Cardiomyopathy in Patients With Acute Ischemic Stroke and Methamphetamine Use: Relevance for Cardioembolic Stroke and Outcome.

BACKGROUND: Methamphetamine use has emerged as a major risk factor for cardiovascular and cerebrovascular disease in young adults. The aim of this study was to investigate a possible association of methamphetamine use with cardioembolic stroke. METHODS AND RESULTS: We performed a retrospective study of patients with acute ischemic stroke admitted at our medical center between 2019 and 2022. All patients were screened for methamphetamine use and cardiomyopathy, defined as left ventricular ejection fraction ≤45%. Among 938 consecutive patients, 46 (4.9%) were identified as using methamphetamine. Compared with the nonmethamphetamine group (n=892), the methamphetamine group was significantly younger (52.8±9.6 versus 69.7±15.2 years; P<0.001), included more men (78.3% versus 52.8%; P<0.001), and had a significantly higher rate of cardiomyopathy (30.4% versus 14.0%; P<0.01). They were also less likely to have a history of atrial fibrillation (8.7% versus 33.4%; P<0.01) or hyperlipidemia (28.3% versus 51.7%; P<0.01). Compared with patients with cardiomyopathy without methamphetamine use, the patients with cardiomyopathy with methamphetamine use had significantly lower left ventricular ejection fraction (26.0±9.59% versus 32.47±9.52%; P<0.01) but better functional outcome at 3 months, likely attributable to significantly younger age and fewer comorbidities. In the logistic regression model of clinical variables, methamphetamine-associated cardiomyopathy was found to be significantly associated with cardioembolic stroke (odds ratio, 1.79 [95% CI, 1.04-3.06]; P<0.05). CONCLUSIONS: We demonstrate that methamphetamine use is significantly associated with cardiomyopathy and cardioembolic stroke in young adults.

Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial.

BACKGROUND: The superiority of balloon angioplasty plus aggressive medical management (AMM) to AMM alone for symptomatic intracranial artery stenosis (sICAS) on efficacy and safety profiles still lacks evidence from randomised controlled trials (RCTs). AIM: To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS. DESIGN: Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) trial is a multicentre, prospective, randomised, open-label, blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS. Patients eligible in BASIS were 35-80 years old, with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis (70%-99%) of a major intracranial artery. The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio. Both groups will receive identical AMM, including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy, intensive risk factor management and life-style modification. All participants will be followed up for 3 years. STUDY OUTCOMES: Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment, is the primary outcome. DISCUSSION: BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients, which may provide an alternative perspective for treating sICAS. TRIAL REGISTRATION NUMBER: NCT03703635; https://www. CLINICALTRIALS: gov.

Rescue therapy after thrombectomy for large vessel occlusion due to underlying atherosclerosis: review of literature.

In this review article, we summarized the current advances in rescue management for reperfusion therapy of acute ischemic stroke from large vessel occlusion due to underlying intracranial atherosclerotic stenosis (ICAS). It is estimated that 24-47% of patients with acute vertebrobasilar artery occlusion have underlying ICAS and superimposed in situ thrombosis. These patients have been found to have longer procedure times, lower recanalization rates, higher rates of reocclusion and lower rates of favorable outcomes than patients with embolic occlusion. Here, we discuss the most recent literature regarding the use of glycoprotein IIb/IIIa inhibitors, angioplasty alone, or angioplasty with stenting for rescue therapy in the setting of failed recanalization or instant/imminent reocclusion during thrombectomy. We also present a case of rescue therapy post intravenous tPA and thrombectomy with intra-arterial tirofiban and balloon angioplasty followed by oral dual antiplatelet therapy in a patient with dominant vertebral artery occlusion due to ICAS. Based on the available literature data, we conclude that glycoprotein IIb/IIIa is a reasonably safe and effective rescue therapy for patients who have had a failed thrombectomy or have residual severe intracranial stenosis. Balloon angioplasty and/or stenting may be helpful as a rescue treatment for patients who have had a failed thrombectomy or are at risk of reocclusion. The effectiveness of immediate stenting for residual stenosis after successful thrombectomy is still uncertain. Rescue therapy does not appear to increase the risk of sICH. Randomized controlled trials are warranted to prove the efficacy of rescue therapy.

Impact of an automated large vessel occlusion detection tool on clinical workflow and patient outcomes.

Purpose: Automated large vessel occlusion (LVO) tools allow for prompt identification of positive LVO cases, but little is known about their role in acute stroke triage when implemented in a real-world setting. The purpose of this study was to evaluate the automated LVO detection tool's impact on acute stroke workflow and clinical outcomes. Materials and methods: Consecutive patients with a computed tomography angiography (CTA) presenting with suspected acute ischemic stroke were compared before and after the implementation of an AI tool, RAPID LVO (RAPID 4.9, iSchemaView, Menlo Park, CA). Radiology CTA report turnaround times (TAT), door-to-treatment times, and the NIH stroke scale (NIHSS) after treatment were evaluated. Results: A total of 439 cases in the pre-AI group and 321 cases in the post-AI group were included, with 62 (14.12%) and 43 (13.40%) cases, respectively, receiving acute therapies. The AI tool demonstrated a sensitivity of 0.96, a specificity of 0.85, a negative predictive value of 0.99, and a positive predictive value of 0.53. Radiology CTA report TAT significantly improved post-AI (mean 30.58 min for pre-AI vs. 22 min for post-AI, p < 0.0005), notably at the resident level (p < 0.0003) but not at higher levels of expertise. There were no differences in door-to-treatment times, but the NIHSS at discharge was improved for the pre-AI group adjusted for confounders (parameter estimate = 3.97, p < 0.01). Conclusion: Implementation of an automated LVO detection tool improved radiology TAT but did not translate to improved stroke metrics and outcomes in a real-world setting.

Intracranial atherosclerosis update for neurointerventionalists.

The management of intracranial atherosclerotic disease (ICAD) has been evolving with advanced imaging, refinements of best medical treatment, and the development of endovascular options. There has been a significant increase in the use of endovascular therapy for symptomatic ICAD in the USA over the past 6 years. The rationale for this review is to update neurointerventionalists in these areas so that evidence-based decisions can be considered when counseling potential patients regarding their risks, benefits, and potential complications. The landmark SAMMPRIS trial demonstrated superiority of aggressive medical management (AMM) over intracranial stenting as an initial treatment. However, the risk of disabling or fatal stroke remains high in patients presenting with stroke treated with AMM. Recent studies showed a significantly lower rate of periprocedural complications from intracranial stenting. Patients who have failed medical treatment may therefore benefit from intracranial stenting, particularly in those with hemodynamic compromise and large vessel embolic stroke. Drug coated angioplasty balloons and drug eluting stents may potentially reduce the risk of in-stent re-stenosis. Large vessel occlusion (LVO) due to underlying ICAD is seen in a subset of thrombectomy-eligible patients. The use of stenting as a rescue therapy in LVO thrombectomy has also shown promising early results.

Methamphetamine use increases the risk of cerebral small vessel disease in young patients with acute ischemic stroke.

Methamphetamine use causes spikes in blood pressure. Chronic hypertension is a major risk factor for cerebral small vessel disease (cSVD). The aim of this study is to investigate whether methamphetamine use increases the risk of cSVD. Consecutive patients with acute ischemic stroke at our medical center were screened for methamphetamine use and evidence of cSVD on MRI of the brain. Methamphetamine use was identified by self-reported history and/or positive urine drug screen. Propensity score matching was used to select non-methamphetamine controls. Sensitivity analysis was performed to assess the effect of methamphetamine use on cSVD. Among 1369 eligible patients, 61 (4.5%) were identified to have a history of methamphetamine use and/or positive urine drug screen. Compared with the non-methamphetamine group (n = 1306), the patients with methamphetamine abuse were significantly younger (54.5 ± 9.7 vs. 70.5 ± 12.4, p < 0.001), male (78.7% vs. 54.0%, p < 0.001) and White (78.7% vs. 50.4%, p < 0.001). Sensitivity analysis showed that methamphetamine use was associated with increased white matter hyperintensities, lacunes, and total burden of cSVD. The association was independent of age, sex, concomitant cocaine use, hyperlipidemia, acute hypertension, and stroke severity. Our findings suggest that methamphetamine use increases the risk of cSVD in young patients with acute ischemic stroke.

Head-to-head comparison of commercial artificial intelligence solutions for detection of large vessel occlusion at a comprehensive stroke center.

Purpose: Despite the availability of commercial artificial intelligence (AI) tools for large vessel occlusion (LVO) detection, there is paucity of data comparing traditional machine learning and deep learning solutions in a real-world setting. The purpose of this study is to compare and validate the performance of two AI-based tools (RAPID LVO and CINA LVO) for LVO detection. Materials and methods: This was a retrospective, single center study performed at a comprehensive stroke center from December 2020 to June 2021. CT angiography (n = 263) for suspected stroke were evaluated for LVO. RAPID LVO is a traditional machine learning model which primarily relies on vessel density threshold assessment, while CINA LVO is an end-to-end deep learning tool implemented with multiple neural networks for detection and localization tasks. Reasons for errors were also recorded. Results: There were 29 positive and 224 negative LVO cases by ground truth assessment. RAPID LVO demonstrated an accuracy of 0.86, sensitivity of 0.90, specificity of 0.86, positive predictive value of 0.45, and negative predictive value of 0.98, while CINA demonstrated an accuracy of 0.96, sensitivity of 0.76, specificity of 0.98, positive predictive value of 0.85, and negative predictive value of 0.97. Conclusion: Both tools successfully detected most anterior circulation occlusions. RAPID LVO had higher sensitivity while CINA LVO had higher accuracy and specificity. Interestingly, both tools were able to detect some, but not all M2 MCA occlusions. This is the first study to compare traditional and deep learning LVO tools in the clinical setting.

Intracranial Arterial Calcifications: Potential Biomarkers of Stroke Risk and Outcome.

Intracranial artery calcifications (IAC), a common and easily identifiable finding on computed tomorgraphy angiography (CTA), has gained recognition as a possible risk factor for ischemic stroke. While atherosclerosis of intracranial arteries is believed to be a mechanism that commonly contributes to ischemic stroke, and coronary artery calcification is well-established as a predictor of both myocardial infarction (MI) and ischemic stroke risk, IAC is not currently used as a prognostic tool for stroke risk or recurrence. This review examines the pathophysiology and prevalence of IAC, and current evidence suggesting that IAC may be a useful tool for prediction of stroke incidence, recurrence, and response to acute ischemic stroke therapy.

Point-of-Care Brain MRI: Preliminary Results from a Single-Center Retrospective Study.

Background Point-of-care (POC) MRI is a bedside imaging technology with fewer than five units in clinical use in the United States and a paucity of scientific studies on clinical applications. Purpose To evaluate the clinical and operational impacts of deploying POC MRI in emergency department (ED) and intensive care unit (ICU) patient settings for bedside neuroimaging, including the turnaround time. Materials and Methods In this preliminary retrospective study, all patients in the ED and ICU at a single academic medical center who underwent noncontrast brain MRI from January 2021 to June 2021 were investigated to determine the number of patients who underwent bedside POC MRI. Turnaround time, examination limitations, relevant findings, and potential CT and fixed MRI findings were recorded for patients who underwent POC MRI. Descriptive statistics were used to describe clinical variables. The Mann-Whitney U test was used to compare the turnaround time between POC MRI and fixed MRI examinations. Results Of 638 noncontrast brain MRI examinations, 36 POC MRI examinations were performed in 35 patients (median age, 66 years [IQR, 57-77 years]; 21 women), with one patient undergoing two POC MRI examinations. Of the 36 POC MRI examinations, 13 (36%) occurred in the ED and 23 (64%) in the ICU. There were 12 of 36 (33%) POC MRI examinations interpreted as negative, 14 of 36 (39%) with clinically significant imaging findings, and 10 of 36 (28%) deemed nondiagnostic for reasons such as patient motion. Of 23 diagnostic POC MRI examinations with comparison CT available, three (13%) demonstrated acute infarctions not apparent on CT scans. Of seven diagnostic POC MRI examinations with subsequent fixed MRI examinations, two (29%) demonstrated missed versus interval subcentimeter infarctions, while the remaining demonstrated no change. The median turnaround time of POC MRI was 3.4 hours in the ED and 5.3 hours in the ICU. Conclusion Point-of-care (POC) MRI was performed rapidly in the emergency department and intensive care unit. A few POC MRI examinations demonstrated acute infarctions not apparent at standard-of-care CT examinations. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Anzai and Moy in this issue.

Blood Pressure and Spot Sign in Spontaneous Supratentorial Subcortical Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage is a potentially devastating cause of brain injury, often occurring secondary to hypertension. Contrast extravasation on computed tomography angiography (CTA), known as the spot sign, has been shown to predict hematoma expansion and worse outcomes. Although hypertension has been associated with an increased rate of the spot sign being present, the relationship between spot sign and blood pressure has not been fully explored. METHODS: We retrospectively analyzed data from 134 patients (40 women and 94 men, mean age 62.3 ± 15.73 years) presenting to a tertiary academic medical center with spontaneous supratentorial subcortical intracerebral hemorrhage from 1/1/2018 to 1/4/2021. RESULTS: A spot sign was demonstrated in images of 18 patients (13.43%) and correlated with a higher intracerebral hemorrhage score (2.61 ± 1.42 vs. 1.31 ± 1.25, p = 0.002), larger hematoma volume (53.49cm3 ± 32.08 vs. 23.45cm3 ± 25.65, p = 0.001), lower Glasgow Coma Scale on arrival (9.06 ± 4.56 vs. 11.74 ± 3.65, p = 0.027), increased risk of hematoma expansion (16.67% vs. 5.26%, p = 0.042), and need for surgical intervention (66.67% vs. 15.52%, p < 0.001). We did not see a correlation with age, sex, or underlying comorbidities. The presence of spot sign correlated with higher modified Rankin scores at discharge (4.94 ± 1.00 vs. 3.92 ± 1.64, p < 0.001). We saw significantly higher systolic blood pressure at the time of CTA in patients with a spot sign (184 mm Hg ± 43.11 vs. 153 mm Hg ± 36.99, p = 0.009) and the highest recorded blood pressure (p = 0.019), although not blood pressure on arrival (p = 0.081). Performing CTA early in the process of blood pressure lowering was associated with a spot sign (p < 0.001). CONCLUSIONS: The presence of spot sign correlates with larger hematomas, worse outcomes, and increased surgical intervention. There is a significant association between spot sign and systolic blood pressure at the time of CTA, with the highest systolic blood pressure being recorded prior to CTA. Although the role of intensive blood pressure management in spontaneous intracerebral hemorrhage remains a subject of debate, patients with a spot sign may be a subgroup that could benefit from this.

Contemporary antiplatelet therapy for secondary stroke prevention: a narrative review of current literature and guidelines.

Antiplatelet therapy is one of the mainstays for secondary stroke prevention. This narrative review aimed to highlight the current evidence and recommendations of antiplatelet therapy for stroke prevention.We conducted advanced literature search for antiplatelet therapy. Landmark studies and randomised controlled trials evaluating antiplatelet therapy for secondary stroke prevention are reviewed. Results from Cochrane systematic review, pooled data analysis and meta-analysis are discussed.Single-antiplatelet therapy (SAPT) with aspirin, aspirin/extended-release dipyridamole or clopidogrel reduces the risk of recurrent ischaemic stroke in patients with non-cardioembolic ischaemic stroke or transient ischaemic attack (TIA). Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute noncardioembolic ischaemic stroke or high-risk TIA. Prolonged use of DAPT is associated with higher risk of haemorrhage without reduction in stroke recurrence than SAPT. Compared with placebo, aspirin reduces the relative risk of recurrent stroke by approximately 22%. Aspirin/dipyridamole and cilostazol are superior to aspirin but associated with significant side effects. Cilostazol or ticagrelor might be more effective than aspirin or clopidogrel in patients with intracranial stenosis.SAPT is indicated for secondary stroke prevention in patients with non-cardioembolic ischaemic stroke or TIA. DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days followed by SAPT is recommended for patients with minor acute noncardioembolic stroke or high-risk TIA. Selection of appropriate antiplatelet therapy should also be based on compliance, drug tolerance or resistance.

Endovascular Thrombectomy for Acute Basilar Artery Occlusion: Latest Findings and Critical Thinking on Future Study Design.

Randomized controlled trials (RCTs) have demonstrated powerful efficacy of endovascular thrombectomy (EVT) for large vessel occlusion in the anterior circulation. The effect of EVT for acute basilar artery occlusion (BAO) in the posterior circulation remains unproven. Here, we highlight the latest findings of observational studies and RCTs of EVT for BAO, with a focus on the predictors of functional outcomes, the limitations of recent RCTs, and critical thinking on future study design. Pooled data from large retrospective studies showed 36.4% favorable outcome at 3 months and 4.6% symptomatic intracranial hemorrhage (sICH). Multivariate logistic regression analysis revealed that higher baseline NIHSS score, pc-ASPECTS < 8, extensive baseline infarction, large pontine infarct, and sICH were independent predictors of poor outcome. Two recent randomized trial BEST (Endovascular treatment vs. standard medical treatment for vertebrobasilar artery occlusion) and BASICS (Basilar Artery International Cooperation Study) failed to demonstrate significant benefit of EVT within 6 or 8 h after stroke symptom onset. The limitations of these studies include slow enrollment, selection bias, high crossover rate, and inclusion of patients with mild deficit. To improve enrollment and minimize risk of diluting the overall treatment effect, futile recanalization and re-occlusion, optimal inclusion/exclusion criteria, including enrollment within 24 h of last known well, NIHSS score ≥ 10, pc-ASPECTS ≥ 8, no large pontine infarct, and the use of rescue therapy for underlying atherosclerotic stenosis, should be considered for future clinical trials.

Comparative Studies of Cerebral Reperfusion Injury in the Posterior and Anterior Circulations After Mechanical Thrombectomy.

Cerebral reperfusion injury is the major complication of mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Contrast extravasation (CE) and intracranial hemorrhage (ICH) are the key radiographical features of cerebral reperfusion injury. The aim of this study was to investigate CE and ICH after MT in the anterior and posterior circulation, and their effect on functional outcome. This is a retrospective study of all consecutive patients who were treated with MT for AIS at University of California Irvine Medical Center between January 1, 2014, and December 31, 2017. Patient characteristics, clinical features, procedural variables, contrast extravasation, ICH, and outcomes after MT were analyzed. A total of 131 patients with anterior circulation (AC) stroke and 25 patients with posterior circulation (PC) stroke underwent MT during the study period. There was no statistically significant difference in admission NIHSS score, blood pressure, rate of receiving intravenous tPA, procedural variables, contrast extravasation, and symptomatic ICH between the 2 groups. Patients with PC stroke had a similar rate of favorable outcome (mRS 0-2) but significantly higher mortality (40.0% vs. 10.7%, p < 0.01) than patients with AC stroke. Multivariate regression analysis identified initial NIHSS score (OR 1.1, CI 1.0-1.2, p = 0.01), number of passes with stent retriever (OR 2.1, CI 1.3-3.6, p < 0.01), and PC stroke (OR 9.3, CI 2.5-35.1, p < 0.01) as independent risk factors for death. There was no significant difference in functional outcomes between patients with and without evidence of cerebral reperfusion injury after MT. We demonstrated that AC and PC stroke had similar rates of cerebral reperfusion injury and favorable outcome after MT. Cerebral reperfusion injury is not a significant independent risk factor for poor functional outcome.

Comparison of Drug-Eluting Stent With Bare-Metal Stent in Patients With Symptomatic High-grade Intracranial Atherosclerotic Stenosis: A Randomized Clinical Trial.

Importance: In-stent restenosis (ISR) is the primary reason for stroke recurrence after intracranial stenting in patients who were treated with a standard bare-metal stent (BMS). Whether a drug-eluting stent (DES) could reduce the risk of ISR in intracranial atherosclerotic stenosis (ICAS) remains unclear. Objective: To investigate whether a DES can reduce the risk of ISR and stroke recurrence in patients with symptomatic high-grade ICAS. Design, Settings, and Participants: A prospective, multicenter, open-label randomized clinical trial with blinded outcome assessment was conducted from April 27, 2015, to November 16, 2018, at 16 medical centers in China with a high volume of intracranial stenting. Patients with symptomatic high-grade ICAS were enrolled, randomized, and followed up for 1 year. Intention-to-treat data analysis was performed from April 1 to May 22, 2021. Interventions: Patients were randomly assigned to receive DES (NOVA intracranial sirolimus-eluting stent system) or BMS (Apollo intracranial stent system) treatment in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy end point was ISR within 1 year after the procedure, which was defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to (within 5 mm) the implanted stent. The primary safety end point was any stroke or death within 30 days after the procedure. Results: A total of 263 participants (194 men [73.8%]; median [IQR] age, 58 [52-65] years) were included in the analysis, with 132 participants randomly assigned to the DES group and 131 to the BMS group. The 1-year ISR rate was lower in the DES group than in the BMS group (10 [9.5%] vs 32 [30.2%]; odds ratio, 0.24; 95% CI, 0.11-0.52; P < .001). The DES group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year (1 [0.8%] vs 9 [6.9%]; hazard ratio, 0.10; 95% CI, 0.01-0.80; P = .03). No significant difference in the rate of any stroke or death within 30 days was observed between the DES and BMS groups (10 [7.6%] vs 7 [5.3%]; odds ratio, 1.45; 95% CI, 0.54-3.94; P = .46). Conclusions and Relevance: This trial found that, compared with BMSs, DESs reduced the risks of ISR and ischemic stroke recurrence in patients with symptomatic high-grade ICAS. Further investigation into the safety and efficacy of DESs is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02578069.

A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy.

Pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3' untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

Left Atrial Dilatation and Reduced Left Ventricular Ejection Fraction Are Associated With Cardioembolic Stroke.

Objective: Left atrial (LA) dilatation and heart failure are independent risk factors for ischemic stroke. The goal of this study is to evaluate the association between LA dilatation and reduced left ventricular ejection fraction (EF) with cardioembolic stroke. Methods: Four hundred fifty-three patients with ischemic stroke admitted to the University of California, Irvine between 2016 and 2017 were included based on the following criteria: age >18 and availability of echocardiogram. Stroke was categorized into cardioembolic and non-cardioembolic. EF was categorized into normal: 52-72% (male), 54-74% (female), mildly abnormal: 41-51% (male), 41-53% (female), moderately abnormal: 30-40%, and severely abnormal: <30%. LA volume was categorized into normal (≤34 ml/m2) vs. enlarged (≥35 ml/m2). Other variables included gender, hypertension [systolic blood pressure (SBP) ≥ 140 or diastolic blood pressure (DBP) ≥ 90], and known history of atrial fibrillation (Afib). Results: Two hundred eighteen patients had cardioembolic, and 235 had non-cardioembolic stroke. Among patients with cardioembolic stroke, 49 (22.4%) and 142 (65%) had reduced EF and enlarged LA, respectively, as compared with 19 (8.1%) and 65 (27.7%) patients with non-cardioembolic stroke (p < 0.0001). The odds of cardioembolic stroke were 2.0 (95% CI: 0.1-6.0) and 8.8 times (95% CI: 1.9-42.3) higher in patients with moderately and severely reduced EF, respectively, than in patients with normal EF. The odds of cardioembolic stroke was 2.4 times (95% CI: 1.5-3.9) higher in patients with enlarged LA than in patients with normal LA size. Compared with patients with normal LA and EF, patients with combined enlarged LA and reduced EF had significantly higher rates of Afib (43.4 vs. 9.0%, p < 0.0001) and cardioembolic stroke (78.3 vs. 43.4%, p < 0.0001). Conclusions: LA dilatation along with reduced EF is a reliable predictor of Afib and cardioembolic stroke. Further studies are warranted to determine the benefit of anticoagulation for secondary stroke prevention in such patient population.