Drug therapy is mainly used to prevent recurrence of stroke or TIA in PFO patients. The PICSS study showed that in patients with PFO combined with CS, the 2-year stroke recurrence rate was 13.2% in the aspirin group; and the 2-year event rate was 16.5% in the warfarin-treated group; there was no statistical difference between the two groups, but the risk of minor bleeding was significantly increased in the warfarin group. Therefore, antiplatelet therapy [aspirin 3-5 mg/(kg/d) or clopidogrel 75 mg/d] is recommended as the treatment of choice. For those with stroke recurrence despite antiplatelet therapy, or those with concomitant deep vein thrombosis (DVT) and hypercoagulable state, warfarin anticoagulation therapy may be switched. There is a lack of data or experience with the use of new oral anticoagulants for prevention and treatment. Although drug therapy is free of surgical risks, it requires long-term treatment, and bleeding is its most significant complication, in addition to poor patient compliance. Some studies have shown that the recurrence rate of stroke is higher in those with PFO combined with ASA, even with effective antiplatelet therapy. 1. Indications ① PFO with CS or TIA with moderate to massive RLS; or recurrence despite antiplatelet or anticoagulation therapy; or definite DVT; ② PFO with intractable or chronic migraine with moderate to massive RLS; ③ PFO with venous thrombosis or lower extremity varicose veins/valvular insufficiency with moderate to massive RLS; ④ Recumbent respiratory-erect hypoxemia ⑤ High risk PFO: PFO combined with ASA or excessive interval activity, large PFO, PFO combined with resting RLS; ⑥ Age 18～60 years old (combined with clear CS, age can be relaxed appropriately). 2. Relative indications ① migraine combined with PFO with moderate RLS; ② PFO with high risk factors for venous thrombosis (prolonged sitting or bed rest, etc.) with moderate RLS; ③ PFO with extracranial arterial embolism; ④ special occupations combined with PFO (such as divers, pilots, etc.); ⑤ hypoxia combined with PFO that is difficult to explain clinically. 3. Contraindications ① cerebral embolism that can be found for any reason, such as cardiogenic cerebral embolism, vasculitis, atherosclerosis; ② contraindication to antiplatelet or anticoagulation therapy, such as severe bleeding within 3 months, significant retinopathy, history of intracranial hemorrhage, significant intracranial disease; ③ inferior vena cava or pelvic vein thrombosis leading to complete obstruction, systemic or local infection, sepsis, intracardiac thrombosis; ④ pregnancy; ⑤ combined pulmonary hypertension or PFO for special access (6) acute stroke within 2 weeks. 4. Perioperative management of blocked PFO (1) Preoperative preparation After signing the informed consent, patients should undergo detailed clinical examination, including assessment of clinical symptoms, other cardiovascular and cerebrovascular diseases, pulmonary artery pressure assessment and anatomical evaluation of PFO, and complete relevant laboratory tests. Cranial CT or MRI should be performed to evaluate stroke; lower extremity venous ultrasound should be performed to understand venous valve function or venous thrombotic status. All patients should complete cTTE and TEE to assess how much PFO-RLS, anatomical features of PFO, presence of thrombus and relationship with surrounding tissues. All patients should receive oral aspirin 3-5mg/kg once daily and clopidogrel 75mg once daily 48h before surgery, and prophylactic antibiotics 1h before surgery. (2) Implantation operation The process of PFO blocking is basically similar to the process of ASD blocking, but has its own special features. One of the difficulties in blocking PFO is how to pass the catheter through the PFO channel. 1/3 of the patients can pass the PFO directly with the guidewire or catheter. 1/3 of the patients need multifunctional catheter guidance, and when the catheter tip is below the level of hepatic vein and pointing to the spinal direction, the PFO can be passed by sending the guidewire forward toward the atrial septum. if the J-shaped tip of the guidewire is straightened and still cannot pass the PFO, it is necessary to pass the PFO in the posterior-anterior position. Once the tip of the catheter reaches the fossa ovalis region, the catheter is rotated back and forth from 8 o’clock to 2 o’clock to pass through the PFO, or in the lower part of the right atrium, the catheter is pointed to the patient’s left (3 o’clock) and rotated clockwise and backward approximately 1/4 turn (6 o’clock) while feeding the catheter forward. The procedure should be done gently and continuously, sometimes requiring repetition of the procedure. Transatrial septal puncture through the foramen ovale is generally not recommended. Another difference between PFO blocking and ASD is the size determination. When blocking an ASD, the maximum diameter needs to be measured, but blocking a PFO focuses more on its structural characteristics. When applying StarFlex and Helex blockers, the blocker should be selected according to the maximum diameter of the PFO and the PFO extension diameter should be measured with a balloon. For Amplatzer blockers, the PFO open diameter is generally not considered, so balloon measurement is not required. However, for PFO combined with ASA or huge PFO, the ASD blocker is considered and the blocker can be selected more reasonably based on the balloon measurement of the extension diameter. Although Cardio SEAL/Star Flex blocker, Amplatzer ASD or PFO blocker, Helex blocker and PremereTM PFO blocking system have been used in overseas clinics, only Amplatzer PFO blocker or similar blockers from China are approved for clinical use in China. Amplatzer PFO blocker is similar to ASD blocker in shape, its models are 18/18mm, 18/25mm, 30/30mm and 25/35mm, the right disc of blocker is larger than the left disc. The ASD blocker is not recommended for PFO blocking because of the difficulty of choosing the size and the ease of choosing the blocker too large, but it is advantageous for PFO combined with ASA and huge PFO. For most PFOs, a medium-sized 18/25mm blocker can be routinely tried first. If the left atrial umbrella is pulled into the right atrium with little force, the 25/35mm blocker needs to be replaced. For PFO combined with giant ASA; long tubular PFO; secondary septum that is particularly thick or thick with aortic root protrusion and immediately adjacent to the fossa ovale, and when there is concern about aortic erosion by the disc of the blocker, a 25/35mm or 30/30mm PFO blocker is chosen directly. The 18/18 mm blocker is rarely used in adults. Large blockers can completely cover the entire PFO fissure, but they cannot fit tightly into the atrial septum and tend to rub against each other with the aorta, with the possibility of eroding the atrial wall. Smaller blockers fit well with the atrial septum and can avoid erosion of the atrial free wall, but may partially cover the PFO fissure, especially when the blocker is placed in a deviated position, there is often residual shunt. Therefore, it is very important to choose a suitable blocker. (3) Postoperative medication and follow-up Routine heparin anticoagulation for 48 h, oral aspirin 3-5 mg/(kg?d) for 6 months and clopidogrel 75 mg/d for 3 months after surgery. Oral warfarin was administered in the presence of atrial fibrillation. Echocardiography should be repeated at 3 months, 6 months and 1 year postoperatively, with emphasis on cTTE or cTCD to determine the presence of RLS, in addition to the position of the blocker, the presence of blocker thrombus and cardiac structures. blocking PFO comorbidities are the same as ASD – but much less common and safer. Aortic erosion is rare, and the main alert is for new arrhythmias. The literature reports that new-onset AF after the application of Star Flex blocker is 7.5%; compared to 3.1% for Amplatzer blocker;. Blocker-triggered atrial fibrillation is about 1%;. V. Surgical treatment Most surgical repair of PFO has been replaced by percutaneous occlusion, which is now mostly applied in special cases, such as the presence of PFO found in the surgical treatment of other cardiac diseases.