Pulsed Field Ablation

Treatment in Paroxysmal
and Persistent Atrial
Fibrillation Patients:
Acute and Long-term
Outcomes from the
PULSED AF Pivotal Trial
Dr. Atul Verma

On behalf of the PULSED AF Investigators

@atulverma_md
Disclosures
Company Relationship
Medtronic Consultant/ Honoraria/ Research grant
Biosense Webster Consultant/ Honoraria/ Research grant
Biotronik Research grant
Bayer Research grant/ Honoraria
Kardium Consultant
Medlumics Consultant/ Honoraria

The PULSED AF study (NCT04198701) was funded by Medtronic, Inc.

Reference materials were requested and obtained from Medtronic, Inc. for portions of this presentation.

The Medtronic PulseSelectTM PFA system is investigational, not approved in the US.
The following data and analyses have not been reviewed by any regulatory bodies,
including FDA.
Introduction
• Catheter ablation is an effective treatment for patients with symptomatic,
drug-refractory atrial fibrillation.1,2

• Thermal modes of ablation are limited by the potential for collateral tissue
damage.3

• Pulsed field ablation creates lesions in cardiac tissue non-thermally and

within milliseconds through the mechanism of irreversible electroporation
(IRE).4,5

• IRE involves tissue exposure to high electric field gradients, inducing cell
membrane hyper-permeabilization leading to cell death. 6

1. Calkins H et al. Europace. 2018;20:e1-e160 4. Stewart MT et al. J Cardiovasc Electrophysiol. 2021;32:958-969.

2. Hindricks G et al. Eur Heart J. 2021;42:373-498. 5. Yarmush ML et al. Annu Rev Biomed Eng. 2014;16:295-320.
3. Cappato R et al. Circ Arrhythm and Electrophysiol. 2010;3:32-38 6. Kotnik T et al. Annu Rev Biomed Eng. 2019;48:63-91.
One application = 4 bipolar, biphasic trains lasting 100-200 ms, 2800-3000 V peak to peak
PULSED AF Study Design
PULSED AF: prospective, global, multi-center, non-randomized paired single-arm trial

41 67 9 150 150
Centers Operators Countries Paroxysmal AF Persistent AF

Key Inclusion Criteria Key Exclusion Criteria

• Prior antiarrhythmic drug failure • Long-standing persistent AF (continuous AF that is
sustained >12 months)
• Diagnosis of recurrent symptomatic paroxysmal or
persistent AF • Left atrial diameter > 5.0 cm
• 18-80 years old • Prior left atrial ablation or surgery
• Patient not on oral anticoagulation therapy for at least 3
weeks prior to procedure

Patients underwent pulmonary vein isolation using the Pulsed Field Ablation System
(PulseSelectTM) and were followed for 12 months
Primary Efficacy Endpoint
Freedom from a composite endpoint of acute procedural failure, arrhythmia recurrence,
repeat ablation, direct current cardioversion, left atrial surgery, or antiarrhythmic drug
escalation through 12 months (excluding a 90-day blanking period)
Pre-Specified Performance Goal: >50% (paroxysmal) or >40% (persistent) at 12 months
All cardiac monitoring was adjudicated by an independent core laboratory

Cardiac Monitoring During Follow-up

1-M 2-M 3-M 4-M 5-M 6-M 7-M 8-M 9-M 10-M 11-M 12-M
TTM Weekly and symptomatic transmissions
ECG X X X
HM X X
Blanking period Post-blanking period
Primary Safety Endpoint
Freedom from a composite of serious procedure and device-related adverse events
Pre-Specified Performance Goal: <13%
All primary safety endpoint events were adjudicated by an independent clinical events committee
Patient Flow Diagram
Enrolled:
383

Paroxysmal 14 Not Ablated: Persistent

AF -Screen failure (4) AF 9 Not Ablated:
(n = 200) -Physician decision (3) (n = 183) -Screen failure (5)
-Withdrawal by patient (3) -Procedure not
-Protocol deviation (1) attempted (3)
-Sponsor request (1) -Sponsor request (1)
-Other (2)

36 Roll-In Patients 24 Roll-In Patients

150 Primary 150 Primary

Cohort Cohort

96% of patients reached 12-month follow-up

Results: Patient Baseline Characteristics
Patient Characteristics Paroxysmal (n = 150) Persistent (n = 150)
Male Sex 64% 75%
Age (years) 63.4 ± 9.9 66.0 ± 9.0
Left Atrial Diameter (mm) 38.7 ± 5.8 42.0 ± 5.0
Left Ventricular Ejection Fraction (%) 60.3 ± 4.8† 57.6 ± 6.4
Years Since AF Onset 3.8 ± 6.2 2.7 ± 3.7
Number of Failed Antiarrhythmic Drugs 1.3 ± 0.6 1.3 ± 0.6
Cardioversions Prior to Enrollment Electrical 22% 62%
Pharmaceutical 10% 7%
Body Mass Index (kg/m2) 28.6 ± 5.9 30.9 ± 6.8
Medical History
Stroke 3% 2%
Transient ischemic attack 1% 2%
Myocardial infarction 5% 5%
Coronary artery disease 21% 21%
Hypertension 49% 65%
Obstructive sleep apnea 20% 31%
Valve dysfunction 15% 11%
Diabetes 16% 14%
CHA2DS2VASc 1.8 ± 1.4 2.1 ± 1.4
Data represented as mean ± SD or percentage; †n=149
Procedural Characteristics
Parameter Paroxysmal (n = 150) Persistent (n = 150)
Acute Pulmonary Vein Isolation 100% 100%

Skin-to-skin Procedure Time (min)* 125 (102-157) 133.5 (107-173)

Device Left Atrial Dwell Time (min)† 58.5 (46-76) 62.5 (51-84)

Time Between First and Last Application 53 (40-68) 60 (45-77)

Fluoroscopy Time (min) 21 (15-31) 23 (14-38)

Total pulsed field ablation energy delivered (sec) 23 (19-28) 27 (23-34)
Number of applications per procedure 43.5 (37-54) 52.5 (44-67)
Type of anesthesia used – no. (%)
General anesthesia 89% 84%
Deep sedation 5% 7%
Conscious sedation 5% 9%
Neuromuscular Blockade Use 5% 7%

Intra-procedural Cardioversions 17% 65%

Max esophageal temperature change from baseline (°c) 0.3 (0.1-0.5) § 0.2 (0.0-0.5) ‖
Mapping / Navigation system used – no. (%)
CARTO 26% 23%
EnSite 57% 59%
Rhythmia 11% 10%
None 5% 8%
Data represented as median (IQR) or percentage; *First sheath in, to last sheath out; †Includes protocol-mandated 20-minute wait period and post-ablation mapping
§Data were available for 67 patients; ‖Data were available for 73 patients.
Primary Efficacy Results
Freedom from a composite endpoint of acute procedural failure, arrhythmia recurrence, repeat ablation, direct current cardioversion,
left atrial surgery, or antiarrhythmic drug escalation through 12 months (excluding a 90-day blanking period)

Paroxysmal Atrial Fibrillation Persistent Atrial Fibrillation

Both paroxysmal and persistent atrial fibrillation cohorts met predetermined effectiveness
performance goals.
Freedom from AT/AF/AFL
Paroxysmal Atrial Fibrillation Persistent Atrial Fibrillation

Freedom from atrial arrhythmia recurrence at 12 months was 69.5% in the paroxysmal and 62.3%
in the persistent atrial fibrillation cohort
Clinical Success
Clinical success was defined as freedom from symptomatic atrial arrhythmia recurrence at 12 months

Paroxysmal Atrial Fibrillation Persistent Atrial Fibrillation

Freedom from symptomatic recurrence is based on trans-telephonic monitoring only

Primary Safety Results
0.7% safety event rate in each cohort
Both paroxysmal and persistent atrial fibrillation cohorts met predetermined safety performance goals (<13%, p=0.002)
) Number with a Primary Safety Event
Primary Safety Event Paroxysmal AF (n = 150) Persistent AF (n = 150)
Within 6 months
Pulmonary vein stenosis (>70% diameter reduction) 0 0
Phrenic nerve injury/diaphragmatic paralysis ongoing at 6 months 0 0
Atrioesophageal fistula 0 0
Within 30 days
Cardiac tamponade/perforation 0 1
Cerebrovascular accident 1 0
Transient ischemic attack 0 0
Major bleeding requiring transfusion 0 0
Myocardial infarction 0 0
Pericarditis requiring intervention 0 0
Vagal nerve injury resulting in esophageal dysmotility or gastroparesis 0 0
Vascular access complications requiring intervention 0 0
Death 0 0
PFA system- or procedure-related cardiovascular and pulmonary adverse event 0 0
prolonging/requiring hospitalization >48 hours (excluding recurrent AF/AFL/AT)
Quality of Life
Quality of life measures indicate a clinically meaningful improvement1-3
AFEQT EQ-5D-5L 22% more patients were
not anxious or depressed
100
Mean AFEQT score
1 +0.05 (p<0.0001) at 12 mo vs. baseline
Paroxysmal AF

Mean EQ-5D-5L
+29.4 (p<0.0001) 89.8 0.91
80 0.8 0.86
11% more patients had no

score
60 0.6 problems doing their
60.4
usual activities at 12 mo
40 0.4 vs. baseline
20 0.2
0 0
Baseline 12 Months Baseline 12 Months
19% more patients were
not anxious or depressed
Persistent AF

100 1
Mean AFEQT score

+0.06 (p<0.0001) at 12 mo vs. baseline

Mean EQ-5D-5L
+29.0 (p=0.001) 91.0 0.92
80 0.8 0.86
21% more patients had no

score
60 0.6 problems doing their
62.0
usual activities at 12 mo
40 0.4
vs. baseline
20 0.2
1, Dorian P et al. Am Heart J. 2013;166:381-
387.e388.
0 0 2, Holmes DN et al. Circ Cardiov asc Qual
Baseline 12 Months Baseline 12 Months Outcomes. 2019;12:e005358.
3, Coretti S et al. Expert Rev Pharmacoecon
Outcomes Res. 2014;14:221-233.

MCID: 5 points AFEQT, 0.3 EQ5D (Holmes et al, 2019; Coretti et al, 2014)
PV Stenosis Sub-Study
No moderate or severe stenosis was observed in 275 pulmonary veins on cardiac computed
tomography or MRI imaging at 3 months

Pulmonary Vein Stenosis Sub-Study

Pulmonary Vein Diameter Change
Moderate Change Severe Change
Vein N* no. (%)1 no. (%)2
All 275 0 (0) 0 (0)
RIPV 63 0 (0) 0 (0)
RSPV 62 0 (0) 0 (0)
RMPV 9 0 (0) 0 (0)
LIPV 63 0 (0) 0 (0)
LSPV 63 0 (0) 0 (0)
LCPV 15 0 (0) 0 (0)

150-70% reduction, 1≥70% reduction.

Cerebral MRI Sub-Study
New silent cerebral lesions were observed in 4 of 45 patients (9%) undergoing cerebral MRI at
baseline and within 72 hours post-ablation

Cerebral MRI Sub-Study

Silent
Number Cerebral
of Lesions --
Cohort Patients no. (%)
Paroxysmal AF 26 2 (8)
Persistent AF 19 2 (11)
Total 45* 4 (9)
Conclusion
• Primary safety endpoint rate of 0.7% observed for both cohorts
• No occurrence of phrenic, esophageal, pulmonary vein injury, or coronary artery spasm
• Both paroxysmal and persistent atrial fibrillation cohorts met predetermined safety performance goals (<13%)

• Acute isolation was demonstrated in 100% of all pulmonary veins

• Both paroxysmal and persistent atrial fibrillation cohorts met predetermined

effectiveness performance goals
• 66.2% freedom from a primary efficacy endpoint event in paroxysmal AF patients
• 55.1% freedom from a primary efficacy endpoint event in persistent AF patients

• Pulsed field ablation resulted in a clinically meaningful improvements in quality of life

• Pulsed field ablation resulted in 79.7% (paroxysmal) and 80.8% (persistent) clinical
success
PULSED AF Committees
Steering Committee
Dr. Atul Verma Southlake Regional Health Center, Toronto, Canada
Dr. Lucas V.A. Boersma St Antonius Hospital, Nieuwegein, Netherlands
Dr. Hugh Calkins Johns Hopkins Hospital, Baltimore, MD

Dr. Prashanthan Sanders Univ of Adelaide & Royal Adelaide Hospital, Adelaide, Australia
Dr. David E. Haines Beaumont Health, Royal Oak, MI
Dr. Francis E. Marchlinski Hospital of the Univ of Pennsylvania, Philadelphia, PA
Dr. Andrea Natale Texas Cardiac Arrhythmia Institute, Austin, TX
Dr. Gerhard Hindricks Heart Center - University of L, Leipzig, Germany
Dr. Douglas L. Packer Mayo Clinic-St. Mary`s Hospital, Rochester, MN

Dr. Karl-Heinz Kuck LANS Cardio, Hamburg, Germany

Clinical Events Committee Data Monitoring Committee

Dr. Wendy Tzou Dr. George Crossley
Dr. Pierre Fayad Dr. Timothy Church
Dr. Peter Friedman Dr. Daryl Gress
Dr. Melissa Robinson Dr. Carina Blomström-Lundqvist
Dr. Jonathan Steinberg Dr. Stephan Willems
Dr. Jeanne Poole
 PULSED AF Investigators
Principal Investigator​ Site Name Principal Investigator​ Site Name
David DeLurgio​ (co-author) Emory Saint Joseph's Hospital (Atlanta GA) Bradley Knight​ Northwestern University
Nitesh Sood (co-author) Southcoast Health System Mattias Duytschaever​ AZ Sint-Jan Brugge-Oostende av
Hiroshi Tada (co-author) University of Fukui Hospital Larry Chinitz​ NYU Langone Medical Center
Robert Hoyt​ Iowa Heart Center John Rhyner​ Mission Hospital
Andrea Natale​ Texas Cardiac Arrhythmia Research Foundation Ángel Arenal Maiz Hospital General Universitario Gregorio Marañón
James Irwin​ BayCare Medical Group Cardiology Ethan Ellis​ Medical Center of the Rockies
David Haines​ Beaumont Health System Jason Andrade​ Vancouver General Hospital
Suneet Mittal​ The Valley Hospital J. Michael Mangrum University of Virginia Medical Center
Sarfraz Durrani​ MedStar Washington Hospital Center Bradley Wilsmore​ John Hunter Hospital
Robert Sangrigoli​ Doylestown Health Cardiology Alexandre Zhao​ CMC - Clinique Ambroise Paré
Luigi Di Biase​ Montefiore Medical Center Raman Mitra​ Northwell Health
Oussama Wazni Cleveland Clinic Alefiyah Rajabali Providence Saint Vincent Medical Center
Atul Verma Southlake Regional Health Centre Sandeep Jain University of Pittsburgh Medical Center
Jose Osorio​ Grandview Medical Center Andre Gauri​ Spectrum Health
Teiichi Yamane​ The Jikei University Hospital Peter Noseworthy Mayo Clinic (Rochester MN)
Tetsuo Sasano Tokyo Medical and Dental University Hospital Vidal Essebag McGill University Health Centre (MUHC)
Hirofumi Tomita Hirosaki University Hospital Jean-Francois Sarrazin​ Institut Universitaire de Cardiologie et de Pneumologie
Sanjaya Gupta​ St. Luke's Mid America Heart Institute de Québec
Helmut Friedrich Pürerfellner​ Ordensklinikum Linz GmbH / Elisabethinen Darryl Wells​ Swedish Medical Center
Francis E Marchlinski​ Hospital of the University of Pennsylvania John Hummel​ The Ohio State University Heart and Vascular Research
Lucas V. A. Boersma​ St. Antonius Ziekenhuis Organization
Hugh Calkins​ The Johns Hopkins Hospital Prashanthan Sanders Royal Adelaide Hospital
Thank you to all PULSED
AF investigators and all
patients

On behalf of Dr. Atul Verma and the

PULSED AF steering committee

@atulverma_md
Announcing publication release: