Risk Of Future Ischemic Stroke Research Articles

Comparison between Novel and Conventional Electrocardiographic Markers of Atrial Cardiomyopathy for identification of Persons at Risk for Ischemic Stroke

Abstract Background Atrial cardiomyopathy is associated with increased risk for future atrial fibrillation (AF) and ischemic stroke. Several ECG-derived parameters have been reported to assess the risk for future ischemic stroke. Purpose To predict risk of future ischemic stroke by comparison of the novel parameter duration of the amplified digital sinus-p-wave (APWD; 80mm/mV; 175mm/sec) vs previously described p-wave indices and clinical risk factors (cerebrovascular disease (CVD), CHADS-VASc-score). Methods P-wave-derived parameters were measured on digital 12-lead-sinus-ECGs (recorded +/- 6 months from the clinical stroke event) using the software "ECG-Precision-Analysis V-1-2023". and clinical CHA2DS2-VASc Score was assessed in 80 patients with ischemic stroke (no history of AF, no oral anticoagulation (OAC)) and compared to 80 control patients (without OAC, AF or ischemic stroke within the next five years). Results Patients with ischemic stroke vs control patients presented a higher CHA2DS2-VASc Score (3.7 vs 3.2, p=0.04), had more frequently heart failure (25% vs 13%, p=0.04) and cerebrovascular atherosclerotic disease with stenosis >40% ((22.5% vs 10%, p=0.032). P-wave indices were as follows in patients who developed ischemic stroke within the next 12 months versus patients without stroke within a follow-up period of five years, respectively: APWD (144 vs 128ms, p<0.0001), non-amplified SPWD (118 vs 116ms, p=0.081), A-PTF-V1 (-4660 vs -3860µV*ms, p=0.005), durations and amplitudes of terminal-p-wave in V1 (A-Duration-V1 (83 vs 79ms, p=0.119), A-Amplitude-V1 (-50µV vs -50µV, p=0.028), and advanced interatrial block (aIAB in 25% vs 3.8% of patients; p<0.0001. The novel ECG-derived parameter (duration of the amplified sinus-P-wave >140ms) was the best predictor for future ischemic stroke (accuracy: 74%, sensitivity and specificity: 61% and 86%, respectively; PPV: 82%; area under ROC: 0.776). Sensitivity and specificity of the SPWD, aPTFV1 and aIAB were significantly lower (SPWD>120ms: sensitivity 35% and specificity 78%, PPV: 61%; aPTFV1 ≤-5000µV*ms, accuracy: 61%, sensitivity 46%% and specificity 75%, PPV: 65%; aIAB: accuracy: 61%, sensitivity 25% and specificity 96%, PPV: 87%). Conclusions Among the currently identified ECG markers of atrial cardiomyopathy, the novel APWD and advanced interatrial block have the best predictive performances for diagnosis of persons at risk for ischemic stroke.Comparison between ECG ParametersPredictive Accuracy of Parameters

Stroke risk assessment in different atrial fibrillation subtypes: CHA2DS2-VASc score and beyond

Abstract Background Patients with atrial fibrillation (AF) have been known to have an inhomogeneous risk of stroke, with several well-documented risk factors including hypertension, history of stroke, and diabetes mellitus that have been incorporated into the CHA2DS2–VASc score to stratify risk levels. Accumulating evidence has suggested that AF subtype, namely persistent AF and paroxysmal AF, also have an impact on stroke development. Purpose This study focused on the impact of AF subtype on stroke risk in a large, long-term follow-up cohort as to provide insight of the impact on ischemic stroke risks. Such findings may play a role in future ischemic stroke risk stratification in selected patients. Methods A total of 7346 AF patients were followed up for 10 years from January 2010 to December 2020 (mean follow-up time 2.74 years). Among these patients, 2460 (33.5%) had persistent or permanent AF (PerAF) and 4886 (66.5%) had paroxysmal AF (PAF). The study evaluated the risk of ischemic stroke between the two groups using Cox models adjusting for all components of the CHA2DS2–VASc score. Analyses were further stratified into the usage of oral anticoagulation (OAC) or no OAC. Results Comparing AF patients based on subtype, it was found that PerAF patients were older, had a higher prevalence of previous stroke, congestive heart failure, PAD, DM, and were more often prescribed anticoagulants. Univariate analysis found patients with PerAF at a higher risk for ischemic stroke (HR 1.262, p<0.001). The results remained significant after multivariate analysis with factors of the CHA2DS2–VASc score (HR 1.234, p<0.001). After stratifying patients according to anticoagulation prescription, PerAF and PAF patients were found to have similar rates of developing ischemic stroke in patients under DOAC. Conclusions Patients with PerAF have a higher risk of stroke during follow-up independent of components of the CHA2DS2VASc score. In patients with OAC use, there was no difference in stroke risk between AF subtypes.Stroke Risk in OAC-naive patientsStroke Risk in OAC-experienced patients

Abstract WP158: Cortical Superficial Siderosis is Associated With Ischemia After Intracerebral Hemorrhage

Background: Ischemia on diffusion weighted imaging (DWI) after intracerebral hemorrhage (ICH) increases the risk of future ischemic stroke. Radiographic markers of small vessel disease, including cerebral microbleeds (CMB), are associated with DWI lesions. Though cortical superficial siderosis (cSS) is also a hemorrhagic small vessel disease subtype, it is unclear if cSS similarly relates to DWI lesions. We hypothesized that cSS would represent a more severe phenotype of small vessel disease and would associate with DWI lesions after ICH independent to other small vessel disease markers. Methods: Using the Intracerebral Hemorrhage Outcomes Project (ICHOP), we included all cases of spontaneous ICH who underwent DWI and susceptibility imaging/gradient echo. DWI hyperintensities were identified if >10mm from the hematoma with decreased ADC signal. cSS were identified as subarachnoid hemosiderin deposition without acute subarachnoid hemorrhage. The relationship of cSS with DWI lesion presence as the outcome was assessed with logistic regression adjusted for ICH score, blood pressure change within 24 hours, and small vessel disease markers (CMB and white matter hyperintensity). Sensitivity analyses were performed to adjust for demographics and ICH location. A secondary analysis using linear regression assessed the association with the number of DWI lesions adjusted for similar covariates. Results: Of 198 patients analyzed, DWI lesions were observed in 31.3% and cSS in 10.6%. The presence of cSS was associated with DWI lesions (adjusted OR 3.72, CI: 1.29-10.72), independent of other small vessel disease markers. Separate sensitivity analyses adjusting for sex, race, and ICH location did not change the association of cSS with DWI lesions. In secondary analyses, cSS was not associated with greater number of DWI lesions counts (b 0.213, CI -0.53-0.63). Discussion: cSS is associated with the presence of DWI lesions, independent to other small vessel disease markers. cSS may represent a severe phenotype of small vessel disease with a risk of ICH recurrence and ischemia. Further work is required to investigate underlying mechanisms and optimal strategies to mitigate competing risks of future hemorrhage and ischemic events in these patients.

Cerebral microbleeds and asundexian in non-cardioembolic ischemic stroke: Secondary analyses of the PACIFIC-STROKE randomized trial.

Cerebral microbleeds are magnetic imaging resonance (MRI) markers of hemorrhage-prone cerebral small vessel disease that predict future risk of ischemic stroke and intracranial hemorrhage (ICrH). There exist concerns about the net benefit of antithrombotic therapy in patients with microbleeds. We aimed to investigate the effects of an oral factor-XIa inhibitor (asundexian), that is hypothesized to inhibit thrombosis without compromising hemostasis, on the development of new microbleeds over time and interactions between microbleeds and asundexian treatment on clinical outcomes. We additionally assessed associations between baseline microbleeds and the risks of clinical and neuroimaging outcomes in patients with non-cardioembolic ischemic stroke. This is a secondary analysis of the PACIFIC-STROKE, international, multi-center Phase 2b double-blind, randomized clinical trial. PACIFIC-STROKE enrolled patients aged ⩾ 45 years with mild-to-moderate non-cardioembolic ischemic stroke who presented within 48 h of symptom onset for whom antiplatelet therapy was intended. Microbleeds were centrally adjudicated, and participants with an interpretable T2*-weighted sequence at their baseline MRI were included in this analysis. Patients were randomized to asundexian (10/20/50 mg daily) versus placebo plus standard antiplatelet treatment. Regression models were used to estimate the effects of (1) all pooled asundexian doses and (2) asundexian 50 mg daily on new microbleed formation on 26-week MRIs. Cox proportional hazards or regression models were additionally used to estimate interactions between treatment assignment and microbleeds for ischemic stroke/transient ischemic attack (TIA) (primary outcome), and ICrH, all-cause mortality, hemorrhagic transformation (HT), and new microbleeds (secondary outcomes). Of 1746 participants (mean age, 67.0 ± 10.0; 34% female) with baseline MRIs, 604 (35%) had microbleeds. During a median follow-up of 10.6 months, 7.0% (n = 122) had ischemic stroke/TIA, 0.5% (n = 8) ICrH, and 2.1% (n = 37) died. New microbleeds developed in 10.3% (n = 155) of participants with adequate follow-up MRIs and HT in 31.4% (n = 345). In the total sample of patients with adequate baseline and 26-week follow-up MRIs (n = 1507), new microbleeds occurred in 10.2% of patients assigned to any asundexian dose and 10.5% of patients assigned to placebo (OR, 0.96; 95% CI, 0.66-1.41). There were no interactions between microbleeds and treatment assignment for any of the outcomes (p for interaction > 0.05). The rates of new microbleeds, HT, and ICrH were numerically less in patients with microbleeds assigned to asundexian relative to placebo. The presence of microbleeds was associated with a higher risk of HT (aOR, 1.6; 95% CI, 1.2-2.1) and new microbleeds (aOR, 4.4; 95% CI, 3.0-6.3). Factor XIa inhibition with asundexian appears safe in patients with non-cardioembolic ischemic stroke and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI. These preliminary findings will be confirmed in the ongoing OCEANIC-STROKE randomized trial. ClinicalTrials.gov Identifier: NCT04304508.

Leukoaraiosis as a Promising Biomarker of Stroke Recurrence among Stroke Survivors: A Systematic Review.

Stroke is the leading cause of functional disability worldwide, with increasing prevalence in adults. Given the considerable negative impact on patients' quality of life and the financial burden on their families and society, it is essential to provide stroke survivors with a timely and reliable prognosis of stroke recurrence. Leukoaraiosis (LA) is a common neuroimaging feature of cerebral small-vessel disease. By researching the literature of two different databases (MEDLINE and Scopus), the present study aims to review all relevant studies from the last decade, dealing with the clinical utility of pre-existing LA as a prognostic factor for stroke recurrence in stroke survivors. Nineteen full-text articles published in English were identified and included in the present review, with data collected from a total of 34,546 stroke patients. A higher rate of extended LA was strongly associated with stroke recurrence in all stroke subtypes, even after adjustment for clinical risk factors. In particular, patients with ischemic stroke or transient ischemic attack with advanced LA had a significantly higher risk of future ischemic stroke, whereas patients with previous intracerebral hemorrhage and severe LA had a more than 2.5-fold increased risk of recurrent ischemic stroke and a more than 30-fold increased risk of hemorrhagic stroke. Finally, in patients receiving anticoagulant treatment for AF, the presence of LA was associated with an increased risk of recurrent ischemic stroke and intracranial hemorrhage. Because of this valuable predictive information, evaluating LA could significantly expand our knowledge of stroke patients and thereby improve overall stroke care.

Using Artificial Intelligence in Predicting Ischemic Stroke Events After Percutaneous Coronary Intervention.

Ischemic stroke (IS) is an uncommon but severe complication in patients undergoing percutaneous coronary intervention (PCI). Despite significant morbidity and economic cost associated with post PCI IS, a validated risk prediction model is not currently available. We aim to develop a machine learning model that predicts IS after PCI. We analyzed data from Mayo Clinic CathPCI registry from 2003 to 2018. Baseline clinical and demographic data, electrocardiography (ECG), intra/post-procedural data, and echocardiographic variables were abstracted. A random forest (RF) machine learning model and a logistic regression (LR) model were developed. The receiver operator characteristic (ROC) analysis was used to assess model performance in predicting IS at 6-month, 1-, 2-, and 5-years post-PCI. A total of 17,356 patients were included in the final analysis. The mean age of this cohort was 66.9 ± 12.5 years, and 70.7% were male. Post-PCI IS was noted in 109 patients (.6%) at 6 months, 132 patients (.8%) at 1 year, 175 patients (1%) at 2 years, and 264 patients (1.5%) at 5 years. The area under the curve of the RF model was superior to the LR model in predicting ischemic stroke at 6 months, 1-, 2-, and 5-years. Periprocedural stroke was the strongest predictor of IS post discharge. The RF model accurately predicts short- and long-term risk of IS and outperforms logistic regression analysis in patients undergoing PCI. Patients with periprocedural stroke may benefit from aggressive management to reduce the future risk of IS.

Abstract WP132: Cerebral Amyloid Angiopathy And Risk Of Ischemic And Hemorrhagic Stroke

Introduction: Cerebral amyloid angiopathy (CAA), a condition characterized by beta amyloid deposition in the cerebral vasculature, is a common cause of intracerebral hemorrhage (ICH) in elderly patients. Radiographic features of CAA such as white matter hyperintensities and cerebral microbleeds are also associated with an increased risk of ischemic stroke. However, there are limited population-based data regarding the risk of incident ischemic and hemorrhagic stroke associated with clinically diagnosed CAA. Methods: We performed a retrospective cohort study using inpatient and outpatient claims from 2016 to 2018 from a nationally representative 5% sample of Medicare beneficiaries. The study exposure was a diagnosis of CAA identified using ICD-10-CM code I68.0. Participants with prevalent stroke were excluded. The primary outcome was any stroke (ischemic or hemorrhagic), and secondary outcomes were ICH, subarachnoid hemorrhage (SAH), and ischemic stroke, assessed separately. These outcomes were identified using validated ICD-10-CM diagnosis codes. Cox proportional hazards regression was used to determine the association between CAA and outcomes after adjustment for demographics and vascular comorbidities. Results: Of the 1.3 million Medicare beneficiaries included, 436 had clinically documented CAA without a prior or concurrent stroke. During a median follow-up of 3.0 years (IQR, 2.3-3.0), incident ischemic stroke occurred in 29,545 patients (2.28%), SAH in 3,340 (0.26%), and ICH in 4,338 (0.34%). In adjusted Cox models, CAA was significantly associated with an increased risk of any stroke (HR, 3.4; 95% CI, 2.5-4.7), ICH (HR, 17.1; 95% CI, 11.1-26.3), and SAH (HR, 6.2; 95% CI, 2.7-13.9). There was a nonsignificant association with ischemic stroke (HR, 1.4; 95% CI, 0.8-2.4). Conclusions: In a nationally representative cohort of Medicare beneficiaries, CAA was associated with a significantly increased risk of future ICH and SAH, but was not significantly associated with an increased risk of future ischemic stroke.

The value of left atrial longitudinal strain in evaluating left atrial appendage spontaneous echo contrast in non-valvular atrial fibrillation.

Spontaneous echo contrast (SEC) observed in transesophageal echocardiography (TEE) is a reliable predictor of the risk of future ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Left atrial strain globally reflects atrial function, remodeling and distensibility. The left atrial appendage (LAA) is a myogenic remnant of the left atrium, which can actively relax and contract. The left atrial appendage (LAA) is an important part of releasing the pressure of the left atrium. The key role of the left atrium is to regulate the left ventricular filling pressure, act as a reservoir for pulmonary venous return during ventricular contraction, and act as a conduit, transferring blood to the Left ventricle during early ventricular diastole. The purpose of this study was to explore the relationship between left atrial function and left atrial appendage spontaneous echo contrast (LAASEC). A retrospective study of 338 patients with non-valvular AF was conducted. Two-dimensional speckle-tracking echocardiography provided the following metrics of LA strain: LA strain during the reservoir phase (LASr), LA strain during the conduit phase (LAScd). LA or LAA has the dense SEC of more than grade 3, which is defined as mud like change or pre thrombosis. Patients with level 3 SEC (n = 81) has lower LASr than those with lower grades of SEC (n = 257) (7.20 ± 3.70 vs. 17.48 ± 8.67, P < 0.001). Multivariate logistic regression model showed that the type of atrial fibrillation (persistent∼), increased heart rate, decreased LASr were independently associated with the dense LAASEC (OR (CI 95%), 5.558 (1.618-19.09), 1.016 (1.006-1.026) 0.002, 1.224 (1.085-1.381), both P < 0.01). Venn Diagram showed that lower CHADVASC2 score groups had dense SEC cases. Receiver operating characteristic (ROC) curve was used for analyzing results and selecting cut off values. The cut off point for LASr < 8.85% and CHADVASC2 score was >2 scores with sensitivity and specificity were 79% and 85%. Lower LASr is independently associated with the dense LAASEC in NVAF and has incremental values superior to clinical scores. The decrease of LASr may be a potential non-invasive parameter for evaluating the higher risk of LAA thrombosis.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

Impact of Peripheral Microvascular Endothelial Dysfunction on White Matter Hyperintensity

BackgroundWhite matter hyperintensity (WMH), characterized by hyperintensities on T2‐weighted fluid‐attenuated inversion recovery brain magnetic resonance imaging, has been linked to an increased risk of ischemic stroke (IS). Endothelial dysfunction is an indicator of vascular dysfunction, predicting the risk of IS. This study aimed to investigate the association between endothelial dysfunction and regional WMH, and its impact on future risk of IS.Methods and ResultsWe enrolled 219 patients (mean age, 53.1±14.1 years; 34.7% men) who underwent peripheral endothelial function assessment using reactive hyperemia peripheral arterial tonometry and brain magnetic resonance imaging without any history of IS. Volumetric WMH segmentation was automatically extrapolated using a validated automated digital tool. Total and juxtacortical WMH volume/intracranial volume (%) increased with aging and became more prominent in patients aged >50 years (n=131) than those aged ≤50 years (n=88) (total WMH: ≤50 years, Pearson r=0.24, P=0.03; >50 years, Pearson r=0.62, P<0.0001; juxtacortical WMH: ≤50 years, Pearson r=0.09, P=0.40; >50 years, Pearson r=0.55, P<0.0001). Reactive hyperemia peripheral arterial tonometry index was negatively associated with total and juxtacortical WMH volume/intracranial volume (%) in patients aged >50 years after adjustment for other covariates (reactive hyperemia peripheral arterial tonometry index, standardized β coefficient −0.17, P=0.04). Juxtacortical WMH volume/intracranial volume (%) was associated with an increased risk of IS during median follow‐up of 6.5 years (hazard ratio, 1.47; 95% CI, 1.05–1.92; P=0.03).ConclusionsPeripheral endothelial dysfunction is associated with an increased volume of juxtacortical WMH in patients aged >50 years, which is a potential marker to predict future risk of IS.

Abstract P604: Incidentally-Discovered Asymptomatic Ischemic Lesions Identified Using Natural Language Processing Are Strong Risk Markers for Future Ischemic Stroke

Background: White matter disease (WMD) and silent brain infarction (SBI) are known to be risk markers for stroke. Nevertheless, the predictive value of these changes when seen incidentally on routinely-obtained neuroimages is unknown. Methods: In this retrospective cohort study, Kaiser Permanente-Southern California health plan enrollees aged ≥ 50 years old with a brain CT or MRI scan between 2009-2019 and without a prior history of ischemic stroke, transient ischemic attack, or dementia were identified. Natural language processing (NLP) was used to identify patients with SBI and WMD on the index neuroimaging report. We used Cox proportional hazards to estimate the risk of future ischemic stroke associated with the presence of SBI and of WMD, controlling for major stroke risk factors. Results: Among 262,875 individuals receiving brain neuroimaging, 13,154 (5.0%) and 78,330 (29.8%) had SBI and WMD, respectively. The Table below summarizes the crude stroke incidence rates. The crude hazard ratio (HR) was 3.40 (95% CI 3.25-3.56) for SBI and 2.63 (95% CI 2.54-2.71) for WMD. In the multivariable model controlling for all major stroke risk factors, the effect of SBI was found to be stronger in younger versus older patients and for MRI- versus CT-discovered lesions. With MRI, the average adjusted HR over time was 2.95 (95% CI 2.53-3.44) for those &lt; age 65 and 2.15 (95% CI 1.91-2.41) for those ≥ age 65. With CT scan, the average adjusted HR over time was 2.48 (95%CI 2.19-2.81) for those &lt; age 65 and 1.81 (95% CI 1.71-1.91) for those ≥ age 65. The adjusted HR associated with a finding of WMD was 1.76 (95% CI 1.69-1.82) and was not modified by age or imaging modality. The effect of SBI decreased gradually over time, while the effect of WMD remained constant. Conclusion: Incidentally-discovered SBI and WMD are common in patients ≥ age 50 and are associated with substantial increases in the risk of subsequent symptomatic stroke. The findings may represent an opportunity for stroke prevention.

Impact of COVID-19 on Future Ischemic Stroke Incidence.

With the ever-expanding population of patients infected with SARS-CoV-2, we are learning more about the immediate and long-term clinical manifestations of coronavirus disease 2019 (COVID-19). Ischemic stroke (IS) is now one of the well-documented additional clinical manifestations of COVID-19. Most COVID-19 related IS cases have been categorized as cryptogenic or embolic stroke of undetermined source (ESUS), which are most often suspected to have an undiagnosed cardioembolic source. COVID-19 is known to also cause cardiac dysfunction, heart failure, and atrial arrhythmias (AA), but the long-term impact of this cardiac dysfunction on stroke incidence is unknown. With millions afflicted with COVID-19 and the ever-rising infection rate, it is important to consider the potential long-term impact of COVID-19 on future IS incidence. Accomplishing these goals will require novel strategies that allow for diagnosis, data capture, and prediction of future IS risk using tools that are adaptable to the evolving clinical challenges in patient care delivery and research.

Incidentally-Discovered Silent Cerebrovascular Disease Identified Using Natural Language Processing Are Strong Risk Markers for Future Ischemic Stroke

Background: White matter disease (WMD) and silent brain infarction (SBI) are known risk markers for stroke. Nevertheless, the predictive value of these changes when seen incidentally on routinely-obtained neuroimages is unknown. Methods: We included patients age ≥ 50 in the Kaiser Permanente Southern California (KPSC) health system scanned between 2009-2019 with a head CT or MRI and no prior history of ischemic stroke, transient ischemic attack, or dementia. We used natural language processing (NLP) to identify patients with SBI and WMD from the corresponding report of the index neuroimage. We used Cox proportional hazards to estimate the risk of future ischemic stroke associated with the presence of SBI and of WMD, controlling for major stroke risk factors. Results: Among 262,875 individuals receiving neuroimaging, NLP identified 13,154 (5·0%) with SBI and 78,330 (29·8%) with WMD. The incidence rate of future stroke was 32·5 (95% CI 31·1, 33·9) per 1,000 patient-years for patients with SBI; 19·3 (95% CI 18·9, 19·8) for patients with WMD and 6.8 (95% CI 6·7, 7·0) for patients without silent cerebrovascular disease. The crude HR associated with SBI was 3.40 (95% CI 3·25 to 3·56); and for WMD was 2·63 (95% CI 2·54 to 2·71). Adjusted for major stroke risk factors, the effect of incidentally-discovered SBI was found to be stronger in younger compared to older patients and for MRI- compared to CT-discovered lesions. With MRI, the adjusted HR was 2·95 (95% CI 2·53 to 3·44) for those = age 65. The adjusted HR associated with a finding of WMD was 1·76 (95% CI 1·69 to 1·82) and was not modified by age or imaging modality. Conclusion: Incidentally-discovered SBI and WMD are common in patients > age 50 and are associated with substantial increases in the risk of subsequent symptomatic stroke. These findings present an opportunity for stroke prevention. Funding Statement: This work was funded by a National Institutes of Health (NIH) grant (R01-NS102233). Declaration of Interests: None to declare. Ethics Approval Statement: The study protocol was approved by Tufts Medical Center’s and KPSC’s Institutional Review Board.

Blood flow volume of left atrial appendage measured by magnetic resonance imaging is improved after radiofrequency catheter ablation of atrial fibrillation

Hemodynamics of left atrial appendage (LAA) is an important factor for future risk of ischemic stroke in atrial fibrillation (AF) patients. Velocity encoded cardiac magnetic resonance imaging (VENC-MRI) can evaluate blood flow volume of LAA without any invasive procedures. We aimed to evaluate the association between radiofrequency catheter ablation (RFCA) and LAA hemodynamics measured by MRI. Consecutive RFCA cases in a single arrhythmia center were retrospectively analyzed. A total of 3120 AF patients who underwent first RFCA were analyzed. Among these patients 360 patients had both pre- and post-RFCA VENC-MRI evaluation. Atrial fibrillation was non-paroxysmal in 174 (48.3%) patients. Mean VENC-MRI (ml/sec) was significantly improved after RFCA with 49.93 ± 32.92 and 72.00 ± 34.82 for pre- and post-RFCA, respectively. Patients with non-paroxysmal AF (∆VENC-MRI = 14.63 ± 40.67 vs. 30.03 ± 35.37; p < .001) and low pre-RFCA VENC-MRI (∆VENC-MRI = 17.19 ± 38.35 vs. 50.35 ± 29.12; p < .001) had significantly higher improvement in VENC-MRI. Those who experienced late recurrence before post-RFCA MRI had significantly less improvement in LAA flow volume (∆VENC-MRI = 15.55 ± 41.41 vs. 26.18 ± 36.77; p = .011). Late recurrence and pre-RFCA VENC-MRI were significantly associated with ∆VENC-MRI after adjusting covariates. Patients who were AF before RFCA but maintained sinus rhythm after RFCA showed greatest improvement in VENC-MRI. Effective rhythm control through RFCA can be associated with significant improvement in LAA hemodynamics. Low pre-RFCA VENC-MRI and absence of late recurrence were associated with greater improvement in LAA hemodynamics.

Gastrointestinal Disorders and Risk of First-Ever Ischemic Stroke.

Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke. We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors. Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15-1.19]) and functional (1.16 [95% CI, 1.15-1.17]), inflammatory (1.13 [95% CI, 1.12-1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12-1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94-1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94-1.00]). In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.

N‐Terminal pro‐B‐type natriuretic peptide and stroke risk across a spectrum of cerebrovascular disease: The REasons for Geographic and Racial Differences in Stroke cohort

BackgroundN‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), a commonly used clinical marker of cardiac function, is associated with the presence of stroke symptoms and is a strong risk factor for future atrial fibrillation, stroke, and all‐cause mortality. Few data are available on the association between NT‐proBNP levels and stroke recurrence. ObjectiveWe studied the relationship between NT‐proBNP and risk of future ischemic stroke across the continuum of preexisting cerebrovascular conditions: asymptomatic, prior stroke symptoms, prior transient ischemic attack (TIA), and prior stroke. MethodsThe Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled 30,239 black and white Americans aged 45 years and older from 2003 to 2007. With 5.4 years follow‐up, baseline NT‐proBNP was measured in 892 participants who developed ischemic stroke and a 4328‐person cohort random sample. Hazard ratios of stroke by baseline NT‐proBNP were calculated in groups based on the presence of prebaseline cerebrovascular conditions. ResultsIn the fully adjusted model, elevated NT‐proBNP was associated with stroke risk in participants without a preexisting cerebrovascular condition (hazard ratio [HR], 2.32; 95% confidence interval [CI], 1.84‐2.94) and in participants with a history of stroke symptoms (HR, 1.67; 95% CI, 1.01‐2.78) or transient ischemic attack (HR, 2.66; 95% CI, 1.00‐7.04) but not among those with prior stroke (HR, 1.26; 95% CI, 0.71‐2.21). ConclusionsThese findings support the potential for NT‐proBNP testing to identify people who are at highest risk for future stroke.

Incremental Prognostic Impact of Peripheral Microvascular Endothelial Dysfunction on the Development of Ischemic Stroke.

BackgroundPeripheral microvascular endothelial dysfunction (PMED) has been linked to an increased risk of cardiovascular events, but there is a lack of information characterizing the predictive value of PMED for future risk of ischemic stroke (IS).Methods and ResultsThis retrospective observational cohort study enrolled 637 patients who underwent non‐invasive microvascular endothelial function assessment using reactive hyperemia peripheral arterial tonometry. Reactive hyperemia peripheral arterial tonometry index ≤2 was defined as PMED. Of 280 patients with PMED, 12 (4.3%) patients developed IS, compared with only 4 (1.1%) of 357 patients without PMED during a median follow‐up of 5.3 years. Patients with PMED had lower IS‐free survival compared with patients without PMED (log‐rank P=0.03). Cox proportional hazard ratio (HR) analyses showed that PMED predicted the incidence of IS, with a HR of 3.43, 95% CI, 1.10–10.63 (P=0.03); adjusted HR of 3.70, 95% CI, 1.18–11.59 (P=0.02) after adjusting for sex, smoking history, and atrial fibrillation; adjusted HR of 3.45, 95% CI, 1.11–10.72 (P=0.03) after adjusting for CHA2DS2‐VASc score; adjusted HR of 5.70, 95% CI, 1.40–23.29 (P=0.02) after adjusting for revised Framingham Stroke Risk Score. Reactive hyperemia peripheral arterial tonometry index improved discrimination of risk for IS after adding reactive hyperemia peripheral arterial tonometry index to CHA2DS2‐VASc score and revised Framingham Stroke Risk Score.ConclusionsPMED was associated with a >3‐fold increased risk of IS. These findings underscore the concept of the systemic nature of endothelial dysfunction, which could act as a potential marker to predict future risk of IS.

Electrocardiographic ST-T Abnormities Are Associated With Stroke Risk in the REGARDS Study.

Background and Purpose- In previous studies, isolated nonspecific ST-segment and T-wave abnormalities (NSSTTAs), a common finding on ECGs, were associated with greater risk for incident coronary artery disease. Their association with incident stroke remains unclear. Methods- The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a population-based, longitudinal study of 30 239 white and black adults enrolled from 2003 to 2007 in the United States. NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG Classification (Minnesota codes 4-3, 4-4, 5-3, or 5-4). Participants with prior stroke, coronary heart disease, and major and minor ECG abnormalities other than NSSTTAs were excluded from analysis. Multivariable Cox proportional hazards regression was used to examine calculate hazard ratios of incident ischemic stroke by presence of baseline NSSTTAs. Results- Among 14 077 participants, 3111 (22.1%) had NSSTTAs at baseline. With a median of 9.6 years follow-up, 106 (3.4%) with NSSTTAs had ischemic stroke compared with 258 (2.4%) without NSSTTAs. The age-adjusted incidence rates (per 1000 person-years) of stroke were 2.93 in those with NSSTTAs and 2.19 in those without them. Adjusting for baseline age, sex, race, geographic location, and education level, isolated NSSTTAs were associated with a 32% higher risk of ischemic stroke (hazard ratio, 1.32 [95% CI, 1.05-1.67]). With additional adjustment for stroke risk factors, the risk of stroke was increased 27% (hazard ratio, 1.27 [95% CI, 1.00-1.62]) and did not differ by age, race, or sex. Conclusions- Presence of NSSTTAs in persons with an otherwise normal ECG was associated with a 27% increased risk of future ischemic stroke.

Advanced ultrasound methods in assessment of carotid plaque instability: a prospective multimodal study

BackgroundA significant proportion of ischemic strokes are caused by emboli from atherosclerotic, unstable carotid artery plaques. The selection of patients for endarterectomy in current clinical practice is primarily based on the degree of carotid artery stenosis and clinical symptoms. However, the content of the plaque is known to be more important for stroke risk. Intraplaque neovascularization (IPN) has recently emerged as a possible surrogate marker for plaque instability. Neo-microvessels from the adventitial vasa vasorum grow into the full thickness of the vessel wall in an adaptive response to hypoxia, causing subsequent intraplaque haemorrhage and plaque rupture. Conventional ultrasound cannot detect IPN. Contrast-enhanced ultrasound and Superb Microvascular Imaging (SMI), have, however, shown promise in IPN assessment. Recent research using Shear Wave Elastography (SWE) has also reported reduced tissue stiffness in the artery wall (reduced mean Young’s modulus) in unstable compared to stable plaques. The purpose of this study is to identify unstable carotid artery plaques at risk of rupture and future ischemic stroke risk using multimodal assessments.MethodsForty five symptomatic and 45 asymptomatic patients > 18 years, with > 50% carotid stenosis referred to Oslo University Hospital ultrasound lab will be included in this on-going project. Patients will undergo contrast enhanced ultrasound, SMI, carotid-MRI and PET-(18F-FDG). Contrast enhanced ultrasound will be analyzed semi-quantitatively (5-levels visual classification) and quantitatively by plotting time-intensity curve analyses to obtain plaque peak contrast enhancement intensity. Plaques removed at carotid endarterectomy will be assessed histologically and the number of microvessels, areas of inflammation, granulation, calcification, lipid and fibrosis will be measured.DiscussionThis multimodality study will primarily provide information on the clinical value of advanced ultrasound methods (SMI, SWE) for the detection of unstable carotid artery plaque in comparison with other methods including contrast-enhanced ultrasound, carotid-MRI and PET-(18F-FDG) using histology as the gold standard. Secondly, findings from the methods mentioned above will be related to cerebrovascular symptoms, blood tests (leukocytes, CRP, ESR, lipoproteins and inflammatory markers) and cardiovascular risk factors at inclusion and at 1-year follow-up. The overall aim is to optimize detection of plaque instability which can lead to better preventive decisions and reduced stroke rate.

Abstract TP178: Pre-existing Volume of White Matter Disease Predicts Ischemic Stroke

Background: Patients are more likely to develop white matter disease (WMD) and microhemorrhage (MH) after ischemic stroke. Little is known about whether stroke patients had an increased prevalence of these findings before a stroke compared to patients who did not go on to develop a stroke. Methods: We retrospectively identified patients admitted to our institution with ischemic stroke between 5/16 - 12/17 who had magnetic resonance imaging (MRI) of the brain between 30 days-2 years prior to their stroke. Age and gender-matched controls for the initial MRI were identified for pair-wise comparison. Automatic segmentations of gray and white matter volumes and manual segmentation of WMD and MH (size&lt;10mm) were completed using 3D Slicer 4.5 and 4.9, respectively. Univariate analyses and multivariate models were performed to determine factors associated with stroke. This included demographic factors and traditional vascular risk factors. Results: Among the 96 patients in our study, stroke patients (n=48, mean age 68, 50% female) had lower rates of cancer (p=0.03) but higher rates of hyperlipidemia (p=0.024) compared to controls. Stroke patients exhibited greater WMD volume (15.7±20.2 vs 7.3±10.4 mL, p= 0.012) compared to controls, but not MH number (p=0.29) or total MH volume (p=0.26). Although history of stroke was associated with new presentation of stroke (72.9% vs 22.9%, p&lt;0.001), prior stroke was not linked to an overall difference in WMD volume (13.7±17.6 vs 9.4±15.3mL, p=0.20), gray to white matter ratio (1.27±0.54 vs 1.21±0.74 mL, p=0.68), MH number (p=0.36) or total MH volume (p=0.39). After adjusting for confounders, pre-existing WMD volume remained an independent predictor of stroke (adjusted OR 1.042 per one point increase, 95% CI 1.001-1.086, p=0.046). Conclusion: Increased volume of white matter disease correlates with a greater risk of future ischemic stroke. These results should be validated in subsequent studies.