Background-Clinical observations of migraine headache symptoms in patients with a patent foramen ovale (PFO), both of which conditions are highly prevalent, have raised the question of a possible pathophysiological relationship. We sought to evaluate the assumption of an association between migraine headaches and the presence of PFO by use of a large case-control study. Methods and Results-We conducted a case-control study to assess the prevalence of PFO in subjects with and without migraine. Case subjects were those with a history of migraine (diagnosed by neurologists at a specialty academic headache clinic). Control subjects were healthy volunteers without migraine 1:1 matched on the basis of age and sex with case subjects. Presence of PFO was determined by transthoracic echocardiogram with second harmonic imaging and transcranial Doppler ultrasonography during a standardized procedure of infused agitated saline contrast with or without Valsalva maneuver and a review of the results by experts blinded to case-control status. PFO was considered present if both studies were positive. Odds ratios were calculated with conditional logistic regression in the matched cohort (nϭ288). In the matched analysis, the prevalence of PFO was similar in case and control subjects (26.4% versus 25.7%; odds ratio 1.04, 95% confidence interval 0.62 to 1.74, Pϭ0.90). There was no difference in PFO prevalence in those with migraine with aura and those without (26.8% versus 26.1%; odds ratio 1.03, 95% confidence interval 0.48 to 2.21, Pϭ0.93). Conclusions-We found no association between migraine headaches and the presence of PFO in this large case-control study. (Circulation. 2010;121:1406-1412.)Key Words: migraine Ⅲ patent foramen ovale Ⅲ echocardiography Ⅲ epidemiology M igraine headache is a chronic disabling condition that affects approximately 6% of men and 15% to 18% of women. [1][2][3] Its peak prevalence is in midlife, and the condition may result in significant functional impairment and loss of productivity and is associated with high healthcare costs. 1 Migraine headache may be preceded by an aura, a neurological disturbance, most commonly visual or sensory, with subsequent complete recovery. Migraine is thought to be caused by both hereditary and environmental factors and is believed to have neurogenic and neurovascular components to its origin, but its pathophysiology remains incompletely understood. Patent foramen ovale (PFO) is a slitlike interatrial defect that is quite common in the general population, with a prevalence of approximately 10% to 25% depending on the population studied and the methodology used for diagnosis. 4 -7 It occurs with equal frequency in men and women and tends to decrease in frequency with age. Editorial see p 1377 Clinical Perspective on p 1412Observational studies have concluded that a lower frequency of migraine attacks occurred after PFO closure for cryptic stroke, whereas others have postulated a relationship between shunt magnitude and migraine attacks. 8 -16 Thus, a hypothesis has em...

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We appreciate Drs Luermans and Bhindi and colleagues' thoughtful comments on our recent publication. We agree that transesophageal compared with transthoracic echocardiography is more sensitive and specific for the diagnosis of patent foramen ovale (PFO) as well as associated anatomic abnormalities such as atrial septal aneurysm (ASA). Although ASA has been shown to be associated with cryptogenic stroke, it remains unclear if this is more common in migraineurs. In our study, there was no difference in the prevalence of PFO with hypermobile septum (defined as atrial septal motion Ͻ10 mm from baseline) or with ASA (Ͼ10 mm) in cases with migraine compared with controls (9.0% versus 7.6% and 0 versus 0.7%, Pϭ0.83, respectively). The prevalence of atrial septal abnormalities seen in our study is consistent with past reports. 1 Numerous studies have also shown excellent accuracy in detecting PFO with the combination of transthoracic echocardiography and transcranial Doppler compared with transesophageal echocardiography. 2,3 The combined use of these modalities to diagnose PFO in our study resulted in higher specificity, increasing the likelihood of finding a true association with migraine, if one existed.We excluded subjects with some preexisting conditions (eg, history of cerebrovascular disease or paradoxical embolism) so as to define a series of cases without other likely consequences of a preexisting PFO, to obtain a valid estimate of the prevalence of PFO in the source population determined by the selected cases. For example, PFO is known to be associated with cerebrovascular disease and thus including patients with prior stroke as cases may result in finding a "false" or misleading association between migraine and PFO. These excluded conditions are also uncommon, with an estimated absolute rate of ischemic stroke of 19 per 100 000 women with migraine per year. 4 Concerning our sample size calculations, the prevalence of PFO varies from 10% to 30%, depending on the diagnostic method and the study population. Prior echocardiography-based population studies have suggested PFO prevalence of 15%. 5 We therefore used an estimate of 15% as the prevalence of PFO for sample size calculation, as well as the assumption that matching on confounders typically leads to an increase in power. The widths of reported confidence intervals reflect the precision of our analysis. Although it is plausible that a weak association between PFO and migraine exists, our confidence intervals for the effect of PFO [0.62, 1.74] support the null effect found in our study (odds ratioϭ1.04, Pϭ0.89). Regarding patients with migraine with aura, we agree that our power within this smaller subset was limited; however, there was no difference in PFO prevalence in those with migraine with aura or those without (odds ratioϭ1.03, Pϭ0.93).Our study provides evidence against a pathophysiologic association between PFO and migraine and, above all, argues against closure of PFO for migraine.

Objectives: Analysis of healthcare expenditure of patients with heart failure for 12 months from the time of index admission. Methods: Manipal Heart Failure Registry (MHFR), established in 2015 in a tertiary care hospital in Southern India, is a prospective observational cohort of patients diagnosed with heart failure. From this registry, we analysed the total expense incurred during index hospitalization from in-patient bills which included the consultation charges, expenses for ICU/ward stay, investigations, interventional procedures and medications. Similarly, the expenses incurred for medications, visits and re-hospitalization(s) during the 12 month follow up period were calculated. Results: A total of 610 patients with mean age of 65.0 6 13.6 years were included among which 59.8% were males and 38.9% had ischemic heart failure. Average duration of index hospitalization was 5.3 days with an average expenditure of INR 59492 (V710). This included the charges for hospitalization and consumables [INR 9210.9 (V110)], investigations [INR 6465.0 (V65)], medicines, devices and procedural charges [INR 38940.1 (V461)], consultation/professional charges [INR 2158.2 (V26)] and expenditure incurred by caregivers [INR 2717.8 (V40)]. Follow up data was available for 98.1% of the patients. Re-hospitalization rate was 10.8% and 34.1% patients had unscheduled visits to the hospital due to worsening symptoms. Average expenses during the 12 months follow-up period was INR 22680 (V268) which included re-hospitalizations, scheduled/unscheduled visits, and medications. Patients who were non-compliant to medicines or were re-hospitalized during the follow up period spent considerably more than those who were not [INR 32876 (V387) vs INR 20899 (V247), p= 0.042; INR 35255 (V416) vs INR 20213 (V237), p= 0.002, respectively]. Conclusions: Healthcare expenditure of patients with heart failure in India is much lower than their western counterparts. Hospitalizations and interventional procedures account for bulk of the expenses incurred. Drug non-compliance is an important and easily avoidable cause for increased healthcare expenditure.

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