Clinical trial NCT05169320: Patient-TAILORed Ablation of Persistent AF Guided by Instantaneous Amplitude and Frequency Modulation Maps (TAILOR-AF)
Official title: Patient-TAILORed Ablation of Atrial Fibrillation Drivers in Persistent Stages Based on Instantaneous Amplitude and Frequency Modulation Criteria (TAILOR-AF)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Persistent Atrial Fibrillation
Lead sponsor: Hospital San Carlos, Madrid
Sponsor class: OTHER
Collaborators: name: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
First posted: 2021-12-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients from the Cardiored1 program (including 4 hospitals in Madrid, Spain) with symptomatic persistent AF in spite of ≥2 PVI previous procedures.

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Freedom from Atrial Fibrillation without antiarrhythmic drugs
timeFrame: After one year of follow-up
Secondary outcomes:
measure: Acute termination of Atrial Fibrillation during the procedure/s
timeFrame: During catheter ablation and/or minimally invasive thoracoscopic surgical procedures
measure: Freedom from Atrial Fibrillation with or without antiarrhythmic drugs
timeFrame: After one year of follow-up
measure: Freedom from Atrial Tachycardia/Flutter with or without antiarrhythmic drugs
timeFrame: After one year of follow-up
Other outcomes:
measure: Comparison of pre-ablation dominant frequencies in atrial electrocardiogram in Hz between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-ablation coefficients of variation of dominant frequencies in 12-lead atrial electrocardiogram (Hz/Hz), between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of the relative difference (%) of intra-procedure pre-ablation and post-ablation dominant frequencies in atrial electrocardiogram, between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of ratio (adimensional) of intra-procedure pre-ablation and post-ablation coefficients of variation of dominant frequencies in 12-lead atrial electrocardiogram, between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of Galectin-3 (ng/mL) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of Interleukin1-ß (pg/mL) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of Tumor Necrosis Factor-α (pg/mL) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of Interleukin-6 (pg/mL) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of procollagen III terminal propeptide (pg/mL) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of procollagen I terminal propeptide (ng/mL) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of cross linked C terminal telopeptide of type I collagen (ng/mL) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of echocardiography-based rigth atrium area (mm2) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of echocardiography-based left atrium area (mm2) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
measure: Comparison of pre-procedure values of echocardiographic/computational tomography 3-dimensional left atrium volume index (mL/m2) between patients with and without Atrial Fibrillation recurrence
timeFrame: After one year of follow-up
Locations:
city: Madrid
country: Spain
facility: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
Study officials:
affiliation: Hospital Clínico San Carlos & CNIC
name: David Filgueiras-Rama, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Quintanilla JG, Alfonso-Almazan JM, Perez-Castellano N, Pandit SV, Jalife J, Perez-Villacastin J, Filgueiras-Rama D. Instantaneous Amplitude and Frequency Modulations Detect the Footprint of Rotational Activity and Reveal Stable Driver Regions as Targets for Persistent Atrial Fibrillation Ablation. Circ Res. 2019 Aug 30;125(6):609-627. doi: 10.1161/CIRCRESAHA.119.314930. Epub 2019 Aug 1.
citation: Rosa G, Quintanilla JG, Salgado R, Gonzalez-Ferrer JJ, Canadas-Godoy V, Perez-Villacastin J, Perez-Castellano N, Jalife J, Filgueiras-Rama D. Mapping Technologies for Catheter Ablation of Atrial Fibrillation Beyond Pulmonary Vein Isolation. Eur Cardiol. 2021 May 17;16:e21. doi: 10.15420/ecr.2020.39. eCollection 2021 Feb.
citation: Quintanilla JG, Shpun S, Jalife J, Filgueiras-Rama D. Novel approaches to mechanism-based atrial fibrillation ablation. Cardiovasc Res. 2021 Jun 16;117(7):1662-1681. doi: 10.1093/cvr/cvab108.