Development of pulsed field ablation

Explore the Medtronic development journey of irreversible electroporation (IRE), pulsed field ablation (PFA), and the science behind the novel cardiac ablation technology.

View the PULSED AF secondary analysis now.

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Caution: Investigational device, limited to investigational use only. Not available for sale in the U.S. The PULSED AF clinical evidence has not been evaluated by the FDA.

PULSED AF clinical trial

PULSED AF clinical results¹ [NCT04198701]

PULSED AF was a global, paired single arm, prospective, non-randomized study that evaluated the safety and effectiveness of the PulseSelect™ pulsed field ablation system for the treatment of patients with paroxysmal (PAF) or persistent (PsAF) atrial fibrillation. The study was conducted in nine countries across 41 sites and 67 operators. The primary analysis included 300 symptomatic AF patients, refractory to class I or III antiarrhythmic drugs, of which 150 were paroxysmal and 150 were persistent. 96% (287) of patients completed 12-month follow-up.

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Primary safety and efficacy endpoint

Primary safety endpoint

0.7%

Primary adverse events

Performance goal of < 13%
(95% CI, 0.1 to 4.6%)

0 PV stenosis
0 Phrenic nerve injury
0 Esophageal events
1 Tamponade
1 Cerebrovascular accident
0 Major bleeding
0 Myocardial infarction

0 Pericarditis
0 Transient ischemic attack
0 Vagal nerve injury
0 Vascular access complications
0 Systemic pulmonary embolism
0 Pulmonary edema
0 Death
0 Cardiovascular hospitalization

12-month effectiveness data

The primary effectiveness endpoint was freedom from a composite of acute procedural failure, arrhythmia recurrence, or antiarrhythmic escalation through 12 months, excluding a 3-month blanking period to allow recovery from the procedure.

PULSED AF monitoring strategy

3-, 6-, 12-month 12-lead ECG
6-, 12-month 24-hour Holter monitor
Weekly trans-telephonic monitoring (TTM) 3–12 months

Primary effectiveness

Acute procedure failure, AF/AFL/AT recurrence, direct cardioversion, repeat ablation, new/reinitiated/increased AADs, any subsequent AF surgery.

Performance goal: > 50% for PAF at 12 months, and > 40% for PsAF at 12 months

66% PAF: (95% CI, 57.9 to 73.2)
55% PsAF: (95% CI, 46.7 to 62.7)

Freedom from AF/AT/AFL

70% PAF
62% PsAF

Clinical success

Freedom from recurrence of any symptomatic atrial arrhythmias (post-hoc analysis).

80% PAF
81% PsAF

Influence of monitoring and burden on QoL and healthcare utilization

Influence of monitoring and burden on QoL and healthcare utilization²

Atrial arrhythmia burden after PFA with the PulseSelect™ system

In PULSED AF, most patients experienced low atrial arrhythmia (AA) burden after PFA with the PulseSelect™ system.
Low AA burden was associated with clinically relevant improvement in quality of life (QoL) and reduced AA-related healthcare utilization (HCU).

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Bar graph showing the atrial arrhythmia burden after pulsed field ablation with the PulseSelect system

1. The majority of patients treated with the PulseSelect™ system experienced 0 burden.

2. After ablation, 8 of 10 patients experienced
< 10% burden (87.1% of the PAF and 81.8% of PsAF).

Impacts of trial monitoring and endpoint definition on PULSED AF and PFA trials

Cardiac monitoring methods significantly impact the reported outcome of a catheter ablation trial when the endpoint is freedom from ≥ 30 seconds of atrial arrhythmia recurrence.
Simulated monitoring strategies demonstrate that freedom from AF/AT/AFL in the PAF and PsAF groups in the PULSED AF trial would improve by > 20% depending on the monitoring strategy employed.

Study design A	Weekly and symptomatic TTM monitoring; 24-hour Holter monitoring at 6 and 12 months; 12-lead ECG at 3, 6, and 12 months.
Study design B	Weekly and symptomatic TTM monitoring from 3–6 months; monthly and symptomatic TTM monitoring from 6–12 months; 24-hour Holter monitoring at 6 and 12 months; 12-lead ECG at 3, 6, and 12 months
Study design C	Median of two 24-hour Holters per patient over 12 months

Bar graph showing the impacts of trial monitoring and endpoint definition on PULSED AF and PFA trials

QoL scores improved post-ablation compared to baseline

Procedural data (ancillary endpoints)

Parameter	Paroxysmal (n = 150)	Persistent (n = 150)
Skin-to-skin procedural time (min)*	134 ± 50 125 (102–157)	145 ± 60 133.5 (107–173)
Device left atrial dwell time (min)^†	65 ± 29 58.5 (46–76)	70 ± 31 62.5 (51–84)
Time between first and last application (min)^†	58 ± 28 53 (40–68)	64 ± 28 60 (45–77)
Fluoroscopy time during procedure (min)	26 ± 17^‡ 21 (15–31)	29 ± 21 23 (14–38)
Total pulsed field ablation energy delivered (sec)	25 ± 8 23 (19–28)	29 ± 10 27 (23–34)
Number of applications per procedure	48 ± 15 43.5 (37–54)	57 ± 20 52.5 (44–67)

PULSED AF pilot results³

Acute pilot results of the PULSED AF trial were first presented as a late-breaking clinical trial at Heart Rhythm Society (HRS) in May 2020 by Dr. Atul Verma. This was the first in-human evaluation of the novel pulsed field ablation system from Medtronic to measure safety and acute effectiveness in 38 patients with paroxysmal or persistent atrial fibrillation followed for 30 days.

Read more about the PULSED AF pilot trial.

Discover results

Therapy delivery with no phrenic nerve injury, esophageal injury, or stroke

Ostial and antral isolation

Maximum esophageal temperature of 36.14 ± 0.34° C

100% acute electrical isolation in 152 pulmonary veins

Average electrode temperature rise of 2.1 ± 2.2º C at one second post-ablation

Medtronic development journey of PFA

Medtronic has completed extensive preclinical and clinical work since 2006 to understand the safety and efficacy of IRE for cardiac ablation.

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2006–2019

2020–2023

The application of irreversible electroporation for pulsed field ablation

Listen to Professor Damijan Miklavčič explain the fundamentals of electroporation and the phenomenon of nonselective transmembrane transport across a cell membrane.

Medtronic Scientific Exchanges

Part 1: Pulsed field ablation: Fundamentals of electroporation

Watch Damijan Miklavčič, Ph.D., Atul Verma, M.D., and Khaldoun Tarakji, M.D. discuss the fundamentals of electroporation and how it applies to pulsed field ablation.

Watch the video

Video still of Damijan Miklavčič, Atul Verma, and Khaldoun Tarakji in their discussion of IRE and how it applies to PFA

Part 2: Pulsed field ablation: Fundamentals of tissue selectivity

Watch Damijan Miklavčič, Ph.D., David Haines, M.D., Atul Verma, M.D., and Khaldoun Tarakji, M.D. discuss the fundamental biology of tissue selectivity, preclinical characterization of collateral tissue effects with PFA technology, and the clinical PULSED AF pilot acute safety and pivotal study design.

View the recording

Video still of Damijan Miklavcic, David Haines, Atul Verma, and Khaldoun Tarakji in discussion of tissue selectivity and PFA

Part 3: Pulsed field ablation: Fundamentals of PULSED AF

Watch John Hummel, M.D., Atul Verma, M.D., and Khaldoun Tarakji, M.D. review the PULSED AF procedural workflow and the long-term results of the PULSED AF pivotal trial.

References

Verma A, Haines DE, Boersma LV, et al. Pulsed Field Ablation for the Treatment of Atrial Fibrillation: PULSED AF Pivotal Trial. Circulation. May 9, 2023;147(19):1422–1432.

Verma A, Haines DE, Boersma LV, et al. Influence of Monitoring and Atrial Arrhythmia Burden on Quality of Life and Healthcare Utilization in Patients Undergoing Pulsed Field Ablation: A Secondary Analysis of the PULSED AF Trial. Heart Rhythm. Published online May 2023.

Verma A, Boersma L, Haines DE, et al. First-in-Human Experience and Acute Procedural Outcomes Using a Novel Pulsed Field Ablation System: The PULSED AF Pilot Trial. Circ Arrhythm Electrophysiol. January 2022;15(1):e010168.

Development of pulsed field ablation

PULSED AF clinical trial

PULSED AF clinical results1 [NCT04198701]

Primary safety and efficacy endpoint

Primary safety endpoint

12-month effectiveness data

PULSED AF monitoring strategy

Primary effectiveness

Freedom from AF/AT/AFL

Clinical success

Influence of monitoring and burden on QoL and healthcare utilization

Influence of monitoring and burden on QoL and healthcare utilization2

Atrial arrhythmia burden after PFA with the PulseSelect™ system

Impacts of trial monitoring and endpoint definition on PULSED AF and PFA trials

QoL scores improved post-ablation compared to baseline

Quality-of-life scores improved post-ablation compared to baseline

Procedural data (ancillary endpoints)

Procedural data (ancillary endpoints)

PULSED AF pilot results3

Medtronic development journey of PFA

2006–2019

2020–2023

The application of irreversible electroporation for pulsed field ablation

Medtronic Scientific Exchanges

Part 1: Pulsed field ablation: Fundamentals of electroporation

Part 2: Pulsed field ablation: Fundamentals of tissue selectivity

Part 3: Pulsed field ablation: Fundamentals of PULSED AF

References

PULSED AF clinical results¹ [NCT04198701]

Influence of monitoring and burden on QoL and healthcare utilization²

PULSED AF pilot results³