Perspective:

The following are 10 points to remember from this update on patent foramen ovale (PFO):

1. Echo contrast studies estimate the prevalence of PFO to be approximately 25% in the general adult population. PFO should therefore be considered a normal variant and not a pathological finding in otherwise asymptomatic patients.

2. Under normal physiologic conditions, there is minimal shunting between the atria in patients with PFO. Maneuvers such as a Valsalva maneuver can cause transient right-to-left shunting.

3. While imaging PFO, diagnostic sensitivity can be increased by injection of agitated saline contrast during the Valsalva maneuver.

4. The presence of PFO appears to be associated with increased risk of cryptogenic stroke. A meta-analysis of retrospective studies showed that patients ages <55 years with a cryptogenic stroke had a PFO prevalence 6 times greater than that of patients with other forms of stroke.

5. Atrial septal aneurysm is frequently associated with PFO. There is debate as to the impact of atrial septal aneurysm on the risk of recurrent stroke.

6. The optimal medical therapy for prevention of recurrent cryptogenic stroke remains controversial. The PFO in Cryptogenic Stroke Study (Circulation 2002;105:2625-31) demonstrated no difference in time to recurrent ischemic stroke or death in patients randomized to warfarin as compared with aspirin.

7. Device closure of PFO for prevention of recurrent cryptogenic stroke remains controversial. Multiple uncontrolled studies have demonstrated improvements in recurrent stroke rates after PFO closure. The recently published CLOSURE I study (N Engl J Med 2012;366:991-9) failed to demonstrate superiority of PFO closure with the STARFlex device over medical therapy with aspirin or warfarin.

8. Three additional trials, including the PC-Trial (Amplatzer PFO occluder), RESPECT (Amplatzer PFO occluder), and REDUCE (HELEX septal occluder) trials are ongoing to study the impact of device closure on recurrent stroke.

9. Off-label closure of PFO has likely significantly slowed recruitment in randomized trials. This may contribute to enrollment bias, as patients considered higher risk for current stroke may undergo off-label closure as opposed to risking randomization to medical therapy.

10. PFO has been reported to have an association with migraine headaches. Multiple anecdotal reports and retrospective studies have demonstrated improvement in migraine headaches with PFO closure. A recent large case-control study (Circulation 2010;121:1406-12) found no association with migraine headaches and the presence of PFO. The double-blind MIST trial, in which controls underwent sham procedure, demonstrated no benefit in the endpoint of cessation of migraine headache. The closure group did show greater reduction in the number of migraine days as compared with the sham procedure group.