Patent Foramen Ovale on Transthoracic Echocardiography and Brain White-Matter Hyperintensities: A Transportability Analysis and Practice-Anchored Risk Framework

Background: Meta-analyses suggest an association between patent foramen ovale (PFO) and white-matter hyperintensities (WMH), but pooled effect sizes do not clarify applicability to routine transthoracic echocardiography (TTE) or provide patient-level risk estimates. Objective: The objective of this study was to evaluate the association between TTE-detected PFO and MRI-defined WMH in routine practice and to develop a practice-anchored framework (PAMAP) that translates literature-derived evidence into individualized risk. Methods: We performed a retrospective, single-center, propensity-matched analysis of 149 adults undergoing TTE and brain MRI (37 PFO-positive, 112 controls). The primary endpoint was WMH (Fazekas ≥ 1). PAMAP synthesized 12 studies; 4 eligible studies were pooled using random-effects meta-analysis to derive a locked shunt coefficient (OR 3.65). The locked model used age and shunt (H); embolic context (E), and atrial stress (A) were neutral until refit. Transportability was assessed at the cohort level (expected vs. observed prevalence) and patient level (calibration, discrimination), followed by a minimal prespecified refit. Results: WMH was more frequent in PFO-positive versus control participants (54% vs. 32%). Literature-based expected prevalence approximated observed prevalence, supporting transportability. The locked model showed acceptable performance (calibration intercept 0.106; slope 0.912; Brier 0.188; AUC 0.756). A parsimonious refit improved performance (Brier 0.176; AUC 0.783), with the shunt term remaining significant (OR 2.45, 95% CI 1.23–4.88). Conclusions: PAMAP translates meta-analytic associations into a transportable patient-level risk framework. In routine TTE-defined PFO populations, the WMH association is preserved, suggesting that incidental PFO may mark early subclinical cerebral injury and enabling calibrated, individualized risk assessment.