Patent Foramen Ovale: The Known and the To Be Known
PFO has been associated with the pathophysiology of several other disease states, including migraine headaches, decompression sickness, peripheral embolism including myocardial and renal infarction, and Alzheimer's dementia. Right-to-left shunting through a PFO can also greatly worsen symptoms in patients with chronic lung diseases associated with hypoxemia, or obstructive sleep apnea/sleep-disordered breathing. In order of magnitude, the amount of right-to-left shunting to cause systemic desaturation is larger than the amount of shunting seen in the general population with a PFO.
Del Sette et al. first reported an association between migraine with aura and the presence of right-to-left shunts detected with transcranial Doppler. The presumed association of PFO with migraines relates to paradoxical embolism or humoral factors that escape degradation in bypassing the pulmonary circulation. Using transthoracic echocardiography, it was shown that among divers with decompression illness, those with large right-to-left shunts had a higher prevalence of migraine with aura in everyday life and after dives than those with no shunt or a smaller shunt. A retrospective evaluation of the effect of transcatheter closure of atrial shunts on migraine symptoms suggested a causal association between right-to-left shunts and migraine with aura, indicating that there may be a subgroup of patients who have severe migraine associated with a large right-to-left shunt in whom closure of the atrial defect may reduce or abolish symptoms. Others have reported complete resolution of migraines in 60% of patients and improvement in symptoms in 40% of patients after transcatheter closure of atrial shunts. Wahl et al. evaluated migraine symptoms at a mean follow-up of 5 years in a retrospective cohort of patients who had transcatheter PFO closure for secondary prevention of paradoxical embolism. The prevalence of migraine with aura and the number of patients on migraine medication decreased significantly, suggesting beneficial reduction of symptoms, especially in migraine with aura.
No association was found between migraines and the presence of PFO in a recent, large case-control study. Moreover, a real benefit of PFO closure for reducing the frequency of migraines has not been shown in a randomized trial. The MIST (Migraine Intervention With STARFlex Technology) trial was a prospective, double-blind (control patients had a sham procedure and evaluating physicians were not supposed to be aware of whether a patient had a device) trial that evaluated the effectiveness of PFO closure in the treatment of migraine with aura. In MIST, 147 patients with a history of severe migraines and without any other indication for PFO device closure were randomized to undergo either device closure or a sham procedure. The patients were treated with aspirin and clopidogrel. No significant difference in the primary outcome of headache cessation was detected between the 2 groups 3 to 6 months after the procedure. On exploratory analysis, excluding 2 outliers, the closure group showed a greater reduction in migraine headache days compared with the sham group. These results could have been affected by several methodology and design reasons, including the selected primary efficacy endpoint, the duration of follow-up, and the medications used in both groups.
Two other trials, PRIMA (PFO Repair in Migraine With Aura) and PREMIUM (Prospective Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the Amplatzer PFO Occluder Compared to Medical Management), are currently under way. Further investigations are necessary to evaluate the causal relationship between migraines and PFO, and until definitive results are available the role of PFO device closure in the treatment of migraines is highly debatable.
Relationship of PFO to Other Diseases
PFO has been associated with the pathophysiology of several other disease states, including migraine headaches, decompression sickness, peripheral embolism including myocardial and renal infarction, and Alzheimer's dementia. Right-to-left shunting through a PFO can also greatly worsen symptoms in patients with chronic lung diseases associated with hypoxemia, or obstructive sleep apnea/sleep-disordered breathing. In order of magnitude, the amount of right-to-left shunting to cause systemic desaturation is larger than the amount of shunting seen in the general population with a PFO.
Migraines
Del Sette et al. first reported an association between migraine with aura and the presence of right-to-left shunts detected with transcranial Doppler. The presumed association of PFO with migraines relates to paradoxical embolism or humoral factors that escape degradation in bypassing the pulmonary circulation. Using transthoracic echocardiography, it was shown that among divers with decompression illness, those with large right-to-left shunts had a higher prevalence of migraine with aura in everyday life and after dives than those with no shunt or a smaller shunt. A retrospective evaluation of the effect of transcatheter closure of atrial shunts on migraine symptoms suggested a causal association between right-to-left shunts and migraine with aura, indicating that there may be a subgroup of patients who have severe migraine associated with a large right-to-left shunt in whom closure of the atrial defect may reduce or abolish symptoms. Others have reported complete resolution of migraines in 60% of patients and improvement in symptoms in 40% of patients after transcatheter closure of atrial shunts. Wahl et al. evaluated migraine symptoms at a mean follow-up of 5 years in a retrospective cohort of patients who had transcatheter PFO closure for secondary prevention of paradoxical embolism. The prevalence of migraine with aura and the number of patients on migraine medication decreased significantly, suggesting beneficial reduction of symptoms, especially in migraine with aura.
No association was found between migraines and the presence of PFO in a recent, large case-control study. Moreover, a real benefit of PFO closure for reducing the frequency of migraines has not been shown in a randomized trial. The MIST (Migraine Intervention With STARFlex Technology) trial was a prospective, double-blind (control patients had a sham procedure and evaluating physicians were not supposed to be aware of whether a patient had a device) trial that evaluated the effectiveness of PFO closure in the treatment of migraine with aura. In MIST, 147 patients with a history of severe migraines and without any other indication for PFO device closure were randomized to undergo either device closure or a sham procedure. The patients were treated with aspirin and clopidogrel. No significant difference in the primary outcome of headache cessation was detected between the 2 groups 3 to 6 months after the procedure. On exploratory analysis, excluding 2 outliers, the closure group showed a greater reduction in migraine headache days compared with the sham group. These results could have been affected by several methodology and design reasons, including the selected primary efficacy endpoint, the duration of follow-up, and the medications used in both groups.
Two other trials, PRIMA (PFO Repair in Migraine With Aura) and PREMIUM (Prospective Randomized Investigation to Evaluate Incidence of Headache Reduction in Subjects With Migraine and PFO Using the Amplatzer PFO Occluder Compared to Medical Management), are currently under way. Further investigations are necessary to evaluate the causal relationship between migraines and PFO, and until definitive results are available the role of PFO device closure in the treatment of migraines is highly debatable.
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