Cryptogenic Ischemic Stroke Research Articles

Abstract 12671: Left Atrial Volumes Corrected for Heart Size are Superior Echocardiographic Measures for Diagnosing Paroxysmal Atrial Fibrillation in Ischemic Stroke and Transient Ischemic Attack Patients

Introduction: The underlying cause of ischemic strokes (IS) and transient ischemic attacks (TIA) is not identified in 25% of the cases. However, asymptomatic paroxysmal atrial fibrillation (PAF) is often assumed to be the cause of the cryptogenic IS or TIA Hypothesis: The aim of this study was to examine if echocardiographic measures of LA volume (LAV) corrected for the left ventricular (LV) length (LAVMax/Min/LV length) could predict PAF in patients with IS and TIA. Methods: We retrospectively included 218 patients who after acute IS or TIA underwent a transthoracic echocardiographic examination in sinus rhythm. Patients were designated as PAF-patients if they had one or more reported incidents of AF before or after their echocardiographic examination. Results: Patients in the PAF group were significantly older (62±13 vs. 52±14 years, p<0.001), had higher CHA2DS2-VASc score (3.3±1.3 vs. 3.8±1.3, p=0.042) and higher National Institutes of Health Stroke Scale (NIHSS) score (2.9±4.9 vs. 1.4±3.3, p=0.016) than patients without PAF. Besides these, no other baseline characteristics (sex, hypertension, diabetes, cholesterol) were associated with PAF. None of the conventional echocardiographic parameters (LV ejection fraction, LV volumes, E/A-ratio, E-wave deceleration time, LAVmax) were significantly associated with PAF. However, the atrial measures corrected for LV length (LAVMax/LV length and LAVMin/LV length) were significantly higher (LAVMax/LV length: 7.6±3.3 mL/cm vs. 6.5± 2.0 mL/cm, p=0.009; LAVMin/LV length: 3.7± 2.1 mL/cm vs. 2.8±1.1 mL/cm, p<0.001) in patients with PAF (Figure), even after adjustment for age, gender, CHA2DS2-VASc and NIHSS scores. Conclusion: In patients with IS and TIA, measures of LA size corrected for LV length are independently associated with the presence of PAF. Applying these may yield better risk stratification for PAF-presence in patients suffering cryptogenic IS and TIA.

Ischemic stroke in young adults

The authors have analyzed the causes of ischemic stroke (IS) in more than 600 young patients examined in the cerebrovascular department of the Neurological Research Center (Moscow) during the period 2003-2016 years. It has been suggested that a wider use of high-resolution MRI and T1 weighted db-fs images as well as intracranial CTA will help to verify more often intracranial dissection and primary cerebral vasculitis that will result in a decrease of cryptogenic IS frequency.

Cryptogenic mechanism in ischaemic stroke patients is a predictor of 5-year survival: A population-based study.

The present study sought to identify factors affecting mortality beyond 28 days in ischaemic stroke patients with whatever ischaemic mechanism. A prospective population-based registry was set up in Brest County, Brittany, France. Demographic data, clinical presentation, vascular risk factors and mortality were collected from January 2008 to December 2012. At "home without help" was used as a surrogate marker for low Rankin (0-1) at discharge from the hospital. IS was classified on the TOAST classification. Overall mortality was calculated using the Kaplan-Meier method. Multivariate analysis of mortality beyond 28 days was implemented, using a Cox model, on significant risk factors identified on univariate analysis. About 3024 IS cases were followed up beyond 28 days. Overall mortality beyond 28 days was 38.49% at 60 months. On multivariate analysis, age (10 years: HR = 1.84; [1.66-2.02]), coronary artery disease (HR = 1.28; [1.05-1.56]), cardiac arrhythmia (HR = 1.36; [1.11-1.67]), peripheral artery disease (HR = 1.66 [1.29-2.13]) and incomplete assessment (HR = 1.39; [1.12-1.74]) were associated with higher mortality risk, whereas female gender (HR = 0.80; [0.68-0.94]), high Glasgow Coma Scale score (GCS > 12) (HR = 0.58; [0.45-0.76]), lacunar syndrome (HR = 0.82; [0.68-0.99], being 'at home without help' (HR = 0.50; [0.41-0.59]) and negative assessment (HR = 0.75; [0.58-0.97], compared to cardioembolism) were associated with better survival probability. Initial clinical status, prior cardiovascular diseases and age was associated with more risk of death: an increment of 10 years almost doubled mortality. Women had more survival probability than men, controlling for age. Ischaemic stroke mechanisms were predictors of late 5-year mortality. Patients with negative assessment, i.e. representing truly cryptogenic ischaemic stroke, had the best survival probability probably due to fewer atherosclerotic markers.

Stroke : Highlights of Selected Articles

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

Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source: Design of the NAVIGATE ESUS randomized trial.

Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.

Practice advisory: Recurrent stroke with patent foramen ovale (update of practice parameter): Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

To update the 2004 American Academy of Neurology guideline for patients with stroke and patent foramen ovale (PFO) by addressing whether (1) percutaneous closure of PFO is superior to medical therapy alone and (2) anticoagulation is superior to antiplatelet therapy for the prevention of recurrent stroke. Systematic review of the literature and structured formulation of recommendations. Percutaneous PFO closure with the STARFlex device possibly does not provide a benefit in preventing stroke vs medical therapy alone (risk difference [RD] 0.13%, 95% confidence interval [CI] -2.2% to 2.0%). Percutaneous PFO closure with the AMPLATZER PFO Occluder possibly decreases the risk of recurrent stroke (RD -1.68%, 95% CI -3.18% to -0.19%), possibly increases the risk of new-onset atrial fibrillation (AF) (RD 1.64%, 95% CI 0.07%-3.2%), and is highly likely to be associated with a procedural complication risk of 3.4% (95% CI 2.3%-5%). There is insufficient evidence to determine the efficacy of anticoagulation compared with antiplatelet therapy in preventing recurrent stroke (RD 2%, 95% CI -21% to 25%). Clinicians should not routinely offer percutaneous PFO closure to patients with cryptogenic ischemic stroke outside of a research setting (Level R). In rare circumstances, such as recurrent strokes despite adequate medical therapy with no other mechanism identified, clinicians may offer the AMPLATZER PFO Occluder if it is available (Level C). In the absence of another indication for anticoagulation, clinicians may routinely offer antiplatelet medications instead of anticoagulation to patients with cryptogenic stroke and PFO (Level C).

Cryptogenic ischemic stroke and silent atrial fibrillation: What is the relationship?

Atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes and associated with silent cerebral infarctions and transient ischemic attacks. Any method that predicts the stroke or unmasks the silent PAF would contribute to the treatment of ischemic stroke. Intraatrial conduction time (ICT) has been shown to be associated with intermittent AF. In this study, we evaluated the value of ICT detected by transthoracic echocardiography in normal population and in patients with cryptogenic stroke (CS) as a risk factor for stroke. The patients with CS and with normal left ventricular function without valvular disease are included in group 1. Patients with atypical symptoms admitted to cardiology clinics without any risk factor for cardiac disease and found to be normal constituted group 2. Age, gender, weight, height, echocardiographic parameters and ICT were compared between groups. 63 and 64 subjects were included in group 1 and 2, respectively. Two groups were similar according to age and gender. Among the parameters studied, left atrial diameter and height of the patients were significantly higher in group 1 (40 ± 2 vs 37 ± 4 mm, p < 0.001 and 167 ± 9 vs 163 ± 9 cm p = 0.027, respectively). ICT was significantly higher in group 1 (131 ± 15 vs 118 ± 13 ms, respectively, p < 0.000). According to ROC analysis, a cut point of 124 ms for ICT with a sensitivity of 74 % and specificity of 73 % in patients with CS (p < 0.001). This study show us, the measurements the ICT determined by means of echocardiography is longer in patients with CS. This simple and noninvasive technique can be applied widely and lead the clinicians to adopt the use of diagnostic and the treatment procedures.

Abstract 209: High Yield of Long-Term Implantable Cardiac Monitoring Following Cryptogenic Ischemic Stroke

Introduction: Long-term post-hospitalization cardiac monitoring has detected occult paroxysmal atrial fibrillation and atrial flutter (PAF) in a substantial minority of cryptogenic ischemic stroke (CIS) patients. Herein, we aim to better define the frequency and clinical significance of PAF detection using the Reveal LINQ insertable cardiac monitor in a population of CIS patients treated at a comprehensive stroke center. Methods: A retrospective consecutive series of CIS patients (n=95; mean age 65.9 years; 56.8% female) with no prior history of PAF had a LINQ placed during the index hospitalization, or soon thereafter, following a negative stroke evaluation. The study cardiac electrophysiologist confirmed the presence of PAF, and other potentially relevant cardiac arrhythmias, and the characteristics of the episodes and any changes in management were recorded. Results: PAF was detected in 22/95 patients (23.2%; atrial fibrillation (AF) 13; atrial flutter (A-flutter) 6; both 3). Median time to first episode was 26 days (range less than 1 day to 398 days). Median longest episode duration for AF was 2.4 hours (range 6 minutes to greater than 99 hours) and for A-flutter was 49 seconds (range 5 to 174 seconds). Antiplatelet therapy was switched to anticoagulation in 20/21 (95.2%) patients with known follow-up, including all newly diagnosed AF patients. Additional potentially relevant arrhythmias included sinus bradycardia (5/95; 5.3%), sinus pauses (5/95; 5.3%) and bigeminy (7/95; 7.4%). Conclusions: LINQ insertion during, or soon after, in-hospital stroke evaluation detected PAF in a substantial proportion of CIS patients with a higher frequency and earlier detection than previous studies. Most episodes were deemed clinically relevant, resulting in anticoagulation initiation in almost all patients. Long-term invasive cardiac monitoring following CIS may have important implications in terms of secondary stroke prevention and the detection of other potentially relevant arrhythmias.

Abstract WP231: Risk Factors for Paroxysmal Atrial Fibrillation and Atrial Flutter Detection Following Cryptogenic Ischemic Stroke

Introduction: Long-term post-stroke insertable cardiac monitor (ICM) implantation has resulted in increasing frequencies of paroxysmal atrial fibrillation and atrial flutter (PAF) detection in a significant proportion of cryptogenic ischemic stroke (CIS) patients. Determining risk factors for PAF detection specific to the CIS population could allow for better selection of patients for ICM implantation. Methods: A retrospective study of CIS patients (n=95; mean age 65.9 years; 56.8% female) implanted with the Reveal LINQ ICM between September 2013 to July 2015. Device implantation was performed during, or soon after, index stroke admission. The study cardiac electrophysiologist confirmed PAF diagnosis. Univariate and multivariate logistic regression analyses compared clinical, laboratory, ECG and echocardiographic variables between patients with and without PAF. Results: PAF was detected in 22/95 (23.2%) patients. Factors associated with PAF detection include older age (mean (yr) 74.0 vs. 63.4; p=0.003), prolonged PR-interval (PR&gt;175 ms; OR 3.88, 95% CI 1.28-11.7), mitral regurgitation (MR; OR 3.36, 95% CI 1.24-9.08), left atrial diameter (LA diameter mean (cm) 3.80 vs. 3.51; p=0.039), and left atrial volume index (LAVI mean (cc/m2); 32.8 vs. 25.0; p=0.037). Controlling for age in the multivariate logistic regression model, obesity (BMI&gt;30; OR 4.80, 95% CI 3.50-9.60) and MR (OR 4.47, 95% CI 3.15-5.79) are independently associated with PAF detection. Conclusion: Long-term cardiac monitoring identified PAF in a substantial number of CIS patients. Older age, prolonged PR, MR, and larger LA diameter and LAVI are significantly associated with PAF diagnosis. Controlling for age, significant independent risk factors include obesity and MR. A larger prospective study is warranted to confirm these findings and to identify other possible risk factors. Ultimately, a risk factor based algorithm could enable better selection of CIS patients for ICM implantation.

Abstract TP218: Transoesophageal Echocardiography in the Diagnostic Work-up of Patients With Embolic Stroke of Undetermined Source: A Necessary Investigation That Should Not Be Overlooked

Background&amp;Purpose: The currently proposed criteria for the definition of embolic strokes of undetermined source (ESUS) do not include investigation with transesophageal echocardiography (TEE) among the mandatory diagnostic work-up. We sought to evaluate the diagnostic yield of TEE in consecutive patients fulfilling ESUS criteria. Methods: We prospectively evaluated ischemic stroke (IS) patients fulfilling ESUS criteria from three tertiary care stroke centers during a twelve month period. All patients underwent additional diagnostic work-up with TEE to estimate both the diagnostic yield and the impact of TEE findings in the therapeutic management of patients with ESUS. Results: We identified 61 patients with ESUS who underwent investigation with TEE [mean age 44.3±11.5 years; 49.2% males; median NIHSS=5 (IQR, 3-8)]. TEE revealed additional findings in 52.4% (95%CI by the adjusted Wald method: 40.2%-64.5%) of the patients. Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) were reported in 27.8% (95%CI: 18.1%-40.2%) and 13.1% (95%CI: 6.5%-24.1%) of the study population respectively. The concurrence of PFO and ASA was reported in 4 patients (6.5%, 95%CI: 2.1%-16.1%). The presence of valvular vegetations was documented in 2 patients (3.2%; 95%CI: 0%-11.8%), while thrombus was found in the left atrium of one patient (1.6%, 95%CI: 0%-9.5%). Complex aortic arch atheromatosis was reported in 6.5% (95%CI: 2.1%-16.1%) of the patients. Neither myxomas, nor ventricular septal defects were found in TEE examinations. TEE findings changed the management in 16.4% (95%CI: 8.9%-27.8%) of the patients. Anticoagulants were initiated in 5 patients, while the other 2 patients with endocarditis received treatment with intravenous antibiotics. Finally, 3 of the 61 patients underwent a PFO-closure procedure due to the large size of the shunt and the previous history of recurrent cryptogenic IS. Conclusions: Our findings suggest that ESUS patients should undergo investigation with TEE in search of potential cardioembolic or aortogenic sources. TEE findings may have a decisive impact on the selection of the appropriate therapeutic approach for these patients.

Abstract TP222: Frequency of Intracranial Arterial Imaging and its Yield in Consecutive Patients with Non-lacunar Cryptogenic Ischemic Stroke: ESUS Global Registry

Background: Atherosclerotic stenosis of large IC arteries is an important cause of stroke. The prevalence of ICS in stroke population differs by ethnicity.We report the frequency of ICS among a global sample of patients with non-lacunar cryptogenic ischemic stroke (NLCIS) who did not have another identifiable cause for stroke i.e. cardioembolic, extracranial LAD, or other specific causes. Hypothesis: We hypothesized that the prevalence rates of ICS will differ according to global regions. Methods: Consecutive patients with recent ischemic stroke were retrospectively surveyed at 19 stroke centers in 19 countries to identify the frequency of IC imaging and its yield. Countries were grouped by World Bank regions. ICS was considered to be significant if there was &gt;50% stenosis in the arteries proximal to the index stroke evidenced by MRA, CTA or TCD. Results: We identified a total of 2145 consecutive ischemic stroke patients among which 475 had NLCIS. IC arterial imaging was carried-out,on average, in 87% of patients. Of these 414 patients, 15% had stenosis proximal to the area of brain ischemia. The frequency of ICS among NLCIS patients was highest in East Asia (27%) and lowest in Pacific (4%). Patients with ICS in Latin America were significantly younger when compared to other 4 regions. Conclusion: IC arterial imaging is carried out in majority of stroke centers in patients with NLCIS, among whom the fraction of IS associated with ICS is substantial throughout the world, averaging about 15%. MRA / CTA had a higher yield than TCD. On average these patients have traditional vascular risk factors except for Latin American patients who are significantly younger with no vascular risk factors.

潜因性脳梗塞と塞栓源不明脳塞栓症：わが国における臨床的意義と潜在性心房細動検出の重要性

発症原因を特定できない潜因性脳梗塞は，病型分類法によって診断基準が異なり，脳梗塞全体に占める頻度も16～39％と研究間で差が大きい．この中に塞栓症が多く含まれると考えられ，塞栓源不明脳塞栓症という概念も提唱された．とくに潜在性心房細動が注目され，植込み型心電図記録計を用いた長期間の観察では3 割の患者に心房細動が同定された．次世代型植込み型心電図記録計は小型で遠隔監視が可能であり，海外では潜在性心房細動の検出目的に用いられている．心房細動を同定できれば，確立した再発予防法として抗凝固薬を使用でき，脳梗塞再発予防に利するであろう．次世代型植込み型記録計を国内で潜在性心房細動検出目的に用いることを日本脳卒中学会から厚生労働省に要望している．使用が承認された場合は，わが国の診療事情に合わせて頭部MRIを含めたより詳細な診断に基づいて，検査に相応しい患者を抽出すべきと考え，その基準を提案する．

Heart Ar­rhythmias in Young Patients with Cryptogenic Ischemic Stroke

Heart Ar­rhythmias in Young Patients with Cryptogenic Ischemic Stroke

The diagnostic yield of transesophageal echocardiography in patients with cryptogenic cerebral ischaemia: a meta‐analysis

The diagnostic utility of transesophageal echocardiography (TEE) in patients with cryptogenic ischaemic stroke (IS) or transient ischaemic attack (TIA) remains controversial. A systematic review and meta-analysis was performed according to PRISMA guidelines to estimate the pooled prevalence of potential cardioembolic causes detected by TEE in prospective observational studies of cryptogenic IS/TIA. Cardiac conditions causally associated with cerebral ischaemia were considered to be intramural thrombi and intracardiac tumors according to ASCO phenotyping of IS. Thirty-five eligible studies, comprising 5772 patients (mean age 53.6 years, 56.9% men) were identified. The most common TEE finding was ascending aorta and/or aortic arch atheroma [51.2% (27.4%-74.5%)], followed by patent foramen ovale (PFO) [43.2% (36.3%-50.4%)]. Complex aortic plaques and large PFOs were reported in 14% (10.2%-18.9%) and 19.5% (16.6%-22.8%) of TEE evaluations. The prevalence of atrial septal aneurysm was 12.3% (7.9%-18.7%) and was significantly higher in conjunction with PFO presence (risk ratio 2.04, 95% confidence interval 1.63-2.54, P < 0.001). The prevalence of left atrial thrombus [3.0% (1.1%-8.3%)] and spontaneous echo contrast [3.8% (2.3%-6.2%)] was low. The prevalence of intracardiac tumors was extremely uncommon [0.2% (0%-0.7%)]. Significant heterogeneity was identified (I(2) > 60%) in the majority of analyses. Heterogeneity was not affected by cryptogenic stroke definition (TOAST versus alternative criteria). After dichotomizing available studies using a cut-off of 50 years, PFO was significantly (P = 0.001) more prevalent in younger than in older patients. Routine TEE in patients with cryptogenic IS/TIA commonly identifies abnormal findings. However, the prevalence of cardiac conditions considered to be causally associated with cerebral ischaemia (intracardiac thrombi and tumors) is low.

Abstract 17804: Echocardiographic and Radiologic Predictors of Atrial Fibrillation in Acute Ischemic Stroke

Introduction: Atrial fibrillation (AF) is an important risk factor for stroke. Approximately 15-25% of cryptogenic ischemic strokes (CIS) are due to AF. Hypothesis: Patients with echocardiographic markers including left atrial dilatation (LAD) and valvular disease and/or radiologic findings including a hyper-dense vessel sign (HDV sign), prior cortical or cerebellar stroke, and hemorrhagic transformation (HT) are more likely to have stroke due to AF. Methods: This is a single center, retrospective case control study of patients admitted with acute ischemic stroke (AIS) from 2008-2013. Patients with a new diagnosis of stroke and a defined stroke etiology (large vessel, cardio-embolic, small vessel and other, TOAST classification) were included. CIS patients or those without imaging/echocardiographic studies were excluded. Images were reviewed for prior stroke, HT, a HDV sign and stroke location (left or right anterior, posterior, multifocal). Echocardiograms were reviewed for LAD, ejection fraction&lt;35%, moderate-severe mitral regurgitation (MR), moderate-severe aortic regurgitation, mitral stenosis, aortic stenosis, left ventricular segmental akinesis, diastolic dysfunction, LVH and patent foramen ovale. Results: Charts of 600 patients were reviewed and 383 patients were included in the analysis. 185 patients had AF as the etiology of their stroke. The remainder had no known AF. Univariate and multivariate logistic regression was performed using SPSS. LAD, moderate to severe MR, HDV sign, and HT were found to accurately predict AF in patients with AIS. LAD had an OR of 6.9 (CI 4.4-10.8, p&lt;.0001) and HDV predicted AF with an OR of 2.2 (CI 1.2-4.2, p&lt;.016) even after controlling for LAD, MR, and HT. Conclusion: Echocardiographic and radiologic markers help predict AF as a stroke etiology in AIS patients. This is the first study, to the best of our knowledge, to show that HDV sign is a positive predictor of AF. Prospective studies with larger cohorts are needed to confirm these findings in CIS patients. These markers could be added to demographic information to enhance prediction of occult AF and the need for chronic cardiac monitoring.

Differential Lesion Patterns on T2WI and FLAIR Sequences in Cryptogenic Stroke Patients With Patent Foramen Ovale.

The purpose of this study was to determine lesion patterns and stroke mechanisms in cryptogenic ischemic stroke patients with patent foramen ovale (PFO) on T2-weighted magnetic resonance imaging and fluid-attenuated inversion recovery sequences combined. Twenty-nine patients with cryptogenic ischemic stroke and an isolated PFO (CS-PFO+ group) compared with 51 cryptogenic stroke patients without PFO (CS-PFO- group) were evaluated and the characteristics of their lesion patterns on T2-weighted and fluid-attenuated inversion recovery sequences combined were investigated. We compared the number, the size, and the distribution of ischemic lesions on magnetic resonance imaging between the 2 groups. Twenty-four of 29 patients had a total of 271 small ischemic lesions (diameter<1 cm) in the CS-PFO+ group against 24 of 51 patients with 156 small ischemic lesions in the CS-PFO- group, respectively; 11.29±8.14 and 6.36±4.33 ischemic lesions per person (P=0.015). Multiple small ischemic lesions occurred more frequently in the CS-PFO+ group (20/29, 69%) than in the CS-PFO- group (16/51, 31%, P=0.001). Subcortical frontal and parietal infarct lesions were more frequent in the CS-PFO+ group (19/29, 66%) than in the CS-PFO- group (18/51, 35%, P=0.009). Multiple small ischemic lesions and subcortical frontal and parietal infarct lesions were significantly associated with cryptogenic stroke patients with PFO, which suggested that paradoxical embolism is the pathogenic mechanism in cryptogenic stroke patients with PFO.

Advances in the Detection and Monitoring of Atrial Fibrillation for Patients with Cryptogenic Ischemic Stroke.

Atrial fibrillation (AF) is a significant etiologic cause of acute ischemic stroke (AIS) that leads to disabling deficits as well as significant morbidity and mortality in this population. Approximately 25 % of AIS is considered to be cryptogenic with no etiology ascertained at the time of the index event. Recent advances from the EMBRACE and CRYSTAL-AF trial have improved detection and treatment of AF and subsequently lead to changes in guidelines. However, with improved detection rates, the duration and frequency cutoffs for treating AF are currently being investigated to ensure optimization of patient selection and subsequent treatment.

Insertable cardiac monitors after cryptogenic stroke--a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation.

Recently, the CRYSTAL AF trial detected paroxysmal atrial fibrillation (AF) in 12.4% of patients after cryptogenic ischaemic stroke (IS) or cryptogenic transient ischaemic attack (TIA) by an insertable cardiac monitor (ICM) within 1 year of monitoring. Our aim was (i) to assess if an AF risk factor based pre-selection of ICM candidates would enhance the rate of AF detection and (ii) to determine AF risk factors with significant predictive value for AF detection. Seventy-five patients with cryptogenic IS/TIA were consecutively enrolled if at least one of the following AF risk factors was present: a CHA2DS2-VASc score ≥4, atrial runs, left atrium (LA) size >45 mm, left atrial appendage (LAA) flow ≤0.2 m/s, or spontaneous echo contrast in the LAA. The electrocardiographic and echocardiographic criteria were chosen as they have been repeatedly reported to predict AF; the same applies for four of the six items of the CHA2DS2-VASc score. The study end-point was the detection of one or more episodes of AF (≥2 min). Seventy-four patients underwent implantation of an ICM; one patient had AF at the date of implantation. After 6 months, AF was detected in 21/75 patients (28%), after 12 months in 25/75 patients (33.3%). 92% of AF episodes were asymptomatic. LA size >45 mm and the presence of atrial runs were independently associated with AF detection [hazard ratio 3.6 (95% confidence interval 1.6-8.4), P = 0.002, and 2.7 (1.2-6.7), P = 0.023, respectively]. The detection rate of AF is one-third after 1 year if candidates for an ICM after cryptogenic IS/TIA are selected by AF risk factors. LA dilation and atrial runs independently predict AF.

Tobacco Use and Cryptogenic Stroke in Young Adults

Cryptogenic stroke is the leading subtype of ischemic stroke in the young. We sought to evaluate the association between traditional cardiovascular risk factors and cryptogenic stroke by using a case-control study. Patients aged 18-54 years, consecutively treated for first-ever cryptogenic ischemic stroke in an academic stroke unit, were compared with subjects from the general population living in the same geographic area. Control subjects were matched for age and sex with patients. We further evaluated the association between significant risk factors and nonobstructive (<50% stenosis) carotid plaque and thrombus among patients with cryptogenic stroke. Odds ratios [OR] were calculated using logistic regression analysis. A total of 155 patients with cryptogenic stroke (66.4% men, mean age 43.5 years [SD 8.4]) were included in the study. Cryptogenic stroke was associated with current tobacco use (42.6% in patients versus 23.9% in control subjects; OR = 2.38, 95% confidence interval [CI] 1.40-4.05, P = .002). Current tobacco use was associated with nonobstructive carotid plaque (OR = 6.22; 95% CI, 2.43-15.9; P = .001) and nonobstructive carotid thrombus (OR = 13.7; 95% CI, 1.42-132.7; P = .03) among the patients. Our case-control study showed a strong link between current tobacco use and cryptogenic stroke in young adults.

Age-specific association of migraine with cryptogenic TIA and stroke: Population-based study.

To determine whether there is an association between previous migraine and cryptogenic TIA or ischemic stroke at older ages. We determined the age-specific associations of history of migraine and Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtype of TIA and ischemic stroke in a population-based cohort study (Oxford Vascular Study; 2002-2012). Among 1,810 eligible patients with TIA or ischemic stroke, 668 (36.9%) had cryptogenic events, of whom 187 (28.0%) had previous migraine. Migraine was more commonly associated with cryptogenic events than with those of known etiology (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.38-2.16, p < 0.0001; cardioembolic 2.00, 1.50-2.66, p < 0.0001; large artery 1.75, 1.20-2.53, p = 0.003; small vessel 1.32, 0.95-1.83, p = 0.096). The association of migraine with cryptogenic events was independent of age, sex, and all measured vascular risk factors (RFs) (adjusted OR 1.68, 1.33-2.13, p < 0.0001) and was strongest at older ages (<55 years, OR 1.11, 0.55-2.23; 55-64 years, 1.48, 0.83-2.63; ≥65 years, 1.81, 1.39-2.36) and in patients without vascular RFs (0 RFs OR 2.62, 1.33-5.15; 1 RF 2.01, 1.35-3.01; 2 RFs 1.80, 1.21-2.68; 3 RFs 1.21, 0.71-2.07; 4 RFs 0.92, 0.28-2.99). Results were consistent for migraine with or without aura and for analyses excluding TIA or stratified by sex or vascular territory of event. In this population-based study of stroke etiology stratified by age, migraine was most strongly associated with cryptogenic TIA and ischemic stroke, particularly at older ages, suggesting a causal role or a shared etiology.