Cardiac stasis imaging, stroke, and silent brain infarcts in patients with nonischemic dilated cardiomyopathy.

Cardioembolic stroke is one of the most devastating complications of nonischemic dilated cardiomyopathy (NIDCM). However, in clinical trials of primary prevention, the benefits of anticoagulation are hampered by the risk of bleeding. Indices of cardiac blood stasis may account for the risk of stroke and be useful to individualize primary prevention treatments. We performed a cross-sectional study in patients with NIDCM and no history of atrial fibrillation (AF) from two sources: 1) a prospective enrollment of unselected patients with left ventricular (LV) ejection fraction <45% and 2) a retrospective identification of patients with a history of previous cardioembolic neurological event. The primary end point integrated a history of ischemic stroke or the presence intraventricular thrombus, or a silent brain infarction (SBI) by imaging. From echocardiography, we calculated blood flow inside the LV, its residence time (TR) maps, and its derived stasis indices. Of the 89 recruited patients, 18 showed a positive end point, 9 had a history of stroke or transient ischemic attack (TIA) and 9 were diagnosed with SBIs in the brain imaging. Averaged TR, [Formula: see text] performed well to identify the primary end point [AUC (95% CI) = 0.75 (0.61-0.89), P = 0.001]. When accounting only for identifying a history of stroke or TIA, AUC for [Formula: see text] was 0.92 (0.85-1.00) with odds ratio = 7.2 (2.3-22.3) per cycle, P < 0.001. These results suggest that in patients with NIDCM in sinus rhythm, stasis imaging derived from echocardiography may account for the burden of stroke.NEW & NOTEWORTHY Patients with nonischemic dilated cardiomyopathy (NIDCM) are at higher risk of stroke than their age-matched population. However, the risk of bleeding neutralizes the benefit of preventive oral anticoagulation. In this work, we show that in patients in sinus rhythm, the burden of stroke is related to intraventricular stasis metrics derived from echocardiography. Therefore, stasis metrics may be useful to personalize primary prevention anticoagulation in these patients.

Left atrial appendage occlusion and patent foramen ovale closure using a steerable sheath and intracardiac echocardiography.

A patient presenting with acute ischemic stroke associated with patent foramen ovale (PFO) had concurrent deep vein thrombosis, pulmonary embolism, and new-onset atrial fibrillation. Upon initiation of anticoagulation therapy, the patient developed hemorrhagic transformation of the stroke. The patient's multiple potential sources of embolic stroke were treated with concomitant left atrial appendage occlusion and PFO closure through the PFO, made possible by using the Steerable Amulet Sheath under 3D-intracardiac echocardiography guidance.

Predictors of Atrial Fibrillation Development in Patients With Embolic Stroke of Undetermined Source: An Analysis of the RE-SPECT ESUS Trial.

BACKGROUND: A proportion of patients with embolic stroke of undetermined source have silent atrial fibrillation (AF) or develop AF after the initial evaluation. Better understanding of the risk for development of AF is critical to implement optimal monitoring strategies with the goal of preventing recurrent stroke attributable to underlying AF. The RE-SPECT ESUS trial (Randomized, Double-Blind Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) provides an opportunity to assess predictors for developing AF and associated recurrent stroke. METHODS: RE-SPECT ESUS was a randomized, controlled trial (564 sites, 42 countries) assessing dabigatran versus aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. Of 5390 patients enrolled and followed for a median of 19 months, 403 (7.5%) were found to develop AF reported as an adverse event or using cardiac monitoring per standard clinical care. Univariable and multivariable regression analyses were performed to define predictors of AF. RESULTS: In the multivariable model, older age (odds ratio for 10-year increase, 1.99 [95% CI, 1.78-2.23]; P<0.001), hypertension (odds ratio, 1.36 [95% CI, 1.03-1.79]; P=0.0304), diabetes (odds ratio, 0.74 [95% CI, 0.56-0.96]; P=0.022), and body mass index (odds ratio for 5-U increase, 1.29 [95% CI, 1.16-1.43]; P<0.001) were independent predictors of AF during the study. In a sensitivity analysis restricted to 1117 patients with baseline NT-proBNP (N-terminal prohormone of brain natriuretic peptide) measurements, only older age and higher NT-proBNP were significant independent predictors of AF. Performance of several published predictive models was assessed, including HAVOC (AF risk score based on hypertension, age ≥75 years, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, and coronary artery disease) and CHA2DS2-VASc (stroke risk score based on congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, previous stroke, transient ischemic attack or thromboembolism [doubled], vascular disease, age 65 to 74 years, and sex category [female]) scores, and higher scores were associated with higher rates of developing AF. CONCLUSIONS: Besides age, the most important variable, several other factors, including hypertension, higher body mass index, and lack of diabetes, are independent predictors of AF after embolic stroke of undetermined source. When baseline NT-proBNP was available, only older age and elevation of this biomarker were predictive of subsequent AF. Understanding who is at higher risk of developing AF will assist in identifying patients who may benefit from more intense, long-term cardiac monitoring. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale: Results From RE-SPECT ESUS.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed. METHODS: Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS. RESULTS: PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO (P for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43-1.14]) for ischemic stroke. CONCLUSIONS: There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239120.

Appropriateness of the Direct Oral Anticoagulants Dosing in the Middle East Gulf Region.

ABSTRACT: Direct oral anticoagulants (DOACs) have proven efficacy to prevent cardioembolic strokes. Data are scarce about the appropriateness of DOAC dosing in the Middle East. We investigated the prevalence of inappropriate DOAC dosing in the region. A cross-sectional study was conducted at our hospital between April 2015 and February 2019 of patients receiving 1 of the 3 available DOACs. Patients with incomplete data sets, those prescribed DOACs for indications other than atrial fibrillation, on DOACs for <30 days, and dialysis patients were excluded. A total of 608 met the inclusion criteria. The mean age was 65.2 ± 13.9 years, and most were men (58.6%). The mean CHA2DS2-VASc score was 3.8 ± 2.0. There were 346 (56.9%) on apixaban, 123 (20.2%) on dabigatran, and 139 (22.9%) on rivaroxaban. The logistic regression model showed that for the 3 agents together, age, eGFR, major bleeding history, and history of prior stroke were significantly associated with the decision to inappropriately underdose (P < 0.05). Fifteen patients had an ischemic stroke after apixaban initiation (5 underdosed and 3 overdosed). Among patients with at least one follow-up encounter, major bleeding occurred in 13 patients (11.7%) with inappropriate dosing compared with 29 patients (6.0%) with appropriate dosing (P = 0.04). Ischemic stroke occurred in 11 patients (9.9%) with inappropriate dosing compared with 15 patients (3.1%) with appropriate dosing (P < 0.01). We concluded that inappropriate DOAC underdosing is common in our region, particularly with apixaban and rivaroxaban. It is associated with increased risk of stroke and bleeding. More education targeting prescribers is needed to encourage adherence to standard dosing criteria.

Burden of oral anticoagulation in embolic stroke of undetermined source without atrial fibrillation.

OBJECTIVE: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies. METHODS: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective. RESULTS: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years). CONCLUSIONS: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

The efficacy and safety of Hirudin plus Aspirin versus Warfarin in the secondary prevention of Cardioembolic Stroke due to Nonvalvular Atrial Fibrillation: A multicenter prospective cohort study.

Background: To investigate the efficacy and safety of hirudin plus aspirin therapy compared with warfarin in the secondary prevention of cardioembolic stroke due to nonvalvular atrial fibrillation (NVAF). Methods: Patients with cardioembolic stroke due to NVAF were prospectively enrolled from 18 collaborating hospitals from Dec 2011 to June 2015. Fourteen days after stroke onset, eligible patients were assigned to the hirudin plus aspirin group (natural hirudin prescribed as the traditional Chinese medicine Maixuekang capsule, 0.75 g, three times daily, combined with aspirin 100 mg, once daily) or the warfarin group (dose-adjusted warfarin targeting international normalized ratio (INR) 2-3, with an initial daily dose of 1.25 mg). Patients were followed up at 1, 2, 3, 6, 9, and 12 months after stroke onset. Time in therapeutic range (TTR) was calculated according to Rosendaal methodology to evaluate the quality of INR management in the warfarin group. The primary efficacy endpoint was the recurrence of stroke within 12 months after stroke onset. Safety was assessed as the occurrence of the composite event "intracranial hemorrhage and other bleeding events, death, and other serious adverse events". The Cox proportional hazard model and Kaplan-Meier curve were used to analyze the efficacy and safety events. Results: A total of 221 patients entered final analysis with 112 patients in the hirudin plus aspirin group and 109 in the warfarin group. Over the whole duration of our study, TTR for patients taking warfarin was 66.5 % ± 21.5%. A significant difference was not observed in the recurrence of stroke between the two groups (3.57% vs. 2.75%; P = 0.728). The occurrence of safety events was significantly lower in the hirudin plus aspirin group (2.68% vs.10.09%; P = 0.024). The risk for efficacy event was similar between the two groups (hazard ratio (HR), 1.30; 95% confidence interval (CI), 0.29-5.80). The safety risk was significantly lower in the hirudin plus aspirin group (HR, 0.27; 95% CI, 0.07-0.95). Kaplan-Meier analysis revealed significant difference in the temporal distribution in safety events (P = 0.023) but not in stroke recurrence (P = 0.726). Conclusion: Significant difference in efficacy was not detected between warfarin group and hirudin plus aspirin group. Compared with warfarin, hirudin plus aspirin therapy had lower safety risk in the secondary prevention of cardioembolic stroke due to NVAF.

Outcomes of Transcarotid Artery Revascularization and Carotid Endarterectomy at a Single Institution.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are accepted revascularization modalities to treat carotid artery stenosis. Higher incidences of perioperative adverse neurological events and death have been reported in patients with transfemoral CAS. Transcarotid artery revascularization (TCAR) is a newer operative technique that involves direct transcervical carotid access, mitigating aortic arch manipulation and minimizing the risk of embolic stroke via cerebral blood flow reversal. Perioperative stroke, myocardial infarction (MI), and death rates have been shown to be similar between TCAR and CEA, with TCAR having fewer complications. The objective of this study was to ascertain the safety and viability of TCAR by evaluating perioperative outcomes. We hypothesized that patients undergoing TCAR and CEA have equivalent outcomes. METHODS: We performed a single-institution retrospective review of a prospectively maintained Vascular Quality Initiative database on patients who underwent TCAR or CEA between 2012 and 2019. A total of 66 TCAR cases from February 2018 to December 2019 and 501 CEA cases from January 2012 to December 2019 were reviewed. Preoperative, intraoperative, and postoperative characteristics as well as perioperative outcomes were captured for the statistical analyses. RESULTS: From 2012 to 2019, 567 patients underwent TCAR or CEA. Patients who underwent TCAR were found to have higher rates of comorbidities compared with CEA. There were no procedure-related strokes in patients who underwent TCAR. There was no statistically significant difference between TCAR and CEA procedure-related strokes (0% vs. 1.0%, P = 0.42). There were 5 CEA procedure-related strokes because of technical problems resulting in thrombosis of the target vessels. Three patients who underwent CEA had strokes unrelated to the operations. Overall, there were no perioperative deaths, MI, cranial nerve injury (CNI), or hematoma in patients who underwent TCAR. There were no complications of surgical site infection, pseudoaneurysm, or arteriovenous fistula among patients who underwent TCAR or CEA. CONCLUSIONS: This single-center retrospective analysis of TCAR and CEA for the treatment of carotid artery disease suggests TCAR can result in equivalent perioperative procedure-related stroke as CEA as well as equivalent incidence of perioperative complications including MI, CNI, hematoma, and death in selected patients or patients with proper anatomy. TCAR may be considered a safe, feasible carotid revascularization option for carotid artery stenosis.

Recurrent Ischemic Stroke - A Systematic Review and Meta-Analysis.

OBJECTIVES: Recurrent stroke remains a challenge though secondary prevention is initiated immediately post-stroke. Stroke subtype may determine the risk of recurrent stroke and require specific preventive measures. We aimed to identify subtype-specific stroke recurrence and associated risk factors over time. METHODS AND MATERIALS: A systematic review was performed using PubMed and Embase for studies including adults >18 years, first-ever ischemic stroke in population-based observational studies or registries, documented TOAST-criteria and minimum 1-year follow-up. Meta-analysis on stroke recurrence rate was performed. Final search: November 2019. RESULTS: The search retrieved 26 studies (between 1997 and 2019). Stroke recurrence rate ranged from 5.7% to 51.3%. Recurrent stroke was most frequent in large artery atherosclerosis (LAA) and cardioembolic (CE) stroke with recurrent stroke similar to index stroke subtype. We identified a lower recurrence rate for small vessel occlusion (SVO) stroke with recurrence frequently of another stroke subtype. Based on a meta-analysis the summary proportion recurrence rate of recurrent stroke in studies using TOAST-criteria = 0.12 and = 0.14 in studies using TOAST-like criteria. Hypertension, diabetes mellitus, atrial fibrillation previous transient ischemic attack, and high stroke severity were independent risk factors for recurrence. CONCLUSION: Stroke recurrence rates seem unchanged over time despite the use of secondary prevention. The highest recurrence rate is in LAA and CE stroke eliciting same subtype recurrent stroke. A lower recurrence rate is seen with SVO stroke with a more diverse recurrence pattern. Extensive workup is important in all stroke subtypes - including SVO stroke. Future research needs to identify better preventive treatment and improve compliance to risk factor prevention to reduce stroke recurrence.

Sex Differences in Management and Outcomes of Cardioembolic Stroke: Post HOC Analyses of the RELAXED Study.

INTRODUCTION: Experimental models have clearly demonstrated sex differences in the pathophysiology of stroke and prognosis, however clinical evidence remains elusive. In this study, we examined sex differences as a post hoc analysis of RELAXED (Recurrent Embolism Lessened by rivaroxaban, an anti-X agent, of Early Dosing for acute IS and TIA with atrial fibrillation) Study. METHODS: We stratified study participants by sex and compared baseline and clinical characteristics as well as clinical outcomes. The primary outcome measure was a good outcome defined as a modified Rankin Scale score of 0-2 at 90 days after stroke. Secondary outcomes were mortality at 90 days, intracranial hemorrhage within 90 days, and recurrence of stroke or transient ischemic attack within 90 days. We constructed a logistic regression model to estimate the adjusted odds ratio of female patients compared with male patients for the primary and secondary outcomes. RESULTS: Of 1303 patients, most were male (57.7%) with a mean age of 74.5 years. Female patients were older with a mean age of 80.6 ± 8.9 years and had significantly less frequent anticoagulation therapy before onset of stroke and more severe NIHSS scores. Good outcome was observed in 51.2% and 63.3% of the females and males (p < 0.0001). The adjusted odds ratio of a good outcome in females was 1.12 (95% confidence interval, 0.44-2.87) (p = 0.81). There were no sex differences in secondary outcomes. CONCLUSION: Adjusted regression analysis found no sex difference in the treatment outcomes at 90 days after stroke with non-valvular atrial fibrillation.

Anticoagulation and Risk of Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source Having No Potential Source of Embolism.

BACKGROUND: This study aimed to determine whether use of oral anticoagulants (OACs) was associated with a reduced risk of recurrent stroke compared with use of antiplatelets (APs) in patients with embolic stroke of undetermined source (ESUS) having no potential source of embolism. METHODS: Of 8,790 patients with acute ischemic stroke registered at 7 centers in the Fukuoka Stroke Registry from June 2007 to May 2017, we included 681 patients (mean age 69.7 [SD 14.1] years, 48.3% men) who experienced ESUS without a potential source of embolism and received OAC alone or AP alone. We estimated hazard ratios (HRs) and 95% confidential intervals (CIs) of recurrent ischemic stroke or any stroke after discharge using a Cox proportional hazards model and Fine and Gray model. RESULTS: During a mean follow-up of 3.4 (SD 1.7) years, event rates of recurrent ischemic stroke were 4.4 per 100 person-years in 489 patients treated with AP and 2.0 per 100 person-years in 192 patients treated with OAC. OAC use was associated with a reduced risk of recurrent ischemic stroke, even after adjusting for potential confounding factors (multivariable-adjusted HR [95% CI], 0.42 [0.23-0.80]) and when additionally considering death as a competing risk (0.45 [0.24-0.85]). The reduced risk of recurrent ischemic stroke was still observed in patients treated with OAC (0.32 [0.15-0.67]) in reference to propensity score-matched patients treated with AP. These associations were maintained for all types of stroke, including ischemic and hemorrhagic stroke. CONCLUSIONS: This nonrandomized observational study suggests that anticoagulation therapy might be associated with a reduced risk of recurrent stroke compared with antiplatelet therapy in patients with ESUS in whom no potential source of embolism was identified. Further study should be performed in consideration of a potential source of embolism even in patients with ESUS.

Dabigatran vs. Aspirin for Secondary Prevention After Embolic Stroke of Undetermined Source　- Japanese Subanalysis of the RE-SPECT ESUS Randomized Controlled Trial.

BACKGROUND: The international Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial did not demonstrate superiority of dabigatran over aspirin for reduction of recurrent strokes in patients with embolic strokes of undetermined source (ESUS). Based on pre-defined subanalyses, the safety and efficacy of dabigatran vs. aspirin in Japanese patients was assessed.Methods and Results:ESUS patients were randomized to receive either dabigatran (150 or 110 mg twice daily) or aspirin (100 mg once daily). Of 5,390 patients randomized, 594 were Japanese. Most Japanese patients (99.8%) underwent brain magnetic resonance imaging for trial screening, compared to 76.8% of non-Japanese (P<0.0001). In the Japanese cohort, over a 19.4-month median follow-up period, recurrent stroke as the primary outcome occurred in 20/294 patients (4.3%/year) in the dabigatran group and 38/300 (8.3%/year) in the aspirin group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.32-0.94). Major bleeding occurred in 12 patients (2.5%/year) and 17 patients (3.5%/year), respectively (HR, 0.72; 95% CI, 0.34-1.52). In contrast, in the non-Japanese cohort, recurrent stroke occurred in 4.1%/year and 4.3%/year, respectively, showing no apparent difference in recurrent stroke for dabigatran vs. aspirin (HR, 0.91; 95% CI, 0.74-1.14). The P-interaction for treatment and region did not reach statistical significance (P=0.09). CONCLUSIONS: Dabigatran was putatively associated with a lower relative risk of recurrent stroke compared with aspirin in Japanese ESUS patients.

Advances in the management of cardioembolic stroke associated with patent foramen ovale.

Patent foramen ovale (PFO) describes a valve in the interatrial septum that permits shunting of blood or thrombotic material between the atria. PFOs are present in approximately 25% of the healthy population and are not associated with any pathology in the vast majority of cases. However, comparisons between patients with stroke and healthy controls suggest that PFOs may be causative of stroke in certain patients whose stroke is otherwise cryptogenic. Options for the diagnosis of PFO include transthoracic echocardiography, transesophageal echocardiography, and transcranial Doppler ultrasonography. PFOs associated with an interatrial septal aneurysm seem to be more strongly linked to risk of recurrent stroke. Therapeutic options for secondary stroke prevention in the setting of a PFO include antiplatelet therapy, anticoagulation, and percutaneous device closure. Recent randomized clinical trials suggest that percutaneous closure reduces the subsequent risk of stroke in appropriately selected patients, with a large relative benefit but small absolute benefit. Referral for percutaneous PFO closure should therefore be considered in certain patients after a multidisciplinary, patient centered discussion. Areas for future study include structural biomarkers to aid in determining the role of PFO closure in older people with possible PFO associated stroke, the role of direct oral anticoagulants, and very long term outcomes after device closure.

Atrial Fibrillation and Stroke.

Atrial fibrillation (AF) is the most common cardiac arrythmia and a major cause of stroke, heart failure, sudden death, and cardiovascular morbidity. AF increases risk of thromboembolic stroke via stasis in the left atrium and subsequent embolization to the brain. In patients with acute ischemic stroke, it is essential that clinicians undertake careful investigation to search for AF. In these patients, up to 23.7% eventually are found to have underlying AF. Oral anticoagulation is effective in prevention of strokes secondary to AF, reducing overall stroke numbers by approximately 64%. Left atrial appendage occlusion is promising for prevention of stroke in AF.

The Effect of Statin Treatment on Outcomes of Cardioembolic Stroke: A Systematic Review and Meta-Analysis of Real-World Studies.

BACKGROUND: Several real-world observational studies have investigated the association between statin treatment and outcomes of cardioembolic stroke. However, substantial uncertainties remain about this association. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to determine the effect of statin treatment on the outcomes of cardioembolic stroke. METHODS: We systematically searched the PubMed and Embase databases for relevant clinical studies. Pooled relative risks (RRs) and 95% confidence intervals (CIs) with a random-effects model were used to assess the outcomes of interest. RESULTS: A total of 18 observational studies published between 2009 and 2020 were included. No randomized clinical trial was found. Compared with non-statin treatment, statin treatment was not associated with a decreased risk of stroke recurrence in patients with cardioembolic stroke [PWCS] (RR, 0.93; 95% CI 0.82-1.06). However, compared with non-statin treatment, statin treatment was associated with a lower risk of all-cause death (RR, 0.59; 95% CI 0.49-0.73) and better functional outcomes (RR, 0.67; 95% CI 0.47-0.97) in PWCS. There was no significant association between statin treatment and major bleeding event risk in PWCS (RR, 0.35; 95% CI 0.06-2.16). Compared with non-statin treatment, statin treatment was not associated with a decreased risk of coronary atherosclerotic disease in PWCS (RR, 1.04; 95% CI 0.96-1.11). CONCLUSIONS: Although the use of statins does not enhance the prevention of stroke recurrence in PWCS, statin treatment is associated with improved clinical outcomes in PWCS. Statins play a beneficial role in the treatment of cardioembolic stroke.

Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source during 3 Years of Prolonged Monitoring with an Implantable Loop Recorder.

BACKGROUND: Undocumented atrial fibrillation (AF) is suspected as a main stroke cause in patients with embolic stroke of undetermined source (ESUS), but its prevalence is largely unknown. This prospective study therefore aimed at delineating the prevalence of AF in patients with ESUS using continuous cardiac monitoring by implantable loop recorder (ILR) with daily remote interrogation over a period of 3 years and its clinical consequences, including recurrent stroke. METHODS: In consecutive patients with an ESUS diagnosis after complete work-up, an ILR was implanted and followed by daily remote monitoring until AF was detected or a follow-up of at least 3 years was completed. Additionally, the ILR was interrogated in-hospital in 6-month intervals. RESULTS: A total of 123 patients (74 male, mean age 65 ± 9 years) were enrolled and completed the 3 years study period. AF was detected in 51 patients (41.4%). In 43 of the 51 AF positive patients (84%) oral anticoagulation was established. Recurrent strokes occurred in 18 patients (14.6%) of this ESUS population, 9 of these patients being AF positive (17.6% of the AF-positive patients) and 9 being AF negative (12.5% of AF-negative patients). Patients with AF were slightly older than patients without AF (63.1 ± 8.8 vs. 67.5 ± 9.6 years, p = 0.12). Other parameters such as CHA2DS2-VASc score, infarct localization, micro- and macroangiopathy, carotid or aortic plaques, or stroke recurrence were not significantly different between groups. CONCLUSION: In ESUS patients, early implantation of an ILR with cardiac monitoring and remote transmission over a 3-year period detected AF in 41.4% and resulted in oral anticoagulation in 84% of these patients.

[Optimizing the detection of subclinical atrial fibrillation after ESUS]. / Optimización de la detección de fibrilación auricular subclínica tras un ESUS.

INTRODUCTION: It has been estimated that approximately 20% of ischemic strokes have a cardioembolic origin and the cause is not detected or there are more than one in 9-25% of ischemic strokes. An adequate diagnostic approach of ESUS would allow an optimization of antithrombotic treatment. OBJECTIVE: Narrative update about the available evidence on the best diagnostic and therapeutic approach among patients with ESUS and how to optimize the detection of atrial fibrillation as a potential cause is reviewed. DEVELOPMENT: A search was conducted on PubMed (MEDLINE), using the MeSH terms [ESUS] + [atrial fibrillation] + [diagnosis] + [treatment]. Original data from clinical trials, prospective and retrospective studies and reviews were selected. CONCLUSIONS: The detection of atrial fibrillation after ESUS is mandatory to optimize the treatment. However, not all patients have the same risk of developing silent atrial fibrillation. There are some factors that increase this risk (left atrium enlargement, elderly, frequent premature supraventricular complexes). In these patients, a more prolonged monitorization could increase the possibility of detecting atrial fibrillation, and consequently, to benefit more from anticoagulant treatment.

TITLE: Optimización de la detección de fibrilación auricular subclínica tras un ESUS.Introducción. Se ha estimado que aproximadamente el 20% de los ictus isquémicos tiene un origen cardioembólico y que no se detecta la causa o que puede haber más de una en el 9-25% de ellos. Un proceso diagnóstico adecuado de ESUS permitiría optimizar el tratamiento antitrombótico. Objetivo. Revisión bibliográfica sobre la evidencia disponible acerca de la mejor aproximación diagnóstica y terapéutica de los pacientes con ESUS y cómo optimizar la detección de la posible fibrilación auricular como causa. Desarrollo. Se realizó una búsqueda a través de PubMed (MEDLINE), mediante los términos MeSH [ESUS] + [atrial fibrillation] + [diagnosis] + [treatment]. Se seleccionaron publicaciones originales de ensayos clínicos, y estudios prospectivos, retrospectivos y de revisión. Conclusiones. La detección de fibrilación auricular tras un ESUS es fundamental para optimizar el tratamiento. Sin embargo, no todos los pacientes tienen el mismo riesgo de presentar fibrilación auricular silente. Existen determinados factores que incrementan este riesgo (dilatación de la aurícula izquierda, edad avanzada, extrasistolia supraventricular frecuente). En estos pacientes, una monitorización más prolongada permitiría aumentar las posibilidades de diagnóstico de la fibrilación auricular y, por lo tanto, beneficiarse, en mayor medida, del tratamiento anticoagulante para evitar ictus recurrentes.

Secondary Stroke Prevention Following Embolic Stroke of Unknown Source in the Absence of Documented Atrial Fibrillation: A Clinical Review.

Approximately one-third of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one-third of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation attributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiology is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk stratifying this cohort of patients.