Patient-TAILORed Ablation of Persistent AF Guided by Instantaneous Amplitude and Frequency Modulation Maps (TAILOR-AF)

Recruiting

• Conditions: Persistent Atrial Fibrillation
• Interventions: Device: Subcutaneous implantable loop recorder (ILR) implantation; Procedure: Mapping and catheter ablation; Procedure: Minimally invasive surgical ablation via thoracoscopy

• Registration Number: NCT05169320
• Lead Sponsor: Hospital San Carlos, Madrid

Brief Summary

Pulmonary vein isolation (PVI) is still considered the cornerstone of catheter ablation for patients with persistent atrial fibrillation (AF). However, ablation outcomes in patients with persistent AF are suboptimal with high recurrence rates after a single PVI procedure.

Recently, the investigators developed a new strategy, which enables precise identification of the driver regions allegedly responsible for the maintenance of persistent AF outside the pulmonary veins. This approach uses a conventional electroanatomical mapping system and novel single-signal algorithms based on automatic and accurate analysis of the instantaneous amplitude and frequency modulations displayed by atrial signals during AF (iAM and iFM, respectively) to locate the spatiotemporally stable regions that drive persistent AF (leading drivers).

This strategy also enables to identify highly complex substrates in which targeting leading driver regions with catheter-based ablation may not be feasible or could be potentially associated with a significantly higher risk of complications. In such patients, the iAM/iFM maps obtained in the index catheter mapping and ablation procedure will be used to guide an additional patient-specific, minimally invasive surgical ablation approach via thoracoscopy, aiming to completely but specifically target all leading driver regions.

The main objective of the TAILOR-AF study is to identify (via iAM/iFM maps), target and ablate AF leading drivers in patients with symptomatic persistent AF recurrences despite ≥2 previous PVI procedures. The methods include a percutaneous catheter mapping and ablation approach followed by a minimally invasive surgical approach via thoracoscopy, if necessary. As a secondary objective we will study the association of underlying blood biomarkers, atrial imaging and surface ECG parameters, with advanced remodeling stages requiring a surgical approach to target leading driver regions.

This is a single center study (Hospital Clínico San Carlos, Madrid, Spain) that will recruit 25 patients with symptomatic persistent AF episodes despite having been submitted to ≥2 PVI prior procedures. All patients will undergo subcutaneous implantable loop recorder (ILR) implantation to address AF burden 1 month before the ablation procedure and at least 1 year after the ablation procedure. The primary outcome of the study will be AF freedom after one year of follow-up off antiarrhythmic drugs.

Detailed Description

The study is co-sponsored by the Fundación para la Investigación Biomédica del Hospital Clínico San Carlos (Madrid, Spain) and the Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.) (Madrid, Spain).

Dr. David Filgueiras-Rama (MD, PhD, affiliation: Hospital Clínico San Carlos) and Dr. Jorge G. Quintanilla (MScEng, PhD, affiliation: Centro Nacional de Investigaciones Cardiovasculares \[CNIC\]) are Co-Principal Investigators of the study.

Study Timeline

• Study First Submitted: 2021-11-26
• Study Start: 2021-12-01
• Study First Submitted QC: 2021-12-21
• Study First Posted: 2021-12-23
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-04
• Last Update Posted: 2023-08-07
• Primary Completion: 2024-06-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Patients with symptomatic persistent AF (defined as a sustained episode lasting ≥ 7 days) despite ≥2 previous PVI, with or without other atrial anatomical targets isolated in previous procedures (e.g. superior vena cava, coronary sinus or others).
2. AF episodes refractory to ≥1 antiarrhythmic drug (flecainide, propofenone, amiodarone or droneradore) or adverse events related to antiarrhythmic drugs that do not allow long-term drug therapy.
3. Age between 18-75 years old.
4. Patients must be willing and able to comply with all peri-ablation and follow-up requirements.
5. Signed informed consent.
6. Confirmed pulmonary vein isolation in the index (in current protocol) procedure.

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Exclusion Criteria

1. Patients with paroxysmal AF (defined as a sustained episode lasting < 7 days).
2. Patients for whom cardioversion or sinus rhythm will never be attempted/pursued.
3. Patients with AF secondary to an obvious reversible cause.
4. Patients with contraindications to systemic anticoagulation with heparin or coumadin or a direct thrombin inhibitor.
5. Non-sustained AF during the mapping procedure.
6. Severe underlying systemic disease (e.g. dementia, any end-disease stage, sepsis, etc).
7. Severe left atrial dilation (left atrial volume >73 ml/m2).
8. Severe underlying cardiac disease (e.g. left ventricular ejection fraction ≤35%, severe non-corrected valvular disease, severe non-corrected coronary artery disease, hypertrophic cardiomyopathy, other inherited arrhythmia syndromes, severe dilated cardiomyopathy with NYHA functional class III, IV).
9. Hemodynamic instability due to any cardiac or non-cardiac disease.
10. Pregnancy.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Case group	Mapping and catheter ablation	Patients with symptomatic persistent AF episodes after previous failure of ≥2 pulmonary vein isolation procedures
Case group	Subcutaneous implantable loop recorder (ILR) implantation	Patients with symptomatic persistent AF episodes after previous failure of ≥2 pulmonary vein isolation procedures
Case group	Minimally invasive surgical ablation via thoracoscopy	Patients with symptomatic persistent AF episodes after previous failure of ≥2 pulmonary vein isolation procedures

Primary Outcome Measures

Name	Time	Method
Freedom from Atrial Fibrillation without antiarrhythmic drugs	After one year of follow-up	Number/Percentage of participants with freedom from Atrial Fibrillation without antiarrhythmic drugs

Secondary Outcome Measures

Name	Time	Method
Freedom from Atrial Tachycardia/Flutter with or without antiarrhythmic drugs	After one year of follow-up	Number/Percentage of participants with freedom from Atrial Tachycardia/Flutter with or without antiarrhythmic drugs
Acute termination of Atrial Fibrillation during the procedure/s	During catheter ablation and/or minimally invasive thoracoscopic surgical procedures	Number/Percentage of participants with acute termination of Atrial Fibrillation during the procedure/s
Freedom from Atrial Fibrillation with or without antiarrhythmic drugs	After one year of follow-up	Number/Percentage of participants with freedom from Atrial Fibrillation with or without antiarrhythmic drugs

Trial Locations

Locations (2)

Centro Nacional de Investigaciones Cardiovasculares (CNIC); 🇪🇸 Madrid, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain