Linking patent foramen ovale with atrial cardiomyopathy: a narrative review of clinical signals, electrophysiology, and translational opportunities

This narrative, hypothesis-generating review examines whether patent foramen ovale (PFO), usually discussed through stroke prevention, may be linked to atrial cardiomyopathy (AtCM) in selected large-shunt and/or atrial septal aneurysm (ASA) phenotypes. We synthesize heterogeneous clinical imaging, electrophysiology, hemodynamic, and translational data rather than a formal systematic evidence base. Observational cohorts and small mechanistic studies suggest associations between high-shunt PFO phenotypes and left atrial enlargement, impaired mechanics, atrial vulnerability (e.g., shorter effective refractory periods or atrial fibrillation inducibility), and post-ablation arrhythmia recurrence; these signals are phenotype-specific, potentially confounded, and do not establish causality. We propose a candidate high-shunt PFO research phenotype based on shunt magnitude and septal morphology (contrast echocardiography and TEE features), with atrial substrate and electrophysiology (EP) measures treated as downstream modifiers/endpoints. Closure-related reverse remodeling, antiarrhythmic effects, and heart-failure outcomes should be interpreted cautiously because existing evidence is largely non-randomized. We outline candidate "shunt-on vs shunt-off" studies with prespecified EP endpoints integrated with hemodynamics and multimodal imaging to test causality, reversibility, and net clinical benefit.