Page 31 - Journal of Structural Heart Disease Volume 2, Issue 5

Letter to the Editor
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macological therapy; this held true for devices as well. These challenges culminated in the termina- tion of MIST II.
Despite these setbacks, investigators have contin- ued to explore the closure of interatrial septal defects and migraine relief. The study by Tayaka and col- leagues [12] provides another link between the pres- ence of RLS and migraines. Their data support the re- ports of a higher prevalence (56%) of migraines in patients with RLS, but also suggest a high prevalence in patients with ASDs (29%). While not an entirely novel nding, the relationship behind ASD and mi- graines has not been the emphasis of investigation. This prospective trial adds little to the body of evi- dence of nonrandomized PFO closure and migraine relief, but it demonstrates that there is potentially an interaction with ASDs, and their closure may impact headaches.
The study by Tayaka et al addresses several gaps of previous trials. The endpoint assessment of headache was based, correctly, on a neurologist’s evaluation. The four-category reporting system for headache severity and frequency provides quanti cation consistent with the real world expectation of improvement. Follow-up was well documented, along with the response to clopidogrel, which may play a role in migraine relief. Notably, relief persisted beyond the termination of clopidogrel at 1 month.
The trial exhibits well-described limitations of nonrandomized clinical studies without control groups or blinding. The assessment of pharmaco- logic therapy for migraine headache was not described, and the evaluation tools did not include a headache diary. These omissions are especially im- portant given that improvement, and speci cally complete resolution, of migraines was high in all patients. Migraine relief was highest in patients after PFO closure but also high after ASD closure, with 15 of 20 patients improving and nearly half of these patients reporting complete resolution. The mean post-procedure follow-up for patients after ASD closure was half of that after PFO closure (22 versus 44 months, respectively). A longer follow-up period overall may have decreased the likelihood that relief was due to placebo and would have been bene cial to evaluate the underlying relationship between RLS and headache.
Journal of Structural Heart Disease, October 2016
Tayaka and colleagues did not specify key meth- ods and procedures, including the imaging protocol for evaluating interatrial septal defect anatomy and RLS. Thus, procedural success was not de ned. Re- lated procedural results were undescribed, namely the presence and quantitation of post-procedural residual shunt in patients after ASD closure, particu- larly in those without improvement of migraine. These descriptions and data are critical to correlating closure with relief, and particularly essential in the study of a clinical syndrome with placebo e ects that may exceed 20% [13].
A large, randomized clinical trial aimed to overcome these limitations and provide a de nitive foundation for evidence-based PFO closure for migraine head- ache. The Prospective, Randomized Investigation to Evaluate Incidence of Headache Reduction in Sub- jects with Migraine and PFO Using the Amplatzer PFO Occluder to Medical Management (PREMIUM) trial was presented in June 2015 at the American Headache Society [14]. PREMIUM was the third trial to examine migraine relief with PFO closure, the second to use the Amplatzer device, and the second to use sham surgery as a control. The primary endpoint of 50% reduction in migraine was not met; there was no di erence in migraine attack frequency in patients who underwent closure (n = 117) versus patients ran- domized to sham and medical therapy (n = 103). Among migraineurs with aura, however, those in the closure group had a higher rate of complete remission than those in the sham group (10.8% versus 1.5%, p = 0.02).
These results are consistent with the compelling body of literature demonstrating migraine relief after PFO closure in the subset of patients who have migraine with aura. The high frequency of large RLS in these pa- tients [8], and the high rate of migraine relief and even complete remission in patients after PFO closure [12, 14], suggest that RLS has a role in migraine pathogenesis. However, study ndings must be cautiously interpreted before changing clinical practice. Currently, there are no studies actively enrolling for PFO closure in patients with headache, and it is purported that the U.S. Food & Drug Administration may want another trial. Fundamental questions for future investigation remain.
• In the absence of a pathologic signature, can we re ne Volume 2, Issue 5:231-233