Substrate ablation as concomitant treatment for left atrial macroreentrant tachycardia (SLICE-LAMRT): rationale and study design

Background Left atrial macroreentrant tachycardias (LAMRTs) are increasing, particularly following atrial fibrillation ablation. Conventional ablation strategies based on activation mapping are limited by the presence of multiple inducible circuits and high recurrence rates. The potential benefit of a substrate-guided approach targeting reproducible anatomical reentry pathways remains unknown. We hypothesize that a substrate-guided approach, targeting reproducible anatomical pathways sustaining reentry rather than only inducible tachycardias, will improve rhythm control and clinical outcomes compared with conventional ablation strategies. Objective The goal of this trial is to determine whether substrate-guided catheter ablation is superior to activation-guided ablation in reducing atrial arrhythmia recurrence in patients with LAMRT. Methods The SLICE-LAMRT trial is an investigator-initiated, prospective, multicenter, randomized (1:1) study conducted at 12 centers in Spain. Patients and clinical event adjudicators are blinded to treatment allocation. Patients with LAMRT and significant left atrial low-voltage substrate are randomized to either a conventional activation-guided ablation strategy, based on high-density mapping and entrainment pacing of clinical and inducible tachycardias, or a substrate-guided approach consisting of a predefined left atrial ablation line set. This study has been registered at ClinicalTrials.gov (NCT05842499). The primary endpoint is atrial tachyarrhythmia recurrence and time to first recurrence after a 3-month blanking period. Secondary endpoints include procedural performance, acute efficacy, major clinical outcomes (including hospitalizations and mortality), and echocardiographic parameters. Safety endpoints include procedure-related adverse events such as death, stroke, cardiac tamponade, vascular complications, and other major complications. Conclusion The SLICE-LAMRT trial will provide the first randomized evidence comparing substrate-guided and activation-guided ablation strategies in LAMRT. By addressing a major unmet clinical need, this study may inform and refine ablation strategies for atypical atrial flutter and support a shift toward substrate-based approaches in complex atrial arrhythmias. Graphical abstract