This pilot study investigates if non-invasive global mapping can guide catheter ablation of atrial fibrillation (AF) by defining personalized targets based on the temporal Stability of local Atrial High-Rate Activity (SAHRA). The study also assesses efficacy and safety of this approach and evaluates potential signals of harm. The main questions it aims to answer are:

• Does ablation of targets defined by non-invasive global mapping improve rates of acute atrial fibrillation termination?
• Does such a personalized ablation approach reduce arrhythmia recurrence rates? Researchers will compare the results of the personalized ablation approach with comparable patients that had undergone a conventional "empirical" ablation approach (pulmonary vein isolation).

Participants will:

• Undergo a personalized catheter ablation approach employing both a non-invasive global mapping system and a conventional intracardiac mapping system
• Visit the clinic 3, 6 and 12 months after ablation for clinical follow-up
• Schedule a telephone visit 9 and 24 months after ablation for clinical follow-up

The aim of this study is to test the feasibility and potential of a personalized, non-invasive mapping-guided ablation approach in patients with persistent atrial fibrillation (AF), who are unlikely to benefit from empirical pulmonary vein isolation alone. As a pilot study, it is designed to assess feasibility and procedural efficacy as well as potential signals of harm.

General Strategy:

Patients with persistent AF planned for catheter ablation are eligible in case of left atrial enlargement.

The study intervention consists of two steps:

1. Empirical pulmonary vein isolation in all patients (current standard of care).

2. A personalized ablation approach targeting up to three additional atrial regions which harbour critical AF-perpetuating sources:

   • Target regions are selected based on the temporal Stability of local Atrial High-Rate Activity (SAHRA) using a non-invasive global mapping system (Acorys, Corify Care).
   • Selected target regions displaying stable high-rate activity are isolated or homogenized according to predefined regional borders based on the 15-segment bi-atrial model of the EHRA and EACVI Clinical Consensus on Standardized Atrial Regionalization.

Inclusion Criteria:

Ablation-naïve patients with:

1. Persistent AF planned for catheter ablation plus
2. Left atrial enlargement (LA diameter ≥45 mm or LA volume index ≥35ml/m2 or LA area ≥20 cm2)

Exclusion Criteria:

• Previous cardiac ablation
• Age <18 years
• Pregnancy or lactation
• Previous stroke/TIA
• Severe left ventricular dysfunction (LVEF <35%)
• Renal failure (GFR <30 ml/min)
• Dermal disease or hypersensitivity predisposing for skin irritation or exanthema

Data underlying published results will be provided upon reasonable request