in-Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation vs pharmacological medicaTION: The i-STRATIFICATION Study

Albert Dasí1, Claudia Nagel2, Leto Riebel1, Michael Pope3, Rohan Wijesurendra3, Tim Betts3, Axel Loewe4, Alfonso Bueno-Orovio1, Blanca Rodriguez1
1University of Oxford, 2Institute of Biomedical Engineering, Karlsruhe Institute of Technology (KIT), 3Oxford University Hospitals NHS Foundation Trust, 4Karlsruhe Institute of Technology (KIT)


Persistent atrial fibrillation (AF) patients show a 50% recurrence after pulmonary vein isolation (PVI), and no consensus is established for following treatment. The aim of our i-STRATICICATION study is to provide evidence for optimal stratification of recurrent AF patients to pharmacological versus ablation therapy, through in-silico trials in 800 virtual atria. The cohort presents variability in anatomy, electrophysiology, and tissue structure (low voltage areas, LVA), and is developed and validated against experimental and clinical data from ionic currents to ECG. AF maintenance is evaluated prior- and post-PVI, and atria with sustained arrhythmia after PVI are independently subjected to seven state-of-the-art treatments for AF. The results of the i-STRATICICATION study show that the right and left atrial volume dictate the success of ablation therapy in structurally-healthy atria. On the other hand, LVA ablation, both in the right and left atrium, is required for atria presenting LVA remodelling and short refractoriness. This atrial refractoriness, mainly modulated by L-type Ca2+ current, ICaL, and fast Na+ current, INa, determines the success of pharmacological therapy. Therefore, our study suggests the assessment of optimal treatment selection using the above-mentioned patient characteristics. This provides digital evidence to integrate human in-silico trials into clinical practice.