Evaluation of Conventional Ablation With or Without Focal Impulse and Rotor Modulation to Eliminate Human AF

Conditions:Atrial Fibrillation
Therapuetic Areas:Cardiology / Vascular Diseases
Age Range:22 - Any
Start Date:April 2016
End Date:July 2020
Contact:Sanjiv Narayan, MD, PhD
Phone:(650) 723-9363

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Randomized Evaluation of Conventional Ablation With or Without Focal Impulse and Rotor Modulation to Eliminate Human Atrial Fibrillation (RECONFIRM): A Randomized Clinical Trial

This prospective randomized study will assess the safety and efficacy of FIRM-guided ablation
(FIRM+PVI) compared to pulmonary vein isolation (PVI) without FIRM, for the treatment of
symptomatic atrial fibrillation.

Atrial fibrillation (AF) affects over 2 millions Americans. AF may reduce cardiac performance
and may result in thrombus formation in the left atrium and thromboembolic events, such as
stroke. Ablation to eliminate the causes of this arrhythmia is increasingly performed since
pharmacological therapy is suboptimal. Ablation currently targets triggers, by ablating left
atrial areas outside the pulmonary veins (pulmonary vein isolation, PVI) in subjects with
symptomatic AF who have failed drugs. Unfortunately, this has mixed success with the best
outcomes being 50-70% freedom from AF at 1 year post ablation.

A major issue with AF therapy is the lack of knowledge about critical regions of the heart
that cause and sustain AF. A recent trial (STAR-AF2) showed that ablating regions empirically
- i.e. without defining their role in AF(lines or fractionated electrograms) - did not
improve patient outcomes compared to PVI alone (Verma et al, NEJM 2015). However, this leaves
us with PVI that had a 50% success rate in that trial and in several other trials even for
paroxysmal AF.

We hypothesize that guiding ablation to critical arrhythmia-targeting zones will improve
success over PVI alone. Specifically, we hypothesize that computational mapping of AF will
find small regions called rotors and focal sources and ablate them, called Focal Impulse and
Rotor Modulation (FIRM) ablation, shows promise at eliminating AF substrates. In many single
center trials, FIRM improves results from PVI alone. This will be among the first randomized
comparisons of FIRM ablation compared to PVI alone, and addresses an important question in
the field.

Inclusion Criteria:

1. Age >21 years

2. Reported incidence of at least two documented episodes of symptomatic paroxysmal or
persistent atrial fibrillation (AF) during the 3 months preceding trial entry (at
least one episode documented by 12-lead ECG or ECG rhythm strip). Ideally, patients
will have implanted continuous ECG recorders in place for >30 days prior to the
procedure to document AF episodes and percentage of time in AF ("burden") prior to

3. Male -or- Women without childbearing potential (surgically sterile or have been
without a period for 12 months), -or- Women of childbearing potential who are not
pregnant per a serum HCG lab test

4. Refractory to at least one Class I or III anti-arrhythmic medications. Drug doses must
be therapeutic and stable

5. Willingness, ability and commitment to participate in baseline and follow-up
evaluations without participation in another clinical trial (unless documented
approval received from both sponsors)

6. Oral anticoagulation required for those subjects who have a score of two or more based
on the following criteria (CHA2DS2VASc)

- congestive heart failure (1 point)

- hypertension (1 point)

- age 75 years or older (2 points)

- diabetes (1 point)

- prior stroke or transient ischemic attack (2 points)

- vascular disease (including coronary artery disease, CAD) (1 point)

- age 65 years or older (1 point)

- gender category: female (1 point) Pre-procedural anticoagulation will ideally
have been continuous for 3 or more weeks prior to the procedure, as clinically
indicated, with INR > 2 in patients taking warfarin.

7. Patient is willing and able to remain on anti-coagulation therapy for a minimum of 3
months post procedure for all subjects, and potentially indefinitely post procedure if
the patient has CHA2DS2VASc score >or= 2

8. Signed, informed consent after a full discussion of the risks and benefits of both
therapy arms, and the concept of randomization

9. NYHA Class 0, I or II and stable on medical therapy for > 3 months

10. Left atrial diameter echocardiography, with documented image of largest dimension)

11. LVEF >or= 40%

12. Sustained AF during procedure: If the patient does not experience spontaneous
sustained AF (>10 min) during the procedure, typically in paroxysmal AF patients,
sustained AF will be induced in routine fashion by burst pacing initially from the
coronary sinus, then from other sites, then with isoproterenol infusion. Using
intensive AF induction methods (Narayan, J Cardiovasc EP; 2012; 23(5): 447-454)
sustained AF is induced in > 90% of paroxysmal AF patients presenting in sinus rhythm.
If AF cannot be sustained, the patient does not meet the inclusion criteria for the
protocol and the patient will undergo AF ablation per physician direction.

Exclusion Criteria:

1. Reversible Cause of Atrial Fibrillation: Atrial fibrillation from a reversible cause
(e.g., surgery, hyperthyroidism, pericarditis); Cardiac or thoracic surgery (e.g.,
valve repair or coronary artery bypass grafting, CABG) within the last 180 days; AF
secondary to electrolyte imbalance, thyroid disease

2. Anti-Coagulation Contraindicated: Contraindication to Heparin; Contraindication to
Warfarin or other novel oral anticoagulants (e.g., dabigatran, rivaroxabanm apixaban);
History of significant bleeding abnormalities

3. Clotting Diathesis: History of significant blood clotting abnormalities, systemic
thrombi or systemic embolization

4. Cardiac Prosthesis: ASD closure device, LAA closure device, prosthetic mitral or
tricuspid valve

5. Thrombus or Mass: Atrial clot/thrombus on imaging such as on a trans-esophageal
echocardiogram (TEE) within 72 hours of the procedure; Intramural thrombus or other
cardiac mass that may adversely affect catheter introduction or manipulation;
Significant pulmonary embolus within 6 months of enrollment

6. Acute illness or active systemic infection or sepsis that may ordinarily warrant
postponement of the procedure

7. History of recent cerebrovascular disease (stroke or TIA) or systemic thromboembolism
within < 6 months

8. Severe Heart Failure: NYHA classes III, IV; Heart failure that is not stable on
medical therapy; Pulmonary edema that may make planned anesthesia or sedation

9. Non-Stable Coronary Disease: Stable/unstable angina or ongoing myocardial ischemia;
Myocardial infarction (MI) within the past 3 months

10. Structural heart disease of clinical significance including:

- Congenital heart disease where the abnormality or its correction prohibit or
increase the risk of ablation

- Acquired heart disease that may increase the risk of ablation, such as
significant ventricular septal defect post myocardial infarction

- Rheumatic valve disease, since this produces a unique AF phenotype

- Extreme left atrial enlargement, defined as LA volume index > 60 ml/m2, in whom
PVI has low success and 55 mm baskets are too small for the atria

11. Planned Cardiac Surgery: If cardiac transplantation or other cardiac surgery are
planned within the 12 months follow period of the trial

12. Life expectancy less than 12 months (the followup period of the trial)

13. Significant pulmonary disease (e.g., COPD) or any other disease that significantly
increase risk to the patient from sedation or anesthesia

14. Untreatable allergy to contrast media

15. Electrolyte imbalance: At the time of the ablation procedure, clinically significant
abnormalities in serum potassium, sodium, magnesium or other electrolytes that affect
the suitability of the patient for ablation at that time
We found this trial at
450 Serra Mall
Stanford, California 94305
(650) 723-2300
Phone: 650-725-5597
Stanford University Stanford University, located between San Francisco and San Jose in the heart of...
Stanford, CA
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San Diego, California 92161
Principal Investigator: David E Krummen, MD
San Diego, CA
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