Investigating oral anticoagulation therapy in AF patient level models

Atrial Fibrillation (AF) is a prevalent cardiac arrhythmia. This thesis addresses the challenges of AF diagnosis and therapy by utilizing patient level computational modeling in cardiac electrophysiology. The focus is on expanding an existing patient-level model, developed at the Cardiovascular Research Institute Maastricht, to simulate oral anticoagulation therapy in virtual patients with different stroke risk levels. The patient-level model, representing virtual patients from birth to 100 years, incorporates Markov states to simulate clinical statuses, including sinus rhythm, AF, pre- and post-stroke, and mortality. The objective of this thesis is to enhance the model's comprehensiveness by simulating the impact of oral anticoagulants on stroke incidence. The four-step approach involves developing parameterizations reflecting diverse stroke risks, modeling the impact of vitamin K antagonists on stroke risk reduction, simulating non-Vitamin K oral anticoagulants based on major clinical trials, and evaluating the model's outcomes against clinical trial data. Commencing with the weak association between symptoms and irregular heart rhythms, the thesis emphasizes the difficulty it presents in promptly diagnosing and administering appropriate anticoagulation for AF. It then explores the usefulness of screening, while recognizing the uncertainties regarding the target population for screening, the optimal screening frequency, and the consequences of AF detection through screening. Utilizing the model's accurate control and visibility, this thesis assesses diverse screening approaches, revealing an increased rate of early AF detection with a minimal effect on the risk of stroke. This thesis contributes to the use of computational modeling as a powerful tool for exploration and prediction in cardiac electrophysiology. The outcomes may have implications for personalized medicine and the optimization of therapeutic interventions in the management of AF.