The goal of this pilot study is to test if noninvasive global mapping can guide catheter ablation defining personalized targets and improve the therapy of atrial fibrillation. It will also test the safety of such an approach. The main questions it aims to answer are:

• Does ablation of targets defined by noninvasive 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 noninvasive 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 and 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

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 spatiotemporal Stability of 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 (Althoff et al. 2025).

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