Percutaneous closure of atrial septal defect (ASD) is a commonly performed procedure in the cardiac catheterization laboratory. In experienced hands, the procedure is performed with a predictable margin of safety. It is known that migraine headache (MHA) can be precipitated after an uncomplicated ASD device closure and can be very distressing for a person who has never experienced it before. There are several hypotheses behind the new-onset headache after ASD device closure, but the exact pathophysiology is still not clearly understood. We write a short account of our patients who experienced migraine-like headaches after ASD device closure and briefly review the literature.
METHODS AND RESULTS
We retrospectively reviewed data of our patients who underwent percutaneous ASD closure between January 2015 and January 2021. There were a total of 325 patients undergoing ASD device closure during this period. The age of the patients ranged from 3 years to 65 years (median 26 years). Five out of 325 patients (1.5%) reported severe headaches within 1-2 weeks of the procedure. All five patients received Amplatzer Septal Occluder (AGA Medical Corporation, Plymouth, Minnesota, United States of America) for closure of ASD. All of them received 100 units/kg of unfractionated heparin for thromboprophylaxis immediately upon insertion of the short groin sheath and activated clotting time was maintained above 200 s during the procedure. All patients except the fourth had a single attempt at device deployment. The fourth patient, who had a short posterior rim needed three attempts before the device could be positioned optimally across the defect. There was no incidence of air embolism at the time of device deployment and all five patients had an uneventful procedure. All patients were given aspirin 5mg/kg for 6 months after device closure. The patient who received a 38 mm Septal Occluder was given clopidogrel 3 mg/kg for 6 months in addition to aspirin. In our ASD series, those who had received an implant of size 30 mm and above were prescribed dual antiplatelet drugs as per the decision of the attending physician.
Headache was reported exclusively by female patients. Our fourth patient [Table 1] who complained of a severe headache on the 2nd day of the procedure underwent a plain CT scan of the brain to check for possible cerebral bleed, which was normal. The other four patients were already discharged before the onset of headache and the symptoms were reported over the phone. Diagnosis of migraine was established based on the guideline of the International Headache Society. Neuroimaging was not needed as the headaches were self-limiting.
For immediate relief of pain, all of them were advised paracetamol at a dose of 15 mg/kg. The third patient needed ibuprofen for her subsequent headache episodes as paracetamol was reportedly ineffective. Three of 5 (60%) patients had a positive family history of migraine. Headache episodes disappeared by 3–6 months in the majority. Table 1 summarizes patients who reported headaches after ASD device closure.
New-onset migraine attacks are reported by about 15% of patients after transcatheter ASD closure. In a retrospective study, Rhodes-Cabeau noted 12% new-onset MHA after ASD closure and 0% after patent foramen ovale closure. The first episode of MHA appeared mostly within 2 weeks of device closure and the majority persisted even after 2 years after the procedure.
Interestingly, a meta-analysis that looked into a change in preexisting MHA and new-onset MHA after ASD device closure reported that 14% of preexisting migraine improved, 37% resolved, and 63% persisted at 12 months of ASD device closure. They found that new-onset MHA ranged from 10% to 18%. Thirty-four percent of which occurred in the 1st week after the procedure, more common in females, the predominant type being migraine with aura. New-onset migraine persisted in 76% at 12 months of follow-up. Triggers for new-onset migraine were difficult to pinpoint; the large size of the defect, deficient retro-aortic rim, and nickel allergy were reported by some of the studies.
In our series, MHA occurred exclusively in female patients. All the defects were large and had deficient retro-aortic rim. There was no significant oversizing of the device. The mean defect-to-device ratio remained at 0.87. None of our patients had a history of headaches, although three had a family history of migraine in mother on retrospective questioning. Even though the aortic rims were deficient in all the patients who suffered migraine, we feel that this is a chance association given that the majority of our patients with ASD are found to have the absent or deficient retro-aortic rim and MHA occurred in a few rare patients.
Because the new-onset MHA maximally occurs within the first 7–14 day period, the probable role of acute pro-inflammatory state after ASD device closure can be considered. Researchers have found a heightened aggregation of platelets, leading to microembolism formation and release of vasoactive substances such as adenosine diphosphate, thromboxane A2, and serotonin. Microembolism in the cerebral vasculature combined with vasoconstriction caused by serotonin leads to the migrainous aura.
The pattern of new-onset MHA within the first 1–2 weeks after intervention corresponds to the pathophysiology of maximal platelet activation and microembolism immediately after device closure procedure and subsiding as the endothelialization gets complete by roughly within 3 months in the majority of patients. However, incomplete endothelialization and late embolic complications such as cerebral and coronary artery thrombosis have been reported well after 12 months of ASD device closure and could also explain the persistence of MHA in some patients beyond 3 months by the same theory.
Two patients reported by Armstrong developed MHA shortly after device closure and decreased in severity over time but persisted. One of them needed long-term migraine prophylaxis. Among the etiological factors implicated was microembolus from the device and release of Nickel at the time of device deployment causing cortical spreading depression linked to the aura. However, these hypotheses do not explain the long-term persistence of MHA.
Fernandes et al. reported a rare case of removal of 22mm Amplatzer Septal Occluder 6 years after its implantation in a 10-year-old boy in whom medical treatment failed to control MHA. In this patient, grade 1 nickel allergy was demonstrated by the skin test. Intraoperatively, the authors noted that the device was not fully endothelialized even after so many years and perhaps that led to persistent platelet activation.
A randomized double-blind clinical trial performed in six university hospitals in Canada reported a statistically significant lower incidence of monthly headache episodes in the first 3 months after device closure in patients who received clopidogrel and aspirin compared to those who received only aspirin and placebo. A total of 171 patients enrolled in this study were 18 years and older, none had preexisting migraine and all of them underwent device closure using Amplatzer Septal Occluder (AGA Medical Corporation, Plymouth, Minnesota, United States of America). Patients were randomized to receive aspirin (80 mg/day) and placebo or aspirin (80 mg/day) and clopidogrel (75 mg/day) with the treatment being initiated within 24 h before device closure and continued for 3 months thereafter. A total of 27 patients had new-onset migraine within 3 months of ASD device closure, the number being significantly lower in the group treated by dual antiplatelet therapy.
With a further follow-up of the same patient group for up to 12 months, Wintzer-Wehekind et al. reported that the severity of new-onset headache episodes reduced or resolved over 6 to 12 months and the incidence of MHA at 6 and 12 months was independent of clopidogrel prescription in the first 3 months. There was no rebound of headache episodes after cessation of clopidogrel at 3 months. Hence, the authors concluded that clopidogrel can be discontinued after 3 months of device closure if used.
A significant proportion of patients and especially those with a family history of migraine are at risk of developing migraine-like headaches after percutaneous ASD device closure and this risk should be discussed beforehand. Prescription of dual antiplatelet agents (aspirin and clopidogrel) may be considered for the first 3 months after percutaneous ASD device closure for those with a past or family history of migraine. Further randomized studies are required to establish the role of routine prescription of dual antiplatelets after this procedure. It is fascinating to note that all the MHA reported, occurred after the use of Amplatzer Septal Occluder (AGA Medical Corporation, Plymouth, Minnesota, United States of America). A head-to-head comparison between Amplatzer Septal Occluder and ceramic coated device (Lifetech Inc.) in this regard could be helpful.
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Conflicts of interest
There are no conflicts of interest.
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