External Validation of SAFE Score to Predict Atrial Fibrillation Diagnosis after Ischemic Stroke: A Retrospective Multicenter Study.

Introduction: The screening for atrial fibrillation (AF) scale (SAFE score) was recently developed to provide a prediction of the diagnosis of AF after an ischemic stroke. It includes 7 items: age ≥ 65 years, bronchopathy, thyroid disease, cortical location of stroke, intracranial large vessel occlusion, NT-ProBNP ≥250 pg/mL, and left atrial enlargement. In the internal validation, a good performance was obtained, with an AUC = 0.88 (95% CI 0.84-0.91) and sensitivity and specificity of 83% and 80%, respectively, for scores ≥ 5. The aim of this study is the external validation of the SAFE score in a multicenter cohort. Methods: A retrospective multicenter study, including consecutive patients with ischemic stroke or transient ischemic attack between 2020 and 2022 with at least 24 hours of cardiac monitoring. Patients with previous AF or AF diagnosed on admission ECG were excluded. Results: Overall, 395 patients were recruited for analysis. The SAFE score obtained an AUC = 0.822 (95% CI 0.778-0.866) with a sensitivity of 87.2%, a specificity of 65.4%, a positive predictive value of 44.1%, and a negative predictive value of 94.3% for a SAFE score ≥ 5, with no significant gender differences. Calibration analysis in the external cohort showed an absence of significant differences between the observed values and those predicted by the model (Hosmer-Lemeshow's test 0.089). Conclusions: The SAFE score showed adequate discriminative ability and calibration, so its external validation is justified. Further validations in other external cohorts or specific subpopulations of stroke patients might be required.

Experience and insights from a prolonged electrocardiographic monitorization with a wearable system after an embolic stroke of unknown source.

BACKGROUND: Embolic cerebrovascular events that remain of unknown etiology after a thorough diagnostic evaluation, are known as Embolic Strokes of Undetermined Source (ESUS). Subclinical atrial fibrillation (AF) represents a significant underlying cause of ESUS. Our aims were to examine the overall diagnostic yield of a prolonged cardiac monitoring wearable system (PCMw) after an ESUS to detect AF and factors associated with it, including the time frame from the ESUS event to PCMw initiation. Additionally, to evaluate the frequency of unexpected arrhythmic events (UAE) and their prognostic implications. METHODS: We retrospectively analyzed 200 ECG recordings (3-leads, 30 days duration) by means of a PCMw in patients with an ESUS to detect AF lasting longer than 30 s, between 2017 and 2021. UAE were defined as arrhythmia events that were not correlated to the main reason of prolonged cardiac monitoring. RESULTS: AF was detected in 21 patients (10.5%). Patients with AF had more left atrial enlargement (OR = 4.22 [1.59-6.85]; p = .01) and atrial arrythmias in the initial 24-h Holter during hospitalization (OR = 5.73 [2.03-16.49]; p = .001). The detection of AF was significatively higher if the PCMw was worn within the first 30 days after the ESUS compared to beyond 30 days (17% vs. 10.3%; p = .002). Fifty three patients (26.5%) had UAE during PCMw. In six of them these findings led to targeted treatment. CONCLUSION: PCMw represents a feasible non-invasive device that could reliably detect subclinical AF episodes after an ESUS. Diagnostic yield was significatively higher when used within the first 30 days after the event, especially in selected patients. UAE were common, but did not impact prognosis.

Neutrophil ß1 adrenoceptor blockade blunts stroke-associated neuroinflammation.

BACKGROUND AND PURPOSE: Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil ß1 adrenoceptors (ß1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that ß1AR blockade will improve stroke outcomes. EXPERIMENTAL APPROACH: Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective ß1AR blocker metoprolol (12.5 mg·kg-1 ) when injected i.v. 10 min before reperfusion. KEY RESULTS: Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1+ ). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via ß1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil-depleted rats upon stroke. In patients suffering an ischaemic stroke, ß1AR blockade by metoprolol reduced circulating neutrophil-platelet co-aggregates. CONCLUSIONS AND IMPLICATIONS: Our findings describe that ß1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.

Fewer COVID-19-associated strokes and reduced severity during the second COVID-19 wave: The Madrid Stroke Network.

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.

[High frequency of endoluminal thrombus in patients with ischaemic stroke following COVID-19]. / Alta Frecuencia de Trombo Endoluminal en pacientes con ictus isquémico tras la infección por Coronavirus 2019.

BACKGROUND: Ischaemic stroke may be a major complication of SARS-CoV-2 infection.Studying and characterising the different aetiological subtypes, clinical characteristics, and functional outcomes may be valuable in guiding patient selection for optimal management and treatment. METHODS: Data were collected retrospectively on consecutive patients with COVID-19 who developed acute focal brain ischaemia (between 1 March and 19 April 2020) at a tertiary university hospital in Madrid (Spain). RESULTS: During the study period, 1594 patients were diagnosed with COVID-19. We found 22 patients with ischaemic stroke (1.38%), 6 of whom did not meet the inclusion criteria. The remaining 16 patients were included in the study (15 cases of ischaemic stroke and one case of transient ischaemic attack).Median baseline National Institutes of Health Stroke Scale score was 9 (interquartile range: 16), and mean (standard deviation) age was 73 years (12.8). Twelve patients (75%) were men. Mean time from COVID-19 symptom onset to stroke onset was 13 days. Large vessel occlusion was identified in 12 patients (75%).We detected elevated levels of D-dimer in 87.5% of patients and C-reactive protein in 81.2%. The main aetiology was atherothrombotic stroke (9 patients, 56.3%), with the predominant subtype being endoluminal thrombus (5 patients, 31.2%), involving the internal carotid artery in 4 cases and the aortic arch in one. The mortality rate in our series was 44% (7 of 16 patients). CONCLUSIONS: In patients with COVID-19, the most frequent stroke aetiology was atherothrombosis, with a high proportion of endoluminal thrombus (31.2% of patients). Our clinical and laboratory data support COVID-19-associated coagulopathy as a relevant pathophysiological mechanism for ischaemic stroke in these patients.

Stroke Acute Management and Outcomes During the COVID-19 Outbreak: A Cohort Study From the Madrid Stroke Network.

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has added challenges to providing quality acute stroke care due to the reallocation of stroke resources to COVID-19. Case series suggest that patients with COVID-19 have more severe strokes; however, no large series have compared stroke outcomes with contemporary non-COVID-19 patients. Purpose was to analyze the impact of COVID-19 pandemic in stroke care and to evaluate stroke outcomes according to the diagnosis of COVID-19. METHODS: Retrospective multicenter cohort study including consecutive acute stroke patients admitted to 7 stroke centers from February 25 to April 25, 2020 (first 2 months of the COVID-19 outbreak in Madrid). The quality of stroke care was measured by the number of admissions, recanalization treatments, and time metrics. The primary outcome was death or dependence at discharge. RESULTS: A total of 550 acute stroke patients were admitted. A significant reduction in the number of admissions and secondary interhospital transfers was found. COVID-19 was confirmed in 105 (19.1%) patients, and a further 19 patients were managed as suspected COVID-19 (3.5%). No differences were found in the rates of reperfusion therapies in ischemic strokes (45.5% non-COVID-19, 35.7% confirmed COVID-19, and 40% suspected COVID-19; P=0.265). However, the COVID-19 group had longer median door-to-puncture time (110 versus 80 minutes), which was associated with the performance of chest computed tomography. Multivariate analysis confirmed poorer outcomes for confirmed or suspected COVID-19 (adjusted odds ratios, 2.05 [95% CI, 1.12-3.76] and 3.56 [95% CI, 1.15-11.05], respectively). CONCLUSIONS: This study confirms that patients with COVID-19 have more severe strokes and poorer outcomes despite similar acute management. A well-established stroke care network helps to diminish the impact of such an outbreak in stroke care, reducing secondary transfers and allowing maintenance of reperfusion therapies, with a minor impact on door-to-puncture times, which were longer in patients who underwent chest computed tomography.

Prehospital selection of thrombectomy candidates beyond large vessel occlusion: M-DIRECT scale.

OBJECTIVE: Current prehospital scales used to detect large vessel occlusion reveal very low endovascular thrombectomy (EVT) rates among selected patients. We developed a novel prehospital scale, the Madrid-Direct Referral to Endovascular Center (M-DIRECT), to identify EVT candidates for direct transfer to EVT-capable centers (EVT-Cs). The scale evaluated clinical examination, systolic blood pressure, and age. Since March 2017, patients closer to a stroke unit without EVT capabilities and an M-DIRECT positive score have been transferred to the nearest EVT-C. To test the performance of the scale-based routing protocol, we compared its outcomes with those of a simultaneous cohort of patients directly transferred to an EVT-C. METHODS: In this prospective observational study of consecutive patients with stroke code seen by emergency medical services, we compared diagnoses, treatments, and outcomes of patients who were closer to an EVT-C (mothership cohort) with those transferred according to the M-DIRECT score (M-DIRECT cohort). RESULTS: The M-DIRECT cohort included 327 patients and the mothership cohort 214 patients. In the M-DIRECT cohort, 227 patients were negative and 100 were positive. Twenty-four (10.6%) patients required secondary transfer, leaving 124 (38%) patients from the M-DIRECT cohort admitted to an EVT-C. EVT rates were similar for patients with ischemic stroke in both cohorts (30.9% vs 31.5%). The M-DIRECT scale had 79% sensitivity, 82% specificity, and 53% positive predictive value for EVT. Recanalization and independence rates at 3 months did not differ between the cohorts. CONCLUSIONS: The M-DIRECT scale was highly accurate for EVT, with treatment rates and outcomes similar to those of a mothership paradigm, thereby avoiding EVT-C overload with a low rate of secondary transfers.

[Multiple coronary embolisms in a woman with risk factors for thromboembolic disease]. / Embolismo coronario múltiple en una mujer con factores de riesgo pra enfermedad tromboembólica.

We report the case of a 33-years-old woman, smoker and taking oral contraceptives, who presented to the emergency room with an anterior ST-elevation myocardial infarction. Thrombolytic treatment was initiated and a few minutes after, chest pain returned and an inferior ST-segment-elevation infarction was diagnosed at that moment. Catheterization revealed multiple embolic occlusion of coronary branches. We discuss tests performed and pathophysiology of myocardial infarction in this patient.