Ablation Techniques for Atrial Fibrillation

(RECONFIRM Trial)

No longer recruiting at 1 trial location

Overseen By Kathleen Mills, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Anti-arrhythmics, Anticoagulants

Must not be taking: Anticoagulant contraindications

Disqualifiers: Recent surgery, Heart failure, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two techniques to treat atrial fibrillation (AF), a condition where the heart beats irregularly and often rapidly. One method uses a standard procedure called pulmonary vein isolation (PVI), while the other adds a new technique called FIRM-guided ablation, which targets specific problem areas in the heart. The trial aims to determine which method is safer and more effective for individuals with persistent AF symptoms despite medication. Individuals who have experienced at least two episodes of AF documented by ECG and have not found success with medication might be suitable candidates for this trial. As an unphased trial, this study provides an opportunity to explore innovative treatments for AF beyond standard medication.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be refractory to at least one Class I or III anti-arrhythmic medication, and your drug doses must be therapeutic and stable. You also need to be on oral anticoagulation if your CHA2DS2VASc score is two or more, and you must remain on anticoagulation therapy for at least 3 months post-procedure.

What prior data suggests that these ablation techniques are safe for treating atrial fibrillation?

Research has shown that adding FIRM-guided ablation to pulmonary vein isolation (PVI) maintains a similar safety level to PVI alone, indicating both treatments are equally safe. Studies indicate that patients receiving FIRM-guided ablation did not experience more side effects than those undergoing standard PVI treatment, suggesting that including FIRM does not increase risk.

For standard AF ablation with PVI alone, research has established it as a generally safe treatment for atrial fibrillation, though it may not cure everyone. This procedure is widely used and has proven safe in various situations.

In summary, both treatments in this trial are well-tolerated by patients, with no significant increase in side effects for the FIRM-guided approach compared to PVI alone. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these ablation techniques for atrial fibrillation because they offer new approaches to targeting abnormal heart rhythms. Conventional AF ablation typically involves pulmonary vein isolation (PVI) to prevent erratic electrical signals. However, the FIRM-guided ablation adds another layer by targeting patient-specific rotors and focal sources, which are believed to be key drivers of atrial fibrillation. This personalized approach has the potential to improve outcomes by addressing the unique patterns of electrical activity in each patient's heart.

What evidence suggests that this trial's ablation techniques could be effective for atrial fibrillation?

This trial will compare two ablation techniques for atrial fibrillation: FIRM-guided ablation plus PVI and Conventional AF Ablation with PVI. Research has shown that FIRM-guided ablation with PVI might not be more effective than PVI alone for treating atrial fibrillation. One study found that adding FIRM, which targets specific heart areas believed to cause irregular heartbeats, did not improve long-term outcomes compared to PVI alone. Another study indicated that FIRM-guided ablation did not better reduce the recurrence of irregular heartbeats than PVI alone. Overall, current evidence suggests that FIRM-guided ablation may not offer additional benefits over standard PVI ablation. ^{1 6 7 8 9}

Who Is on the Research Team?

Sanjiv Narayan, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

Adults over 21 with symptomatic atrial fibrillation, stable on medical therapy for 3+ months, and a left atrial diameter ≤5.5cm. Must have had at least two episodes of AF in the last three months and be refractory to one anti-arrhythmic medication. Participants need to agree to anticoagulation post-procedure and not be pregnant or planning pregnancy.

Inclusion Criteria

I am older than 21 years.

Your heart's pumping function is at least 40%.

I have had at least two episodes of AF in the last 3 months, confirmed by an ECG.

Exclusion Criteria

I have had a heart attack in the last 3 months or have ongoing heart issues.

You are not expected to live for at least 12 months, which is the length of the trial.

I have not had a stroke, TIA, or blood clot in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo FIRM-guided ablation plus PVI or conventional AF ablation with PVI

1 day

1 visit (in-person)

Blinding Period

Initial 3 month blanking period for healing and stabilization post-ablation

12 weeks

Follow-up

Participants are monitored for freedom from AF/AT and quality of life improvements

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Conventional AF Ablation with PVI
• FIRM-guided ablation plus PVI

Trial Overview The study is testing if adding FIRM (Focal Impulse and Rotor Modulation) to conventional PVI (Pulmonary Vein Isolation) is safer and more effective for treating atrial fibrillation than PVI alone. Patients are randomly assigned to either treatment group.

How Is the Trial Designed?

Group I: FIRM-guided ablation plus PVI Experimental Treatment 1 Intervention

These patients will be treated by ablation of patient-specific rotors and focal sources (FIRM). Conventional ablation (PVI) will then be performed as part of the standard of care procedure.

Group II: Conventional AF Ablation with PVI Active Control 1 Intervention

These patients will be treated by conventional AF ablation by pulmonary vein isolation (PVI) alone.

Conventional AF Ablation with PVI is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Pulmonary Vein Isolation for:

• Symptomatic atrial fibrillation
• Paroxysmal atrial fibrillation
• Persistent atrial fibrillation

Approved in United States as Pulmonary Vein Isolation for:

• Symptomatic atrial fibrillation
• Paroxysmal atrial fibrillation
• Persistent atrial fibrillation

Approved in Canada as Pulmonary Vein Isolation for:

• Symptomatic atrial fibrillation
• Paroxysmal atrial fibrillation
• Persistent atrial fibrillation

Approved in Japan as Pulmonary Vein Isolation for:

• Symptomatic atrial fibrillation
• Paroxysmal atrial fibrillation
• Persistent atrial fibrillation

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Both the Smart Touch and nMARQ catheters were effective in achieving pulmonary vein isolation (PVI) in patients with atrial fibrillation, with similar long-term success rates observed in both groups over follow-up periods of around 18-19 months.

The nMARQ catheter had a shorter procedural time for paroxysmal atrial fibrillation, although there was a 2.7% need to switch to the Smart Touch catheter to complete PVI in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiofrequency Ablation of Atrial Fibrillation: Nonrandomized Comparison of Circular versus Point-by-Point "Smart" Ablation for Achieving Circumferential Pulmonary Vein Isolation and Curing Arrhythmic Symptoms. Rosso, R., Chorin, E., Levi, Y., et al.[2022]

A systematic review of six studies involving 674 patients found that FIRM-guided ablation, with or without pulmonary vein isolation (PVI), did not significantly reduce the recurrence of all-atrial arrhythmias compared to PVI alone after an average follow-up of 18.8 months.

There were no significant differences in complication rates between patients undergoing FIRM-guided ablation and those receiving PVI alone, suggesting that FIRM-guided ablation does not improve safety outcomes either.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal impulse and rotor modulation guided ablation versus pulmonary vein isolation for atrial fibrillation: A meta-analysis of head-to-head comparative studies. Romero, J., Gabr, M., Alviz, I., et al.[2021]

FIRM-guided catheter ablation for atrial fibrillation resulted in significantly lower arrhythmia-free survival at 12 months (25%) compared to cryoballoon pulmonary vein isolation (CB2-PVI) which had an 87% success rate.

The FIRM group also experienced a higher rate of repeat ablations (70%) compared to the CB2-PVI group (14.1%), indicating that FIRM-guided ablation may be less effective in maintaining stable sinus rhythm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stand-alone Focal Impulse and Rotor Modulation (FIRM) ablation versus second-generation cryoballoon pulmonary vein isolation for paroxysmal atrial fibrillation. Tilz, RR., Yalin, K., Lyan, E., et al.[2022]

A meta-analysis of 46 trials involving 8,500 participants found that adding autonomic modulation or hybrid ablation to pulmonary vein isolation (PVI) significantly reduces the recurrence of atrial arrhythmia by 53.1% and 59.1%, respectively, compared to PVI alone.

These findings suggest that adjunctive therapies can enhance the effectiveness of PVI in treating atrial fibrillation, but further large-scale studies are needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary vein isolation plus adjunctive therapy for the treatment of atrial fibrillation: a systematic review and meta-analysis. Bussa, R., Nudy, M., Ahmed, M., et al.[2023]

In a study of 113 patients with persistent atrial fibrillation, the combination of pulmonary vein antrum isolation (PVAI) with posterior wall and non-PV trigger ablation (group 3) resulted in the highest success rate, with 76% of patients free from atrial fibrillation after 12 months, compared to only 14% in the rotor-only ablation group (group 1).

The study found that rotor-only ablation had poor outcomes, leading to its early termination for futility, while PVAI combined with rotor ablation (group 2) showed lower efficacy and longer procedure times compared to the more comprehensive approach in group 3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Rotor Ablation in Nonparoxysmal Atrial Fibrillation Patients: Results From the Randomized OASIS Trial. Mohanty, S., Gianni, C., Mohanty, P., et al.[2017]

In a study of 154 patients with persistent atrial fibrillation who underwent total thoracoscopic ablation, those who received additional cavotricuspid isthmus (CTI) ablation had a significantly higher 5-year survival rate free from recurrent atrial tachyarrhythmia (52.5% vs 41.4%).

The multivariable analysis indicated that CTI ablation was associated with a reduced risk of recurrent atrial tachyarrhythmia, suggesting that adding CTI ablation may enhance the effectiveness of total thoracoscopic ablation in patients with long-standing atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additional cavotricuspid isthmus ablation may reduce recurrent atrial tachyarrhythmia after total thoracoscopic ablation for persistent atrial fibrillation. Gwag, HB., Jeong, DS., Hwang, JK., et al.[2019]

Adding FIRM-guided ablation to pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) resulted in a slight increase in quality-adjusted life years (QALYs) and a cost of $34,452 per QALY gained, suggesting it may be a cost-effective treatment option.

The majority of costs were associated with the initial ablation procedure, but the lower recurrence of AF with FIRM led to significant savings on medications and repeat procedures, indicating that FIRM could be particularly valuable for patients with more severe AF symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost effectiveness of focal impulse and rotor modulation guided ablation added to pulmonary vein isolation for atrial fibrillation. Baykaner, T., Duff, S., Hasegawa, JT., et al.[2019]

Patients with atrial fibrillation (AF) who underwent pulmonary vein isolation plus additional atrial ablations (PVI+) had a significantly higher rate of maintaining normal sinus rhythm in the first year compared to those who only had PVI, with a relative risk of 1.10 based on 21 randomized controlled trials and 3 non-randomized trials.

The most notable improvement was seen with PVI+ left atrial linear ablations, which showed a relative risk of 1.16, indicating that this specific approach may enhance the effectiveness of AF treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of catheter ablation strategies for rhythm control in patients with atrial fibrillation: a meta-analysis. Assasi, N., Xie, F., Blackhouse, G., et al.[2021]

In a study of 75 young adults under 35 with lone atrial fibrillation, radiofrequency catheter ablation showed a 62.7% success rate in preventing atrial tachyarrhythmia recurrence after a single procedure, increasing to 69.3% after an average of 1.2 procedures.

The study found that having non-pulmonary vein triggers significantly increased the risk of recurrence, highlighting the importance of identifying the type of atrial fibrillation for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catheter ablation for lone atrial fibrillation in individuals aged under 35 years. Chen, J., Wang, H., Zhou, M., et al.[2019]

Magnetic resonance imaging (MRI) in seven patients with posterior ankle impingement (PAI) syndrome revealed common findings of bone contusions in the os trigonum and lateral talar tubercle, indicating these are prevalent issues in PAI.

MRI effectively identified both bone and soft-tissue abnormalities associated with PAI syndrome, including fluid accumulation in the flexor hallucis longus tendon sheath, highlighting its usefulness in diagnosing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posterior ankle impingement syndrome: MR imaging findings in seven patients. Bureau, NJ., Cardinal, E., Hobden, R., et al.[2006]

In a multicenter trial involving 51 patients with paroxysmal atrial fibrillation, FIRM-guided ablation without pulmonary vein isolation (PVI) showed significantly lower long-term success rates (31.3%) compared to PVI (80%) after 12 months.

The study highlighted that while FIRM-guided ablation successfully eliminated AF rotors, it was not as effective as PVI, reinforcing the importance of PVI as the standard treatment for paroxysmal AF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal Impulse and Rotor Modulation Ablation vs. Pulmonary Vein isolation for the treatment of paroxysmal Atrial Fibrillation: results from the FIRMAP AF study. Tilz, RR., Lenz, C., Sommer, P., et al.[2022]

In a study of 250 patients, 74% showed increased signal in the proximal fibular collateral ligament (FCL) on MRI, but less than 5% had clinical signs of injury, indicating that this MRI finding is common and often not associated with actual pathology.

The study highlights the importance of correlating MRI findings with clinical symptoms, suggesting that increased signal in the proximal FCL may not be a cause for concern unless accompanied by specific clinical signs of injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased signal of the fibular collateral ligament of the knee on MRI, clinically significant? Alexander, AA., Yeager, AN., Motamedi, K., et al.[2023]

In a study of 232 patients, varus stress radiographs were found to be more sensitive than MRI for diagnosing fibular collateral ligament (FCL) injuries, with sensitivities of 70% and 66% respectively.

MRI was more effective in detecting acute FCL injuries, while varus stress radiographs were better for chronic injuries, suggesting that using both imaging methods together can improve diagnostic accuracy for FCL injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Accuracy of Varus Stress Radiographs Versus Magnetic Resonance Imaging in Diagnosing Fibular Collateral Ligament Grade III Tears. Kane, PW., DePhillipo, NN., Cinque, ME., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8139814/

Focal Impulse and Rotor Modulation Ablation vs. ... This study sought to compare the safety and effectiveness of Focal Impulse and Rotor Modulation (FIRM)-guided ablation as the sole ablative strategy with PVI ...

2. ahajournals.org ahajournals.org/doi/10.1161/JAHA.121.022346?doi=10.1161/JAHA.121.022346

Prospective Randomized Trial of Rotor Ablation vs ... Ablation of focal or rotational sources have been proposed to improve the success of pulmonary vein isolation (PVI) in patients with persistent ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02456233

Evaluation of Conventional Ablation With or Without Focal ... This prospective randomized study will assess the safety and efficacy of FIRM-guided ablation (FIRM+PVI) compared to pulmonary vein isolation (PVI) without FIRM ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33844385/

Focal impulse and rotor modulation guided ablation versus ... FIRM-guided ablation with or without PVI did not provide any benefit in improving all-atrial arrhythmia recurrence at follow-up when compared to PVI alone.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/jce.15564

Stand‐alone Focal Impulse and Rotor Modulation (FIRM) ... De novo ablation of AF using FIRM-guided AF ablation results in shorter arrhythmia-free survival after 12 months compared to CB2-PVI and a need ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32202003/

Meta-analysis of pulmonary vein isolation ablation for atrial ... LF approaches have similar clinical efficacy and safety as CF approaches for PVI. LF approaches are associated with shorter procedure time, ...

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

Safety and efficacy of catheter ablation for atrial fibrillation ... This study aimed to assess the safety and feasibility of catheter ablation for AF in an ADSC in a non-hospital setting.

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2800186

Effect of Catheter Ablation Using Pulmonary Vein Isolation ... Importance Pulmonary vein isolation (PVI) alone is less effective in patients with persistent atrial fibrillation (AF) compared with paroxysmal ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2307291

Pulsed Field or Conventional Thermal Ablation for ... Pulsed field versus cryoballoon pulmonary vein isolation for atrial fibrillation: efficacy, safety, and long-term follow-up in a 400-patient cohort. Circ ...