Morphotype-based risk stratification in patients with patent foramen ovale using computational fluid dynamics

Patent Foramen Ovale (PFO) is a congenital cardiac anomaly, anatomically persistent in approximately 25% of the adult population. While traditionally associated with paradoxical embolism and cryptogenic stroke, increasing evidence suggests a functional link between PFO and migraine with aura. However, the biomechanical mechanisms underlying these associations remain poorly defined, particularly regarding the role of PFO morphology in modulating local hemodynamics and red blood cell (RBC) mechanical stress. This study employs computational fluid dynamics (CFD) combined with Lagrangian particle tracking to assess the impact of PFO tunnel geometry on flow behavior and RBC loading across eight representative morphologies. Velocity fields, wall shear stress (WSS), and particle-level stress histories were computed under physiologically calibrated boundary conditions replicating Valsalva-induced shunting. Results reveal a dichotomy between elongated/narrow and short/wide morphotypes, with the former exhibiting jet-like flows, higher WSS, and significantly elevated RBC stress metrics (up to 31 Pa and 0.49 Pas of stress accumulation). The length-to-mean-quadratic-diameter ratio () emerged as a strong predictor of mechanical exposure (), while outlet diameter correlated with potential systemic desaturation. This dual-scale analysis reveals a mechanistic connection between pathological stress levels and tunnel geometry, identifying as a candidate index for future imaging-based stratification of PFO-related clinical risk.