Electroporation for Atrial Fibrillation

((SMILE-AF) Trial)

No longer recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of two heart procedures for treating paroxysmal atrial fibrillation (PAF), a condition characterized by irregular heartbeats. The trial compares pulsed-field ablation, which scars heart tissue to prevent irregular beats, performed on the pulmonary veins alone versus on both the pulmonary veins and the back wall of the left atrium. Suitable participants have experienced noticeable PAF symptoms, with episodes lasting less than a week, and are undergoing their first ablation procedure. As an unphased trial, this study allows participants to contribute to innovative research that could enhance future treatment options for 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 prior data suggests that this technique is safe for treating paroxysmal atrial fibrillation?

Research shows that pulsed field ablation (PFA) for treating atrial fibrillation is generally safe. Studies have found a low rate of complications for those undergoing only the pulmonary vein isolation (PVI) procedure. Serious issues like inflammation around the heart (pericarditis) and heart attacks occur rarely, affecting only a small number of patients.

When the procedure includes both PVI and left atrial posterior wall isolation (PWI), research also supports its safety. Studies have shown good results, with high success in targeting problem areas and maintaining a normal heart rhythm over time.

Overall, both treatment options, whether PVI alone or with PWI, are usually well-tolerated. Complications are uncommon, and many patients experience significant benefits from these procedures. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for atrial fibrillation because they offer a novel approach using pulsed field ablation (PFA). Unlike traditional methods that use thermal ablation to isolate the pulmonary veins, PFA uses electrical pulses to target the heart tissue, potentially reducing damage to surrounding areas and minimizing complications. The combination of Pulmonary Vein Isolation (PVI) and Left Atrial Posterior Wall Isolation (PWI) is particularly intriguing as it aims to enhance the effectiveness of the treatment by addressing additional areas of the heart that might contribute to atrial fibrillation. This innovative technique could lead to more precise and safer outcomes for patients, offering a promising alternative to current standard treatments.

What evidence suggests that this trial's treatments could be effective for paroxysmal atrial fibrillation?

In this trial, participants will receive either Pulmonary Vein Isolation (PVI) alone or a combination of Pulmonary Vein Isolation and Left Atrial Posterior Wall Isolation (PWI). Studies have shown that PVI alone manages atrial fibrillation effectively in about 56% to 57% of cases, with more than half of the patients experiencing fewer episodes of irregular heartbeats. Research indicates that adding PWI to PVI does not significantly enhance the likelihood of remaining free from irregular heart rhythms. Although PWI is safe and effective initially, it does not appear to reduce the recurrence of atrial fibrillation more than PVI alone. Thus, PVI remains a reliable option for managing this condition. ^{2 4 5 6 7}

Who Is on the Research Team?

Jorge E Romero, MD

Principal Investigator

Massachusetts General Hospital

William H Sauer, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5633714/

The Short and Long-Term Efficacy of Pulmonary Vein Isolation ...

Following a single procedure, at 48.8-months follow-up a 56% and 57% success rate could be achieved, while after repeat ablation (second ablation: 18 pts in ...

2.

jamanetwork.com

jamanetwork.com/journals/jama/fullarticle/2800186

Effect of Catheter Ablation Using Pulmonary Vein Isolation ...

Among patients with persistent AF undergoing first-time catheter ablation, the addition of PWI to PVI did not improve freedom from atrial arrhythmias compared ...

3.

jacc.org

jacc.org/doi/10.1016/j.jacc.2025.03.515

Pulsed Field Ablation for Persistent Atrial Fibrillation

Primary effectiveness was 63.5% (57.3% lower confidence limit) at 1 year, with 8.5% patients having a single, isolated atrial fibrillation ...

4.

ahajournals.org

ahajournals.org/doi/10.1161/JAHA.123.029651

Long‐Term Impact of Additional Ablation After Pulmonary ...

The present study demonstrated that left atrial ablation in addition to PVI significantly reduced 3‐year AF/AT recurrence. In particular, ...

5.

heartrhythmjournal.com

heartrhythmjournal.com/article/S1547-5271(25)00125-0/fulltext

Safety and efficacy of catheter ablation for atrial fibrillation ...

The median procedure duration was 58 (50–70) minutes, with successful PVI achieved in all cases. Two patients required same-day hospital ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39870306/

Safety and effectiveness of pulsed field ablation for ...

Conclusions: Pulsed field ablation for PVI and posterior wall ablation was an efficient and safe procedure with low rate of complications and high percentage of ...

7.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.064959

Safety and Effectiveness of Pulsed Field Ablation to Treat ...

As shown in Figure S5, there was no significant center variation in outcomes; the 12-month freedom from atrial arrhythmia ranged between 76% and 79% across the ...