The Cost and the Value of Stroke Care in Greece: Results from the SUN4P Study.

The aim of this study was to measure the one-year total cost of strokes and to investigate the value of stroke care, defined as cost per QALY. The study population included 892 patients with first-ever acute strokes, hemorrhagic strokes, and ischemic strokes, (ICD-10 codes: I61, I63, and I64) admitted within 48 h of symptoms onset to nine public hospitals located in six cities. We conducted a bottom-up cost analysis from the societal point of view. All cost components including direct medical costs, productivity losses due to morbidity and mortality, and informal care costs were considered. We used an annual time horizon, including all costs for 2021, irrespective of the time of disease onset. The average cost (direct and indirect) was extrapolated in order to estimate the national annual burden associated with stroke. We estimated the total cost of stroke in Greece at EUR 343.1 mil. a year in 2021, (EUR 10,722/patient or EUR 23,308 per QALY). Out of EUR 343.1 mil., 53.3% (EUR 182.9 mil.) consisted of direct healthcare costs, representing 1.1% of current health expenditure in 2021. Overall, productivity losses were calculated at EUR 160.2 mil. The mean productivity losses were estimated to be 116 work days with 55.1 days lost due to premature retirement and absenteeism from work, 18.5 days lost due to mortality, and 42.4 days lost due to informal caregiving by family members. This study highlights the burden of stroke and underlines the need for stakeholders and policymakers to re-organize stroke care and promote interventions that have been proven cost-effective.

Prediction of long-term outcomes by arterial stiffness and pressure wave reflections in patients with acute stroke: the Athens Stroke Registry.

BACKGROUND AND PURPOSE: Stroke patients' management might be improved by addressing the role of aortic stiffness (carotid-femoral pulse wave velocity: cfPWV) and pressure wave reflections (PWRs, augmentation index: AIx) in their pathogenesis and outcome. We tested the hypothesis that cfPWV and AIx, separately and combined, predict long-term outcomes [all-cause mortality, incidence of cardiovascular events, stroke recurrence and disability defined by modified Ranking Scale (mRS) ≥3] in patients with acute stroke, using data from the 'Athens Stroke Registry'. METHODS: Data from 552 patients (70% men, age: 66.1 ±â€Š10.4 years, 13.4% deaths from any cause, 21.2% cardiovascular events, 14.1% stroke recurrences and 20.1% poor mRS, mean follow-up 68.4 ±â€Š41.4 months) were analyzed. RESULTS: The main findings were that: high aortic stiffness (cfPWV > 13 m/s) alone is an independent predictor of all-cause mortality and cardiovascular (CV) events, but not of stroke recurrence and poor functional outcome; evaluated separately from aortic stiffness, neither low nor high PWRs have any prognostic value; even after multiple adjustments, patients with both high aortic stiffness (cfPWV > 13 m/s) and low PWRs (Aix < 22%) have almost two-fold higher hazard ratio, not only for all-cause mortality and CV events but also for stroke recurrence and poor functional outcome. CONCLUSIONS: The present study provides evidence about the role of aortic stiffness, PWRs and their combined incremental value in the long-term survival, morbidity, and functional disability after acute stroke.

Stroke Units Necessity for Patients, Web-Based "SUN4P" Registry: Descriptive Characteristics of the Population.

The aim of this study was to present the descriptive characteristics of the Stroke Units Necessity for Patients (SUN4P) registry. METHODS: The study population derived from the web-based SUN4P registry included 823 patients with first-ever acute stroke. Descriptive statistics were used to present patients' characteristics. RESULTS: The vast majority of patients (80.4%) had an ischemic stroke, whereas 15.4% had a hemorrhagic stroke. Hypertension was the leading risk factor in both patients. The patients with ischemic stroke had higher prevalence of traditional cardiovascular risk factors such as diabetes mellitus, dyslipidemia and smoking and most commonly cryptogenic stroke (39%). National Institutes of Health Stroke Scale (NIHSS) was higher among patients with hemorrhagic in comparison to those with ischemic stroke (10.5 vs 6 respectively). Moreover, all patients had similar rate of disability prior to stroke, as shown by Modified Rankin Scale (mRS=0). CONCLUSIONS: These data are in accordance with current evidence and should be thoroughly assessed in order to ensure optimal therapeutic management of stroke patients.

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score.

BACKGROUND AND AIMS: Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. METHODS: We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. RESULTS: Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; -1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; -3 points for left ventricular ejection fraction <35%; 1 point for the presence of any supraventricular extrasystole recorded during all available 12-lead standard electrocardiograms performed during hospitalization for the ESUS; -2 points for subcortical infarct; -3 points for the presence of non-stenotic carotid plaques. The rate of new incident AF during follow-up was 1.97% among the 42.3% of the cohort who had a score of ≤0, compared to 26.9% in patients with > 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. CONCLUSIONS: The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ Unique identifier: NCT02766205.

Access of Stroke Patients' to Optimal Healthcare Technology in Greece: Messages to Policy Makers.

The aim of this study was to evaluate accessibility of stroke patients to optimal healthcare technology in Greece. Methods: The study population consisted of 313 first ever stroke patients derived from the "Stroke Units Necessity for Patients, SUN4P" registry. Descriptive statistics were used, to present patients' characteristics and resources utilization Results: The vast majority of patients (91.7%) conducted a CT scan during the acute phase (within the first 24hours). Almost, (65%) were admitted to wards of Internal Medicine Departments, whereas only 21% of patients were admitted to a Stroke Unit. Of note, a total of 6.9% of ischemic stroke patients received intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Conclusions: Preliminary results from SUN4P underline the urgent necessity for the re-organization of acute stroke care in Greece, as rates of admissions to stroke units and rtPA treatment during the acute phase are currently below optimal.

Developing Patients' Experiences Database After Hospital Discharge: Another Step in Improving Stroke Care.

The aim of this study was to assess stroke patients' experiences in regards to hospital stay and during discharge. A cross-sectional study with retrospective data collection was conducted including patients (n=135) with first-ever acute stroke, who were admitted in seven Public Hospitals in Greece ("Stroke Units Necessity for Patients, SUN4P" registry). The translated version of the NHS-Stroke Questionnaire in the Greek was used. 48.2% of patients rated their overall experience from the care they received as very good/excellent. 66% of patients reported that they participated in decision making about their care and 21.5% reported not having received help from the hospital's social services regarding any benefits/aids, thus lowering their overall patient experience score (p=0.017). Decision and policymakers must consider factors affecting stroke patients 'experiences during their hospitalization. The development of a national stroke patients' experiences database can help prioritize relevant actions and draw up a commonly accepted management and services redesign framework for patients.

Characteristics and outcomes of Embolic Stroke of Undetermined Source according to stroke severity.

BACKGROUND AND AIMS: Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. METHODS: In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan-Meier product limit method. RESULTS: In 772 patients (median NIHSS: 6 (interquartile range: 3-12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27-2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73-1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44-1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05-2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2-48.6) vs. 36.6% (27.8-47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5-50.0) vs. 34.0% (26.0-43.6) respectively; log-rank test: 4.54, p = 0.033). CONCLUSIONS: Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.

Left atrial diameter thresholds and new incident atrial fibrillation in embolic stroke of undetermined source.

BACKGROUND AND PURPOSE: We analyzed consecutive patients with embolic stroke of undetermined source (ESUS) from three prospective stroke registries to compare the prognostic performance of different LAD thresholds for the prediction of new incident AF. METHODS: We calculated the sensitivity, specificity, positive prognostic value (PPV), negative prognostic value (NPV) and Youden's J-statistic of different LAD thresholds to predict new incident AF. We performed multivariate stepwise regression with forward selection of covariates to assess the association between the LAD threshold with the highest Youden's J-statistic and AF detection. RESULTS: Among 675 patients followed for 2437 patient-years, the mean LAD was 38.5 ± 6.8 mm. New incident AF was diagnosed in 115 (17.0%) patients. The LAD threshold of 40mm yielded the highest Youden's J-statistic of 0.35 with sensitivity 0.69, specificity 0.66, PPV 0.27 and NPV 0.92. The likelihood of new incident AF was nearly twice in patients with LAD > 40 mm compared to LAD ≤ 40 mm (HR:1.92, 95%CI:1.24-2.97, p = 0.004). The 10-year cumulative probability of new incident AF was higher in patients with LAD>40 mm compared to LAD ≤ 40 mm (53.5% and 22.4% respectively, log-rank-test: 28.2, p < 0.001). The annualized rate of stroke recurrence of 4.0% in the overall population did not differ significantly in patient above vs. below this LAD threshold (HR:0.96, 95%CI:0.62-1.48, p = 0.85). CONCLUSIONS: The LAD threshold of 40 mm has the best prognostic performance among other LAD values to predict new incident AF after ESUS. The diagnostic yield of prolonged cardiac rhythm monitoring in patients with LAD ≤ 40 mm seems low; therefore, such patients may have lower priority for prolonged cardiac monitoring.

Supraventricular Extrasystoles on Standard 12-lead Electrocardiogram Predict New Incident Atrial Fibrillation after Embolic Stroke of Undetermined Source: The AF-ESUS Study.

BACKGROUND: The diagnosis of covert atrial fibrillation (AF) remains a major challenge to guide secondary prevention of patients with embolic stroke of undetermined source (ESUS). AIMS: We analyzed consecutive ESUS patients from 3 prospective stroke registries to assess whether the presence of supraventricular extrasystoles (SVE) on standard 12-lead electrocardiogram (ECG) is associated with the detection of AF (primary outcome), stroke recurrence and death (secondary outcomes) during follow-up. METHODS: We measured the number of SVEs in all available ECGs of patients hospitalized for ESUS. Multivariate stepwise regression with forward selection of covariates assessed the association between SVE (classified in 4 groups according to their number per 10 seconds of ECG: no SVE, >0-1SVEs, >1-2SVEs, and >2SVEs) and outcomes during follow-up. The Kaplan-Meier product limit method estimated the 10-year cumulative probabilities of outcomes in each SVE group. We calculated the negative prognostic value (NPV) of the presence of any SVE to predict new AF, defined as the probability that AF will not be detected during follow-up if there is no SVE. RESULTS: Among 853 ESUS patients followed for 2857 patient-years (median age: 67 years, 43.0% women), 226 (26.5%) patients had at least 1 SVE at the standard 12-lead ECGs performed during hospitalization. AF was detected in 125 (14.7%) of patients in the overall population during follow-up: 8.9%, 22.5%, 28.1%, and 48.3% in patients with no SVE, greater than 0-1SVE, greater than 1-2SVE and greater than 2SVE respectively. In multivariate regression analysis, compared to patients with no SVEs, the corresponding hazard-ratios were 1.80 [95% confidence intervals (95%CI):1.06-3.05], 2.26 (95%CI:1.28-4.01) and 3.19 (95%CI:1.93-5.27). The NPV of the presence of any SVE for the prediction of new AF was 91.4%. There was no statistically significant association of SVE with the risk of ischemic stroke recurrence and death. CONCLUSIONS: In ESUS patients without SVEs during hospitalization, the probability that AF will not be detected during a follow-up of 3.4 years is more than 91%.

External Performance of the HAVOC Score for the Prediction of New Incident Atrial Fibrillation.

Background and Purpose- The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0-4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods- In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results- In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0-4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37-3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%-73.3%). Conclusions- The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.

A tool to identify patients with embolic stroke of undetermined source at high recurrence risk.

OBJECTIVE: A tool to stratify the risk of stroke recurrence in patients with embolic stroke of undetermined source (ESUS) could be useful in research and clinical practice. We aimed to determine whether a score can be developed and externally validated for the identification of patients with ESUS at high risk for stroke recurrence. METHODS: We pooled the data of all consecutive patients with ESUS from 11 prospective stroke registries. We performed multivariable Cox regression analysis to identify predictors of stroke recurrence. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score externally assessing its discrimination and calibration. RESULTS: In 3 registries (884 patients) that were used as the derivation cohort, age, leukoaraiosis, and multiterritorial infarct were identified as independent predictors of stroke recurrence and were included in the final score, which assigns 1 point per every decade after 35 years of age, 2 points for leukoaraiosis, and 3 points for multiterritorial infarcts (acute or old nonlacunar). The rate of stroke recurrence was 2.1 per 100 patient-years (95% confidence interval [CI] 1.44-3.06) in patients with a score of 0-4 (low risk), 3.74 (95% CI 2.77-5.04) in patients with a score of 5-6 (intermediate risk), and 8.23 (95% CI 5.99-11.3) in patients with a score of 7-12 (high risk). Compared to low-risk patients, the risk of stroke recurrence was significantly higher in intermediate-risk (hazard ratio [HR] 1.78, 95% CI 1.1-2.88) and high-risk patients (HR 4.67, 95% CI 2.83-7.7). The score was well-calibrated in both derivation and external validation cohorts (8 registries, 820 patients) (Hosmer-Lemeshow test χ2: 12.1 [p = 0.357] and χ2: 21.7 [p = 0.753], respectively). The area under the curve of the score was 0.63 (95% CI 0.58-0.68) and 0.60 (95% CI 0.54-0.66), respectively. CONCLUSIONS: The proposed score can assist in the identification of patients with ESUS at high risk for stroke recurrence.

Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source.

Background We aimed to assess the prevalence and degree of overlap of potential embolic sources (PES) in patients with embolic stroke of undetermined source (ESUS). Methods and Results In a pooled data set derived from 3 prospective stroke registries, patients were categorized in ≥1 groups according to the PES that was/were identified. We categorized PES as follows: atrial cardiopathy, atrial fibrillation diagnosed during follow-up, arterial disease, left ventricular disease, cardiac valvular disease, patent foramen ovale, and cancer. In 800 patients with ESUS (43.1% women; median age, 67.0 years), 3 most prevalent PES were left ventricular disease, arterial disease, and atrial cardiopathy, which were present in 54.4%, 48.5%, and 45.0% of patients, respectively. Most patients (65.5%) had >1 PES, whereas only 29.7% and 4.8% of patients had a single or no PES, respectively. In 31.1% of patients, there were ≥3 PES present. On average, each patient had 2 PES (median, 2). During a median follow-up of 3.7 years, stroke recurrence occurred in 101 (12.6%) of patients (23.3 recurrences per 100 patient-years). In multivariate analysis, the risk of stroke recurrence was higher in the atrial fibrillation group compared with other PES, but not statistically different between patients with 0 to 1, 2, or ≥3 PES. Conclusions There is major overlap of PES in patients with ESUS. This may possibly explain the negative results of the recent large randomized controlled trials of secondary prevention in patients with ESUS and offer a rationale for a randomized controlled trial of combination of anticoagulation and aspirin for the prevention of stroke recurrence in patients with ESUS. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02766205.

Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source.

OBJECTIVE: To investigate the association between the presence of ipsilateral nonstenotic carotid plaques and the rate of detection of atrial fibrillation (AF) during follow-up in patients with embolic strokes of undetermined source (ESUS). METHODS: We pooled data of all consecutive ESUS patients from 3 prospective stroke registries. Multivariate stepwise regression assessed the association between the presence of nonstenotic carotid plaques and AF detection. The 10-year cumulative probabilities of AF detection were estimated by the Kaplan-Meier product limit method. RESULTS: Among 777 patients followed for 2,642 patient-years, 341 (38.6%) patients had an ipsilateral nonstenotic carotid plaque. AF was detected in 112 (14.4%) patients in the overall population during follow-up. The overall rate of AF detection was 8.5% in patients with nonstenotic carotid plaques (2.9% per 100 patient-years) and 19.0% in patients without (5.0% per 100 patient-years) (unadjusted hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.37-0.84). The presence of ipsilateral nonstenotic carotid plaques was associated with lower probability for AF detection (adjusted HR 0.57, 95% CI 0.34-0.96, p = 0.03). The 10-year cumulative probability of AF detection was lower in patients with ipsilateral nonstenotic carotid plaques compared to those without (34.5%, 95% CI 21.8-47.2 vs 49.0%, 95% CI 40.4-57.6 respectively, log-rank-test: 11.8, p = 0.001). CONCLUSIONS: AF is less frequently detected in ESUS patients with nonstenotic carotid plaques compared to those without. CLINICALTRIALSGOV IDENTIFIER: NCT02766205.

Renal Function and Risk Stratification of Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods- We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results- In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99-1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87-1.73) or categorical covariate (likelihood-ratio test 2.59, P=0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60-89, 21.7% for eGFR 45-59, 19.2% for eGFR 30-44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P=0.63). The results were similar for the outcome of death. Conclusions- The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

20-year trends of characteristics and outcomes of stroke patients with atrial fibrillation.

Background The accurate knowledge of secular trends in prevalence, characteristics and outcomes of patients with ischemic stroke and atrial fibrillation allows better projections into the future. Aim We aimed to report the overall, age- and sex-specific secular trends of characteristics and outcomes of patients with acute ischemic stroke (AIS) and atrial fibrillation between 1993 and 2012 in the Athens Stroke Registry. Methods We used Joinpoint regression analysis to calculate the average annual percent changes and 95% confidence intervals. Results Among 3314 stroke patients, 1044 (31.5%) had atrial fibrillation. Between 1993 and 2012, there was an average annual reduction of 0.8% (95% CI: -1.5%; 0.0%) in the proportion of atrial fibrillation patients among all AIS patients, whereas the proportion of newly diagnosed atrial fibrillation patients among all atrial fibrillation patients increased annually by an average of 7.1% (95% CI: 5.4%;8.9%). Among all atrial fibrillation patients, there was an average annual reduction of 2.9% (95% CI: -2.7; -3.2%) in the proportion of previously known atrial fibrillation patients, followed by an annual average reduction of 2.4% (95% CI: -1.2; -3.6%) in the proportion of previously known atrial fibrillation patients not receiving any antithrombotic treatment at admission. During that period, there was an increase in the average annual proportion of previously known atrial fibrillation patients treated with anticoagulants (6.4%, 95% CI: 1.2;11.9%) and aspirin (2.3%, 95% CI: -0.4;5.0%) at admission; an average annual increase in the proportion of atrial fibrillation patients who were prescribed anticoagulant was apparent both for patients with mRS<4 (3.5%) and mRS: 4-5 (7.2%), while the proportion of atrial fibrillation patients who were prescribed aspirin or no antithrombotic at discharge was annually reduced (5.8% for mRS<4; 1.6% for mRS: 4-5 and 7.1% for mRS<4;5.3% for mRS: 4-5 respectively). Stroke recurrences were annually reduced by an average of 5.8% (95% CI: -8.6; -3.0%), along with cardiovascular events (6.5%, 95% CI: -8.3; -4.7%) and deaths (7.9%, 95% CI: -9.2; -6.5%). Conclusions Between 1993 and 2012, the proportion of atrial fibrillation patients on proper antithrombotic treatment and the rate of newly diagnosed atrial fibrillation increased significantly. Rates of stroke recurrence, cardiovascular events, and mortality reduced significantly.

Age- and sex-specific analysis of patients with embolic stroke of undetermined source.

OBJECTIVE: To investigate whether the correlation of age and sex with the risk of recurrence and death seen in patients with previous ischemic stroke is also evident in patients with embolic stroke of undetermined source (ESUS). METHODS: We pooled datasets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. We performed Cox regression and Kaplan-Meier product limit analyses to investigate whether age (<60, 60-80, >80 years) and sex were independently associated with the risk for ischemic stroke/TIA recurrence or death. RESULTS: Ischemic stroke/TIA recurrences and deaths per 100 patient-years were 2.46 and 1.01 in patients <60 years old, 5.76 and 5.23 in patients 60 to 80 years old, 7.88 and 11.58 in those >80 years old, 3.53 and 3.48 in women, and 4.49 and 3.98 in men, respectively. Female sex was not associated with increased risk for recurrent ischemic stroke/TIA (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.84-1.58) or death (HR 1.35, 95% CI 0.97-1.86). Compared with the group <60 years old, the 60- to 80- and >80-year groups had higher 10-year cumulative probability of recurrent ischemic stroke/TIA (14.0%, 47.9%, and 37.0%, respectively, p < 0.001) and death (6.4%, 40.6%, and 100%, respectively, p < 0.001) and higher risk for recurrent ischemic stroke/TIA (HR 1.90, 95% CI 1.21-2.98 and HR 2.71, 95% CI 1.57-4.70, respectively) and death (HR 4.43, 95% CI 2.32-8.44 and HR 8.01, 95% CI 3.98-16.10, respectively). CONCLUSIONS: Age, but not sex, is a strong predictor of stroke recurrence and death in ESUS. The risk is ≈3- and 8-fold higher in patients >80 years compared with those <60 years of age, respectively. The age distribution in the ongoing ESUS trials may potentially influence their power to detect a significant treatment association.

Embolic Stroke of Undetermined Source and Detection of Atrial Fibrillation on Follow-Up: How Much Causality Is There?

BACKGROUND: There is increasing debate whether atrial fibrillation (AF) episodes during follow-up in patients with embolic stroke of undetermined source (ESUS) are causally associated with the event. AF-related strokes are more severe than strokes of other etiologies. In this context, we aimed to compare stroke severity between ESUS patients diagnosed with AF during follow-up and those who were not. We hypothesized that, if AF episodes detected during follow-up are indeed causally associated with the index event, stroke severity in the AF group should be higher than the non-AF group. METHODS: Dataset was derived from the Athens Stroke Registry. ESUS was defined by the Cryptogenic Stroke/ESUS International-Working-Group criteria. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score. Cumulative probabilities of recurrent stroke or peripheral embolism in the AF and non-AF ESUS groups were estimated by Kaplan-Meier analyses. RESULTS: Among 275 ESUS patients, AF was detected during follow-up in 80 (29.1%), either during repeated electrocardiogram monitoring (18.2%) or during hospitalization for stroke recurrence (10.9%). NIHSS score was similar between the two groups (5 [2-13] versus 5 [2-14], P = .998). More recurrent strokes or peripheral embolisms occurred in the AF group compared with the non-AF group (42.5% versus 13.3%, P = .001). CONCLUSIONS: Stroke severity is similar between ESUS patients who were diagnosed with AF during follow-up and those who were not. Given that AF-related strokes are more severe than strokes of other etiologies, this finding challenges the assumption that the association between ESUS and AF detected during follow-up is as frequently causal as regarded.

Risk Stratification for Recurrence and Mortality in Embolic Stroke of Undetermined Source.

BACKGROUND AND PURPOSE: The risk of stroke recurrence in patients with Embolic Stroke of Undetermined Source (ESUS) is high, and the optimal antithrombotic strategy for secondary prevention is unclear. We investigated whether congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and stroke or transient ischemic attack (TIA; CHADS2) and CHA2DS2-VASc scores can stratify the long-term risk of ischemic stroke/TIA recurrence and death in ESUS. METHODS: We pooled data sets of 11 stroke registries from Europe and America. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group. Cox regression analyses were performed to investigate if prestroke CHADS2 and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or TIA, vascular disease, age 65-74 years, sex category (CHA2DS2-VASc) scores were independently associated with the risk of ischemic stroke/TIA recurrence or death. The Kaplan-Meier product limit method was used to estimate the cumulative probability of ischemic stroke/TIA recurrence and death in different strata of the CHADS2 and CHA2DS2-VASc scores. RESULTS: One hundred fifty-nine (5.6% per year) ischemic stroke/TIA recurrences and 148 (5.2% per year) deaths occurred in 1095 patients (median age, 68 years) followed-up for a median of 31 months. Compared with CHADS2 score 0, patients with CHADS2 score 1 and CHADS2 score >1 had higher risk of ischemic stroke/TIA recurrence (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.41-4.00 and HR, 2.72; 95% CI, 1.68-4.40, respectively) and death (HR, 3.58; 95% CI, 1.80-7.12, and HR, 5.45; 95% CI, 2.86-10.40, respectively). Compared with low-risk CHA2DS2-VASc score, patients with high-risk CHA2DS2-VASc score had higher risk of ischemic stroke/TIA recurrence (HR, 3.35; 95% CI, 1.94-5.80) and death (HR, 13.0; 95% CI, 4.7-35.4). CONCLUSIONS: The risk of recurrent ischemic stroke/TIA and death in ESUS is reliably stratified by CHADS2 and CHA2DS2-VASc scores. Compared with the low-risk group, patients in the high-risk CHA2DS2-VASc group have much higher risk of ischemic stroke recurrence/TIA and death, approximately 3-fold and 13-fold, respectively.

The Pathophysiological Mechanism Is an Independent Predictor of Long-Term Outcome in Stroke Patients with Large Vessel Atherosclerosis.

BACKGROUND: Etiopathological mechanisms underlying ischemic stroke play a crucial role in long-term prognosis. We aimed to investigate the association between the mechanism of stroke due to large vessel disease, and long-term outcome. METHODS: All consecutive patients registered in the Athens Stroke Registry with atherosclerotic stroke between 1993 and 2010 were included in the analysis. The patients were subdivided into 3 groups according to the presumed underlying mechanism: low-flow infarcts, artery-to-artery embolism, and intrinsic atherosclerosis. They were followed up for up to 10 years or until death. The end points of the study were 10-year all-cause mortality, stroke recurrence, and composite cardiovascular events. RESULTS: Five hundred two patients were classified as follows: 156 (31%) as low-flow (watershed) strokes, 256 (51%) as artery-to-artery embolic strokes, and 90 (18%) as intrinsic atherosclerotic strokes. The cumulative probability of 10-year mortality rate was similar between groups of patients with different stroke mechanisms: 49.9% (95% confidence interval [CI], 38.5-61.3) for patients with low-flow mechanism, 47.6% (95% CI, 39.4-55.8) for patients with artery-to-artery embolism, and 48.5% (95% CI, 34.0-63.0) for patients with intrinsic atherosclerosis. Patients in the intrinsic atherosclerosis group had significantly higher risks of recurrence (adjusted hazard ratio [HR] = 2.1; 95% CI, 1.19-3.73) compared with those in the artery-to-artery embolism group. Moreover, patients in the intrinsic atherosclerosis and low-flow groups had significantly higher risks of composite cardiovascular events compared with those in the artery-to-artery embolism group (adjusted HR = 1.94; 95% CI, 1.26-3.00; and adjusted HR = 1.64; 95% CI, 1.13-2.38, respectively). CONCLUSION: Low-flow and intrinsic atherosclerosis strokes are associated with a high risk for future cardiovascular events and stroke recurrence. However, long-term mortality is similar across different subgroups.

Embolic Strokes of Undetermined Source in the Athens Stroke Registry: An Outcome Analysis.

BACKGROUND AND PURPOSE: Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. METHODS: Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan-Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox-regression to investigate whether stroke type was outcome predictor. RESULTS: 2731 patients were followed-up for a mean of 30.5±24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%-72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%-42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%-35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%-31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52-0.94]). CONCLUSIONS: Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes.