Secondary Stroke Prevention in Cryptogenic Stroke and Embolic Stroke of Undetermined Source (ESUS)

Introduction: Cryptogenic strokes account for up to 40% of ischemic strokes. Atrial fibrillation (AF) is a known cause of ischemic stroke. Current data shows that occult AF can be detected by implantable devices at higher rates than conventional cardiac rhythm monitoring. There are, however, limited data available on risk factors and outcomes associated with AF detection by implantable loop recorders (ILRs). Objective: To investigate the risk factors and outcomes associated with occult AF detected by ILR in patients with cryptogenic stroke. Methods: We conducted a retrospective chart review of patients admitted with cryptogenic stroke at Ascension St John Hospital and Ascension Macomb-Oakland Hospital in Michigan who had ILRs placed from 1/1/2016 to 1/31/2020. Data were collected on demographics, comorbidities, treatment and outcomes. AF detection was defined as continuous AF for 30 seconds. Data were analyzed using Student’s t-test, the χ2 test and logistic regression. Results: We reviewed 172 patients, 52.3% male, 56.4% white, mean age 62.7 ± 13.6 years. The incidence of AF detection by ILR was 14% (24/172) over a mean follow-up of 12.75 ± 10.71 months. The mean duration of monitoring prior to AF detection was 4.5 months (range:1 day to 14 months). The median duration of AF was 6 minutes (range: 37.2 seconds to 11.3 hours). From univariable analysis, older age (p=0.03), male sex (p=0.09), embolic stroke pattern on imaging (p=0.06), and lack of AF symptoms (p=0.001) were associated with AF detection by ILR. From multivariable analysis, patients with detected AF were more likely to be older (OR=1.04, p=0.04), male (OR=3.6, p=0.03), asymptomatic (OR=6.3, p=0.01), and have an embolic stroke pattern on imaging (OR=3.3, p=0.04). 95.7% of patients with confirmed AF were started on anticoagulation for secondary stroke prevention. There was no difference in the incidence of stroke post-hospitalization between those with AF detection and those without (16% vs. 16.4%, p=0.96). Conclusions: In patients with cryptogenic stroke, age, gender, stroke pattern, and lack of AF symptoms are independent predictors of occult AF detection by ILR. Most patients with confirmed AF were started on anticoagulation for secondary stroke prevention and had low stroke recurrence rates.

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

Journal of the American Heart Association ◽

10.1161/jaha.121.021045 ◽

2021 ◽

Author(s):

Irum D. Kotadia ◽

Iain Sim ◽

Rahul Mukherjee ◽

Daniel O’Hare ◽

Amedeo Chiribiri ◽

...

Keyword(s):

Atrial Fibrillation ◽

Stroke Prevention ◽

Structural Changes ◽

Stroke Risk ◽

Cryptogenic Stroke ◽

Embolic Stroke ◽

Stroke Recurrence ◽

Secondary Stroke Prevention ◽

Unknown Source ◽

The Relationship

Abstract 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.

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DABIGATRAN VERSUS ACETYLSALICYLIC ACID FOR SECONDARY STROKE PREVENTION IN PATIENTS WITH EMBOLIC STROKE OF UNDETERMINED SOURCE: RATIONALE, DESIGN AND BASELINE DATA FROM RE-SPECT ESUS™

10.26226/morressier.5aeac941521e300021138028 ◽

2018 ◽

Cited By ~ 2

Author(s):

Hans-Christoph Diener

Keyword(s):

Acetylsalicylic Acid ◽

Stroke Prevention ◽

Baseline Data ◽

Embolic Stroke ◽

Secondary Stroke Prevention

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Three year incidence and duration of atrial fibrillation episodes among a large, real-world population of cryptogenic stroke patients with insertable cardiac monitors

European Heart Journal ◽

10.1093/ehjci/ehaa946.0394 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P.D Ziegler ◽

J.D Rogers ◽

M Richards ◽

A.J Nichols ◽

S.W Ferreira ◽

...

Keyword(s):

Atrial Fibrillation ◽

Real World ◽

Stroke Prevention ◽

Detection Rate ◽

Large Population ◽

Cryptogenic Stroke ◽

World Population ◽

Median Frequency ◽

Secondary Stroke Prevention

Abstract Background/Introduction The primary goal of monitoring for atrial fibrillation (AF) after cryptogenic stroke (CS) is secondary stroke prevention. Therefore, long-term monitoring of CS patients with insertable cardiac monitors (ICMs) is likely important to ensure appropriate secondary stroke prevention therapy, regardless of when AF is detected after the index event. However, long-term data on the incidence and duration of AF from real-world populations are sparse. Purpose To investigate the long-term incidence and duration of AF episodes in real-world clinical practice among a large population of patients with ICMs placed for AF detection following CS. Methods We included patients from a large device manufacturer's database who received an ICM for the purpose of AF detection following CS and were monitored for up to 3 years. All detected AF episodes (≥2 minutes) were adjudicated. We quantified the AF detection rate for various episode duration thresholds using Kaplan-Meier survival estimates, analyzed the maximum duration of AF episodes, and measured the time to initial AF detection. Results A total of 1247 patients (65.3±13.0 years, 53% male) were included and followed for 763±362 days. AF episodes (n=5456) were detected in 257 patients, resulting in a median frequency of 5 episodes [IQR 2–19] per patient. At 3 years, the AF detection rate for episodes ≥2 minutes was 24.2%. The AF detection rates at 3 years for episodes ≥6 minutes, ≥30 minutes, and ≥1 hour were 22.4%, 20.6%, and 19.1%, respectively. The median duration of the longest detected AF episode was 4.4 [IQR 1.2–13.9] hours and the median time to AF detection was 129 [IQR 45–354] days. Conclusion AF episodes were detected via ICMs in approximately one-quarter of CS patients within 3 years of follow-up. More than 75% of patients with AF detected had episodes lasting ≥1 hour and half had episodes lasting ≥4 hours. Detection of the first AF episode typically occurred beyond the range of conventional ambulatory monitors. Long-term surveillance of CS patients is likely important given the appreciable incidence, frequency, and duration of these AF episodes. Funding Acknowledgement Type of funding source: None

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Patent foramen ovale and cryptogenic stroke: diagnosis and updates in secondary stroke prevention

Stroke and Vascular Neurology ◽

10.1136/svn-2018-000173 ◽

2018 ◽

Vol 3 (2) ◽

pp. 84-91 ◽

Cited By ~ 8

Author(s):

Kristy Yuan ◽

Scott Eric Kasner

Keyword(s):

Patient Selection ◽

Stroke Prevention ◽

Patent Foramen Ovale ◽

Clinical Decision Making ◽

Cryptogenic Stroke ◽

Clinical Decision ◽

Current Evidence ◽

Secondary Stroke Prevention ◽

Foramen Ovale ◽

Pfo Closure

The patent foramen ovale (PFO), given its high prevalence in the general population and especially in patients with cryptogenic stroke, has long generated investigation and debate on its propensity for stroke by paradoxical embolism and its management for stroke prevention. The pendulum has swung for percutaneous PFO closure for secondary stroke prevention in cryptogenic stroke. Based on a review of current evidence, the benefit from PFO closure relies on careful patient selection: those under the age of 60 years with few to no vascular risk factors and embolic-appearing stroke deemed cryptogenic after thorough evaluation. As these data look towards influencing guideline statements and device approvals in the future, patient selection remains the crucial ingredient for clinical decision making and future trials.

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Anticoagulants as more effective secondary prevention for embolic stroke of undetermined source: retrospective cohort study

10.21203/rs.2.88/v1 ◽

2018 ◽

Author(s):

Yuya Sakakura ◽

Yoichiro Homma ◽

Tomoya Arakawa ◽

Tokutaro Tanaka

Keyword(s):

Ischemic Stroke ◽

Likelihood Ratio ◽

Stroke Prevention ◽

Small Sample Size ◽

Small Sample ◽

Embolic Stroke ◽

Rank Test ◽

Ratio Test ◽

Secondary Stroke Prevention ◽

Stroke Center

Abstract Background: Whether anticoagulants or antiplatelets are more effective for secondary stroke prevention for embolic stroke of undetermined source (ESUS) remains unknown. These two treatments were compared retrospectively. Methods: Of 779 acute ischemic stroke inpatients between January 2012 and December 2014 in our stroke center, 110 patients met our ESUS criteria were compared. Antiplatelets were used in 81 patients, and anticoagulants were used in 29. ESUS criteria by Hart et al., except for extracranial atherosclerosis, were used. In all patients, intracranial magnetic resonance angiograms were obtained, and the infarct was diagnosed with positive diffusion studies. The primary outcome was recurrence-free survival. Score-tests for the hazard ratio assumption and for covariate effects in the Cox proportional hazard model were performed. To estimate hazard ratios, a likelihood ratio test and the Kaplan-Meier method and log-rank test were used. This study protocol was approved by the Institutional Review Board of the hospital. Results: The mean follow-up period was 84.0±65.5 weeks, and 14 patients treated with antiplatelets and one treated with anticoagulants developed recurrent ischemic stroke. The antiplatelet group had a significantly higher risk of recurrence than the anticoagulant group (p=0.0293, likelihood ratio 0.144, 95% confidence interval [CI]: 0.019-1.096). Multivariate analysis also showed a similar result (p=0.013, likelihood ratio -1.94, 95% CI: 0.01-0.72, respectively). Conclusions: These findings suggest that anticoagulants are more effective than antiplatelets for secondary stroke prevention for ESUS patients, although this was a non-randomized, single-center, retrospective analysis with a small sample size. Further studies are needed to accumulate enough evidence.

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