2.1 Study population and data collection
The study was conducted at Xuanwu Hospital, Capital Medical University in Beijing, spanning from January 2021 to January 2022. Patients diagnosed with a patent foramen ovale (PFO) through transesophageal echocardiography (TEE) or bubble transcranial Doppler (Bubble-TCD) and identified with a hypercoagulable condition by laboratory tests were eligible for enrollment. Based on the aforementioned findings, participants were categorized into two groups: those receiving dual antiplatelet therapy after PFO closure (antiplatelet group) and those receiving anticoagulant plus mono antiplatelet therapy after PFO closure (anticoagulant group). Patients were meticulously selected based on the following criteria:
Inclusion criteria:
1)Patients with migraine that other causes cannot explain except for PFO;
2)Age ranging from 16 to 65;
3)No sex preference.
Exclusion criteria:
1) Patients declining TEE or Bubble-TCD.;
2) Severe, acute, or life-threatening conditions, including acute cardio-cerebrovascular diseases, severe organ failure, and infections;
3) History of cancer or other neck and head disorders;
4) Contraindications to enhanced magnetic resonance imaging (MRI);
5) Patient with atrial septal aneurysm and atrial fibrillation(AF);
Demographic details of these groups, including sex, age, symptoms, and medical history (smoking, hypertension, diabetes, and coronary diseases), were collected and analyzed. Notably, this study encompassed blurred vision and double vision within the category of visual disorders.
2.2. Evaluation of patent foramen ovale
All participants underwent either TEE or bubble-TCD screening while performing the Valsalva maneuver to detect the presence of PFO. Patients with an inadequate temporal bone window for bubble-TCD exclusively underwent TEE. TEE or bubble-TCD procedures were conducted and evaluated by two experienced independent echocardiographers. PFO size was categorized as small (1–9 bubbles), medium (10–20 bubbles), or large (> 20 bubbles) based on the bubble-TCD results[5, 6].
2.3 Evaluation of hypercoagulable disease
Indices related to aberrant blood coagulation (e.g., protein C/S resistance, antithrombin III, D-dimer, fibrinogen, etc.), along with antibodies linked to connective tissue diseases (such as antinuclear antibodies, antistreptolysin O, antiphospholipid antibody), and other factors like inflammatory markers (e.g., erythrocyte sedimentation rate, C-reactive protein) were evaluated. Moreover, patients with venous thrombosis include deep vein thrombosis (DVT) and cerebral venous thrombosis (CVT) were also enrolled. Comparable assessments for hypercoagulable disorders were based on baseline examinations and electronic medical records.
2.4Treatment and follow-up
For PFO cases, treatment options include dual antiplatelet therapy after PFO closure and anticoagulant plus mono antiplatelet therapy after PFO closure. An experienced cardiologist conducted conscious sedation-guided PFO closure using fluoroscopy. Following closure, the patients in antiplatelet group received dual antiplatelet medication (100 mg aspirin and 75 mg clopidogrel per day) for six months[7]; Patients in anticoagulation group taking DOACs (rivaroxaban or dabigatran) with mono antiplatelet were prescribed anticoagulants based on risk factors, clinical characteristics, and diagnostics. Treatments were promptly initiated, and clinical and neuroimaging follow-up occurred 12 months post-device placement via telephone interviews or outpatient visits. Symptom relief was evaluated, categorized as considerably improved, slightly better, or unchanged from baseline. Documentation included neurological events like stroke, transient ischemic episodes (TIA), significant bleeding, and mortality (Fig. 1).
2.5 Approvals and consents
This trial was approved by Institutional Ethics Committee (Xuanwu Hospital, Capital Medical University), and all patients signed consent forms prior to study enrollment.
2.6 Statistical analysis
Descriptive statistics were calculated for all qualitative data. All the values in the text and tables are presented as mean standard deviation (mean ± SD) and analyzed with Student t-test. Categorical variables are reported as numbers and percentages, and they were analyzed with chi-square test, as appropriate. Clinical improvement of migraine relief was determined as ranked data, and compared using the Kruskal-Wallis Test. Variable data adjusted for age, sex. Risk reduction was estimated with the Cox proportional hazards model. Comparisons by randomised treatment assignment were not adjusted for any covariates. Two-sided p-values < 0.05 were considered nominally statistically significant. All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) software version 25.0 for Windows.