Common ECG Abnormalities in Patients with Acute Stroke

Establishing new approaches for the prevention and treatment of stroke relies on identifying modifiable risk factors that contribute to the development of this complex disease. Mendelian randomization (MR) studies, analogous to naturally occurring randomized trials, can assess causality of potentially modifiable biomarkers and offer new insights into biological pathways. Stroke is the second leading cause of death worldwide and the chief determinant of long-term disability. Stroke is a heterogeneous disease arising from several distinct underlying pathologies and is typically classified as ischemic or hemorrhagic, and further subclassified using imaging data. Ischemic stroke (IS), including its 3 main subtypes: small vessel disease, large vessel disease, and cardioembolic stroke, accounts for ≈80% of stroke and is the result of an interrupted blood supply, leading to localized areas of ischemia in the brain. Small vessel disease may be a consequence of nonatherosclerotic, as well as atherosclerotic, mechanisms that result in an occlusion of the small perforating arteries, whereas large vessel disease results from occlusions or emboli from plaque rupture in larger vessels, such as a carotid artery. Cardioembolic stroke arises typically from emboli from the heart. By contrast, hemorrhagic stroke is a consequence of intracerebral hemorrhage (bleeding into the brain) or subarachnoid hemorrhage (bleeding into the subarachnoid space). These diverse stroke subtypes have distinct underlying pathologies reflecting different risk factor distributions. MR studies, using genetic variants as instrumental variables, afford a powerful approach to assessing causality of risk factors and avoid biases inherent in observational studies, including confounding and reverse causation. This review considers the contribution of MR studies to stroke epidemiology and their relevance to understanding risk factors and new therapeutic targets for stroke. Meta-analyses of large prospective studies have enhanced our knowledge of classical and emerging risk factors for stroke.1–4 Classical risk factors for stroke include nonmodifiable characteristics, …

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …

Background: The advent of mechanical thrombectomy in acute stroke care has reignited interest in the arena of neuro-inflammation and neuro-plasticity to optimize stroke management and further improve outcome. Even though there is an early evidence suggesting increased risk of ischemic stroke (IS) in pro-inflammatory states like lupus, rheumatoid and even multiple sclerosis, cardiovascular risk factor association has yet to be comprehensively studied in Multiple Sclerosis (MS). This is the first ever North American Study focusing on prevalence of ischemic stroke in the largest MS cohort. Method: This retrospective study included all patients diagnosed with MS from 2000 to 2016, identified using ICD-9/10 codes. The data were extracted from the Cerner's Health Facts database. From the pool of MS patients, IS was identified and their comorbidities are identified. Multiple logistic regression was used to evaluate the odds of having IS in patients with MS. Statistical analysis performed by the SAS v ersion 9.4, Cary, NC, USA. Result: A total of 83,222 patients with a diagnosis of MS were identified. IS was officially diagnosed in 2,159 (2.59%) and intracerebral hemorrhage (ICH) in 191 (0.22%) patients with MS. Patients with MS had 1.6 times more likelihood of having an IS as compared to non-MS patients (p<0.0001). The study identified the presence of vascular risk factors in the patients with MS. Patients who had MS and had ages between 41-64 (OR 1.75, CI 1.51-2.03), hypertension (OR 4.77, CI 4.201-5.412), Coronary Artery Disease (OR 2.09, CI 1.843-2.380), heart failure (OR 1.38, CI 1.175-1.621), atrial fibrillation (OR 1.61, CI 1.361-1.894), diabetes mellitus (OR 1.58, CI 1.40-1.76), peripheral vascular disease (OR 2.38, CI 1.90-2.98), and smoking (OR 1.29, CI 1.15-1.45) were more likely to have an IS as compared to those who did not have MS and these risk factors. Conclusion: This is one of the largest MS cohort studies confirming prior reports of higher incidence of IS in MS population, especially in the 41-64 age group, after adjusting for cardiovascular risk factors. Future prospective epidemiological and molecular studies can open new diagnostic and treatment avenues.

Coronary evaluation in patients with stroke: Recognizing the risk

Introduction Atrial Fibrillation (AF) causes 15% of ischaemic strokes. The National Clinical Guideline for Stroke recommends at least 24 hours of cardiac monitoring and a longer duration if cardio-embolic stroke is suspected. The British Heart Rhythm Society suggests up to 72 hours of cardiac monitoring. Currently, there is little data on the use of telemetry in detecting AF in acute strokes. Our study aims to evaluate the detection rate of new onset AF in acute stroke with telemetry and to determine if there was any correlation between the duration of telemetry and the detection rate of AF. Method All patients with ischaemic stroke who were admitted to stroke ward over a 3-month period were retrospectively analysed. Exclusion criteria were patients who were known to have AF, had new AF on admission electrocardiogram, patients receiving palliative care, patients who were discharged home early without having a telemetry and patients with missing records. Results 61 patients met the inclusion criteria and 5 (8.2%) had AF on telemetry. Two patients had AF on day 1, one on day 2 and two on day 3. All of these patients were anticoagulated. The duration of telemetry ranged between 1- 19 days however no AF was detected beyond the third day of this study. Conclusions AF was detected in 8% of patients with ischaemic stroke within the first 72 hours of admission. Among the patients in whom AF was detected, 5% were detected between 24 hours and 72 hours of admission. Studies (EMBRACE and CRYSTAL trials) have shown that prolonged cardiac monitoring (30 days and 6 months to a year respectively) resulted in higher detection rates of AF. This study suggests that patients with ischaemic stroke should be monitored for at least 72 hours due to a higher detection rate of AF.

Risk factors and incidence of ischemic stroke in Taiwanese with nonvalvular atrial fibrillation—A nation wide database analysis

Background and purpose: To date, there have been no thorough investigations on the possible role of atrial fibrillation (AF) pattern in stroke recurrence during early-phase post stroke. We investigated for differences in ischemic outcome between patients with paroxysmal AF (PAF) and those with sustained AF (SAF), within 90 days from acute ischemic stroke (AIS). Methods: Patients from the RAF and RAF-DOAC study databases were categorized into 2 groups: PAF and SAF (persistent + permanent AF). Early recurrence was defined as the composite of ischemic stroke, transient ischemic attack and symptomatic systemic embolism within 90 days from AIS. Results: A total of 2,150 patients (1,155 females, 53.7%) were enrolled: 930 (43.3%) had PAF and 1220 (56.7%) SAF. Patients with SAF were on average older, were more likely to have: diabetes mellitus, hypertension, a history of stroke/TIA, congestive heart failure, atrial enlargement, pacemaker and a high NIHSS. During the 90-day follow-up, 107 recurrent ischemic events were recorded from index stroke. Multivariate analysis for predictive factors of early ischemic recurrence indicated that SAF was associated with a non-significant increase in ischemic events at 90 days, compared to PAF (HR 1.23; 95% CI 0.74-2.04; p = 0.418) (Figure). Conclusions: PAF and SAF patients with acute stroke resulted having similar risks of ischemic recurrence within 90 days from index event. Therein, these findings suggest that AF pattern should not influence decision making concerning the timing of anticoagulant administration after an acute stroke.

d’Esterre, CD1, 3 Qazi, E1, 3 Patil, S1, 3 Almekhlafi, M3, 1 Lee, T2, 3 Demchuk, A1, 3 Goyal, M1, 3 Menon, B1, 3; 1. University of Calgary, Calgary, AB; 2. University of Western Ontario, London, ON; 3. Calgary Stroke Program, Calgary, AB Background : For ischemic stroke, CT Perfusion (CTP) may change thrombolytic/endovascular treatment decisions when compared to NCCT/CTA alone. Two distinct thresholds may be useful in this regard: separation of 1) non-salvageable tissue (infarct core) from salvageable electrically silent tissue (penumbra), and 2) penumbra from benign oligemia (hypoperfused, but will survive if clot persists). Methods : CTP (120s,8cm) was performed on 180 patients within 12hrs of ischemic stroke. Two patient cohorts were analyzed: (1) recanalization (TICI 2b,3) 6s. For group (2) CBF, CBV, and Tmax values were obtained from within the final infarct region, and total ipsilateral hemisphere, excluding infarction. CBF, CBV and Tmax were used in univariate regression models. Results : For group (1)[n=11], mean time from CTP to recanalization was 60±19min. CBF parameter (thresholds for gray and white matter 7.2 and 5.2 ml•min-1•(100g)-1) had the highest sensitivity (90.9%) and specificity (81.8%) for infarction. For group (2)[n=15], the Tmax parameter (thresholds for gray and white matter 11.3s and 11.8s) had the highest sensitivity (86.6%) and specificity (80.0%) for penumbra. Conclusion : Knowing the status of recanalization within 90mins of CTP allows for accurate delineation of infarct core, as …

Introduction: Stroke is the fifth leading cause of death in the US and a major cause of disability. Atrial fibrillation (AF) increases the risk of ischemic stroke fivefold. Cardioembolic stroke in patients with AF is associated with high mortality. The association of elevated cardiac troponin with mortality in patients with acute ischemic stroke has been studied previously; however, there is limited data in subgroups of ischemic stroke etiology. We sought to determine the association of troponin elevation at presentation with 90-day all-cause mortality in patients with acute ischemic stroke and AF. Methods: The I nitiation of A nticoagulation after C ardioembolic Stroke (IAC) study is a multicenter cohort drawn from eight US Stroke Centers. We included consecutive patients hospitalized with acute ischemic stroke and AF between 2015-2018, who had an initial baseline cardiac troponin I (bcTnI) obtained at presentation. The primary outcome was all-cause mortality at 90 days from stroke onset. We undertook multivariable logistic regression to determine the association between elevated bcTnl (≥0.1 ng/mL) and 90-day mortality. Results: Of the 2084 patients enrolled in IAC, 1889 patients had 90-day follow-up of which 1461 patients had bcTnI available. 239 of the included patients (16.4%) had an elevated bcTnl, and death within 90-days occurred in 323 patients (22.1%). Elevated bcTnI was associated with 90-day mortality in univariable analysis (49.4% vs 24.9%; OR 1.71, 95% CI 1.17-2.50, p<0.001). This association persisted after adjusting for potential confounders: age, NIHSS, coronary artery disease, congestive heart failure and initial systolic blood pressure (OR 1.71, 95% CI 1.17-2.50, p=0.006); and in sensitivity analysis adding CrCl to the adjusted model above (OR 1.57, 95% CI 1.03-2.39, p=0.037). Conclusion: In acute ischemic stroke patients with AF, elevated bcTnI was independently associated with 90-day all-cause mortality.

### Case A 68-year-old right-hand-dominant man was brought to the hospital because of a speech disturbance and right arm and leg weakness. He awoke with these deficits and was last known to be symptom-free when retiring to bed the previous evening 8 hours earlier. His past medical history was notable for coronary heart disease, the patient having underwent coronary artery bypass surgery 7 years previously for unstable angina, but he had no known history of myocardial infarction. He also had hypertension and hyperlipidemia, and smoked 1 pack of cigarettes daily for more than 40 years. He had no history of calf claudication. His hypertension was being treated with a diuretic and β-adrenergic receptor blocker. He was also prescribed 325 mg of aspirin daily and an HMG CoA-reductase inhibitor (statin); however, his wife remarked that he often forgot to take his medications. His last total cholesterol was 240 mg/dL, with LDL cholesterol of 130 mg/dL. He had a strong family history of coronary heart disease after the age of 50. He had no known drug allergies. #### Physical Examination The patient’s blood pressure was 195/100 mm Hg in both arms, with a regular pulse of 90 bpm. His weight was 225 lb (body mass index: 31.4 kg/m2). His lungs were clear to auscultation. Cardiac examination showed a laterally displaced point of maximum impulse with an S4 gallop and a soft nonradiating systolic murmur at the base. His abdomen was obese without organomegaly and no abdominal bruits were detected. He had no rashes and no joint deformities. The left superficial temporal artery pulse was stronger than the right. There were soft bilateral anterior cervical bruits, left louder than right, but no supraclavicular bruits. There were bilateral femoral bruits. Radial pulses were 2+ and symmetric. Dorsalis pedis and posterior tibial pulses were 1+. …

Clinical management of patients with acute stroke and the approach used for secondary prevention depends upon clarification of pathogenesis. Although most strokes are a consequence of cerebrovascular disease, ≈15% to 20% of ischemic (nonhemorrhagic) strokes have been attributed to cardiogenic embolism.1 In practice, determination of the stroke mechanism is fraught with uncertainty, particularly when the possibility of thromboembolism emanating from atherosclerotic lesions in the aorta or cervical arteries is considered. When cardiogenic embolism is suspected, cardiac ultrasound is the principal method used to identify the potential source. The finding of left atrial enlargement has been shown to bear a significant relationship to the risk of stroke in a multivariate analysis of population-based data from the Framingham Heart Study2. The most frequent confounding variable is atrial fibrillation, occurring in >2 million patients in North America and in over half of all patients with cardiogenic embolism. Criteria for selection of patients with acute ischemic stroke for transesophageal echocardiography (TEE) to search for a potential cardiac source of embolism are controversial, particularly because cardiogenic embolism is often an uncertain diagnosis that is inferred merely on the basis of the finding of potential cardiac source. Even after extensive investigation, ≈40% of ischemic stroke patients have no clearly identifiable pathogenesis (cryptogenic stroke).3 In one study, 62% of patients younger than 60 years of age without an obvious source of cerebral infarction and 23% of those with arterial lesions had potential sources of cardiogenic embolism identified by TEE ( P =0.0007 for the difference).4 See p 2625 Among the cardiac anomalies detected by TEE that have been implicated as risk factors for stroke are patent foramen ovale (PFO) and atrial septal aneurysm (ASA).5,6⇓ The foramen ovale, a remnant of the fetal circulation, remains patent through adulthood in ≈1 in 4 …

Objective Percutaneous left atrial appendage closure(LAAC)has been developed for stroke prevention for high-risk atrial fibrillation(AF)patients in recent years.For AF patients complicated with coronary artery disease(CAD), trpl anti-coagulation was related with high bleeding risk, thus we hypothesized that LAAC might yield benefit for its lower hemorrhagic risk compared to oral anticoagulants.This is a retrospective, single-center study aimed to investigate the safety and efficacy of LAAC in high-risk AF patients with coronary artery disease. Methods From May 2014 to November 2015, 36 AF patients with CAD underwent percutaneous LAAC operations at Wuhan Asia Heart Hospital.All CADs were confirmed by coronary angiography or coronary artery CTA.The clinical feature, LAA morphology, LAAC procedure and follow-up data of these patients were reviewed. Results Thirty-six patients were included, who were all high-risk NVAF patients complicated with stable CAD.The average CHA2DS2-VASc score was 2.94±1.43, and the average HAS-BLED score was 2.00 ±0.79.Successful left atrial appendage closures were achieved in all 36 patients.There was one case of ischemic stroke during peri-operative period, which responded well to drug therapy.During the 12 months of follow-up, there was no major bleeding or ischemic stroke/system embolism.33 patients completed TEE 45 days post-operative, which revealed 7 patients with residual flows of (2.67±1.50) mm, and 2 device-related thrombi, who continued anti-coagulatants.34 patients discontinued warfarin/dabigatran at 45 days after LAAC operations. Conclusion This study showed that percutaneous LAA closure could be performed as an effective and safe alternative for stroke prevention in high-risk NVAF patients complicated with stable CAD. Key words: Atrial fibrillation; Left atrial appendage closure; Coronary artery disease.

See related article, p 1226. High cardiac troponin T (cTn) levels reflect myocardial damage in heart failure patients and predict poor prognosis in various cardiomyopathies and stroke. Cerebrovascular and cardiovascular diseases are major causes of death and disability worldwide. Ischemic stroke is a frequent complication in cardiac diseases, and cardiac complications commonly cause early clinical worsening and death after stroke. Acute myocardial infarction is a common complication of acute ischemic stroke (AIS); ≈4% of AIS patients will die from myocardial infarction in the 3 months after stroke, and 19% will suffer a cardiac event.1,2 AIS is an established cause of nonacute myocardial infarction hypertroponinemia, previously reported as 20% to 60%.3–5 Can these risk factors, such as cTn elevation and cardiac changes, influence mortality after stroke? To this regard, Wrigley et al6 analyzed data of biracial population of 1.3 million is largely representative of the United States in terms of median age, proportion of black subjects, and economic status. The analysis was done in adult patients (aged 20 …

Background In recent years air pollution (AP) has become one of the most important nonclassical risk factors for cardiovascular diseases (CVD). Guidelines suggest that high-risk patients should avoid regions with high AP levels, however, there is a lack of research conducted in areas with low or moderate AP concentrations. Purpose To analyze the effects of AP on ischemic stroke (IS) incidence and identify the most vulnerable age and sex groups. Moreover, we aim to assess, how region settings (such as density of population, alcohol or tobacco consumption, atrial fibrillation (AF) prevalence and CVD mortality) impact the effects of AP. Methods The study covered 709 counties in Poland in 2011-2020. IS incidence data (ICD-10 I63.X) and AP concentrations (PM2.5, NO2, CO, O3, benzo(a)pyrene (B(a)P) and SO2) were obtained from the National Health Fund and Inspectorate for Environmental Protection, respectively. In collaboration with the National Research Institute, taking into account weather conditions and the flow of people, we modeled AP levels for all 709 counties. To analyze the effects of AP we used quasi-Poisson generalized additive models. The covariates were weather conditions, day of the week, bank holidays and seasonal trends. Results are presented as relative risks (RRs) and 95% confidence intervals (95% CI) per interquartile range (IQR) increase in AP on the day of exposure. Results We recorded 146,262 cases of IS with a dominance of females (51.2%) and people over 65 years old (77.62%). Exposure to PM2.5, NO2, B(a)P and SO2 increased the risk of ischemic stroke onset by respectively 2.4%, 1%, 0.8% and 0.6% in the overall population on the day of exposure [Figure 1]. We found similar negative effects for the same four air pollutants in the female population and younger adults. None of the analyzed air pollutants had an impact on men, whereas exposure to PM2.5, NO2 and SO2 was associated with an increased risk of IS in the elderly. People in high alcohol and tobacco consumption areas were more vulnerable to AP. There was an association between the increased 4 air pollutants (PM2.5, NO2, B(a)P and SO2) concentrations and the IS risk in low AF prevalence areas. In contrast, only PM2.5 and SO2 had the same effect in the high AF occurrence setting. Exposure to all air pollutants except O3 caused an increased risk of IS in counties with lower CVD mortality rates. The exposure–response associations of AP levels with IS incidence were positive and the curves showed an increase. Then at higher concentrations, the slopes flatten, especially in the case of NO2 and SO2 [Figure 2]. Conclusions AP might act as a trigger for IS, even at low concentrations. Young, active woman is the most vulnerable phenotype to AP. Harmful health habits seem to further increase the negative effects of AP. "Survival bias" might contribute to the lower influence of AP in high CVD mortality areas. The prevalence of AF seems to not impact the effects of AP. Acute effects of various air pollutants. Exposure–response curves.

<i>Stroke</i> : Highlights of Selected Articles