Patent Foramen Ovale: Epidemiology, Risk Factors, Pathophysiology, Clinical Features, Diagnosis, and Management

FIGURE 1. Epidemiological profile of PFO and stroke attribution risk. (A) The prevalence of PFO varies across different populations. It is present in approximately 25% of the general population, although it gradually declines with advancing age, as revealed by autopsy data. In contrast, PFO is detected in nearly 50% of patients with cryptogenic stroke (CS), reaching up to 60% among young patients with CS, and in 40–60% of patients with migraine with aura (MA). (B) Not all PFOs identified in patients with CS are pathogenic. Among all ischemic strokes (IS), approximately 38% are classified as CS, which can be further classified as having causative PFOs (38%), incidental PFOs (13%), or no PFOs (48%). (C) The stroke attribution risk for individuals with PFO depends on both clinical characteristics and PFO morphology. Young age, high‐risk PFO anatomy, and low cardiovascular disease (CVD) risk are associated with a higher probability of PFO‐related stroke, whereas old age and high CVD risk indicate alternative stroke etiologies instead of PFO. The RoPE score and the PASCAL classification system are practical tools for evaluating the causal likelihood of PFO in patients with stroke.…

FIGURE 2. Pathophysiological mechanisms of PFO‐related stroke. The key mechanism underlying PFO‐related stroke is mediated by paradoxical embolism. (A) Multiple predisposing factors, including genetic susceptibility, hypercoagulation, pulmonary embolism, deep vein thrombosis (DVT), microbiome alterations, Valsalva maneuver, and abnormal cardiac structure, may increase thromboembolic risk and augment right‐to‐left shunt (RLS). (B) High‐risk PFO anatomies, including large RLS, a long tunnel, a large size, atrial septal aneurysm (ASA), Chiari network, and Eustachian valves, may facilitate in situ thrombus formation and promote emboli transit. (C) The paradoxical emboli from the venous system can traverse the PFO and enter the arterial system, while in situ thrombi formed within the PFO tunnel may also dislodge and contribute to arterial embolism, ultimately resulting in ischemic stroke. Abbreviationss: ASA, atrial septal aneurysm; DVT, deep vein thrombosis; RLS, right‐to‐left shunt.

FIGURE 3. The diagnostic workflow and classification of PFO. The diagnostic workflow of PFO can be summarized into the following steps. (A) Patients presenting with cerebral diseases, such as CS/TIA, migraine, or epilepsy, systemic embolism, or other PFO‐associated conditions, such as DCS and hypoxemic diseases, undergo further evaluation. (B) The initial evaluation aims to identify potential stroke etiologies through comprehensive clinical evaluation, including medical history, careful neurological and physical examination, as well as auxiliary examinations such as brain CT or MRI, vascular imaging, coronary CTA, ECG, Holter or rhythm monitoring, and laboratory tests. (C) After exclusion of alternative stroke etiologies, PFO detection is performed using cTCD, TTE/cTTE, and TEE/cTEE, each providing complementary information on RLS level and PFO anatomy. (D) By combining the characteristics from the above steps, PFO can be divided into low‐risk (no or small shunt, no high‐risk anatomies, low RoPE score, and unlikely PASCAL classification) or high‐risk (high‐risk anatomies, presence of predisposing factors, high RoPE score, and possible/probable PASCAL classification). High‐risk PFOs may…

FIGURE 4. The clinical management decision‐making process for PFO. The clinical management of PFO requires a systematic and individualized process. (A) When a patient is suspected of having a PFO, clinicians should determine whether the PFO is an incidental finding or is associated with symptoms, followed by assessment of PFO morphology to identify high‐risk anatomies. (B) Then, a comprehensive evaluation should be conducted to identify predisposing factors, possible stroke etiologies, and alternative mechanisms leading to the clinical presentations. (C) After a comprehensive evaluation, the causality of PFO should be determined using risk stratification tools such as the RoPE score and PASCAL classification. The presence of clinical symptoms, high‐risk PFO anatomies, high RoPE scores, possible or probable PASCAL classification, and low CVD risk collectively indicate high causality. (D and E) Next, individualized treatment strategies should be developed by a multidisciplinary team including cardiologists, neurologists, or other symptom‐related specialists. For those with incidental PFO, intervention is generally unnecessary. For those with low‐causative PFO, medical therapy and long‐term…