Hidden Slow Conduction Ablation for Recurrent Atrial Fibrillation: Unmasking the Arrhythmogenic Substrate (Unmask-AF)

Official title

Hidden Slow Conduction Ablation for Recurrent Atrial Fibrillation: Unmasking the Arrhythmogenic Substrate

Overview

Over recent years, pulmonary vein isolation (PVI) procedures have demonstrated progressively enhanced efficacy and safety, resulting in a substantial increase in the number of atrial fibrillation ablations, not only as a first-line treatment but also for repeat procedures. However, there is still a notable lack of randomized evidence in this area, which limits guidance and decision-making in clinical practice. Recently, the investigators found that employing short-coupled atrial extrastimuli revealed highly fragmented or double atrial evoked electrograms (EGMs) in AF patients, termed as hidden slow conduction (HSC). Identifying HSC sites may provide insight into the early identification of the arrhythmogenic substrate, offering a potential target for ablation This multi-center, prospective, randomized, controlled trial will include two arms: one investigational (PV reconnection + HSC) and one control (PV reconnection). All the subjects will be followed for 12 months after the ablation procedure. The aim of our study is to investigate the impact of ablating HSC sites on arrhythmia recurrence in repeat ablation procedures. The hypothesis is that the additional ablation of HSC zones may improve the freedom from atrial arrhythmia recurrence after repeat ablation procedure.

Interventions

• Procedure Pulmunary veins reconnection plus hidden slow conduction ablation
  Ablation of pulmonary veins reconnections plus the search and ablation of hidden slow conductions sites (HSC) in the left atrium. HSC sites are defined as EGMs showing highly fragmented or double electrograms in response atrial triple extrastimulus, presenting normal or fractionated electrogram in the sinus rhythm. After checking for PV's conduction breakthroughs, point-by point ablation targeting HSC-EGMs will be performed. The end point for HSC+ ablation will be reached with loss of local c
• Procedure Pulmunary veins (PV) reconnection ablation only
  Each vein will be re-assessed by observing PV potentials along the PV ostia and by pacing from the distal bipole of the ablation catheter (10mA at 2ms) within the lesion set with failed capture of the left atrium. In case of PVs reconnection touch-up applications will be performed at the earliest potential site, identified by comparing far-field atrial EGM to near-field local EGM timing, until isolation will be achieved (entrance and exit block).

Primary outcome measures

• Atrial arrhythmias recurrence [Time frame: up to 12 moths]

Secondary outcome measures (5)

• Burden of atrial arrhythmias [Time frame: up to 12 moths]
• incidence of periprocedural complications (pericardial effusion) [Time frame: up to 12 months]
• Use of antiarrhythmic drugs [Time frame: up to 12 months]
• incidence of periprocedural complications (peripheral complication) [Time frame: up to 12 moths]
• incidence of periprocedural complications (transient ischemic attack or stroke) [Time frame: up to 12 months]

Eligibility criteria

Inclusion criteria

• Recurrent paroxysmal AF (continuous AF episode lasting longer than 30 s but terminating spontaneously or with intervention within 7 days of onset), recurrent persistent AF (continuous AF episode lasting longer than 7 days but < 1 year) and recurrent long standing persistent AF (continuous AF ≥1 year in duration, in patients where rhythm control management is being pursued)
• Previous PVI procedure
• Age > 40 years
• Willing and capable of providing consent
• Able and willing to comply with all follow-up testing and requirements

Exclusion criteria

• Additional left atrial ablations during the previous procedures (es. posterior wall isolation, anterior line, roof line, CFAE and others)
• Acute illness, active systemic infection, or sepsis
• Presence of intracardiac thrombus, myxoma, tumor, interatrial baffle or patch or other abnormality that precludes catheter introduction or manipulation.
• Severe mitral regurgitation
• Women who are pregnant, lactating, or who are planning to become pregnant during the course of the clinical investigation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Pokushalov E, Romanov A, De Melis M, Artyomenko S, Baranova V, Losik D, Bairamova S, Karaskov A, Mittal S, Steinberg JS. Progression of atrial fibrillation after a failed initial ablation procedure in patients with paroxysmal atrial fibrillation: a randomized comparison of drug therapy versus reablation. Circ Arrhythm Electrophysiol. 2013 Aug;6(4):754-60. doi: 10.1161/CIRCEP.113.000495. Epub 2013 PMID 23748210
• Saglietto A, Falasconi G, Soto-Iglesias D, Francia P, Penela D, Alderete J, Viveros D, Bellido AF, Franco-Ocana P, Zaraket F, Turturiello D, Marti-Almor J, Berruezo A. Assessing left atrial intramyocardial fat infiltration from computerized tomography angiography in patients with atrial fibrillation. Europace. 2023 Dec 6;25(12):euad351. doi: 10.1093/europace/euad351. PMID 38011712
• Silva Garcia E, Lobo-Torres I, Fernandez-Armenta J, Penela D, Fernandez-Garcia M, Gomez-Lopez A, Soto-Iglesias D, Fernandez-Rivero R, Vazquez-Garcia R, Acosta J, Bisbal F, Cano-Calabria L, Berruezo A. Functional mapping to reveal slow conduction and substrate progression in atrial fibrillation. Europace. 2023 Nov 2;25(11):euad246. doi: 10.1093/europace/euad246. PMID 37961921

Identifiers

NCT: NCT06657170 · Unmask-AF

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗