 
X 
X 
X 
Device Performance 
 
X 
 
 
 
 
 
 
AERP 
 
X 
 
 
 
 
 
 

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discontinuation on the STUDY EXIT Case Report Form.  An investigator may also withdraw a patient from 
study participation at any time and shall report the reason for withdrawal to the Sponsor. 
 
A subject may be withdrawn from the clinical investigation for the following reasons: 
• 
Subjects may choose to withdraw from the clinical investigation under the terms of the Declaration 
of Helsinki and their consent documentation without having to give a reason;  
• 
Any unanticipated adverse reaction which is, in the opinion of the Investigator, related to the 
treatment and will endanger the well-being of the patient if treatment is continued;  
• 
Development of any intercurrent illness(es), infection or condition(s) that might interfere with the 
Clinical Investigational Plan;  
• 
Non-compliance with the clinical investigation procedures deemed by the Investigator to be 
sufficient to cause discontinuation;  
• 
Any problem deemed by the Investigator to be sufficient to cause discontinuation.  
Investigator will treat all subjects discontinued from the investigation due to an unanticipated adverse 
reaction, directly related to the investigation, until the reaction resolves.  
Investigator will not replace subjects who have withdrawn from the clinical investigation if they were 
treated with the investigational device.  If possible, Investigator will perform any procedures or 
assessments planned for the subject at the time of withdrawal.  
If the decision to terminate the study is made by the sponsor or the study doctor, the Ethics Committee 
that approved the study must be notified immediately and will evaluate the reasons for the termination 
of the study. In urgent cases, the study will be terminated to ensure study participant safety, and the 
Ethics Committee will be notified as soon as possible. 
 
8.7 Early Termination of Clinical Investigation 
Both the Sponsor and Investigator reserve the right to terminate the clinical investigation at any time.  
The sponsor may suspend or prematurely terminate either a clinical investigation site or the entire clinical 
investigation for significant and documented reasons. Such reasons are as follows: 
• 
If suspicion of an unacceptable risk to subjects arises during the clinical investigation, or when so 
instructed by the EC or regulatory authorities, the sponsor may suspend the clinical investigation 
while the risk is assessed. The sponsor may terminate the clinical investigation if an unacceptable 
risk is confirmed. 
• 
Monitoring or auditing identifies serious or repeated deviations on the part of an investigator. 
 
After review of the clinical safety data, the Sponsor and Investigator may agree to terminate the clinical 
investigation if necessary. If necessary, and after review and consultation with Principal Investigator, 
Sponsor will make a final determination on whether to terminate the study. 
A principal investigator, EC, or regulatory authority may suspend or prematurely terminate participation 
in the clinical study at the investigation sites for which they are responsible. 
If suspension or premature termination occurs, the terminating party shall justify its decision in writing 
and promptly inform the other parties with whom they are in direct communication.  The Principal 
Investigator and sponsor will keep each other informed of any communication received from either the 
EC or the regulatory authority. 
If, for any reason, the sponsor suspends or prematurely terminates the investigation at an individual 
investigation site, the sponsor shall inform the responsible regulatory authority as appropriate and ensure 
that the EC is notified, either by the principal investigator or by the sponsor. If the suspension or 
premature termination was in the interest of safety, the sponsor shall inform all other principal 
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If suspension or premature termination occurs: 
• 
The sponsor remains responsible for providing resources to fulfil the obligations from the protocol 
and existing agreements for following up the subjects enrolled in the clinical investigation, and 
• 
The Principal Investigator or his/her authorized designee will promptly inform the enrolled subjects 
at his/her investigation site, if appropriate. 
 
8.8 Adverse Event Reporting 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the investigational medical device. All adverse events are to be reported on the ADVERSE EVENT 
Case Report Form. All adverse events will be documented with the date of occurrence, relatedness to 
device or procedure, severity, action taken, resolution and any pertinent additional information as 
identified in MDCG 2020-10/1 and MDR Art. 80(2).  
Adverse events associated with users or other persons may be documented separate from adverse events 
associated with the subject, taking into account the data privacy regulations. 
 
Adverse events are classified based on the definitions as follows (ISO 14155). 
 
Adverse event (AE): any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, whether or 
not related to the investigational medical device. 
NOTE 1 This definition includes events related to the investigational medical device or the comparator 
(if applicable). 
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 investigational 
medical devices. 
Adverse device effect (ADE): adverse event related to the use of an investigational medical device. 
NOTE: This definition includes adverse events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the investigational 
medical device. In addition, this definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
Serious Adverse Event (SAE) Any adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users, or other persons as defined by one or 
c) more of the following: 
1. 
life-threatening illness or injury, 
2. 
permanent impairment of a body structure or a body function including chronic diseases, 
or, 
3. 
in-patient or prolonged hospitalization, or 
4. 
medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function, 
d) foetal distress, foetal death or a congenital physical or mental impairment or birth defect. 
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, without 
serious deterioration in health, is not considered a serious adverse event. 

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Serious health threat: signal from any adverse event or device deficiency that indicates an imminent 
risk of death or a serious deterioration in the health in subjects, users or other persons, and that 
requires prompt remedial action for other subjects, users or other persons 
Note: This would include events that are of significant and unexpected nature such that they become 
alarming as a potential serious health hazard or possibility of multiple deaths occurring at short 
intervals. 
Serious adverse device effect (SADE): adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
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. 
Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, severity 
or outcome has been identified in the risk assessment. 
Device Deficiency: Any inadequacy in the identity, quality, durability, reliability, usability, safety or 
performance of  an investigational device, including malfunction, use errors or inadequacy in 
information supplied by the manufacturer. 
Device Malfunction: failure of an investigational medical device to perform in accordance with its 
intended purpose when used in accordance with the instructions for use or CIP, or IB. 
User Error: user action or lack of user action while using the medical device (3.34) that leads to a 
different result than that intended by the manufacturer or expected by the user. 
Note 1: Use error includes the inability of the user to complete a task. 
Note 2: Use errors can result from a mismatch between the characteristics of the user, user interface, 
task or use environment. 
Note 3: Users might be aware or unaware that a use error has occurred. 
Note 4: An unexpected physiological response of the patient is not by itself considered a use error. 
Note 5: A malfunction of a medical device that causes an unexpected result is not considered a use 
error. 
 
Adverse Event Reporting- Clinical site role: 
The Investigator will document all Serious Adverse Events (SAE) and Serious Adverse Device Effects (SADE), 
including device deficiencies in the study participant’s patient file and report it to the Sponsor, within 24-
hours of knowledge of event. 
 
In categorising the adverse event and observed device deficiency the principal investigator shall refer to 
ISO 14155 Annex F- Adverse event categorization. The investigator will document the action taken in 
relation to the investigational device and to other treatments. 
 
The Investigator will also report to the EC, without unjustified delay, all serious adverse events and 
device deficiencies that could have led to a serious adverse device effect. This information shall be 
promptly followed by detailed written reports. The Investigator must notify the sponsor once the EC has 
been notified. 
 
The principal investigator shall supply the sponsor, upon sponsor's request, with any additional 
information related to the safety reporting of a particular event. Source data are preferentially 
immediately transferred to the ADVERSE EVENT CRF. When medical reports (lab results, examinations, 
etc.) associated with adverse events are submitted to the CRO or sponsor, all personal subject 

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information (name, address, etc.) MUST be removed or redacted. The redacted materials must be 
identified only with the Site and subject’s study numbers. 
 
The investigator will monitor all AEs until they are resolved, determined to be a chronic condition or the 
subject is lost to follow-up. The investigator will report all AEs regardless of whether they are anticipated 
or unanticipated and regardless of classification, seriousness, severity, outcome or causality. 
 
Assessment of Adverse Event Severity: 
Where the determination of AE severity rests on medical judgment, the determination of severity must 
be made with the appropriate involvement of a medically qualified investigator.  
The severity of AEs will be graded using the following definitions: 
Mild  
awareness of sign, symptom, or event, but easily tolerated 
Moderate:  
discomfort enough to cause interference with usual activity and may warrant intervention 
Severe: 
incapacitating with inability to do usual activities or significantly affects clinical status and 
warrants intervention. 
 
Relationship to the Device and related procedure: 
The principal Investigator is required to assess whether there is a reasonable possibility that the Study 
Device or procedure caused or contributed to an AE.  The relationship between the use of the device and 
procedure and the occurrence of each adverse event shall be assessed and categorized and recorded in 
ADVERSE EVENT CRF. 
During this assessment, clinical judgement shall be used and the relevant documents, such as the 
Investigator’s Brochure, the Clinical Investigation Plan or the Risk Analysis Report shall be consulted. The 
presence of confounding factors, such as concomitant medication/treatment, the natural history of the 
underlying disease, other concurrent illness or risk factors shall also be considered.  
 
Each SAE will be classified according to four different levels of causality as described below per MDCG 
2020-10/1: 
 
1. Not related: Relationship to the device, comparator or procedures can be excluded when: 
− 
the event has no temporal relationship with the use of the investigational device, or the procedures 
related to application of the investigational device; 
− 
the serious adverse event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 
− 
the discontinuation of medical device application or the reduction of the level of activation/exposure 
- when clinically feasible - and reintroduction of its use (or increase of the level of 
activation/exposure), do not impact on the serious adverse event; 
− 
the event involves a body-site or an organ that cannot be affected by the device or procedure; 
− 
the serious adverse event can be attributed to another cause (e.g. an underlying or concurrent illness/ 
clinical condition, an effect of another device, drug, treatment or other risk factors); 
− 
the event does not depend on a false result given by the investigational device used for diagnosis, 
when applicable; 
In order to establish the non-relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device / procedures and the adverse event. 
 
2. Possible: The relationship with the use of the investigational device or comparator, or the relationship 
with procedures, is weak but cannot be ruled out completely. Alternative causes are also possible (e.g. an 

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underlying or concurrent illness/ clinical condition or/and an effect of another device, drug or treatment). 
Cases where relatedness cannot be assessed, or no information has been obtained should also be 
classified as possible. 
 
3. Probable: The relationship with the use of the investigational device or comparator, or the relationship 
with procedures, seems relevant and/or the event cannot be reasonably explained by another cause. 
 
4. Causal relationship: the serious adverse event is associated with the investigational device, comparator 
or with procedures beyond reasonable doubt when: 
the event is a known side effect of the product category the device belongs to or of similar devices and 
procedures; 
− 
the event has a temporal relationship with investigational device use/application or procedures; 
− 
the event involves a body-site or organ that 
o 
the investigational device or procedures are applied to; 
o 
the investigational device or procedures have an effect on; 
− 
the serious adverse event follows a known response pattern to the medical device (if the response 
pattern is previously known); 
− 
the discontinuation of medical device application (or reduction of the level of activation/exposure) 
and reintroduction of its use (or increase of the level of activation/exposure), impact on the serious 
adverse event (when clinically feasible); 
− 
other possible causes (e.g. an underlying or concurrent illness/ clinical condition or/and an effect of 
another device, drug or treatment) have been adequately ruled out; 
− 
harm to the subject is due to error in use; 
In order to establish the relatedness, not all the criteria listed above might be met at the same time, 
depending on the type of device/procedures and the serious adverse event. 
 
The sponsor and the investigators will distinguish between the serious adverse events related to the 
investigational device and those related to the procedures (any procedure specific to the clinical 
investigation). An adverse event can be related both to procedure and the investigational device. 
Complications caused by concomitant treatments not imposed by the clinical investigation plan are 
considered not related. 
Similarly, several routine diagnostic or patient management procedures are applied to patients regardless 
of the clinical investigation plan. If routine procedures are not imposed by the clinical investigation plan, 
complications caused by them are also considered not related. 
 
In some particular cases the event may not be adequately assessed because information is insufficient or 
contradictory and/or the data cannot be verified or supplemented. The sponsor and the Investigators will 
make the maximum effort to define and categorize the event and avoid these situations.  
 
Where an investigator assessment is not available and/or the sponsor remains uncertain about classifying 
the serious adverse event, the sponsor should not exclude the relatedness; the event should be classified 
as “possible” and the reporting should not be delayed. 

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Adverse Event Reporting - Sponsor role: 
The sponsor is responsible for the classification of adverse events and ongoing safety evaluation of the 
clinical investigation. 
The sponsor will review the investigator's assessment of all adverse events and all device deficiencies and 
determine if an independent review is required by the Clinical Events Committee as described in section 
13.9. 
 
The sponsor must report to regulatory authorities, within the required time period as identified in table 
1, all serious adverse events and device deficiencies that could have led to a serious adverse device effect, 
including serious health threat. The sponsor will report this information in a Summary Reporting Form as 
outlined in MDCG 2020-10/1 and MDR Art. 80(2) or as provided by the regulatory authority.  
 
Table 1: Competent Authorities Reporting timelines 
Time period 
Reportable events 
Immediately, but not later than 2 calendar 
days after awareness by sponsor of a new 
reportable event or of new information in 
relation with an already reported event. 
For all reportable events as described in section 5 
MDCG 2020-10/1 and MDR Art. 80(2):which indicate 
an imminent risk of death, serious injury, or serious 
illness and that requires prompt remedial action for 
other patients/subjects, users or other persons or a 
new finding to it. 
Immediately, but not later than 7 calendar 
days following the date of awareness by the 
sponsor of the new reportable event or of 
new information in relation with an already 
reported event. 
Any other reportable events as described in section 
MDCG 2020-10/1 and MDR Art. 80(2) or a new 
finding/update to it. 
The sponsor shall ensure that the EC and the regulatory authorities are informed of significant new 
information about the clinical investigation. 
 
In the case of a multicentre clinical investigation, the sponsor will inform all principal investigators in 
writing of all the serious adverse events at all investigation sites that have been reported to the sponsor. 
 
In the case of a serious adverse device effects the sponsor will determine whether the risk analysis needs 
to be updated and assess whether corrective or preventive action is required. 
 
8.9 Anticipated Adverse Events 
The following adverse events have been identified for the atrial deganglionation and for the open-chest 
cardiac surgery. 
Note:  Arrhythmia events are not uncommon during cardiac surgery procedures and will not be identified 
as adverse events if AE/SAE definitions per section 8.8 are not met. 
Study-specific SAEs that may be directly related to atrial deganglionation: 
Note:  Each event must first meet the SAE definition as described in section 8.8 to be defined as an 
SAE. 
1. 
Emergency during the procedure requiring change in surgical strategy 
2. 
Atrial perforation or excessive bleeding (excessive bleeding is defined as bleeding which 
requires any blood transfusion). 
3. 
Hemothorax or pleural effusion 

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4. 
Pericarditis 
5. 
Pericardial effusion 
6. 
Cardiac tamponade (if either surgical or percutaneous drainage is required). 
7. 
Constrictive pericarditis, requiring re-operation. 
8. 
Documented atrial or ventricular arrhythmia during hospital stay 
9. 
Newly developed sinus node dysfunction. 
10. 
Newly developed first, second or third degree AV block 
11. 
Persistent chest pain 
12. 
Phrenic nerve damage 
13. 
Hypotension 
14. 
Prolonged Hospitalization 
15. 
Vasovagal reactions during hospital stay 
16. 
Perforation of great vessels 
17. 
Perforation of lung 
18. 
Perforation of esophagus 
19. 
Myocardial damage 
20. 
Burns  
21. 
Ventricular fibrillation 
22. 
Coronary sinus damage 
23. 
Pulmonary vein stenosis 
24. 
Infection 

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SAEs related to open-chest CABG surgery: 
Note:  Each event must first meet the SAE definition as described in section 8.8 to be defined as an 
SAE. 
1. 
Death (within the first 30 days post-operative or > 30 days if procedure related 
2. 
Cardiac or respiratory arrest/depression during hospital stay 
3. 
Stroke (resulting in neurological deficit lasting more than 24 hours or lasting 24 hours or less 
with a brain imaging study showing infarction). 
4. 
Transient Ischemic Attack (TIA) or a neurological deficit lasting less than 24 hours, and if an 
imaging study is performed showing no evidence of infarction. 
5. 
Myocardial infarction (according to ESC Guidelines definition) 
6. 
Documented atrial or ventricular arrhythmia during hospital stay 
7. 
Congestive heart failure, including volume overload 
8. 
Prolonged Hospitalization 
9. 
Coronary artery dissection, spasm or occlusion 
10. 
Perforation of the lung 
11. 
Hemothorax or pleural effusion 
12. 
Pneumothorax 
13. 
Persistent pneumothorax (requiring intervention) 
14. 
Pneumonia  
15. 
Pulmonary edema 
16. 
Pulmonary embolism 
17. 
Pulmonary hypertension 
18. 
Pericarditis 
19. 
Pericardial effusion 
20. 
Cardiac tamponade (if either surgical or percutaneous drainage is required). 
21. 
Constrictive pericarditis, requiring re-operation. 
22. 
Thrombosis – deep vein thrombosis or pulmonary embolism 
23. 
Significant chest wound 
24. 
Anesthesia or paralytic drug reaction 
 
8.10 Emergency Contact Details for Reporting Adverse Device Effects 
Contact Name: Barry O’Brien 
Phone  +353 87 2934292 
Email: barry.obrien@atrianmedical.com 
 
8.11 Device Deficiencies and Malfunctions 
All device deficiencies related to the identity, quality, durability, reliability, safety or performance of the 
medical devices shall be documented and reported to the Sponsor. 
The DEVICE DEFICIENCY FORM is specific for reporting all device deficiencies, or malfunctions that occur 
during the course of the trial, whether or not they were associated with an adverse event. Device 
Deficiency Forms should be submitted to the Sponsor within 24 hours of the occurrence defining the 
device deficiency. Where possible, the investigational device should be returned to the study Sponsor 
for analysis as soon as possible from the time of the failure or malfunction. An investigation of device 
failures and malfunctions will be conducted by the study sponsor. Any adverse events associated to 
device deficiencies or malfunctions should be recorded in the Adverse event form. In these cases the 

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Sponsor should review the risk analysis to determine if appropriate corrective and preventive actions are 
in place to protect the safety of subjects, users, and other persons. 
 

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9. Study Conduct 
 
9.1 Ethics 
This study will be conducted in conformity with the ethical principles stated in the latest version of the 
Declaration of Helsinki (2013), the applicable guidelines for good clinical practices, MEDDEV 2.7/4 
(Guidelines on Clinical investigations: a guide for manufacturers and notified bodies) and NB-MED 2.7/3 
(Clinical investigations: serious adverse event reporting), ISO 14155 (Clinical Investigation of Medical 
Devices for Human Subjects – Good Clinical Practice), or the applicable local and international regulations, 
whichever provide the greater protection of the individual. The clinical investigation plan and other 
relevant documentation shall be submitted to the appropriate Ethics Committee for review. In countries 
in which additional requirements apply (e.g., notification to, or approval from the Competent Authority), 
the study may start only after all regulatory requirements are fulfilled. 
 
9.2 Regulatory Considerations 
The study will be reviewed by the relevant Ethics Committees, and by the relevant Competent Authority 
as well. The study will not start without the written approval of the Ethics Committee and, where needed, 
the Competent Authority approval and after the completion of any other local regulation requirement. 
 
9.3 Investigator Responsibilities 
The role of the Principal Investigator (PI) is to implement the day-to-day conduct of this clinical 
investigation as well as to ensure data integrity and the rights, safety and well-being of the subjects 
involved in the clinical investigation in accordance with ISO 14155 for the conduct of clinical investigations 
of medical devices. The PIs shall be qualified by education, training and experience for the proper conduct 
of this clinical investigation. The investigative sites will have the required number of eligible subjects, a 
qualified investigation team, and adequate facilities for the foreseen duration of this study. The PIs will 
provide the sponsor copies of all communication with the EC, will perform safety reporting to both the 
sponsor and the EC according to EC requirements and to this clinical investigational plan and will promptly 
report to the EC any deviations that affect the right, safety, or well-being of the subject, or the scientific 
integrity of the clinical investigation, as required by local regulations. The PIs shall ensure compliance with 
the Informed Consent process and with the clinical investigational plan/protocol and will provide 
adequate medical care to the subjects during and after their participation in the clinical investigation. 
 
9.4 Confidentiality and Data Protection 
All subject data is identified with the unique patient identifier number. After obtaining subject’s consent, 
the investigator will permit the study monitor, independent auditor or regulatory agency personnel to 
review that portion of the subject’s medical record that is directly related to the study. This shall include 
all study relevant documentation including subject medical history to verify eligibility, laboratory test 
result reports, admission/discharge summaries for hospital admissions occurring while the subject is in 
the study, and autopsy reports for any deaths occurring during the study (where available). Health data 
will be recorded and forwarded to the sponsor of the study, AtriAN Medical Ltd, and to participating Ethics 
Committees and Competent Authorities, for evaluation as required. Any information that is obtained in 
connection with this study that can be identified with the subjects will remain confidential. Any data that 
may be published in scientific journals will not reveal the identity of the study participants. 
 
 

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10. Insurance 
In order to cover possible damage to health, in relation to participation in this study, AtriAN Medical has, as required 
by law, obtained appropriate insurance coverage. 
 
 
11. Protocol Deviations 
The Investigator is not allowed to deviate from the protocol without prior approval by AtriAN Medical and prior 
review and documented approval from the governing Ethics Committee and/or Competent Authority. Prior 
approval is not needed for minor deviations in relation to timing of follow-ups provided the investigator notifies the 
sponsor or monitor once such a deviation occurs. 
 
Under emergency circumstances, deviations from the clinical investigation plan to protect the rights, safety and 
well-being of human subjects may proceed without prior approval of the sponsor and the Ethics Committee. 
Reports of any deviation from the clinical investigational plan as per above emergency circumstances will be 
reported to the Sponsor and to the Ethics Committee as soon as possible after detection, but no later than twenty-
four (24) hours from the time of the deviation. 
Deviations must be documented on the appropriate PROTOCOL DEVIATION Case Report Form. 
Any report of withdrawal of Ethics Committee approval will be submitted to the Sponsor within five (5) working 
days. 
 
Protocol deviations will be summarized by the designated Clinical Study Monitor and analysed by AtriAN Medical 
for the impact to the overall integrity of the study.  Input from an independent statistician and/or a CEC (clinical 
events committee) may be obtained to determine if the deviation warrants disqualifying the Investigator.  
Disqualification is warranted when an investigator has repeatedly or deliberately violated governing regulations or 
has repeatedly or deliberately submitted false information in any report.  Where protocol deviations occur, which 
do not warrant disqualification from a study, AtriAN Medical will implement appropriate corrective and preventive 
actions, including repeat training as deemed necessary. 
 
 
12. Device Accountability 
Access to investigational devices shall be controlled and the investigational devices shall be used only in the clinical 
investigation and according to the CIP.  The sponsor shall keep records to document the physical location of all 
investigational devices from shipment of investigational devices to the investigation sites until return or disposal. 
When the enrolment is complete, the investigator shall return to the study sponsor any unused devices and a copy 
of the completed device inventory.  The investigator’s copy of the device reconciliation report must document any 
unused devices that have been returned to the study sponsor. 
 
The Principal Investigator is responsible to keep records documenting the receipt, use and return or disposal of the 
investigational devices.  For that, a form (Device Accountability Log) will be provided to the site that will record the 
model, lot number, and date received by the site. 
Upon receipt of devices, the Device Accountability Log must be completed and the contents of the packaging 
inspected for: 
• 
Any evidence of damage that could affect the integrity of the device (generator or catheter) 
• 
Any evidence of damage that could affect the sterility of the device (catheter only) 
• 
Any issues with the packaging should be brought to the attention of the study sponsor as soon as possible. 
 
 

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13. Study Management 
 
13.1 Data Management  
The Sponsor will be responsible for the organization and entry of all clinical data collected during the 
study. Standardized Case Report Forms (CRFs) will be provided by the Sponsor and used to record study 
subject data. The Principal Investigator is responsible for ensuring accuracy and completeness of all study 
documents. CRF completion instructions and training is to be provided by the sponsor. 
The Investigator will be queried on errors concerning data completeness and consistency. All activities will 
be performed according to Standard Operating Procedures and applicable regulatory requirements. 
 
13.2 Data Collection 
Each patient will automatically be assigned with a unique, sequential patient identifier. CRF worksheets 
will be completed for each study patient based on the source documents and then entered into the EDC 
system.  Instances of incomplete or inconsistent data will be resolved with the site through issuing a query 
or other means of communication, as necessary. The site is responsible to respond and/or correct the 
data for all queries issued in a timely manner. All queries and changes to the data is automatically tracked 
within the audit trail. 
Completed CRF worksheets will be verified by a monitor against the subject’s medical records and verified 
against the EDC system entries before the site can apply electronic signatures. 
 
13.3 Source Documents 
Source documents may include a patient’s medical record, hospital charts, clinic charts, the Investigator’s 
study files, questionnaires, and the results of diagnostic tests such as laboratory tests, electrocardiograms, 
CT angiograms, MR angiograms, echocardiograms and the like.  The Investigator’s copy of the CRFs 
(worksheets) serves as part of the Investigator’s record of a patient’s study-related data. 
The Investigator is responsible for ensuring that data are properly recorded in each patient’s source data, 
CRF-worksheets (paper hardcopies) and related documents and ensure timely transfer to the CRF. The 
Investigator who signs the Protocol Signature Page should sign the CRFs requiring signatures to ensure 
that the observations and findings are recorded correctly and completely. 
Source data from baseline through the 12-month follow-up shall be uploaded/transferred to the database. 
All CRFs will be reviewed for completeness, accuracy and clarity. Queries for missing or unclear data will 
be made as necessary and have to be answered within 10 business days 
 
13.4 Record Retention 
All study-related correspondence, patient records, consent forms, records of the distribution and use of 
the investigational products, and copies of CRFs should be maintained on file for 15 years past the 
completion of the study.  AtriAN Medical requires that it be notified in writing if the Investigator intends 
to leave the hospital so that both parties can be assured a new responsible person is appointed in the 
hospital. 
 
13.5 Study Summary 
The Sponsor is responsible for preparing a final report in accordance with ISO 14155 requirements. The PI 
will review and sign the document, and AtriAN Medical will supply it to the governing Ethics Committees 
and to the respective regulatory authorities. 
 
 

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13.6 Amendments to the Protocol 
Any modifications to the CIP shall be agreed and signed by the investigator(s).  The amendment should be 
submitted to their respective Ethics Committee that originally approved the investigation, and, where 
applicable, also to the Competent Authority.  A summary explaining the changes, the rationale for changes 
and other documents will be provided in accordance with applicable requirements, to ECs and regulatory 
authorities. 
 
13.7 Monitoring 
Sponsor personnel or their designees will perform study site monitoring. The site will be visited per the 
monitoring plan to ensure that the study is conducted in full compliance with all applicable regulations, 
and with the study protocol. 
o 
Written IRB / Ethics Committee approval for conduct of the study 
o 
Text of the site’s approved written study-specific patient consent document 
o 
Signed Investigator's Agreement 
o 
Signed Clinical Trials Agreement (CTA) 
o 
Site Signed Activation Letter 
Monitoring will ensure continued protocol compliance, adequate patient enrolment, accurate data 
reporting, the reporting of adverse events and adequate accounting of study device shipments. 
Monitoring shall require 100% source data verification (SDV) to validate accuracy of data transcribed to 
the CRFs. 
At the close of the study at an investigational site, the clinical monitor will make a final on-site visit. The 
purpose of this visit is to collect all outstanding study data documents, ensure that the investigator's files 
are accurate and complete, review record retention requirements with the investigator, make a final 
accounting of all study supplies shipped to the investigator, provide for appropriate disposition of any 
remaining supplies, and ensure that all applicable requirements are met for the study. The observations 
and actions made at this visit will be documented as a final report for investigator and sponsor acceptance. 
 
13.8 Monitor or Designee Names and Addresses 
Site 
Monitor 
Tbilisi Heart & 
Vascular Clinic 
Clinical Accelerator, 11 Saakadze Descent “LTD Panorama”, Floor 3, Office 306, 
Tbilisi 0160, Georgia. 
Na Homolce 
Hospital, Prague 
High Tech Med Consult, 155 00 Prague 5, Frimlova 1322/4e, Czech Republic 
 
13.9 Clinical Events Committee 
The Sponsor will coordinate the convening of meetings of the Clinical Events Committee (CEC) in 
accordance with the Quality Assurance Procedure and the Charter specific to this study.  The CEC has the 
responsibility to review all Adverse Events requiring classification, level of severity, relatedness to device 
and/or procedure and resolution that are in question and may make recommendations as to procedure 
based on their findings.  Their recommendations may include the termination of the trial.  All recorded 
minutes of their actions will be kept on file and available for review as requested. All sites will be kept 
informed of any decisions made by this CEC. 
 
 

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Confidential. Unauthorized use is prohibited. Do not reproduce, distribute or use 
without the expressed written consent of AtriAN Medical 
14. Ethics Committee Approval 
This clinical investigation will not begin until the required approvals are obtained for the appropriate EC or 
national regulatory authority. 
 
 
15. Statement of Compliance 
The study is conducted in full accordance with the principles in the latest version of the “Declaration of Helsinki” 
(2013) and with other local laws and regulations. 
The study will not commence until written approval has been obtained from the Ethics Committee and regulatory 
authority where applicable.  
No changes are anticipated to be made to the device during the study.  Any changes that must be made will be 
qualified before being implemented to the same functional specifications used for the original product. 
 
 
16. Publication Policy 
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. Study subjects 
shall be identified on study documentation by a unique study identification number. The investigational site may 
maintain a separate identification log, however all study documentation and/or medical records collected and used 
for study purposes will remain anonymous so that an individual study subject cannot be identified outside the study. 
It is the intention of the sponsor that the results of the study will be published. Upon the prior written consent of 
Sponsor, Investigator shall have the rights to publish papers related to the Study. Individual investigators cannot 
publish on the study or a sub-set of the study before the full study results are published. If the sponsor decides not 
to publish the full study, then investigators may publish their own data. Investigators cannot publish on the system 
technology without written permission from the sponsor. 
If written permission from the Sponsor is provided, the PI may publish and/or present the results of the Study 
conducted at their site, provided that, prior to any such publication or presentation, the site and/or the PI shall 
furnish the Sponsor with two (2) hard copies and one electronic copy of any materials intended for publication or 
presentation at least sixty (60) days prior to the submission of manuscripts. 
 
 

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Page 43 of 47 
 
Confidential. Unauthorized use is prohibited. Do not reproduce, distribute or use 
without the expressed written consent of AtriAN Medical 
17. Revision History 
Change 
Control 
Form 
Number 
Revision 
Description of Change 
Effective Date 
Form-249 
A 
Initial Release 
Refer to CompanionQMS for 
Date and Time. 
Form-259 
B 
Updates include the following: 
a) Page 1 Cover Page - identifying Principal 
Investigator for all sites,  
b) Page 6 Study Synopsis & page 19 Section 6.8 
Patient Exclusion Criteria - remove start date to 
accommodate Covid19 
c) Page 20 Section 6.4 Sample size - to include “up 
to” 30 patients 
d) Page 21 Paralytic Agent – updated to include 
Rocuronium 
e) Page 24 Ablation of GPs – inclusion to 
document occurrence of electrical 
cardioversion or defibrillation 
f) Page 37 Section 13.9 Clinical Events Committee, 
update to refine requirements. 
Refer to CompanionQMS for 
Date and Time. 
Form-267 
C 
Updates to: 
a) Section 8 Study procedure and Data Collection 
to provide clarification on AERP Measurement, 
b) Section 13.4 Record Retention - modified 
retention period from 5 years to 15 years to 
align General Data Protection Regulation(EU) 
2016/679 and Clinical Directive 2001/20/EC 
requirements 
Refer to CompanionQMS for 
Date and Time. 
Form-278 
D 
Updates for: 
Removal of removal of Spirometry and Exercise 
tests from Synopsis for Clinical Study Requirements 
and Schedule of Tests and from section 8 Study 
Procedure and Data Collection and section 8.4 
Schedule of Events. 
Inclusion of temperature of the heart for AERP 
measurement. 
Typographical error correction for documenting 
electrical cardioversion or defibrillation during the 
procedure. 
Refer to CompanionQMS for 
Date and Time. 
Form-287 
E 
Updates for inclusion of 24-hour Holter to the 30 
Day Follow-Up, in the following sections: 
Study Synopsis 
Ablation of GPs, and 
Schedule of Events 
Refer to CompanionQMS for 
Date and Time. 

DESCRIPTION: CIP-001 Clinical Investigation Plan for OCED System 
Rev: H 
 
 
Page 44 of 47 
 
Confidential. Unauthorized use is prohibited. Do not reproduce, distribute or use 
without the expressed written consent of AtriAN Medical 
Change 
Control 
Form 
Number 
Revision 
Description of Change 
Effective Date 
Form-295 
F 
Complete rewrite of section 8.8 Adverse Event 
Reporting to align with requirements of ISO 
14155:2020 and MDCG 2020-10/1 ‘Safety 
reporting in clinical investigations of medical 
devices under the Regulation”. 
Update Investigators signature Page to provide 
additional clarity. 
Updates throughout to align with requirements of 
ISO 14155:2020, as follows: 
a) Section 5 Risk Benefit Analysis 
b) Inclusion of Section 8.10 for Emergency 
Contact Details for Reporting ADE,  
c) Modification to Section 8.11 Device 
Deficiencies and Malfunctions 
d) Section 15 Statement of Compliance 
Refer to CompanionQMS for 
Date and Time. 
Form-308 
G 
Removed Petr Neuzil, MD as PI for Prague on cover 
page. 
Section 8 Study Procedure and Data Collect, 
updated as follows: 
a) Measurement of AERP modified to allow 
measurements to be taken one or more of the 
following sites, i.e. left atrial appendage, left 
atrium and right atrium. 
b) Inclusion of -1/+2˚C tolerance of temperature 
of heart. 
c) Update pacing output from 10 mA to range of 
10-20 mA. 
d) Intermediate AERP modified to optional 
requirement at the discretion of the operator 
as per modified figure 5. 
Refer to CompanionQMS for 
Date and Time. 
Form-349 
H 
a) Removal of references to, and details of 
activities at, UMC Amsterdam as patients will 
not be enrolled there. 
b) Typographical corrections and minor 
formatting throughout. 
c) Cover Page - updated for inclusion of new 
revision and date 
d) Section 8 - Updated pulse width from 2ms to 
include a range of 2-3 ms to accommodate for 
patient to patient variability (anatomy and 
adipose tissue effects, etc.) and variability in 
pacing wire contact area mean higher values 
may sometimes be needed. 
Refer to CompanionQMS for 
Date and Time. 

DESCRIPTION: CIP-001 Clinical Investigation Plan for OCED System 
Rev: H 
 
 
Page 45 of 47 
 
Confidential. Unauthorized use is prohibited. Do not reproduce, distribute or use 
without the expressed written consent of AtriAN Medical 
Change 
Control 
Form 
Number 
Revision 
Description of Change 
Effective Date 
e) Section 8.9 - update to include additional 
clarification for SAEs related to atrial 
deganglionation and open-chest CABG surgery. 
 
 
 

DESCRIPTION: CIP-001 Clinical Investigation Plan for OCED System 
Rev: H 
 
 
Page 46 of 47 
 
Confidential. Unauthorized use is prohibited. Do not reproduce, distribute or use 
without the expressed written consent of AtriAN Medical 
18. Bibliography 
 
1 Camm AJ, Lip GY, De Caterina R 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. European heart journal 2012;33:2719-47. 
2 Friberg L, Tabrizi F, Englund A. Catheter ablation for atrial fibrillation is associated with lower incidence of stroke and death: 
data from Swedish health registries. European heart journal 2016;37:2478-87. 
3 Kuck KH, Brugada J, Furnkranz A et al. Cryoballoon or Radiofrequency Ablation for Paroxysmal Atrial Fibrillation. The New 
England journal of medicine 2016;374:2235-45. 
4 Tilz RR, Rillig A, Thum A-M et al. Catheter ablation of long-standing persistent atrial fibrillation: 5-year outcomes of the 
Hamburg sequential ablation strategy. Journal of the American College of Cardiology 2012;60:1921-1929. 
5 Calkins H, Kuck KH, Cappato R et al. 2012 HRS/EHRA/ECAS Expert consensus statement on catheter and surgical ablation of 
atrial fibrilation: recommendations for patient selection, procedural techniques, patient management and follow-up, 
definitions, endpoints, and research trial design. Heart rhythm : the official journal of the Heart Rhythm Society 2012;9:632-
696. 
6 Willems S, Klemm H, Rostock T et al. Substrate modification combined with pulmonary vein isolation improves outcome of 
catheter ablation in patients with persistent atrial fibrillation: a prospective randomized comparison. European heart journal 
2006;27:2871-2878. 
7 Nademanee K, Lockwood E, Oketani N, Gidney B. Catheter ablation of atrial fibrillation guided by complex fractionated atrial 
electrogram mapping of atrial fibrillation substrate. Journal of cardiology 2010;55:1-12. 
8 Narayan SM, Krummen DE, Clopton P, Shivkumar K, Miller JM. Direct or coincidental elimination of stable rotors or focal 
sources may explain successful atrial fibrillation ablation: on-treatment analysis of the CONFIRM trial (Conventional ablation 
for AF with or without focal impulse and rotor modulation). Journal of the American College of Cardiology 2013;62:138-47. 
9 Pokushalov E, Romanov A, Artyomenko S et al. Ganglionated plexi ablation directed by high-frequency stimulation and 
complex fractionated atrial electrograms for paroxysmal atrial fibrillation. Pacing and clinical electrophysiology : PACE 
2012;35:776-84. 
10 Katritsis DG, Pokushalov E, Romanov A et al. Autonomic denervation added to pulmonary vein isolation for paroxysmal atrial 
fibrillation: a randomized clinical trial. Journal of the American College of Cardiology 2013;62:2318-25. 
11 Verma A, Jiang CY, Betts TR et al. Approaches to catheter ablation for persistent atrial fibrillation. The New England journal 
of medicine 2015;372:1812-22. 
12 Po SS, Scherlag BJ, Yamanashi WS et al. Experimental model for paroxysmal atrial fibrillation arising at the pulmonary vein-
atrial junctions. Heart rhythm : the official journal of the Heart Rhythm Society 2006;3:201-8. 
13 Patterson E, Po SS, Scherlag BJ, Lazzara R. Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation. 
Heart rhythm : the official journal of the Heart Rhythm Society 2005;2:624-631. 
14 E Pokushalov et al. Long-Term Suppression of Atrial Fibrillation by Botulinum Toxin Injection Into Epicardial Fat Pads in 
Patients Undergoing Cardiac Surgery. Circ Arrhythm Electrophysiol 2015; 8: 1334-1341. 
15 Romanov A, Pokushalov E, Ponomarev D et al. Long-term suppression of atrial fibrillation by botulinum toxin injection into 
epicardial fat pads in patients undergoing cardiac surgery: three-year follow-up of a randomized study. Heart rhythm : the 
official journal of the Heart Rhythm Society 2019;16(2):172-177. 
16 Waldron NH, Cooter M, Haney JC et al. Temporary autonomic modulation with botulinum toxin typa A to reduced atrial 
fibrillation after cardiac surgery. Heart rhythm : the official journal of the Heart Rhythm Society 2019;16(2).  
17 de Groot JR. Botulinum toxin injection in the autonomic ganglion plexi to prevent postoperative atrial fibrillation: More than 
a cosmetic treatment. Heart rhythm : the official journal of the Heart Rhythm Society 2019;16:185-186.  
18 Al-Atassi T et al. Mapping and Ablation of Autonomic Ganglia in Prevention of Postoperative Atrial Fibrillation in Coronary 
Surgery. Canadian Journal of Cardiology 2014; 30: 1202-1207. 
19 Konstantino Y et al. Postoperative Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery Predicts Long-Term 
Atrial Fibrillation and Stroke. IMAJ 2016; 18: 678-682 
20 Krul SP, Meijborg VM, Berger WR et al. Disparate response of high-frequency ganglionic plexus stimulation on sinus node 
function and atrial propagation in patients with atrial fibrillation. Heart rhythm : the official journal of the Heart Rhythm Society 
2014;11:1743-51. 
21 Lo LW, Scherlag BJ, Chang HY, Lin YJ, Chen SA, Po SS. Paradoxical long-term proarrhythmic effects after ablating the "head 
station" ganglionated plexi of the vagal innervation to the heart. Heart rhythm : the official journal of the Heart Rhythm Society 
2013;10:751-7. 
 

DESCRIPTION: CIP-001 Clinical Investigation Plan for OCED System 
Rev: H 
 
 
Page 47 of 47 
 
Confidential. Unauthorized use is prohibited. Do not reproduce, distribute or use 
without the expressed written consent of AtriAN Medical 
 
22 Pokushalov E, Romanov A, Shugayev P et al. Selective ganglionated plexi ablation for paroxysmal atrial fibrillation. Heart 
rhythm : the official journal of the Heart Rhythm Society 2009;6:1257-64. 
23 Driessen AH, Berger WR, Krul SP et al. Ganglion Plexus Ablation in Advanced Atrial Fibrillation: The AFACT Study. J Am Coll 
Cardiol 2016;68:1155-65. 
24 Rossmeisl JH, Jr., Garcia PA, Pancotto TE et al. Safety and feasibility of the NanoKnife system for irreversible electroporation 
ablative treatment of canine spontaneous intracranial gliomas. Journal of neurosurgery 2015;123:1008-25. 
25 Lambert L, Horejs J, Krska Z et al. Treatment of locally advanced pancreatic cancer by percutaneous and intraoperative 
irreversible electroporation: general hospital cancer center experience. Neoplasma 2016;63:269-73. 
26 Narayanan G, Bhatia S, Echenique A, Suthar R, Barbery K, Yrizarry J. Vessel patency post irreversible electroporation. 
Cardiovascular and interventional radiology 2014;37:1523-9. 
27 Weaver JC, Smith KC, Esser AT, Son RS, Gowrishankar TR. A brief overview of electroporation pulse strength-duration space: 
a region where additional intracellular effects are expected. Bioelectrochemistry (Amsterdam, Netherlands) 2012;87:236-43. 
28 Yarmush ML, Golberg A, Sersa G, Kotnik T, Miklavcic D. Electroporation-based technologies for medicine: principles, 
applications, and challenges. Annual review of biomedical engineering 2014;16:295-320. 
29 Reddy VY, Koruth J, Jais P et al. Ablation of Atrial Fibrillation With Pulsed Electric Fields: An Ultra-Rapid, Tissue-Selective 
Modality for Cardiac Ablation. JACC Clin Electrophysiol 2018;4:987-995. 
30 Reddy VY, Neuzil P, Koruth JS et al. Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial Fibrillation. Journal of the 
American College of Cardiology 2019;74:315-326. 
31 Madhavan M, Venkatachalam KL, Swale MJ et al. Novel Percutaneous Epicardial Autonomic Modulation in the Canine for 
Atrial Fibrillation: Results of an Efficacy and Safety Study. Pacing and clinical electrophysiology : PACE 2016;39:407-17. 
32 Padmanabhan D, Naksuk N, Killu AK et al. Electroporation of epicardial autonomic ganglia: Safety and efficacy in medium-
term canine models. J Cardiovasc Electrophysiol 2019;30:607-615.  
33 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European Heart Journal 
2016; 37: 2893-2962. 

Attachment 3: External Approval for CIP-001 Rev G under Change Request Form-349 
 
Page 1 of 1 
 
Approval Sign-off 
 
By signing this page, the approver acknowledges that they have read and understood the change, 
and, where applicable, agree to adhere with the requirements of the document. 
Document 
Number 
CIP-001 
Title 
Clinical Investigation Plan for OCED 
System 
Revision 
G to H 
Description of 
Change/Approval 
Updates identified as follows: 
a) Removal of references to, and details of activities at, UMC Amsterdam 
as patients will not be enrolled there. 
b) Typographical corrections and minor formatting throughout. 
c) Cover Page - updated for inclusion of new revision and date 
d) Section 8 - Updated pulse width from 2ms to include a range of 2-3 ms 
to accommodate for patient to patient variability (anatomy and adipose 
tissue effects, etc.) and variability in pacing wire contact area means 
higher values may sometimes be needed. 
e) Section 8.9 - update to include additional clarification for SAEs related to 
atrial deganglionation and open-chest CABG surgery. 
Name 
Title/Function 
Signature 
Date 
Jack Slovick 
Regulatory Affairs on behalf of 
AtriAN Medical 
 
 
Laura Minarsch 
Clinical Consultant on behalf of 
AtriAN Medical 
 
 
Prof. Dr. J.R. (Joris) 
de Groot,  
Cardiologist/Electrophysiologist 
- Medical Advisor 
 
 
 
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