Medical Treatment With or Without Transcatheter Patent Foramen Ovale Closure

Prior treatment

• Need for chronic anticoagulation therapy.
• Any contraindication for antiplatelet therapy (aspirin, clopidogrel, ticagrelor).
• History of prior valve surgery or transcatheter valve repair.
• Prior surgical or endovascular treatments of PFO or ASD.

Other illness

• Lacunar (small vessel) stroke.
• Uncontrolled hypertension (systemic pressure values \>160/90 mmHg despite optimal medical treatment).
• History of myocardial infarction or coronary intervention. (percutaneous coronary intervention, coronary artery bypass graft).
• Presence of deep venous thrombosis at the time of index stroke as evaluated by Doppler ultrasonography.
• Significant (moderate or severe) valvular disease as evaluated by echocardiography.
• History of congestive heart failure.
• Other specific cause of stroke identified (eg, arteritis, dissection, migraine/vasospasm, and drug abuse).
• Rheumatic heart disease.
• Active cancer.
• Severe pulmonary artery hypertension (systolic pulmonary pressure \>60 mmHg).
• Failure to provide signed informed consent.

Lab values

• Left ventricular ejection fraction \<50% as evaluated by TTE.

Age

• Any medical condition determining a life expectancy \<2 years.

Other

• -≤60 year-old
• Permanent or paroxysmal atrial fibrillation/flutter (clinically apparent or detected by continuous ECG monitoring).
• Presence of extracranial or intracranial atherosclerosis causing ≥50% luminal --stenosis in arteries supplying the area of ischemia.
• Presence of complex atheroma plaques at the ascending aorta-aortic arch (≥4-mm-thick, ulcerated or containing mobile thrombi) as evaluated by TEE.
• Presence of intracardiac thrombus as evaluated by TEE.
• Severe chronic kidney dysfunction defined an estimated glomerular filtration rate \<30 ml/min/m2 or need for dialysis.
• Isolated ASD or ASD associated with PFO but with a hemodynamically significant left-to-right shunt requiring closure.
• Left atrial enlargement defined as a left atrial diameter \>41 mm in men and ≥39 mm in women.
• Presence of high burden of premature atrial contractions (\>500 per 24 hrs) as evaluated by continuous ECG monitoring.
• Follow-up impossible or expected poor compliance.
• Presence of an inferior vena cava filter.
• Functional dependency as measured by a modified Rankin Scale score \>3 (unable to attend to own bodily needs without assistance and unable to walk unassisted).
• Participation in another randomized study.

• Cryptogenic stroke
• Age \>60 years
• Right-to-left shunt as evaluated by echocardiography (TEE).