Cryptogenic Stroke Population Research Articles

Rates of therapeutic interventions in a large real-world cohort with insertable cardiac monitors

Abstract Background Insertable cardiac monitors (ICMs) provide up to several years of continuous monitoring and have demonstrated high diagnostic yields for arrhythmia detection. However, the rates of arrhythmia-related therapeutic interventions following ICM implant have not been comprehensively characterized across indicated patient populations. Purpose To quantify rates of arrhythmia therapies in a large, real-world U.S. cohort of ICM patients. Methods De-identified patients receiving a Reveal LINQ ICM between Oct 1, 2016 – Sept 30, 2020 with no prior cardiac implantable electronic devices (CIEDs) and ≥1 year of follow-up in the Optum Clinformatics® Data Mart claims database were identified (N=17,037). Patients were stratified by indication for ICM placement: N=431 (2.5%) of patients were indicated for AF ablation monitoring, 2,193 (12.9%) for AF management, N=4,852 (28.5%) Cryptogenic stroke, N=1,252 (7.3%) Palpitations, 1,346 (7.9%) Suspected AF, 6,716 (39.4%) Unexplained syncope, and 247 (1.4%) Ventricular tachycardia (VT). Each patient was followed in the claims database after ICM insertion until end of continuous claims enrollment, end of database, or death. Therapeutic interventions for arrhythmias were characterized during follow-up, including procedures (CIED implants, cardioversion, and ablation) and arrhythmia medication initiation (antiarrhythmics, rate-control medications, and oral anticoagulants). Results Mean(SD) follow-up in the claims database post ICM placement was 3.4(1.3) years; 52.4% of patients were female, and mean age was 70.8(11.9) years. Overall, 54.5% of patients received a therapeutic intervention during follow-up, with 25.0% of patients receiving a therapeutic procedure and 44.0% initiating an arrhythmia-related medication (table). The highest procedure rates included implantable pulse generator (IPG) implants in the Unexplained syncope population (21.4% of patients) and cardiac ablations in the populations receiving ICM for known AF (27.8% of AF ablation monitoring patients and 23.5% of AF management patients). Medication initiation rates were highest for oral anticoagulants in the Cryptogenic stroke population (31.0% of patients). The mean time from ICM insertion to therapeutic action was 13(13) months for procedures and 7(11) months for medication initiation. Conclusions In a large sample of real-world ICM patients, more than half received a therapeutic intervention after ICM placement. Time to intervention was lengthy and showed substantial variability amongst patients, underscoring the importance of long-term continuous monitoring to uncover clinically-relevant arrhythmia findings.

Diagnostic Yield of Extended Cardiac Patch Monitoring in Cryptogenic Stroke Patients (P11-5.032)

<h3>Objective:</h3> To evaluate the diagnostic yield of detecting atrial fibrillation (AF) and/or atrial flutter (AFL) with extended cardiac patch monitoring in our cryptogenic stroke population. <h3>Background:</h3> Cryptogenic stroke accounts for 15–40% of yearly strokes with increased incidence in younger patients. It is standard of care at our comprehensive stroke center located in the stroke belt to discharge cryptogenic stroke patients with a 14-day continuous cardiac monitoring patch (Zio) to evaluate for paroxysmal AF/AFL. <h3>Design/Methods:</h3> We propose to conduct a retrospective chart review from January 2019 to June 2022 (3.5 years) of all adult stroke patients with a discharge diagnosis of ischemic stroke using the Get With The Guidelines stroke database at our institute. We will be analyzing all cryptogenic stroke patients who were discharged with a Zio patch. The following data points will be collated; demographics, baseline stroke risk factors, left atrium volume, Zio patch results including wear time, analyzed time, AF burden, duration the first episode of AF detected, patient events, and other irregular arrhythmias. Our preliminary data from January 2021 to June 2022 (18 months), observed 270 cryptogenic stroke discharges. Out of which, 165 met the eligibility criteria and were discharged with a Zio patch. <h3>Results:</h3> AF/AFL was detected in 14 patients (8.5%). The mean duration before the first episode of paroxysmal AF (PAF) was 3.7 days and the median duration was 1.5 days. 43 percent of PAF occurred after 48 hours. <h3>Conclusions:</h3> The preliminary data demonstrated a relatively low yield of AF/AFL detection with Zio patch monitoring in our cryptogenic stroke population. We plan to complete the prespecified data collection period to achieve a larger sample size and further analyze independent risk factors for AF/AFL detection and patient compliance. <b>Disclosure:</b> Dr. Rice has nothing to disclose. Dr. Lucioni has nothing to disclose. Mr. Aiello has nothing to disclose. Dr. Ranasinghe has nothing to disclose.

Cost-effectiveness of an insertable cardiac monitor to detect atrial fibrillation in patients with cryptogenic stroke.

Background: We assessed cost-effectivenessof insertable cardiac monitors (ICMs) in a US cryptogenic strokepopulation. Materials & methods: We modelled lifetime costs and quality-adjusted life years for three monitoring strategies post cryptogenic stroke: ICM starting immediately, ICM starting after Holter monitoring (delayed ICM)and standard of care involving intermittent ECG and Holter monitoring. Patient characteristics and detection efficacy were based on the CRYSTAL-AF trial. AF detection altered the modelled anticoagulation therapy and subsequent stroke and bleed risks. Results & conclusion: Immediate ICM was found to be cost-effective versus standard of care and cost-saving versus delayed ICM. Results were robust to sensitivity analyses. ICMs are a cost-effective diagnostic tool for the prevention of recurrent stroke in a US cryptogenic stroke population.

Real-world experience with implantable loop recorder monitoring to detect subclinical atrial fibrillation in patients with cryptogenic stroke: The value of p wave dispersion in predicting arrhythmia occurrence

PurposeWe hypothesized patients implanted with ILRs for cryptogenic stroke in “real life” clinical practice will show an AF detection rate comparable to prior clinical studies, and that clinical or imaging features may help to identify those at higher risk of AF detection. MethodsA retrospective chart review was conducted of all patients who presented with cryptogenic stroke and received an ILR at an academic medical center from 2015 to 2017 with an active inpatient stroke service. The electronic health record and remote monitoring were used to identify occurrence of AF. ResultsA total of 178 patients who received ILRs for cryptogenic stroke were included. Overall, after a thorough evaluation for other etiologies of stroke, 35 (19.6%) were found to have AF detected. Mean follow-up was 365 days with a median time to detection of 131 days. Advanced age (p = 0.001), diastolic dysfunction on echo (p = 0.03), as well as ECG findings of premature atrial contractions (PACs) and p wave dispersion (PWD) > 40 ms were found to be predictive of AF detection (p = 0.04, p < 0.001, respectively). On multiple regression analysis, the only independent predictor of AF detection was PWD > 40 ms. ConclusionAfter a thorough evaluation to exclude other etiologies for stroke, approximately 20% of patients of our cryptogenic stroke population were found to have AF with ILR surveillance. Advanced age, diastolic dysfunction, as well as ECG findings of PACs and increased PWD may help to predict those at higher risk of AF detection, while PWD was the only independent predictor. This has important clinical implications, as better prediction of AF may help identify those at highest risk and might subsequently aid in guiding therapy.

PCV27 COST-EFFECTIVENESS OF INSERTABLE CARDIAC MONITORS VERSUS STANDARD OF CARE OR SHORT-TO-LONG-TERM ECG MONITORING TO IDENTIFY ATRIAL FIBRILLATION AFTER CRYPTOGENIC STROKE

Insertable cardiac monitors (ICMs) are more likely than standard of care (SoC) intermittent external ECG monitors to detect atrial fibrillation (AF) in patients with cryptogenic stroke (CS). Anticoagulation is proven to decrease recurrent stroke risk in patients with documented AF. We aimed to evaluate the cost-effectiveness of immediate ICM at hospital discharge versus a ‘short-to-long-term monitoring’ (STLM) approach (7-day ECG monitor followed by ICM in patients remaining undiagnosed) and versus SoC, in a CS population. A lifetime Markov model assessed the cost-effectiveness of immediate ICM vs. STLM vs. SoC, from a US payer perspective. Patient characteristics and AF detection rates were based on the CRYSTAL-AF trial: three-year diagnostic yield was 30% with ICM and 3% in SoC; 1% of STLM patients are diagnosed with initial 7-day monitor. AF detection resulted in a change from aspirin to NOAC, unless precluded by prior bleeds. Subsequent risks of ischemic strokes and bleeding events were modeled based on published literature. Costs and effects were discounted at 3% annually. Immediate ICM was associated with a 0.20 quality-adjusted life year (QALY) gain compared to SoC (6.99 vs. 6.79) and $6,588 higher per-patient costs, resulting in an incremental cost-effectiveness ratio of $33,169 per QALY gained. ICM’s expected value improved with increased recurrent stroke risk. Compared to STLM, immediate ICM was associated with lower costs ($54,480 vs. $54,665), and a modest benefit in outcomes (gain of 0.0011 QALYs) making it economically dominant for AF detection. In sensitivity analysis, the immediate ICM approach remained cost-saving when varying the duration of initial short-term monitor (1-, 2-, 21-, and 30-days). ICMs are a cost-effective diagnostic tool for the prevention of recurrent stroke in a US cryptogenic stroke population. Immediate ICM was cost-saving compared to STLM, due to the cost and low diagnostic yield of short-term monitoring and delay in AF detection.

TCT-822 Patent Foramen Ovale (PFO) closure compared to medical therapy for prevention of stroke recurrence in cryptogenic stroke population: Systematic Review and Meta-Analysis

Background Closure of a Patent Foramen Ovale(PFO), may play a role in reducing the risk of recurrent strokes in the cryptogenic stroke population. With recent new evidence published, we aimed to conduct a review of currently available randomised controlled trials(RCT) in order to evaluate the utility of percutaneous device closure of PFO compared to medical therapy in prevention of recurrent strokes. Our aim was to compare the incidence of recurrent stroke between the 2 approaches and also to compare the incidence of transient ischaemic attacks(TIA) and major bleeding between the 2 approaches. Methods A comprehensive search of major databases was performed. We included comparative RCTs, where outcomes of percutaneous PFO closure with medical therapy were available in patients with cryptogenic stroke and a PFO. Results Six studies were included with total of 3560 patients. Incidence of recurrent stroke was significantly less in the PFO closure group compared to medical therapy (2.86% vs. 5.09%, OR 0.49, 95% CI 0.35 – 0.70, p < 0.0001). Incidence of TIA was not significantly different in both PFO closure group compared to medical therapy (2.75% vs. 3.83%, OR 0.79, 95% CI 0.54 – 1.15, p = 0.22). Major bleeding was shown to not be significantly different in PFO closure group compared to medical therapy (1.64% vs. 1.76%, OR 0.90, 95% CI 0.54 – 1.49, p = 0.68) either. Sub group analysis of patients with ASA, comparing PFO closure group to medical therapy showed significant benefit in terms of stroke prevention in the PFO closure group (3.02% vs. 7.99%, OR 0.39, 95% CI 0.21 – 0.72, p = 0.002). Sub group analysis of large intra-atrial shunt similarly showed significant benefit in terms of stroke prevention in the PFO closure group (1.43% vs. 5.40%, OR 0.26, 95% CI 0.13 – 0.51, p < 0.0001). Download : Download high-res image (119KB)Download : Download full-size image Conclusion When combining all trials published so far, our analysis demonstrates a net beneficial effect of PFO closure overall. Our study also highlights the need of a dedicated RCT to explore PFO closure compared to oral anticoagulation to reduce the likelihood of bias in the future.

Patent Foramen Ovale Closure Compared to Medical Therapy for Prevention of Stroke Recurrence in Cryptogenic Stroke Population: Systematic Review and Meta-Analysis

Introduction: Closure of a patent foramen ovale (PFO) may play a role in reducing the risk of recurrent strokes in the cryptogenic stroke population. With recent new evidence being published, this study aimed to conduct a review of currently available randomised, controlled trials (RCT), in order to evaluate the utility of percutaneous device closure of PFO compared to medical therapy in preventing recurrent strokes. The aim was to compare the incidence of recurrent stroke between the two approaches and of transient ischaemic attacks (TIA) and major bleeding between the two approaches.

PFO Closure for Cryptogenic Stroke: A Review and Clinical Treatment Algorithm.

With a high prevalence in the general population of approximately 25%, and a prevalence in the cryptogenic stroke population approaching 40%, the propensity of a patent foramen ovale (PFO) to precipitate or enable stroke, especially in young, otherwise healthy individuals, has been the subject of much debate. With proof of concept achieved via imaging modalities documenting thrombus-in-transit, and the development of minimally-invasive percutaneous approaches to closure, multiple observational studies and, more recently, several completed randomized controlled trials have sought to answer the question of when and in whom PFO closure should occur. We describe the historical context of PFO closure and review the observational and randomized control trial evidence in this field, culminating in the recent Food and Drug Administration approval of the first dedicated closure device for PFO. Guidelines and consensus statements are discussed, and a novel treatment algorithm is proposed. Future directions in PFO closure will include new devices, further data from completed and upcoming clinical trials, and potential expansion into other disease states associated with PFO.

Long-term detection of atrial fibrillation with insertable cardiac monitors in a real-world cryptogenic stroke population

The long-term incidence of atrial fibrillation (AF) in cryptogenic stroke (CS) patients has been explored in carefully controlled clinical trials but real-world data are limited. We investigated the two-year incidence of AF in real-world clinical practice among a large cohort of patients with an insertable cardiac monitor (ICM) placed for AF detection following CS. Patients in the de-identified Medtronic Discovery™ Link database who received an ICM (Reveal LINQ™) for the purpose of AF detection following CS were included and monitored for up to 2years. All detected AF episodes (≥2min) were adjudicated. We quantified the AF detection rate using Kaplan-Meier survival estimates, analyzed the median time to initial detection of AF, and simulated the ability of various intermittent monitoring strategies to detect AF. A total of 1247 patients (65.3±13.0years, 53% male) were included and followed for 579±222days. AF episodes (n=4183) were detected in 238 patients, resulting in an AF detection rate of 21.5% at 2years. The median time to AF detection was 112 [IQR 35-293] days. Intermittent monitoring for AF detection was inferior to continuous ICM monitoring with sensitivities ranging from 2.9% (annual 24-hour Holter) to 29.9% (quarterly 7-day Holters), p<0.001. AF episodes were detected via continuous monitoring with ICMs in approximately 1 of every 5 CS patients within 2years of follow-up. The vast majority of patients with AF would not have been detected with conventional external ambulatory monitors. ICMs should therefore be considered in the evaluation of CS patients.

Carotid Bulb Webs as a Cause of "Cryptogenic" Ischemic Stroke.

Carotid webs are intraluminal shelf-like filling defects at the carotid bulb with recently recognized implications in patients with recurrent ischemic stroke. We sought to determine whether carotid webs are an under-recognized cause of "cryptogenic" ischemic stroke and to estimate their prevalence in the general population. A retrospective review of neck CTA studies in young patients with cryptogenic stroke over the past 6 years (n = 33) was performed to determine the prevalence of carotid webs compared with a control group of patients who received neck CTA studies for reasons other than ischemic stroke (n = 63). The prevalence of carotid webs in the cryptogenic stroke population was 21.2% (95% CI, 8.9%-38.9%). Patients with symptomatic carotid webs had a mean age of 38.9 years (range, 30-48 years) and were mostly African American (86%) and women (86%). In contrast, only 1.6% (95% CI, 0%-8.5%) of patients in the control group demonstrated a web. Our findings demonstrate a statistically significant association between carotid webs and ischemic stroke (OR = 16.7; 95% CI, 2.78-320.3; P = .01). Carotid webs exhibit a strong association with ischemic stroke, and their presence should be suspected in patients lacking other risk factors, particularly African American women.

Update on the Management of Patent Foramen Ovale in 2017: Indication for Closure and Literature Review

Patent foramen ovale (PFO) is a common congenital abnormality with a high prevalence of approximately 25 % in the general population and an even higher incidence of about 40 % in the cryptogenic stroke population. PFO closure in cryptogenic stroke patients as a treatment modality for the secondary prevention of recurrent stroke has been much debated and studied. Several completed randomized clinical trials sought to answer the question of whether PFO closure is beneficial for cryptogenic stroke patients. Until the most recent of these trials, no significant benefit had been demonstrated. Based on newer evidence, in October 2016 the US Food and Drug Administration approved the first dedicated closure device for PFO. This review article describes the association between PFO and cryptogenic stroke, reviews current diagnostic modalities of PFO assessment, discusses management approaches, and reviews randomized clinical trials, practice guidelines, and consensus statements. Associations between PFO and other conditions such as migraine headaches, platypnea-orthodeoxia syndrome, and decompression sickness in divers are also briefly reviewed.

The Evolution and Application of Cardiac Monitoring for Occult Atrial Fibrillation in Cryptogenic Stroke and TIA.

The evaluation of the stroke and transient ischemic attack (TIA) patient has been historically predominated by the initial evaluation in the hospital setting. As the etiology of stroke has eluded us in approximately one third of all acute events, the medical community has been eager to seek the answer to this mystery. In recent years, we have seen an explosion of innovations and trends allowing for a more detailed post stroke assessment strategy aimed at the identification of occult atrial fibrillation as the etiologic cause for the cryptogenic event. This has been achieved through the evolution and aggressive application and study of prolonged and advanced cardiac monitoring. This review is aimed to clarify and elucidate the standard and novel cardiac monitoring methods that have become available for use by the medical community and expected in the higher level care of cryptogenic stroke and TIA patients. These cardiac monitoring methods and devices are as heterogeneous as our patient population and have their own advantages and disadvantages. Many factors may be taken into consideration in choosing the appropriate cardiac monitoring method and are highlighted for consideration in this review. With a judicious approach to investigating the cryptogenic stroke population, and applying a wealth of novel treatment options, we may move forward into a new era of stroke prevention.

Abstract W P191: Patient Compliance High with Long-Term Continuous ECG Monitor

Introduction: Long term ECG monitoring to detect atrial fibrillation in a cryptogenic stroke is now the emerging standard of care. The advent of patch based ECG monitors raises the question of patient compliance with this new modality. Hypothesis: We assessed the hypothesis that patient compliance, as measured by Leads-On detection for patch based ECG monitoring, is constant over time. Methods: We performed a retrospective analysis from ZIO® Patch (Patch) devices (iRhythm, San Francisco, CA). The Patch is a continuous recording single lead ECG monitor that can be worn for up to 14 days. The primary endpoint of Leads-On is the percentage of time the device is applied to the patient during the wear period, which was derived from a second channel in the device. The data are gathered by ZEUS software and exported in a CSV file. The compliance data were analyzed overall and in categories at days: 0-1, 1-2, 2 to 7, &gt;7 to 10 and &gt;10 to 14. A secondary endpoint, percent Analyzable Time (percentage of ECG record that was available for detection by the algorithm during the wear period and signifies signal quality), was assessed for the same time increments. Results: The dataset consisted of 18,885 records. The total wear time ranged from 0.10 up to 14.01 days, with a median of 12.51. The medians and interquartile ranges for the percent Leads On and percent of Analyzable Time were 100% (99.99-100%) and 97.99% (94.64-99.26%). In Table 1, the interquartile ranges for percent Leads On and Analyzable Time was wider when the Patch was worn less than a day, but remains above 74%. Total wear time in days n Percent Leads On Percent Analyzable Time Median Interquartile Range Median Interquartile Range 0.10-&lt;1 105 99.65 86.52-100 92.86 74.19-96.97 1-&lt;2 407 100 99.88-100 97.37 90.96-99.02 2-&lt;7 4124 100 100-100 97.96 94.3-99.26 7-&lt;10 2963 100 99.98-100 97.79 94.33-99.19 10+ 11286 100 100-100 98.07 95.00-99.29 Conclusion: Patient compliance with long term ECG patch monitors is high as measured by Leads-On detection. High patient compliance results in a large volume of quality ECG. Further study is needed to compare patient compliance with ECG patch based monitors with other monitoring modalities, particularly in the cryptogenic stroke population.

Index Event Bias as an Explanation for the Paradoxes of Recurrence Risk Research

Index Event Bias as an Explanation for the Paradoxes of Recurrence Risk Research