Electroporation Treatment for Early AF Management in Heart Failure With Preserved Ejection Fraction (HFpEF) Pilot Study
Phase: NA
Conditions: Atrial Fibrillation (AF)
Sponsor: Cardioangiologisches Centrum Bethanien

 
 
 
 
E-TEAM  -  HFpEF 
Electroporation Treatment for Early AF Management in Heart Failure 
with preserved Ejection Fraction (HFpEF) Pilot Study 
 
 
 
 
 
 
 
 
 
 
 
Prof.  Dr. med. K.R. Julian Chun 
MVZ CCB Frankfurt und Main Taunus GbR 
Am Agaplesion Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
Tel.: +49 69 945028 110 
Fax: + 49 69 945028 119 
E-Mail: j.chun@ccb.de 
 
 
 
 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
2 
 
Table of Content 
 
1. 
Abbreviations .................................................................................................................................. 3 
2. 
Responsibilities ................................................................................................................................ 4 
3. 
Background ...................................................................................................................................... 6 
4. 
Methods .......................................................................................................................................... 6 
5. 
Ablation ........................................................................................................................................... 7 
6. 
Endpoints ......................................................................................................................................... 7 
6.1   Inclusion and Exclusion Criteria ....................................................................................................... 8 
6.1.1 
Inclusion Criteria .............................................................................................................. 8 
6.1.2 
Exclusion Criteria ............................................................................................................. 8 
6.2   Study course .................................................................................................................................... 9 
6.2.1   Visit 1, Pre-procedural, Day -2 to 0 ..................................................................................... 10 
6.2.2   Visit 2, Pulmonary Vein Isolation, FARAPULSE-Ablation .................................................... 10 
6.2.3   Visit 3, Hospital Discharge .................................................................................................. 11 
6.2.4   Visit 4, 3 Months Follow-Up after PVI/Randomization (± 7 Days) ...................................... 11 
6.2.5   Visit 5, 6 Months Follow-Up after PVI/Randomization (± 14 Days) .................................... 11 
6.2.6   Visit 6, 12 Months Follow-Up after PVI/Randomization (± 14 Days) .................................. 11 
6.3   Repeat ablation ............................................................................................................................. 11 
7.     Participant withdrawal or termination of participation ................................................................ 12 
8.     Statistical Analysis .......................................................................................................................... 12 
9.     Adverse Events ............................................................................................................................... 12 
10.   Documentation .............................................................................................................................. 13 
11.   Study organization ......................................................................................................................... 13 
12.   References ..................................................................................................................................... 14 
 
 
 
 
 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
3 
 
1. Abbreviations 
AAD 
AE 
Antiarrhythmic drug 
Adverse event 
AF 
atrial fibrillation 
FpC 
FARAPULSE Catheter 
CRF 
case report form 
EC  
Ethics Committee 
ECG 
Electrocardiography 
ECV 
electrical cardioversion 
ESC 
European Society of Cardiology 
ER 
Emergency Room 
ICF 
Informed Consent Form 
LA 
Left atrial/atrium 
PV 
pulmonary vein 
PVI 
Pulmonary vein isolation   
RFC 
radiofrequency current 
SAE 
Serious adverse event 
TEE 
transesophageal echocardiogram 
TTE 
transthoracic echocardiogram 
UADE 
unanticipated adverse device effect 
 
 
 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
4 
 
2. Responsibilities 
Role 
Name 
Address 
Signature 
 
 
 
 
 
 
Primary Investigators 
 
 
Prof.  Dr. med.  
KR Julian Chun 
MVZ CCB Frankfurt und 
Main Taunus GbR 
Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
 
 
 
 
______________ 
<Date> 
 
 
 
 
______________ 
<Signature> 
 
 
Priv. Doz. Dr. med. 
Boris Schmidt 
 
 
MVZ CCB Frankfurt und 
Main Taunus GbR 
Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
 
 
 
 
______________ 
<Date> 
 
 
 
 
______________ 
<Signature> 
 
 
 
 
 
Sub - Investigators 
 
 
Dr. 
med. 
Stefano 
Bordignon 
 
 
MVZ CCB Frankfurt und 
Main Taunus GbR 
Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
 
 
 
 
______________ 
<Date> 
 
 
 
 
______________ 
<Signature> 
 
Dr. med. Shaojie Chen 
 
 
MVZ CCB Frankfurt und 
Main Taunus GbR 
Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
 
 
 
 
______________ 
<Date> 
 
 
 
 
______________ 
<Signature> 
 
 
Dr. Shota Tohoku 
 
 
MVZ CCB Frankfurt und 
Main Taunus GbR 
Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
 
 
 
 
______________ 
<Date> 
 
 
 
 
______________ 
<Signature> 
 
 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
5 
 
 
 
Investigator Signature Page 
 
Electroporation Treatment for Early AF Management in Heart Failure with 
preserved Ejection Fraction (HFpEF) Pilot Study – E-TEAM 
 
 
Investigator Statement 
I have read this protocol and agree to conduct this study in accordance with all stipulations of the 
Clinical Investigation Plan, any applicable standards for the conduct of clinical investigations with 
human patients, any requirements imposed by the responsible competent authority/ethics 
committee, any other applicable local, institutional or legal requirements and in accordance with 
the principles outlined in the Declaration of Helsinki. 
 
 
Institution 
Institution address / stamp 
 
 
 
 
____________________________           ____________________________         ____________________________ 
        Name 
 
 
 
Signature 
 
 
       Date 
 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
6 
 
3. Background 
Atrial fibrillation (AF) represents the most common sustained arrhythmia in western societies. 
Currently, in Germany, approximately two million patients are affected by AF and are exposed to an 
increased risk of stroke, heart failure and mortality 1. AF often coexists with heart failure with 
preserved ejection fraction (HFpEF)2 3. Due to the co-occurrence of AF and HFpEF in this population 
many patients require emergency hospitalization. However, diagnosis and optimal therapy of this 
combined entity remains often uncertain despite of recent developments. Due to the progressive 
ageing of our society and demographic development, the number of AF patients is expected to double 
over the next several years 4. Moreover, AF has emerged as one of the most common reasons for 
patients seeking treatment in emergency rooms (ER) who are subsequently admitted for in-hospital 
treatment 5. For many years, it has been well established that second line catheter ablation is more 
effective than escalation of antiarrhythmic drug treatment (AAD) with regards to rhythm control 6. 
However, technical complexity of AF ablation, safety concerns and lack of reproducibility has limited 
widespread utilization of the former gold standard of radiofrequency current (RF) energy ablation. 
Importantly, the globally-performed CABANA trial failed to demonstrate reduction of mortality, but 
confirmed a lower AF burden following ablation therapy 7. Recently, the randomized EAST strategy trial 
comparing rhythm control (achievement of sinus rhythm via intervention) vs. best medical care (rate 
control medication) demonstrated a 20% reduction of clinical endpoints such as cardiovascular 
mortality, stroke, embolism in the group randomized to rhythm control 8. However, RF catheter 
ablation was utilized in only 20% of patients. Interestingly, very recently three independent 
randomized trials compared first line single shot PVI (Cryoballoon) vs. AAD treatment in more than 700 
patients 9, 10, 11. Importantly, the findings were uniformly showing increased efficacy for first line 
ablation using single shot device. The Farapulse electroporation device has demonstrated its ease in 
use, very short procedure times and a high procedural safety even in complex anatomy 12 13. Catheter 
ablation using electroporation (non-thermal energy source) differs substantially from thermal energy 
sources such as Cryo or RF energy and demonstrated a favorable safety profile. (Ekanem et al. Europace 
2022).Thus, the concept of an early rhythm control strategy using a safe and reproducible single-shot 
ablation technology, such as electroporation, appears to be suitable to investigate the role of a 
stringent rhythm control in AF patients with HFpEF vs. usual care after emergency hospitalization.  
4. Methods 
Symptomatic paroxysmal AF patients diagnosed with HFpEF seeking emergency treatment that meet 
all inclusion and none of the exclusion criteria will be randomized according to E-TEAM in two groups 
(1:1 randomization) as follows: 
  
Group 1: early catheter ablation within 7 days post AF-related emergency treatment using the 
FARAPULSE electroporation technology (n = 100) 
 
OR 
Group 2: best medical AF treatment including rhythm and rate control (n=100) 
All patients will receive (direct) oral anticoagulation and heart failure treatment according to their 
CHA2DS2-VASC Score and current ESC guidelines 1 2. 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
7 
 
5. Ablation 
The FARAPULSE AF ablation system represents a unique single shot ablation technology associated 
with a high rate of acute and durable PV isolation 14. In principle, electroporation delivers a cardiac 
selective ablation, thus sparing non-cardiac tissue. The endpoint of the catheter ablation procedure is 
defined to PVI. Therefore, this technology offers a unique beneficial profile combining a high 
procedural efficacy and safety.  
6. Endpoints 
The primary endpoint is a composite of cardiovascular hospitalization (worsening heart failure, acute 
coronary syndrome, AF/AT recurrence, cardioversions, re-ablations), death, systemic embolism, stroke 
(ischemic, hemorrhagic) and emergency (E) treatment for cardiovascular reasons. 
Secondary endpoints are defined to safety parameters such peri-procedural complications (major 
bleeding requiring intervention, phrenic nerve palsy, pericardial tamponade, thromboembolic events, 
atrio-esophageal fistula, death) or discontinuation of AAD due to side effects and documented 
recurrence of AF or any atrial tachyarrhythmia lasting longer than 30 seconds between day 90 and 365 
after the index procedure as well as number of nights spent in the hospital per year.  
Study Design 
The proposed pilot study is a prospective, randomized, single-center feasibility study, enrolling 200 
patients with symptomatic paroxysmal AF. Per protocol, 100 patients will undergo a FARAPULSE 
electroporation PVI and 100 patients will receive standard AF medical treatment.  
Prior enrollment, all patients will be informed on the risk and benefits of the PVI procedure as well as 
the medical treatment. In addition, particular information on the rationale of the study, including a 
detailed risk/benefit analysis, will be provided to all patients.  
After obtaining written informed consent and randomization, patients will be treated according to the 
assigned groups (FARAPULSE electroporation PVI vs. optimized medical care). Follow-Up duration is 12 
months. Importantly, cross-over between both groups is strongly discouraged. If deterioration occurs 
in group 2, PVI is advised. 
Risk-Benefit-Analysis 
Catheter ablation of paroxysmal AF represents an invasive procedure but is linked to a lower AF 
recurrence rate if compared to medical treatment. Participants in Group 2 (control group) will receive 
best medical treatment including the option for electrical cardioversions and AAD treatment. 
The novel energy source using electroporation appears to be appealing due to its potential of short 
procedure times and cardiomyocyte selectivity resulting in a benign safety profile. The participants in 
Group 1 will be scheduled to receive the ablation therapy early after the AF diagnosis (within 7 days).  
In general, catheter ablation for AF is an invasive treatment associated with potential complications. 
Of note, as stated above electroporation appears to be associated with a very benign risk profile. 
General AF related complications and corresponding incidences are summarized in the following: 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
8 
 
 
Vascular access complications such as vascular damage, neural damage, hematoma, bleeding 
(approx. 2-3%) 
 
Pericardial tamponade (<1%) 
 
Systemic Infection (<1%) 
 
Thrombo-embolic complications including air embolism, transient ischemic attack and stroke 
(<1%) 
 
Pulmonary vein stenosis or occlusion (<0,5%) 
 
Atrio-esophageal fistula (< 1‰) 
 
Death (< 0.1‰) 
All devices utilized for the ablation procedure are fully licensed, CE mark approved and are used in the 
clinical routine. Patients randomized to Group 2 will receive standard medication including all non-
interventional options for a rhythm control strategy in the treatment of paroxysmal AF. Therefore, no 
patient will be exposed to a higher risk due to the participation in the E-TEAM-Trial. 
6.1   Inclusion and Exclusion Criteria 
6.1.1 Inclusion Criteria 
1. Seeking emergency (E) treatment including emergency room (ER) presentation 
2. Paroxysmal AF diagnosed according to current ESC guidelines 
3. Diagnosis of HFpEF according to ESC guidelines 2021 (clinical symptoms, EF>50%, objective 
evidence of functional abnormality: LV diastolic dysfunction, NT-proBNP (non acute setting): 
sinus rhythm: 125pg/ml or AF: 365pg/ml, vs. acute HF: >450 pg/ml if aged <55 years, >900 
pg/ml if aged between 55 and 75 years and >1800 pg/ml if >75ys. 
4. Age between 18 and 80 years 
5. Left atrial size, LA < 55mm 
6. Left ventricular ejection fraction, EF >50% 
7. Patients able to provide informed consent and willing to comply with all pre-, post- and 
follow-up requirements as per study protocol 
6.1.2 Exclusion Criteria 
1. Currently participating in an interventional (drug, device, biologic, etc.) clinical trial 
2. Any disease that limits life expectancy to less than one year 
3. Contraindications for PVI 
4. Contraindication for AAD therapy 
5. Active systemic infection 
6. Thrombocytosis, thrombocytopenia 
7. Known pre-existing hemi-diaphragmatic paralysis 
8. Any untreated or uncontrolled hyperthyroidism or hypothyroidism 
9. Reduced immune function or otherwise at high risk for infection per physician discretion 
10. Active malignancy or history of chemotherapy or radiation treatment 
11. Prior left atrial ablation or surgical procedure (including left atrial appendage closures) 
12. Any cardiac surgery, myocardial infarction, PCI/PTCA or coronary artery stenting which 
occurred within the 3 months before the eligibility assessment 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
9 
 
13. Instable angina pectoris 
14. Primary pulmonary hypertension 
15. Any condition contraindicating chronic anticoagulation 
16. Any cerebral ischemic event (strokes or TIAs) which occurred within the 3 months before the 
consent date 
17. Presence of any cardiac prosthetic valves 
18. Left atrial diameter > 55 mm (anteroposterior) by TTE 
19. Presence of any pulmonary vein stents 
20. Presence of any pre-existing pulmonary vein stenosis (identified by CT or MRI and defined as 
at least 70% reduction of the PV diameter) 
21. Endocarditis, pericarditis or pericardial effusion 
22. Pregnant or breastfeeding women or women of childbearing potential not on adequate birth 
control. 
23. Substance abuse 
24. Unwilling to follow the study protocol and to attend follow-up visits 
6.2   Study course 
 
 
 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
10 
 
6.2.1   Visit 1, Pre-procedural, Day -2 to 0 
Following emergency hospital admission diagnostic work up including physical examination, 12 lead 
ECG, emergency blood examination (NT-proBNP) and chest X-ray initial cardiac ultrasound. Initiation 
and optimization of emergency therapy including iv diuretics if required. Routine diagnostic work up 
during hospital stay including daily clinical evaluation, weight loss determination, complete cardiac 
ultrasound, 12 lead ECG, telemetry, routine blood examination (30 ml) for blood cell count, INR, 
creatinine, ALAT, ASAT, electrolytes, TSH, NT-proBNP according to clinical needs.  
Randomization (1:1) will be performed by the E-TEAM after all the patients’ questions were clarified 
and the ICF was signed. All patients randomized to Group 1 will proceed to preparation of Visit 2, 
pulmonary vein isolation. The patients randomized in Group 2 will receive best medical treatment and 
if rhythm control was attempted TEE guided cardioversion and AAD according to the patients clinical 
needs as well as all information regarding the medical treatment. 
In order to exclude intracardiac thrombi, a transesophageal echocardiogram (TEE) will be performed 
in patients randomized to Group 1 and considered at risk for thrombus formation and stratified to 
rhythm control (Group 2, before cardioversion). In case of TEE proven LAA thrombus the scheduled AF 
ablation or cardioversion can be postponed.  
6.2.2   Visit 2, Pulmonary Vein Isolation, FARAPULSE-Ablation 
The FARAPULSE ablation procedure will be performed during deep sedation using midazolam, fentanyl 
and a continuous infusion of propofol. Vital parameters will be monitored. For catheter access, two 8F 
sheaths will be inserted into the femoral veins guided by ultrasound. One multipolar diagnostic 
catheter will sequentially be placed in the coronary sinus and right ventricle to pace for in case of need. 
Single transseptal puncture and insertion of one 8.5 F transseptal sheath will be followed by PV 
angiographies. Using the FARAPULSE catheter, pulmonary vein (PV) electrograms will be recorded. 
Unfractionated heparin will be administered to maintain an activated clotting time between 300 and 
400s. The FARAPULSE catheter will be advanced via a steerable sheath to the LA and sequential PV 
isolation will be performed for each individual PV following the recommended dosing strategy (1+7 
applications: 4 basekt, 4 flower configuration). In case of incessant AF or atrial flutter, additional 
ablation including right atrial isthmus ablation is allowed. At the end of the ablation procedure, the 
patients will undergo transthoracic echocardiography (TTE) on the table to exclude acute pericardial 
effusion. 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
11 
 
6.2.3   Visit 3, Hospital Discharge 
Until discharge, all patients will be monitored using telemetry and all patients in Group 1 will undergo 
a repeat TTE to exclude pericardial effusion and a daily 12 lead electrocardiography (ECG) to document 
the heart rhythm. A blood sample (20 ml) will be routinely collected to exclude bleeding (blood cell 
count) or renal function deterioration (creatinine and electrolytes). Therapeutic anticoagulation 
preferentially using a novel oral anticoagulant (NOAC) over Vitamin K antagonist will be initiated or 
resumed the evening after the procedure and maintained for at least 8 weeks after ablation. Continued 
anticoagulation will be performed if necessary, according to the individual CHA2DS2-Vasc-Score. In 
both groups early cardioversions in case of very early recurrence during the index hospital stay are 
allowed. AAD treatment in Group 1 should be avoided and should be stopped after 3 months, in Group 
2 AAD treatment is allowed if rhythm control was selected according to the patients clinical profile. 
Total nights spent in hospital will be counted. 
6.2.4   Visit 4, 3 Months Follow-Up after PVI/Randomization (± 7 Days) 
An outpatient visit including the collection of a brief history (complications, medication), physical 
examination, 12 lead ECG, TTE and 72h-Holter-ECG will be performed at 3 Months ± 7 Days post 
procedure (Group 1) or post randomization (Group 2). All antiarrhythmic drugs (AAD) except beta-
blockers prescribed for other medical conditions (i.e. arterial hypertension) have to be stopped for all 
patients in Group 1. If necessary, all medication including AAD for the patients in Group 2 should be 
adjusted. 
6.2.5   Visit 5, 6 Months Follow-Up after PVI/Randomization (± 14 Days) 
An outpatient visit including the collection of a brief history (complications, medication), physical 
examination, 12 lead ECG, TTE and 72h-Holter-ECG will be performed at 6 Months ± 14 Days post 
procedure (Group 1) or post randomization (Group 2). 
6.2.6   Visit 6, 12 Months Follow-Up after PVI/Randomization (± 14 Days) 
An outpatient visit including the collection of a brief history (complications, medication), physical 
examination, 12 lead ECG, TTE and 72h-Holter-ECG will be performed at 12 Months ± 7 Days post 
procedure (Group 1) or post randomization (Group 2).  
6.3   Repeat ablation 
No blanking period will be utilized in this study. During the first 90 days after the index procedure any 
arrhythmia recurrence shall be treated conservatively, e.g. by antiarrhythmic medication and/or ECV. 
Of note, re-ablation is strongly discouraged within the first 3 months. At day 90 however, all AAD drugs 
should be stopped in the ablation group and all re-ablation afterwards will meet the primary endpoint. 
In case of re-ablation the patient has reached the primary endpoint. The Follow-Up visits should be 
continued as per protocol. 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
12 
 
7. Participant withdrawal or termination of participation 
Prior to study entry, all participants will be informed that they are free to withdraw from the study at 
any time and for any reason without prejudice to their future medical care by a physician or the 
institution. Participants are free to withdraw from participation in the study at any time upon request. 
The withdrawal will cause no penalty or loss of benefits, to which the patients may otherwise be 
entitled. The investigator may ask and document the patients’ motivation. 
An investigator may also terminate a patients’ participation in the study if: 
• Withdrawal is in the subjects’ best interest. 
• Subject withdraws consent. 
• Subject is lost to follow up. 
 
8. Statistical Analysis 
No interim-analysis will be performed.  
The following events will trigger a premature study termination:  
• Occurrence of serious adverse events in more than 10% of the study population associated 
with the ablation procedure. Of note, re-hospitalization for cardiovascular reasons meets the 
primary study endpoint. 
• Occurrence of any unexpected, currently unknown complication or risk (Change of Risk-
Benefit Ratio).  
Occurrence of >10% major procedural complications defined as cardiac tamponade, stroke/TIA, air 
embolism, major bleeding the study has to be stopped. Of note re-hospitalization for cardiovascular 
reasons meets the primary endpoint.”  
 
 
9.   Adverse Events 
All adverse events (AEs) experienced by participants during the study, beginning with the first study 
related procedure and continuing through the end of study, will be recorded on case report forms 
(CRFs). Occurrences of atrial fibrillation and atrial flutter will be recorded and reported on as part of 
the efficacy assessment, and are not considered adverse events. 
Serious adverse events (SAEs) are events that place the participants health in jeopardy and that occur 
despite following all labeling precautions and instructions for use and where all attempts at correction 
by medical intervention do not resolve the event. All SAEs must be reported to the Ethics Committee 
(EC) within 48 hours of the investigator becoming aware of the SAE. Re-hospitalization for 
cardiovascular reasons is part of the primary endpoint and therefore does not qualify as an SAE. 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
13 
 
An unanticipated adverse device effect (UADE) is defined as any SAE on health or safety, or any life-
threatening problem or death caused by, or associated with, the device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence in the investigational 
plan or application. An UADE is also defined as any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of participants. 
Should an UADE occur, the investigator is required to notify the EC as soon as possible, but in no event 
later than 10 working days after the investigator first learns of the event. An immediate evaluation of 
any UADE will be conducted. If there is significant new information that could affect the risk/benefit 
analysis as given in Section 7.1 of this protocol, the ECs will be informed and if appropriate, actions 
such as study hold, patient re-consent or study termination will be taken. 
All participant deaths must be immediately reported to the EC (24 h upon investigators knowledge). 
When possible and permitted by family members, an autopsy shall be performed. The death 
certificate, coroner's report, and laboratory and autopsy reports, if available, should be provided to 
the EC. 
 
10. Documentation 
All patient data will be documented in CRFs. Personal data such as name, address, contact data etc. 
are excluded from the documentation in the eCRF. Names of all patients will be pseudomized and 
underlie national data protection laws. The principal investigator will conserve the patient 
identification list, the signed informed consent forms and the original data including the patient chart 
for 15 years. 
 
11. Study organization 
Principle Investigators:  Prof. Dr. med. K.R. Julian Chun 
MVZ CCB Frankfurt und Main Taunus GbR 
Am Agaplesion Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
Tel.: +49 69 945028 110 
Fax: + 49 69 945028 119 
E-Mail: j.chun@ccb.de  
 
Priv. Doz. Dr. med. Boris Schmidt 
MVZ CCB Frankfurt und Main Taunus GbR 
Am Agaplesion Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
Tel.: +49 69 945028 110 
Fax: + 49 69 945028 119 
E-Mail: b.schmidt@ccb.de 
Study Coordinators: 
Bojana Languille, Negin Azimi-Hashemi, Ines Timmermanns 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
14 
 
MVZ CCB Frankfurt und Main Taunus GbR 
Am Agaplesion Markus Krankenhaus 
Wilhelm-Epstein Str. 4 
60431 Frankfurt am Main 
Tel.: +49 69 945028 157 / -144 / -146 
Fax: + 49 69 945028 119 
E-Mail: studienabteilung@ccb.de 
12. References 
1.  
Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, 
Castella M, Dan G-A, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane 
DA, Lebeau J-P, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, 
Van Putte BP, Watkins CL, ESC Scientific Document Group, Kirchhof P, Kühne M, Aboyans 
V, Ahlsson A, Balsam P, Bauersachs J, Benussi S, Brandes A, Braunschweig F, Camm AJ, 
Capodanno D, Casadei B, Conen D, Crijns HJGM, Delgado V, Dobrev D, Drexel H, Eckardt 
L, Fitzsimons D, Folliguet T, Gale CP, Gorenek B, Haeusler KG, Heidbuchel H, Iung B, Katus 
HA, Kotecha D, Landmesser U, Leclercq C, Lewis BS, Mascherbauer J, Merino JL, Merkely 
B, Mont L, Mueller C, Nagy KV, Oldgren J, Pavlović N, Pedretti RFE, Petersen SE, Piccini 
JP, Popescu BA, Pürerfellner H, Richter DJ, Roffi M, Rubboli A, Scherr D, Schnabel RB, 
Simpson IA, Shlyakhto E, Sinner MF, Steffel J, Sousa-Uva M, Suwalski P, Svetlosak M, 
Touyz RM, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, Boriani G, Castella M, Dan 
G-A, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau J-P, 
Lettino M, Lip GYH, Pinto FJ, et al. 2020 ESC Guidelines for the diagnosis and management 
of atrial fibrillation developed in collaboration with the European Association for Cardio-
Thoracic Surgery (EACTS). Eur Heart J. 2021;42:373–498.  
2.  
McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, 
Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, 
Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, 
McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, 
Rosano GMC, Ruschitzka F, Kathrine Skibelund A, ESC Scientific Document Group, de Boer 
RA, Christian Schulze P, Abdelhamid M, Aboyans V, Adamopoulos S, Anker SD, Arbelo E, 
Asteggiano R, Bauersachs J, Bayes-Genis A, Borger MA, Budts W, Cikes M, Damman K, 
Delgado V, Dendale P, Dilaveris P, Drexel H, Ezekowitz J, Falk V, Fauchier L, Filippatos G, 
Fraser A, Frey N, Gale CP, Gustafsson F, Harris J, Iung B, Janssens S, Jessup M, Konradi A, 
Kotecha D, Lambrinou E, Lancellotti P, Landmesser U, Leclercq C, Lewis BS, Leyva F, 
Linhart A, Løchen M-L, Lund LH, Mancini D, Masip J, Milicic D, Mueller C, Nef H, Nielsen 
J-C, Neubeck L, Noutsias M, Petersen SE, Sonia Petronio A, Ponikowski P, Prescott E, 
Rakisheva A, Richter DJ, Schlyakhto E, Seferovic P, Senni M, Sitges M, Sousa-Uva M, 
Tocchetti CG, Touyz RM, Tschoepe C, Waltenberger J, Adamo M, Baumbach A, et al. 2021 
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur 
Heart J. 2021;42:3599–3726.  
3.  
Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner–La Rocca H-P, 
Choi D-J, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, 
Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski 
P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, 
Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, 

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
15 
 
Brueckmann M, Pocock SJ, Zannad F, Packer M. Empagliflozin in Heart Failure with a 
Preserved Ejection Fraction. N Engl J Med. 2021;385:1451–1461.  
4.  
Di Carlo A, Bellino L, Consoli D, Mori F, Zaninelli A, Baldereschi M, Cattarinussi A, 
D’Alfonso MG, Gradia C, Sgherzi B, Pracucci G, Piccardi B, Polizzi B, Inzitari D, National 
Research Program: Progetto FAI. La Fibrillazione Atriale in Italia, Aliprandi ML, Bonsangue 
E, Locatelli P, Saurgnani P, Senziani LG, Tarantini D, Rota RP, Boninsegni R, Feltrin T, 
Lancia E, Latella F, Monici G, Portera F, Ceccherini S, Borello G, Contartese A, D’Amico A, 
D’Urzo G, Grillo GC, Mellea F, Ramondino C. Prevalence of atrial fibrillation in the Italian 
elderly population and projections from 2020 to 2060 for Italy and the European Union: 
the FAI Project. EP Eur. 2019;21:1468–1475.  
5.  
Gallagher C, Hendriks JM, Giles L, Karnon J, Pham C, Elliott AD, Middeldorp ME, Mahajan 
R, Lau DH, Sanders P, Wong CX. Increasing trends in hospitalisations due to atrial 
fibrillation in Australia from 1993 to 2013. Heart. 2019;105:1358–1363.  
6.  
Piccini JP, Lopes RD, Kong MH, Hasselblad V, Jackson K, Al-Khatib SM. Pulmonary Vein 
Isolation for the Maintenance of Sinus Rhythm in Patients With Atrial Fibrillation: A Meta-
Analysis of Randomized, Controlled Trials. Circ Arrhythm Electrophysiol. 2009;2:626–633.  
7.  
Packer DL, Mark DB, Robb RA, Monahan KH, Bahnson TD, Poole JE, Noseworthy PA, 
Rosenberg YD, Jeffries N, Mitchell LB, Flaker GC, Pokushalov E, Romanov A, Bunch TJ, 
Noelker G, Ardashev A, Revishvili A, Wilber DJ, Cappato R, Kuck K-H, Hindricks G, Davies 
DW, Kowey PR, Naccarelli GV, Reiffel JA, Piccini JP, Silverstein AP, Al-Khalidi HR, Lee KL, 
for the CABANA Investigators. Effect of Catheter Ablation vs Antiarrhythmic Drug 
Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial 
Fibrillation: The CABANA Randomized Clinical Trial. JAMA. 2019;321:1261.  
8.  
Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, 
Haase D, Haegeli LM, Hamann F, Heidbüchel H, Hindricks G, Kautzner J, Kuck K-H, Mont 
L, Ng GA, Rekosz J, Schoen N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, 
Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G. Early 
Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med. 
2020;383:1305–1316.  
9.  
Kuniss M, Pavlovic N, Velagic V, Hermida JS, Healey S, Arena G, Badenco N, Meyer C, Chen 
J, Iacopino S, Anselme F, Packer DL, Pitschner H-F, Asmundis C de, Willems S, Di Piazza F, 
Becker D, Chierchia G-B, for the Cryo-FIRST Investigators. Cryoballoon ablation vs. 
antiarrhythmic drugs: first-line therapy for patients with paroxysmal atrial fibrillation. EP 
Eur. 2021;23:1033–1041.  
10.  Wazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, Niebauer M, Makati K, 
Halperin B, Gauri A, Morales G, Shao M, Cerkvenik J, Kaplon RE, Nissen SE. Cryoballoon 
Ablation as Initial Therapy for Atrial Fibrillation. N Engl J Med. 2021;384:316–324.  
11.  Andrade JG, Wells GA, Deyell MW, Bennett M, Essebag V, Champagne J, Roux J-F, Yung 
D, Skanes A, Khaykin Y, Morillo C, Jolly U, Novak P, Lockwood E, Amit G, Angaran P, Sapp 
J, Wardell S, Lauck S, Macle L, Verma A. Cryoablation or Drug Therapy for Initial 
Treatment of Atrial Fibrillation. N Engl J Med. 2021;384:305–315.  

E-TEAM- Electroporation Treatment for Early AF Management Pilot Study    
 
E-TEAM, Protocol Version 2.0, 13Oct2022 
 
16 
 
12.  Reddy VY, Dukkipati SR, Neuzil P, Anic A, Petru J, Funasako M, Cochet H, Minami K, 
Breskovic T, Sikiric I, Sediva L, Chovanec M, Koruth J, Jais P. Pulsed Field Ablation of 
Paroxysmal Atrial Fibrillation. JACC Clin Electrophysiol. 2021;7:614–627.  
13.  Tohoku S, Schmidt B, Bordignon S, Chen S, Bologna F, Urbanek L, Pansera F, Chun KRJ. 
Pulsed Field Ablation for Persistent Superior Vena Cava. JACC Case Rep. 2022;4:301–305.  
14.  Reddy VY, Neuzil P, Koruth JS, Petru J, Funosako M, Cochet H, Sediva L, Chovanec M, 
Dukkipati SR, Jais P. Pulsed Field Ablation for Pulmonary Vein Isolation in Atrial 
Fibrillation. J Am Coll Cardiol. 2019;74:315–326.