Hemodynamics affects factor XI/XII anticoagulation efficacy in patient-derived left atrial models.

Area of Science:

• Cardiovascular Medicine
• Computational Biology
• Biophysics

Background:

• Atrial fibrillation (AF) increases thromboembolic risk due to blood stasis in the left atrial appendage (LAA).
• Current anticoagulation strategies balance efficacy against bleeding risk.
• Novel anticoagulants like factor XI/XII inhibitors offer potential for reduced bleeding but require efficacy validation.

Purpose of the Study:

• To investigate how patient-specific blood flow patterns in the LA and LAA influence thrombosis risk.
• To evaluate the effectiveness of factor XI/XII inhibitors in preventing thrombosis under varying hemodynamic conditions.
• To test the hypothesis that LA/LAA hemodynamics affect anticoagulation efficacy.

Main Methods:

• Simulated blood flow and coagulation in patient-specific LA anatomies using 4D CT imaging.
• Employed a detailed 32-coagulation factor system and computational fluid dynamics.
• Utilized a multi-fidelity modeling approach to accelerate 247 simulations across 13 patients with diverse conditions.

Main Results:

• Simulations mapped thrombin concentration, peaking within the LAA.
• Coagulation metrics stratified patients into no, moderate, and high thromboembolic risk categories.
• High-risk patients exhibited slower LAA flows and longer residence times, necessitating stronger factor XI/XII inhibition for effective anticoagulation.

Conclusions:

• Patient-specific LA/LAA hemodynamics are critical determinants of both thromboembolic risk and anticoagulation effectiveness.
• Methodology enables personalized coagulation risk assessment and tailored anticoagulation therapy.
• This approach represents a significant advancement in applying digital twins to cardiovascular medicine.