Electroporation for Atrial Fibrillation

((SMILE-AF) Trial)

Recruiting at 6 trial locations

Overseen By Angel E Armas, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Persistent AF, Previous ablation, Valve surgery, Thromboembolic event, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1-2 hours

450 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy and safety between pulmonary vein isolation (PVI) alone versus PVI with left atrial (LA) posterior wall isolation (PWI) using pulsed-field ablation (PFA) in the treatment of patients with paroxysmal atrial fibrillation (PAF).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Pulmonary Vein Isolation and Left atrial Posterior Wall Isolation for Atrial Fibrillation?

Research shows that combining Pulmonary Vein Isolation (PVI) with Left Atrial Posterior Wall Isolation (PWI) can improve outcomes for patients with atrial fibrillation, as it may reduce the recurrence of the condition. Additionally, Pulsed Field Ablation (PFA) is a promising method for performing PVI, as it effectively isolates the pulmonary veins with fewer complications. ^{1 2 3 4 5}

Is Electroporation for Atrial Fibrillation safe for humans?

Pulsed Field Ablation (PFA), a type of electroporation used for treating atrial fibrillation, has been shown to be safe in humans. In a study with 100 patients, PFA was performed without any serious complications, suggesting it is a safe method for isolating pulmonary veins in atrial fibrillation treatment. ^{1 3 5 6 7}

How is the treatment of Pulmonary Vein Isolation and Left Atrial Posterior Wall Isolation for atrial fibrillation different from other treatments?

This treatment is unique because it combines Pulmonary Vein Isolation (PVI) with Left Atrial Posterior Wall Isolation (PWI), which has been shown to improve outcomes in patients with atrial fibrillation by reducing recurrence rates. Additionally, using Pulsed Field Ablation (PFA) for this procedure minimizes damage to surrounding tissues, reducing the risk of complications compared to traditional methods like radiofrequency or cryotechnology. ^{1 2 3 5 8}

Research Team

Jorge E Romero, MD

Principal Investigator

Mass General Brigham

William H Sauer, MD

Principal Investigator

Mass General Brigham

Eligibility Criteria

This trial is for patients with paroxysmal atrial fibrillation, a type of irregular heartbeat. Specific eligibility criteria are not provided, but typically participants would need to be diagnosed with the condition and meet certain health standards.

Inclusion Criteria

I am between 21 and 90 years old.

Stated willingness to comply with all study procedures and availability for the duration of the study

At least one symptomatic episode of PAF lasting <7 days, documented on electrocardiogram (ECG), Holter, ZioPatch, ILR, or smartwatch recording in the year prior to enrollment

Exclusion Criteria

I have a history of blood clotting or bleeding issues.

I have a history of severe high blood pressure in the lungs.

Pacing dependent patients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo pulmonary vein isolation (PVI) alone or PVI with posterior wall isolation (PWI) using pulsed field ablation (PFA)

1-2 hours

1 visit (in-person)

Blinding Period

A 3-month blanking period where participants are closely monitored and anti-arrhythmic drug (AAD) therapy is discontinued

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment using an implantable loop recorder (ILR)

12 months

Treatment Details

Interventions

• Pulmonary Vein Isolation alone
• Pulmonary Vein Isolation and Left atrial Posterior Wall Isolation

Trial Overview The study compares two heart procedures: one where only the pulmonary veins are isolated (PVI), and another where PVI is combined with isolation of the left atrial posterior wall using pulsed-field ablation (PFA).

Participant Groups

Group I: Pulmonary Vein Isolation and Posterior Wall Isolation ( PVI+PWI) Active Control 1 Intervention

Pulsed field ablation of the pulmonary veins and the posterior wall of the left atrium.

Group II: Pulmonary Vein Isolation (PVI) only Active Control 1 Intervention

Pulsed field ablation of the pulmonary veins only.

Pulmonary Vein Isolation alone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Pulmonary Vein Isolation for:

• Paroxysmal Atrial Fibrillation
• Persistent Atrial Fibrillation

Approved in United States as Pulmonary Vein Isolation for:

• Paroxysmal Atrial Fibrillation
• Persistent Atrial Fibrillation

Approved in Canada as Pulmonary Vein Isolation for:

• Paroxysmal Atrial Fibrillation
• Persistent Atrial Fibrillation

Approved in Japan as Pulmonary Vein Isolation for:

• Paroxysmal Atrial Fibrillation
• Persistent Atrial Fibrillation

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Boston Scientific Corporation

Industry Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Databean

Industry Sponsor

Trials

6

Recruited

780+

Findings from Research

In patients with paroxysmal or persistent atrial fibrillation, combining pulmonary vein isolation (PVI) with posterior wall isolation (PWI) using cryoballoon ablation significantly improved long-term freedom from recurrent atrial fibrillation (74.3% vs. 46.0%) and all atrial tachyarrhythmias (71.4% vs. 38.1%) compared to PVI alone.

Despite longer procedure times and the need for adjunct radiofrequency in some cases, the safety profile was similar between PVI alone and PVI+PWI, indicating that the enhanced efficacy of PVI+PWI does not come at the cost of increased adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of adjunct posterior wall isolation in atrial fibrillation patients with cardiac implantable electronic devices. Aryana, A., Thiemann, AM., Pujara, DK., et al.[2023]

In a study of 390 patients with persistent atrial fibrillation, combining pulmonary vein isolation (PVI) with posterior wall isolation (PWI) using cryoballoon ablation resulted in significantly greater isolation of the posterior wall and total left atrial area compared to PVI alone.

Patients undergoing PVI+PWI experienced higher rates of atrial fibrillation termination and lower recurrence of atrial arrhythmias after 12 months, indicating that this combined approach is both safe and more effective than PVI alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posterior wall isolation using the cryoballoon in conjunction with pulmonary vein ablation is superior to pulmonary vein isolation alone in patients with persistent atrial fibrillation: A multicenter experience. Aryana, A., Baker, JH., Espinosa Ginic, MA., et al.[2022]

In a review of six studies involving 1334 patients with persistent atrial fibrillation (AF), adding posterior wall isolation (PWI) to pulmonary vein isolation (PVI) significantly reduced the recurrence rate of AF from 29.1% to 19.8%.

Adjunctive PWI did not increase the risk of atrial flutter or tachycardia, nor did it lead to more procedure-related complications, indicating it is a safe and effective addition to standard PVI for persistent AF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of adjunctive posterior wall isolation in persistent atrial fibrillation: A meta-analysis. Salih, M., Darrat, Y., Ibrahim, AM., et al.[2021]

In a study of 100 patients with symptomatic atrial fibrillation, the pulsed field ablation (PFA) catheter demonstrated effective pulmonary vein isolation (PVI) in all cases, confirming its efficacy in treating AF.

The procedure was found to be safe, with only two cases of bleeding at the access site reported, and it was quick to learn, showing no significant difference in procedure times between senior and junior operators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with pulsed field ablation for atrial fibrillation. Magni, FT., Mulder, BA., Groenveld, HF., et al.[2022]

Pulsed Field Ablation (PFA) is a safe and effective method for pulmonary vein isolation (PVI) in patients with symptomatic atrial fibrillation, as demonstrated in a study of 100 patients with no serious complications reported during or after the procedure.

PFA uses high amplitude electrical pulses to ablate heart tissue while minimizing damage to surrounding areas, addressing the risks associated with traditional methods like radiofrequency ablation and cryotechnology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pulsed Field Ablation shows promise - Experiences from the first 100 patients in Sweden]. Tabrizi, F., Scheel, S., Falasca Zamponi, A., et al.[2023]

The PIVoTAL trial is a multicenter, randomized controlled study involving 366 patients with symptomatic persistent atrial fibrillation (persAF) to compare the efficacy of pulmonary vein isolation (PVI) alone versus PVI combined with posterior wall isolation (PWI) using a cryoballoon.

The primary goal of the study is to determine if the combination of PVI and PWI leads to lower rates of atrial fibrillation recurrence at 12 months compared to PVI alone, with outcomes monitored through regular electrocardiograms and ambulatory monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left atrial posterior wall isolation in conjunction with pulmonary vein isolation using cryoballoon for treatment of persistent atrial fibrillation (PIVoTAL): study rationale and design. Aryana, A., Pujara, DK., Allen, SL., et al.[2022]

In a first-in-human study involving 178 patients with paroxysmal or persistent atrial fibrillation (AF), the use of a focal catheter that can switch between radiofrequency ablation (RFA) and pulsed field ablation (PFA) achieved 100% acute success in creating lesions for pulmonary vein isolation.

After nearly a year of follow-up, the study reported a high rate of freedom from atrial arrhythmias, with 78.3% for paroxysmal AF and 77.9% for persistent AF, and an impressive 84.8% for persistent AF patients treated with the optimized PULSE3 waveform, indicating both efficacy and durability of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Focal Ablation Catheter Toggling Between Radiofrequency and Pulsed Field Energy to Treat Atrial Fibrillation. Reddy, VY., Peichl, P., Anter, E., et al.[2023]

In a study of 126 patients with paroxysmal atrial fibrillation, incorporating high dominant frequency (DF) sites during pulmonary vein isolation (PVI) led to a higher success rate in maintaining freedom from atrial arrhythmias, achieving 78.7% efficacy compared to 66.1% with conventional methods.

The modified PVI approach also resulted in fewer repeat procedures (6.6% vs 23%), indicating that targeting high-frequency AF nests may enhance the long-term effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized comparison of modified pulmonary vein isolation versus conventional pulmonary vein isolation in patients with paroxysmal atrial fibrillation. Lin, YJ., Chang, SL., Lo, LW., et al.[2012]

References

1. United States pubmed.ncbi.nlm.nih.gov

Outcomes of adjunct posterior wall isolation in atrial fibrillation patients with cardiac implantable electronic devices. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Posterior wall isolation using the cryoballoon in conjunction with pulmonary vein ablation is superior to pulmonary vein isolation alone in patients with persistent atrial fibrillation: A multicenter experience. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical outcomes of adjunctive posterior wall isolation in persistent atrial fibrillation: A meta-analysis. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Initial experience with pulsed field ablation for atrial fibrillation. [2022]

5. Sweden pubmed.ncbi.nlm.nih.gov

[Pulsed Field Ablation shows promise - Experiences from the first 100 patients in Sweden]. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Left atrial posterior wall isolation in conjunction with pulmonary vein isolation using cryoballoon for treatment of persistent atrial fibrillation (PIVoTAL): study rationale and design. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A Focal Ablation Catheter Toggling Between Radiofrequency and Pulsed Field Energy to Treat Atrial Fibrillation. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A prospective, randomized comparison of modified pulmonary vein isolation versus conventional pulmonary vein isolation in patients with paroxysmal atrial fibrillation. [2012]