Cryptogenic Ischemic Stroke Patients Research Articles

Left atrial longitudinal strain behavior in patients with cryptogenic stroke - a case control study

Abstract Background A significant percentage of ischemic strokes classified as cryptogenic stroke (CS) where the definition is varied according to the type of classification used. Left atrial (LA) function has a role in determining the possible cardio-embolic source of stroke. Using speckle tracking transthoracic echocardiography (TTE) we can detect the early changes in left atrial function by measuring left atrial longitudinal strain (LALS). Aim To evaluate the left atrial stain in patients with a cryptogenic stroke as compared to a healthy papulation. Method and results We recruited 50 cryptogenic ischemic stroke patients with mean age of 44.7 years and 50 % were male who treated consecutively as for first CS, and 50 age-and sex-matched healthy stroke-free controls. Using Speckle tracking TTE analysis we measured the global , passive and active longitudinal LA strain corresponding to the reservoir (LASRES), conduit(LASCD), and contractile function(LASCT),respectively in addition to standard other LA parameters and filling pressure parameters of Left ventricle(LV) in both group. Data were compared using t-test and Mann-Whitney test. Cryptogenic stroke patients as compared with controls had significantly reduced value of all components of LALS [Mean value of LASRES, LASCD and LASCT in CS group versus control group were 25.15±6.79 versus 43.95±4.62 (P-value <0.01), 14.41±3.53 versus 25.68±3.30 (P- value <0.01), 10.73±3.35 versus 18.28±1.60 (P-value <0.01) respectively] (Figure 1 and Figure 2). There were no significant differences in means of LA area and LA volume index in both groups (P value >0.05). Between parameters of LV filling pressures, it was noticed that early diastolic transmitral flow velocity (E) and early diastolic velocity at annulus (E’) were statistically lower in CS patients as compared to control group (P-value <0.01). In addition, the Cluster and Discriminant analysis used confirmed that LASRES, LASCD and LASCT were significantly lower in value in cryptogenic stroke patients in comparison to Control group which can be used to detect early LA dysfunction. Conclusion LA longitudinal strain in all components were significantly impaired in patients with CS. Measuring LALS parameters can be useful in determining early LA dysfunction in cryptogenic stroke patients.Figure 1-left atrial strain components.Figure 2 -left atrial strain component.

Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls (P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18–34.5) and severe periodontitis with an OR of 7.48 (1.24–44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87–23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01–6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72–40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.

Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults

BackgroundIncidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored. ObjectivesThe purpose of this study was to assess the association between increased LA stiffness and CIS in young adults. MethodsIn the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e’ velocity (E/e′)/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness. ResultsIncreased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05). ConclusionsLA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725)

Multikingdom oral microbiome interactions in early-onset cryptogenic ischemic stroke.

Although knowledge of the role of the oral microbiome in ischemic stroke is steadily increasing, little is known about the multikingdom microbiota interactions and their consequences. We enrolled participants from a prospective multicentre case-control study and investigated multikingdom microbiome differences using saliva metagenomic datasets (n = 308) from young patients diagnosed with cryptogenic ischemic stroke (CIS) and age- and sex-matched stroke-free controls. Differentially abundant taxa were identified using Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC2). Functional potential was inferred using HUMANn3. Our findings revealed significant differences in the composition and functional capacity of the oral microbiota associated with CIS. We identified 51 microbial species, including 47 bacterial, 3 viral, and one fungal species associated with CIS in the adjusted model. Co-abundance network analysis highlighted a more intricate microbial network in CIS patients, indicating potential interactions and co-occurrence patterns among microbial species across kingdoms. The results of our metagenomic analysis reflect the complexity of the oral microbiome, with high diversity and multikingdom interactions, which may play a role in health and disease.

Stroke in Patients with Atrial Fibrillation: Epidemiology, Screening, and Prognosis.

Atrial fibrillation (AF) is the most common sustained arrythmia and one of the strongest risk factors and causal mechanisms of ischemic stroke (IS). Acute IS due to AF tends to be more severe than with other etiology of IS and patients with treated AF have reported to experience worse outcomes after endovascular treatment compared with patients without AF. As cardioembolism accounts for more than a fifth of ISs and the risk of future stroke can be mitigated with effective anticoagulation, which has been shown to be effective and safe in patients with paroxysmal or sustained AF, the screening of patients with cryptogenic IS (CIS) for AF is paramount. Embolic stroke of undetermined source (ESUS) is a subtype of CIS with a high likelihood of cardioembolism. The European Stroke Organization and European Society of Cardiology guidelines recommend at least 72 h of screening when AF is suspected. The longer the screening and the earlier the time point after acute IS, the more likely the AF paroxysm is found. Several methods are available for short-term screening of AF, including in-hospital monitoring and wearable electrocardiogram recorders for home monitoring. Implantable loop monitors provide an effective long-term method to screen patients with high risk of AF after IS and artificial intelligence and convolutional neural networks may enhance the efficacy of AF screening in the future. Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists in both primary and secondary prevention of IS in AF patients. Recent data from the randomized controlled trials (RCT) also suggest that early initiation of DOAC treatment after acute IS is safe compared to later initiation. Anticoagulation treatment may still predispose for intracranial bleeding, particularly among patients with prior cerebrovascular events. Left atrial appendix closure offers an optional treatment choice for patients with prior intracranial hemorrhage and may offer an alternative to oral anticoagulation even for patients with IS, but these indications await validation in ongoing RCTs. There are still controversies related to the association of found AF paroxysms in CIS patients with prolonged screening, pertaining to the optimal duration of screening and screening strategies with prolonged monitoring techniques in patients with ESUS. In this review, we summarize the current knowledge of epidemiology, screening, and prognosis in AF patients with stroke.

Propensity-score matched analysis of patent foramen ovale closure in real-world study cohort with cryptogenic ischemic stroke

IntroductionPatent foramen ovale (PFO) occurs in 25% of the general population and in 40% of cryptogenic ischemic stroke patients. Recent trials support PFO closure in selected patients with cryptogenic stroke. We examined the outcomes of transcatheter PFO closure in a real-world study cohort with cryptogenic stroke. MethodsConsecutive ischemic stroke patients who were classified as cryptogenic on the TOAST aetiology and diagnosed with a PFO were included. All patients underwent either transcatheter PFO closure or medical therapy. A 2:1 propensity score matching by sex and Risk-of-Paradoxical-Embolism (RoPE) score was performed. Multivariable regression models adjusted for sex and RoPE score. ResultsOur cohort comprised 232 patients with mean age 44.3 years (SD 10.8) and median follow-up 1486.5 days. 33.2% were female. PFO closure (n=84) and medical therapy (n=148) groups were well-matched with <10% mean-difference in sex and RoPE score. Two patients in the treated group (2.4%) and seven in the control group (4.7%) had a recurrent ischemic stroke event. Multivariable Cox regression demonstrated a hazard-ratio of 0.26 (95%CI 0.03-2.13, P=0.21) for PFO closure compared to control. The incidence of atrial fibrillation (AF) detected post-PFO closure was similar between the treated and control (1.19% vs 1.35%, multivariable logistic regression odds-ratio 0.90, 95%CI 0.04-9.81, P=0.94). There were no major periprocedural complications documented. The difference in restricted mean survival-time free from stroke at two years between treated and control was 26.2 days (95%CI 5.52-46.85, P=0.013). ConclusionsIn this Asian cohort, we report a low incidence of ischemic stroke recurrence and new-onset AF in patients who underwent PFO closure. When compared to the medical therapy group, there was no significant difference in the incidence of stroke recurrence and new-onset AF. Further studies involving larger real-world cohorts are warranted to identify patients who are more likely to benefit from PFO closure.

24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults

Background In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls. Patients and Methods In this substudy of the international multicenter case–control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18–49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status. Results 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20–12.42), in participants without antihypertensives (4.86; 1.07–22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47–36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37–17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged. Conclusions Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution. Key Messages Nocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale. It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

Markers of early vascular aging are not associated with cryptogenic ischemic stroke in the young: A case-control study

Background and PurposeWe aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study. MethodsWe enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS. ResultsPatients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women). ConclusionsHigher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS.

Supraventricular Runs in 7-Day Holter Monitoring Are Related to Increased Incidence of Atrial Fibrillation in a 3-Year Follow-Up of Cryptogenic Stroke Patients Free from Arrhythmia in a 24 h-Holter.

Introduction: Silent atrial fibrillation (AF) is a common cause of cryptogenic ischemic stroke (CIS). The 24-h-Holter is insufficient to reveal an occult arrhythmic cause of stroke and the strategy to select the patients for long-term monitoring is missing. Objectives: The aim of the study was to evaluate 7-day-Holter monitoring to identify cases with the arrhythmic cause of stroke in CIS patients in whom 24-h-Holter was free from arrhythmia, and to assess the relation between supraventricular (SV) runs in baseline Holter and the incidence of AF in a 3-year follow-up period. Methods: 78 patients (aged 60 ± 9 years, 45 males) with CIS and no arrhythmic findings in 24-h-Holter were enrolled. All patients had 7-day-Holter monitoring after stroke and were followed up for 36 months, and then 7-day Holter was repeated. We assessed SV runs (≥5 QRS) in the initial 7-day Holter and analyzed the relation of the findings with clinical characteristics of novel AF episodes revealed early after stroke and during a 3-year follow-up. Results: Baseline 7-day-Holter revealed SV runs in 36% of patients and AF in 9% of cases. During a 3-year follow-up, 8 additional cases were confirmed, both in standard care and in repeated Holter (a total of 19% of AF cases). There was no difference with regard to CHADS2VASc score (3.6 ± 1.1 vs. 3.4 ± 1.5; p = NS) and left atrium parameters between patients with SV runs and the non-arrhythmic group. Patients with SV runs had a higher incidence of AF both after stroke and in a 3-year follow-up (46% vs. 4%, RR 11.6, p < 0.001). In 8 cases, patent foramen ovale was detected during follow-up. Conclusions: A strategy of baseline 7-day-Holter monitoring after stroke allows for disclosing SV runs in every third case and AF in 9% of stroke survivors. Patients with SV runs have a higher incidence of AF (RR 11.6, p < 0.001) and should be considered for extended continuous ECG monitoring.

Abstract P654: Predicting Afib in Cryptogenic Ischemic Stroke Patients With Implantable Loop Recorders

Paroxysmal atrial fibrillation (Afib) detection in cryptogenic stroke is difficult but essential because it changes management. We describe a scoring system that discriminates between cryptogenic ischemic stroke patients with implantable loop recorder (ILR) that were and were not found to have Afib. Consecutive cryptogenic stroke cases from cardiology’s ILR registry for a 2-year period (7/2017-7/2019) were reviewed. We used standardized case report forms to perform chart abstraction. Cases were excluded if ILR was not placed after the index stroke event, stroke etiology workup was not available, or data was incomplete. Patients found to have Afib on ILR were compared to those without evidence of Afib on ILR. We devised a novel scoring system using variables associated with Afib detection and compared its ability to classify Afib detection against CHA2DS2-VASc and LADS. One hundred fifty-seven patients met inclusion criteria. Afib was detected in 12% of cases (9% at 6 months, 10% at 12 months). The median time from ILR placement to Afib detection was 110 days (IQR 37, 507). Median time from Afib detection to the start of anticoagulation was 3 days (IQR 0, 8). The PAL-CrISP score ranges 0 to 7: age (70=0, ≥70=4), history of antihypertensive medication (no=0, yes=2), PR interval (≤200msec=0, &gt;200msec=1). Of those found to have Afib via ILR, 74% (14/19) had a PAL-CrISP score ≥ 6. PAL-CrISP performed better at predicting Afib detection in cryptogenic ischemic stroke patients with ILR (AUC 0.810, 95% CI 0.706-0.913) than CHA2DS2-VASc (AUC 0.650, 95% CI 0.525-0.774) and LADS (AUC 0.745, 95% CI 0.624-0.866). Using only age, home medication review, and an EKG, the novel PAL-CrISP score performs better at predicting Afib detection than the CHA2DS2-VASc and LADS scores in cryptogenic ischemic stroke patients with an ILR.

72 hour Holter monitoring, 7 day Holter monitoring, and 30 day intermittent patient-activated heart rhythm recording in detecting arrhythmias in cryptogenic stroke patients free from arrhythmia in a screening 24 h Holter

IntroductionAccording to recent studies, silent atrial fibrillation (AF) is a common cause of cryptogenic ischemic stroke (CIS). 12-lead electrocardiogram (ECG) and 24 h Holter are not efficient to reveal an occult arrhythmic cause of stroke.ObjectivesThe aim of the study was to evaluate 72 h Holter, 7 day Holter monitoring, and intermittent single-lead ECG recording in patients with CIS to identify cases with the arrhythmic cause of stroke in patients with CIS in whom 24 h ECG Holter was free from arrhythmia.Methods72 patients (aged 60 ± 9 years, 44 males) with CIS and no arrhythmic findings in 24 h Holter were enrolled. All patients had 7 day Holter monitoring and received handheld ECG recorder (CheckMe, Viatom) for ambulatory 30 ± 3 days ECG recording. AF, supraventricular tachycardia (SVT runs of ≥5 QRS), and other arrhythmias were assessed in the first 72 h of Holter recording, in 7 day-recording, and in handheld ECG strips.Results72 h-recording revealed AF in four cases (5.6%) and SVT in 18 (25%) cases. 7 day Holter confirmed AF in seven patients (10%) and SVT in 27 patients (37.5%). There was no difference in regards to CHADS2VASc score between patients with SVT and non-arrhythmic group (3.6 ± 1.1 vs 3.4 ± 1.6; p = NS). Symptoms did not correlate with findings. Patient-activated handheld ECG recorders were used with good compliance. The mean number of recordings was 49 ± 30. Except for PACs, there was only one case of AF documented in 3,531 strips.Conclusions7 day Holter performs better than 72 h and reveals supraventricular arrhythmias in every third and AF in 10% of CIS patients who were free from arrhythmia in 24 h ECG monitoring. 30 day intermittent ECG monitor does not yield diagnostic value in CIS.

Left Atrial Dynamics Is Altered in Young Adults With Cryptogenic Ischemic Stroke: A Case-Control Study Utilizing Advanced Echocardiography.

BackgroundIschemic stroke in young individuals often remains cryptogenic. Some of these strokes likely originate from the heart, and atrial fibrosis might be one of the etiological mechanisms. In this pilot study, we investigated whether advanced echocardiography findings of the left atrium (LA) of young cryptogenic stroke patients differ from those of stroke‐free controls.Methods and ResultsWe recruited 30 cryptogenic ischemic stroke patients aged 18 to 49 years and 30 age‐ and sex‐matched stroke‐free controls among participants of the SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study (NCT01934725). We measured basic left ventricular parameters and detailed measures of the LA, including 4‐dimensional volumetry, speckle tracking epsilon, strain rate, and LA appendix orifice variation. Data were compared as continuous parameters and by tertiles. Compared with controls, stroke patients had smaller LA reservoir volumes (10.2 [interquartile range, 5.4] versus 13.2 [5.4] mL; P=0.030) and smaller positive epsilon values (17.8 [8.5] versus 20.8 [10.1]; P=0.023). In the tertile analysis, stroke patients had significantly lower left atrial appendage orifice variation (3.88 [0.75] versus 4.35 [0.90] mm; P=0.043), lower LA cyclic volume change (9.2 [2.8] versus 12.8 [3.5] mL; P=0.023), and lower LA contraction peak strain rate (−1.8 [0.6] versus −2.3 [0.6]; P=0.021). We found no statistically significant differences in left ventricular measures.ConclusionsThis preliminary comparison suggests altered LA dynamics in young patients with cryptogenic ischemic stroke, and thus that LA wall pathology might contribute to these strokes. Our results await confirmation in a larger sample.

Risk of recurrent ischemic stroke in young cryptogenic patients with embolic stroke of undetermined source

In young patients, cause of ischemic stroke (IS) remains very often cryptogenic and thus effectiveness of secondary prevention may be uncertain. Elderly cryptogenic IS patients (CIS) with ESUS (Embolic Stroke of Undetermined Source) have a higher risk of recurrent IS (RIS). The aim was to compare risk of RIS between ESUS and other young CIS patients. The study set consisted of young acute IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). In all patients, brain ischemia was confirmed on CT/MRI. Admission ECG, serum specific cardiac and thrombophilia markers, neurosonology, TEE, 24-hour and 3-week ECG-Holter were performed to assess cause of IS according to the ASCOD classification. Of 279 enrolled patients < 50 years (153 males, mean age 41.1 ± 7.8 years), 199 (71%) were identified as cryptogenic and 106 (59 males, mean age 40.7 ± 7.5 years) fulfilled ESUS criteria. During the follow-up with a median of 17 months, two (2%) ESUS and 4 (4%) other CIS patients suffered from RIS (p=0.421). The mean time to RIS did not differ between both groups (14 vs. 27 months, p=0.248). One-year risk of RIS was 0 for ESUS and 0.025 (95% CI: 0-0.059) for other CIS patients (p=0.248). Conclusion: The risk of RIS was very low and did not differ between young ESUS and other CIS patients. Supported by the grant of Ministry of Health of Czech Republic n. 17-30101A and IGA LF UP_008_2019.

Carotid Webs in Cryptogenic Ischemic Strokes: A Matched Case-Control Study

Background: Young individuals with symptomatic carotid webs may be predisposed to ischemic strokes. However, evidence remains scarce. This investigation reports the frequency of carotid webs among patients with cryptogenic strokes compared to a control group. Methods: Consecutive cryptogenic ischemic strokes and trauma patients were identified. Additional inclusion criteria required age 18-60 years and availability of head/neck computed tomography (CT) angiography. CT angiogram (CTA) neck images were evaluated independently by 2 fellowshiptrained specialists. A carotid web was defined by a shelf-like, linear filling defect in the posterior internal carotid artery bulb. Results: Of 1877 patients presenting with ischemic strokes in 2015-2017, 165 were diagnosed with cryptogenic strokes, 51 of whom met the inclusion criteria of age and CTA availability. Fifty one trauma cases were matched for age and sex. After imaging analysis, 13 carotid webs (25%) were identified in the 51 cryptogenic stroke group versus 0 (0%; P < .001) in trauma subjects. Thirty-nine of the 51 cryptogenic ischemic stroke patients were found with carotid anterior distribution infarcts, of which 9 (23%) were found with ipsilateral carotid webs. There were more proximal large vessel occlusions in the cryptogenic patients with carotid webs, compared to those without (P = .04). All carotid webs led to less than 30% degree of stenosis. Conclusions: Carotid webs were found at a significantly higher frequency in patients with cryptogenic ischemic strokes compared to controls, indicating a potentially thrombogenic nature of these lesions in young patients. Additionally, intracranial large vessel occlusions were more common in patients with symptomatic carotid webs, presenting with ipsilateral strokes.

Incidence, characteristics and outcomes in patients with embolic stroke of undetermined source: A population-based study

Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10–25) and 16.6 (95%CI: 10–24) per 100,000 person-years. Patients with ESUS were younger (p < .001) and had lower median admission NIHSS-scores (p < .001). Functional outcomes were more favorable in ESUS at 28, 90 and 365 days. ESUS was independently (p = .033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, −3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence, mortality and functional improvement on multivariable analyses. In conclusion we found that ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Abstract TP199: Incidence, Characteristics and Outcomes in Patients With Embolic Stroke of Undetermined Source: A Population-based Study

Introduction: Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Methods: Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. Results: We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10-25) and 16.6 (95%CI: 10-24) per 100,000 person-years. Patients with ESUS were younger [median age 68 years (IQR:61-75) vs. 79 years (IQR:73-83); p&lt;0.001] and had lower median admission NIHSS-scores [4 points (IQR:2-8) vs. 8 points (IQR:5-16); p&lt;0.001]. Functional outcomes were more favorable in ESUS at 28 [median mRS-score: 2 (IQR:1-3) vs. 4 (IQR:3-6)], 90 [median mRS-score: 1 (IQR:0-2) vs. 4 (IQR:2-6)] and 365 days [median mRS-score: 1 (IQR:0-2) vs. 5 (IQR:2-6)]. ESUS was independently (p=0.033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, -3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence (HR: 0.22, 95%CI: 0.01-4.06), mortality (HR: 0.25, 95%CI: 0.02-4.36) and functional improvement (1-point shift in mRS-scores; cOR: 1.47, 95%CI: 0.59-3.70) on multivariable analyses. Conclusions: ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Cost-effectiveness of percutaneous patent foramen ovale closure as secondary stroke prevention

Objective: Compared to medical therapy alone, percutaneous closure of patent foramen ovale (PFO) further reduces risk of recurrent ischemic strokes in carefully selected young to middle-aged patients with a recent cryptogenic ischemic stroke. The objective of this study was to evaluate the cost-effectiveness of this therapy in the context of the United Kingdom (UK) healthcare system.Methods: A Markov cohort model consisting of four health states (Stable after index stroke, Post-Minor Recurrent Stroke, Post-Moderate Recurrent Stroke, and Death) was developed to simulate the economic outcomes of device-based PFO closure compared to medical therapy. Recurrent stroke event rates were extracted from a randomized clinical trial (RESPECT) with a median of 5.9-year follow-up. Health utilities and costs were obtained from published sources. One-way and probabilistic sensitivity analyses (PSA) were performed to assess robustness. The model was discounted at 3.5% and reported in 2016 Pounds Sterling.Results: Compared with medical therapy alone and using a willingness-to-pay (WTP) threshold of £20,000, PFO closure reached cost-effectiveness at 4.2 years. Cost-effectiveness ratios (ICERs) at 4, 10, and 20 years were ₤20,951, ₤6,887, and ₤2,158, respectively. PFO closure was cost-effective for 89% of PSA iterations at year 10. Sensitivity analyses showed that the model was robust.Conclusions: Considering the UK healthcare system perspective, percutaneous PFO closure in cryptogenic ischemic stroke patients is a cost-effective stroke prevention strategy compared to medical therapy alone. Its cost-effectiveness was driven by substantial reduction in recurrent strokes and patients’ improved health-related quality-of-life.

Cryptogenic Ischemic Stroke Patients with Left Atrial Enlargement are More Likely to Have Paroxysmal Atrial Fibrillation (P6.243)

Cryptogenic Ischemic Stroke Patients with Left Atrial Enlargement are More Likely to Have Paroxysmal Atrial Fibrillation (P6.243)

Prevalence and Risk Factors for Paroxysmal Atrial Fibrillation and Flutter Detection after Cryptogenic Ischemic Stroke

Long-term cardiac monitoring with implantable loop recorders (ILRs) has revealed occult paroxysmal atrial fibrillation and flutter (PAF) in a substantial minority of cryptogenic ischemic stroke (CIS) patients. Herein, we aim to define the prevalence, clinical relevance, and risk factors for PAF detection following early poststroke ILR implantation. A retrospective study of CIS patients (n = 100, mean age 65.8 years; 52.5% female) who underwent ILR insertion during, or soon after, index stroke admission. Patients were prospectively followed by the study cardiac electrophysiologist who confirmed the PAF diagnosis. Univariate and multivariate analyses compared clinical, laboratory, cardiac, and imaging variables between PAF patients and non-PAF patients. PAF was detected in 31 of 100 (31%) CIS patients, and anticoagulation was initiated in almost all (30 of 31, 96.8%). Factors associated with PAF detection include older age (mean [year] 72.9 versus 62.9; P = .003), white race (odds ratio [OR], 4.5; confidence interval [CI], 1.8-10.8; P = .001), prolonged PR interval (PR > 175 ms; OR, 3.3; CI, 1.2-9.4; P = .022), larger left atrial (LA) diameter (mean [cm] 3.7 versus 3.5; P = .044) and LA volume index (mean [cc/m2]; 30.6 versus 24.2; P = .014), and lower hemoglobin (Hb)A1c (mean [%] 6.0 versus 6.4; P = .036). Controlling for age, obesity (body mass index > 30 kg/m2; OR, 1.2; CI, 1.1-1.4; P = .033) was independently associated with PAF detection. PAF was detected with high prevalence following early postcryptogenic stroke ILR implantation and resulted in significant management changes. Older age, increased PR interval, LA enlargement, and lower HbA1c are significantly associated with PAF detection. Controlling for age, obesity is an independent risk factor. A larger prospective study is warranted to confirm these findings.

Abstract WMP63: Prevalence of Occult Paroxysmal Atrial Fibrillation in Non-Cryptogenic Ischemic Stroke Patients

Background: Paroxysmal atrial fibrillation (PAF) is often asymptomatic and is more prevalent than persistent AF in patients with ischemic stroke (IS). Long-term monitoring with insertable cardiac monitors (ICM) yields an up to 30% PAF detection rate in cryptogenic IS patients. Yet, the prevalence of PAF in patients with a presumed stroke etiology other than AF remains unknown. Methods: Prospective cohort study of non-cryptogenic IS patients implanted within 10 days of stroke onset with the Reveal LINQ ICM (n=47 enrolled, 45/47 (95.7%) implanted). Patients were monitored until PAF detection (adjudicated by study cardiologist) or minimum of 12 months. Inclusion required a defined stroke etiology other than AF based on standard stroke evaluation (including ≥24 hour cardiac telemetry), age≥40, and either a virtual CHADS2 score ≥3, or ≥2 PAF related comorbidities (COPD, hyperthyroidism, obesity, prior MI, PR interval &gt;175ms, or renal impairment). Patients with high-risk cardiac sources, recent MI or cardiac bypass surgery, pacemaker or defibrillator, permanent anticoagulation indication or contraindication, and pregnancy were excluded. Results: Mean age 64.8 years (range 40-88 years), 15/47 (31.9%) female, mean virtual CHADS2 score 3.5 (range 3 to 5), mean CHA2DS2-VASc score 4.5 (range 3 to 8), and 8/47 (17.0%) had ≥2 PAF comorbidities. Lacunar stroke etiology predominated (n=33), followed by extracranial atherosclerotic stenosis (n=4), cardioembolic (n=3), arch atheroembolic (n=3), intracranial atherosclerosis (n=4), and extracranial dissection (n=2). Five had multiple potential sources. Interim analysis (mean monitoring 264 days, range 0 to 642 days) demonstrates 3/45 (6.7%) implanted patients have PAF (range of longest AF episode: 0.3 to 18.7 hours). Mean time to PAF diagnosis 162.7 days (range 9-356 days). All were started on anticoagulation. There was 1 device related complication (skin erosion) and 1 patient had recurrent stroke. Conclusions: Occult PAF in non-cryptogenic IS patients is infrequent and may reflect the background prevalence of PAF in this demographic. Despite this, long-term cardiac monitoring may promote optimization of stroke prevention therapy for a small but unanticipated proportion of these patients.