Background and Purpose-Occult paroxysmal atrial fibrillation (AF) is found in a substantial minority of patients with cryptogenic stroke. Identifying reliable predictors of paroxysmal AF after cryptogenic stroke would allow clinicians to more effectively use outpatient cardiac monitoring and ultimately reduce secondary stroke burden. Methods-We analyzed a retrospective cohort of consecutive patients who underwent 28-day mobile cardiac outpatient telemetry after cryptogenic stroke or transient ischemic stroke. Univariate and multivariable analyses were performed to identify clinical, echocardiographic, and radiographic features associated with the detection of paroxysmal AF. Results-Of 227 patients with cryptogenic stroke (179) or transient ischemic stroke (48), 14% (95% confidence interval, 9%-18%) had AF detected on mobile cardiac outpatient telemetry, 58% of which was ≥30 seconds in duration. Age >60 years (odds ratio, 3.7; 95% confidence interval, 1.3-11) and prior cortical or cerebellar infarction seen on neuroimaging (odds ratio, 3.0; 95% confidence interval, 1.2-7.6) were independent predictors of AF. AF was detected in 33% of patients with both factors, but only 4% of patients with neither. No other clinical features (including demographics, CHA 2 DS 2 -VASc [combined stroke risk score: congestive heart failure, hypertension, age, diabetes, prior stroke/transient ischemic attack, vascular disease, sex] score, or stroke symptoms), echocardiographic findings (including left atrial size or ejection fraction), or radiographic characteristics of the acute infarction (including location, topology, or number) were associated with AF detection. Conclusions-Mobile cardiac outpatient telemetry detects AF in a substantial proportion of cryptogenic stroke patients. Age >60 years and radiographic evidence of prior cortical or cerebellar infarction are robust indicators of occult AF. Patients with neither had a low prevalence of AF.

Background and Purpose Enhanced angiogenesis facilitates neurovascular remodeling processes and promotes brain functional recovery after stroke. Previous studies from our laboratory demonstrated that valproate (VPA), a histone deacetylase (HDAC) inhibitor, protects against experimental brain ischemia. The present study investigated whether VPA could enhance angiogenesis and promote long-term functional recovery after ischemic stroke. Methods Male rats underwent middle cerebral artery occlusion (MCAO) for 60 minutes followed by reperfusion for up to 14 days. Assessed parameters were: locomotor function via rotarod test; infarct volume via T2-weighted magnetic resonance imaging; microvessel density via immunohistochemistry; relative cerebral blood flow (rCBF) via perfusion-weighted imaging; protein levels of pro-angiogenic factors via Western blotting; and matrix metalloproteinase (MMP)-2/9 activities via gelatin zymography. Results Post-ischemic VPA treatment robustly improved the rotarod performance of MCAO rats on days 7 and 14 after ischemia, and significantly reduced brain infarction on day 14. Concurrently, VPA markedly enhanced microvessel density, facilitated endothelial cell proliferation, and increased rCBF in the ipsilateral cortex. The transcription factor hypoxia-inducible factor (HIF)-1α and its downstream pro-angiogenic factors, vascular endothelial growth factor (VEGF) and MMP-2/9, were upregulated after MCAO and significantly potentiated by VPA in the ipsilateral cortex. Acetylation of histone-H3 and H4 was robustly increased by chronic VPA treatment. The beneficial effects of VPA on rotarod performance and microvessel density were abolished by HIF-1α inhibition. Conclusions Chronic VPA treatment enhances angiogenesis and promotes functional recovery after brain ischemia. These effects may involve HDAC inhibition and upregulation of HIF-1α and its downstream pro-angiogenic factors VEGF and MMP-2/9.