Patients with small atrial shunts live a normal life span with no intervention. Large shunts usually cause disability by age 40 years. Because left-to-right shunts and RV overload tend to increase with normal age-related reduction in LV (and subsequently LA) compliance, guidelines suggest that closure of all left-to-right shunts greater than 1.5:1 should be accomplished either by a percutaneous device or by surgery if any right heart structures are enlarged at all. If the pulmonary systolic pressure is more than two-thirds the systemic systolic pressure, then pulmonary hypertension may preclude ASD closure. Testing with transient balloon occlusion of the shunt, with pulmonary vasodilators, or with both may be required in the presence of pulmonary hypertension. Preservation of the cardiac output after transient balloon occlusion and evidence for preserved pulmonary vasoreactivity with pulmonary vasodilator testing all favor closure when pulmonary hypertension and at least a 1.5:1 left-to-right shunt are present. After age 40 years, cardiac arrhythmias (especially atrial fibrillation) and heart failure occur with increased frequency due to the chronic right heart volume overload. Paradoxical systemic arterial embolization also becomes more of a concern as RV compliance is lost and the left-to-right shunt begins to reverse.
PFOs are usually not associated with significant shunting, and therefore the patients are hemodynamically asymptomatic and the heart size is normal. However, PFOs can be responsible for paradoxical emboli and are a possible cause of cryptogenic strokes in patients under age 55 years. Interestingly, the risk of recurrent paradoxical emboli is low regardless of whether the PFO is closed or not, and that observation has reduced the value of closing these defects in cryptogenic stroke. Further confounding the advantage of PFO closure for cryptogenic stroke or transient ischemic attack (TIA) has been the discovery of frequent bouts of paroxysmal atrial fibrillation using 30-day monitoring in these patients, suggesting atrial fibrillation is actually the real stroke/TIA risk factor in some patients.
Occasionally, a PFO that has not been pathologic may become responsible for cyanosis, especially if the RA pressure is elevated from pulmonary or RV hypertension or from severe tricuspid regurgitation.
Surgery involves stitching or patching of the foramen. Anomalous pulmonary venous connections are baffled to the LA through the sinus venosus defect when such anomalous veins are present. For ostium secundum ASDs, percutaneous closure by use of a variety of devices is preferred over surgery when the anatomy is appropriate (usually this means there must be an adequate atrial septal rim around the defect to secure the occluder device). The most common percutaneous closure devices include the “Amplatzer” dumbbell shaped device of nitinol mesh and polyester fiber and the “Helex” nitinol coils that have an ePTFE patch material. In both cases, endothelial tissue grows in and over the device after 3–6 months.
Patients who have hypoxemia (especially upon standing or with exercise) should have the PFO closed if no other cause for hypoxemia is evident and there is right-to-left shunting demonstrated through the PFO. For patients with cryptogenic stroke or TIA, it remains uncertain whether closure of the PFO, either by open surgical or percutaneous techniques, has any advantage over anticoagulation with either warfarin, a direct-acting oral anticoagulant (DOAC), or aspirin. Five major randomized clinical trials evaluating the advantage of PFO closure in cryptogenic stroke (at ages greater than 55 years). Three of the five trials did not show an advantage of device closure over medical therapy with antiplatelet or anticoagulation medication; however, two of the five suggested there may be a role. The FDA has approved one device for use when both a cardiologist and neurologist feel the PFO contributed to a TIA or stroke. The CLOSURE 1 trial did not demonstrate a clear advantage to PFO closure with a percutaneous device compared to medical therapy with aspirin. Two additional trials comparing device closure with medical therapy were reported in 2012–2013. RESPECT (Randomized Evaluation of recurrent Stroke comparing PFO Closure to current standard Treatment) randomized 980 patients, and PCTRIAL (Percutaneous Closure of patent foramen ovale versus medical treatment in patients with cryptogenic stroke TRIAL) randomized 414 patients. Neither trial met the superiority composite end point (death, nonfatal stroke, TIA, or peripheral embolism), but both trials had much fewer events in the medical arms than prior studies had suggested. The PC Trial was a randomized trial of 414 patients reported in 2013 and, again did not meet a composite endpoint. The GORE REDUCE trial with the Helex device randomized 664 patients and the results favored device over medical therapy (reduced recurrent stroke from 1.7 to 0.39 per 100 patient-years). The CLOSE TRIAL had three arms, closure, antiplatelet therapy and anticoagulant therapy, after cryptogenic stroke. Closure was favored over the antiplatelet arm at 5 years.
From a practical standpoint, patients younger than 55 years with cryptogenic stroke/TIA and no other identifiable cause except for the presence of a PFO should still be considered for PFO closure. A workup for any causes for hypercoagulability and a 30-day monitor should also be part of the clinical assessment to exclude other potential causes for cryptogenic stroke/TIA. In meta-analysis of data in patients with cryptogenic stroke/TIA and PFO who have their PFO closed, ischemic stroke recurrence is less frequent compared with patients receiving medical treatment. Atrial fibrillation is more frequent but mostly transient in patients who have device closure. There is no difference in TIA, all-cause mortality, or myocardial infarction (MI) between those treated with medicine versus a closure device. In a large, multicenter trial in France among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation.
PFO closure is also occasionally recommended for deep sea divers to help prevent the “bends” due to nitrous oxide shunting. Despite much fanfare from small studies suggesting an advantage, there are no strong data to confirm an advantage in PFO closure for patients suffering from migraine headaches. One randomized, placebo-controlled trial did not show a lessening of migraine events with PFO closure.