Editors' Note: Prolonged Cardiac Monitoring and Stroke Recurrence: A Meta-analysis

Advances in Neurocardiology: Focus on Atrial Fibrillation.

Atrial fibrillation (AF), commonly encountered in patients with ischemic stroke and transient ischemic attack (TIA), confers a 5-fold increased risk of ischemic stroke.1,2 AF-related strokes are associated with an ≈50% increased risk of disability and 60% increased risk of death at 3 months compared with strokes of other etiologies.3 Paroxysmal AF (PAF), a self-terminating recurrent form of cardiac arrhythmia that comprises between 25% and 62% of AF cases, may present as a brief single episode of arrhythmia or as clusters of abnormal rhythm of variable duration, sometimes evolving into a more persistent or permanent form.4 The self-terminating nature of PAF may lead to its underdiagnosis and consequent use of less effective treatment strategies (aspirin instead of oral anticoagulation) in poststroke patients. To address the underdiagnosis of PAF in patients with ischemic stroke and TIAs, several treatment guidelines have singled out the identification of PAF as an important goal after a stroke/TIA.5–8 The diagnosis of PAF, however, poses a challenge. Several features of AF (such as its brief duration, episodic frequency, and asymptomatic presentations) make its detection difficult and elusive to bedside screening measures, such as pulse monitoring and routine ECGs. To date, several studies have explored the use of prolonged noninvasive and invasive cardiac monitoring devices to identify AF but with variable success. After detection of AF, a cardioembolic mechanism is often inferred and anticoagulation occasionally prescribed for secondary stroke prevention. The routine use of cardiac monitoring to identify patients with PAF who will benefit from anticoagulation has been reported to be cost-effective.9 In this review, we provide an overview of the different methods of cardiac monitoring, summarize studies that investigated the incidence of PAF after stroke, and highlight gaps in our understanding of the pathogenic and prognostic significance of AF …

Background and CaseThis case report exemplifies the clinical application of non-invasive photoplethysmography (PPG)-based rhythm monitoring in the awakening mobile health (mHealth) era to detect symptomatic and asymptomatic paroxysmal atrial fibrillation (AF) in a cryptogenic stroke patient. Despite extensive diagnostic workup, the etiology remains unknown in one out of three ischemic strokes (i.e., cryptogenic stroke). Prolonged cardiac monitoring can reveal asymptomatic atrial fibrillation in up to one-third of this population. This case report describes a cryptogenic stroke patient who received prolonged cardiac monitoring with an insertable cardiac monitor (ICM) as standard of care. In the context of a clinical study, the patient simultaneously monitored his heart rhythm with a PPG-based smartphone application. AF was detected simultaneously on both the ICM and smartphone application after three days of monitoring. Similar AF burden was detected during follow-up (five episodes, median duration of 28 and 34 h on ICM and mHealth, respectively, p = 0.5). The detection prompted the initiation of oral anticoagulation and AF catheter ablation procedure.ConclusionThis is the first report of the cryptogenic stroke patient in whom PPG-based mHealth was able to detect occurrence and burden of the symptomatic and asymptomatic paroxysmal AF episodes with similar precision as ICM. It accentuates the potential role of PPG-based mHealth in prolonged cardiac rhythm monitoring in cryptogenic stroke patients.

Prolonged poststroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of patients with ischemic stroke (IS) with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We evaluated the association between PCM and the institution of stroke preventive strategies and stroke recurrence. We searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or TIA receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random effects model. To explore for differences between the monitoring strategies, we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT). We included 8 studies (5 RCTs, 3 observational; 2,994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in RCTs (risk ratio [RR] 3.91, 95% CI 2.54-6.03; RR 2.16, 95% CI 1.66-2.80, respectively) and observational studies (RR 2.06, 95% CI 1.57-2.70; RR 2.01, 95% CI 1.43-2.83, respectively). PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR 0.29, 95% CI 0.15-0.59), but not in RCTs (RR 0.72, 95% CI 0.49-1.07). In indirect analyses of RCTs, the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with Holter monitors and external loop recorders. PCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.

Background and Purpose: Prolonged cardiac rhythm monitoring can reveal a substantial proportion of ischemic stroke (IS) patients with atrial fibrillation (AF). We sought to evaluate the potential utility of available prolonged cardiac rhythm monitoring strategies with respect to secondary stroke prevention. Methods: We searched Medline and Scopus databases to identify randomized controlled clinical trials (RCTs) comparing AF detection, anticoagulation initiation and stroke recurrence rates in patients with history of recent IS or transient ischemic attack (TIA) receiving cardiac rhythm monitoring with implantable loop recorders (ILRs), 30-days external loop recorders or Holter monitors. We performed a network meta-analysis to combine direct and indirect evidence for any given pair of monitoring devices that were evaluated within a trial and reported effect estimates with risk ratios (RRs) and corresponding 95% confidence intervals (95%CIs). Results: We identified 5 RCTs including a total of 2202 patients (mean age 68 years, 40% women). In indirect analyses the likelihood of AF detection and anticoagulation initiation was higher for both ILR (RR=8.48, 95%CI: 3.41, 21.06; RR=3.29, 95%CI: 1.70-6.39) and external loop recorders (RR=3.06, 95%CI: 1.66, 5.61; RR=1.63, 95%CI: 1.03-2.58) compared to Holter devices. The probability of AF detection and anticoagulation initiation was lower for Holter and external loop recorders compared to ILR devices (RR=0.36, 95%CI: 0.15, 0.85 and RR=0.50, 95%CI: 0.25-0.98, respectively). No difference in the risk of stroke recurrence was found in the indirect comparisons of different cardiac rhythm monitoring strategies. Conclusion: The likelihood of AF detection and anticoagulation initiation after an ischemic stroke or TIA is higher with ILRs compared to both external loop recorders and Holter devices.

Prolonged cardiac monitoring (PCM) improves detection of atrial fibrillation (AF) after cryptogenic stroke. We summarize current research supporting the use of PCM as part of the cryptogenic stroke evaluation, while highlighting areas that require more investigation. Despite increased AF detection with longer durations of PCM, more definitive research is needed to demonstrate how PCM improves clinical outcomes. The optimal type, timing, and length of cardiac monitoring after cryptogenic stoke remains unknown. Clinical calculators will be important to risk stratify which cryptogenic stroke patients are most likely to benefit from PCM. Currently, AF detection after cryptogenic stroke should prompt consideration of anticoagulation, but it is unclear if all durations and timing of AF after stroke should be treated the same. PCM remains an important part of the cryptogenic stroke work up, and detection of AF allows for anticoagulation initiation. Additional research is needed to further refine our application of PCM to cryptogenic stroke.

Prolonged cardiac monitoring (PCM) substantially improves the detection of subclinical atrial fibrillation (AF) among patients with history of ischemic stroke (IS), leading to prompt initiation of anticoagulants. However, whether PCM may lead to IS prevention remains equivocal. In this systematic review and meta-analysis, randomized-controlled clinical trials (RCTs) reporting IS rates among patients with known cardiovascular risk factors, including but not limited to history of IS, who received PCM for more than 7 days versus more conservative cardiac rhythm monitoring methods were pooled. Seven RCTs were included comprising a total of 9048 patients with at least one known cardiovascular risk factor that underwent cardiac rhythm monitoring. PCM was associated with reduction of IS occurrence compared to conventional monitoring (Risk Ratio: 0.76; 95% CI: 0.59-0.96; I 2 = 0%). This association was also significant in the subgroup of RCTs investigating implantable cardiac monitoring (Risk Ratio: 0.75; 95% CI: 0.58-0.97; I 2 = 0%). However, when RCTs assessing PCM in both primary and secondary prevention settings were excluded or when RCTs investigating PCM with a duration of 7 days or less were included, the association between PCM and reduction of IS did not retain its statistical significance. Regarding the secondary outcomes, PCM was related to higher likelihood for AF detection and anticoagulant initiation. No association was documented between PCM and IS/transient ischemic attack occurrence, all-cause mortality, intracranial hemorrhage, or major bleeding. PCM may represent an effective stroke prevention strategy in selected patients. Additional RCTs are warranted to validate the robustness of the reported associations.

The cause of ischemic stroke or transient ischemic attack (TIA) remains unclear after initial cardiac monitoring in approximately one-third of patients. Randomized controlled trials (RCTs) showed that the prolonged cardiac monitoring of patients with cryptogenic stroke or TIA increased detection of atrial fibrillation (AF). We aimed to perform a meta-analysis of all RCTs that evaluated the prolonged monitoring ≥7 days in patients with cryptogenic stroke or TIA. We searched PubMed, EMBASE, Cochrane CENTRAL, and relevant references for RCTs without language restriction (inception through December 2014) and performed meta-analysis using random effects model. Detection of AF, use of anticoagulation at follow-up, recurrent stroke or TIA, and mortality were major outcomes. Four RCTs with 1149 total patients were included in the meta-analysis. Prolonged cardiac monitoring ≥7 days compared to shorter cardiac monitoring of ≤48 hours duration increased the detection of AF (≥30 seconds duration) in patients after cryptogenic stroke or TIA (13.8% vs. 2.5%; odds ratio [OR], 6.4; 95% confidence interval [CI], 3.50-11.73; P < 0.00001; I(2) , 0%]. It also increased the odds of AF detection of any duration (22.6% vs. 5.2%; 5.68[3.3-9.77]; P < 0.00001; I(2) , 0%). The patients who underwent prolonged monitoring were more likely to be on anticoagulation at follow-up (2.21[1.52-3.21]; P < 0.0001; I(2) , 0%). No differences in recurrent stroke or TIA (0.78[0.40-1.55]; P = 0.48; I(2) , 0%) and mortality (1.33[0.29-6.00]; P = 0.71; I(2) , 0%] were observed between two strategies. Prolonged cardiac monitoring improves detection of atrial fibrillation and anti-coagulation use after cryptogenic stroke or TIA and therefore should be considered instead of shorter duration of cardiac monitoring.

Atrial fibrillation is a major cause of ischemic stroke. Technological advances now support prolonged cardiac rhythm monitoring using either surface electrodes or insertable cardiac monitors. Four major randomized controlled trials show that prolonged cardiac monitoring detects subclinical paroxysmal atrial fibrillation in 9% to 16% of patients with ischemic stroke, including in patients with potential alternative causes such as large artery disease or small vessel occlusion; however, the optimal monitoring strategy, including the target patient population and the monitoring device (whether to use an event monitor, insertable cardiac monitor, or stepped approach) has not been well defined. Furthermore, the clinical significance of very short duration paroxysmal atrial fibrillation remains controversial. The relevance of the duration of monitoring, burden of device-detected atrial fibrillation, and its proximity to the acute ischemic stroke will require more research to define the most effective methods for stroke prevention in this patient population.

AI-ECG for Prediction of Occult Atrial Fibrillation in Patients With Stroke Who Undergo Prolonged Cardiac Monitoring

Introduction: Approximately 25% of strokes are classified as cryptogenic (CS), while greater than 50% have an identifiable or ‘known’ etiology (KS). Several studies have demonstrated that prolonged cardiac monitoring (PCM) after cryptogenic stroke substantially increases the detection of atrial fibrillation (AF), but the yield of PCM in KS stroke is unknown. As a result, the majority of guidelines recommend restricting PCM to patients with cryptogenic stroke. If the detection of AF in KS is no different to cryptogenic stroke, it would suggest that this group too would similarly benefit from PCM, with the potential to impact therapeutic decisions (e.g. initiating anticoagulation). Methods: In a cross-sectional study, we compared AF detection by PCM (minimum of 48 hrs) between CS and KS patients without a previous diagnosis of AF. We developed a multivariate logistic regression model by including known and significant clinical, echocardiographic, and radiological factors known to be associated with the detection of AF. We reported results as odds ratios (OR) and 95% confidence intervals (95% CI). Results: We included 561 ischemic stroke patients, 376 with CS and 185 with KS. The median duration of PCM was 167h for CS and 48h for KS. AF was detected in 30 of 376 (8%) CS patients, and 20 of 185 (7.9%) KS patients. Age, history of thyroid disease, clinical presentation of dysarthria, wake-up stroke, and left atrial volume index on echocardiography were significantly associated with a new diagnosis of AF after stroke in the univariable analysis and were thus included in the logistic regression analysis. Additionally, duration of PCM was included in the multivariate model. After adjustment for potential confounders, AF detection by PCM was not significantly higher for CS than KS (OR 0.95, 95% CI 0.25-3.32, P=0.94). Conclusion: To the best of our knowledge this is the first study directly comparing the incidence of AF between CS and KS as the pre-specified primary outcome. Our findings suggest that CS and KS patients have similar rates of AF detection by PCM. Future prospective research is required to confirm these findings and to determine the cost-effectiveness of PCM in non-cryptogenic stroke patients.

Prolonged cardiac rhythm monitoring reveals atrial fibrillation (AF) in 16-42% of patients who undergo monitoring for up to 6 months after a cryptogenic stroke. The feasibility of prolonged cardiac monitoring, AF detection rates and the impact of earlier screening after suspected cardioembolic infarct in a community setting is unknown. Methods: This prospective study examined patient compliance and AF detection rates with prolonged cardiac monitoring started within 30 days of a stroke/TIA. 181 patients ≥ 55 years old with a suspected cardioembolic stroke/TIA that occurred in the preceding 30 days were referred for 30-day cardiac monitoring. Patients were educated about reasons for monitoring and test procedures for 15-20 minutes. A Spiderflash-t or Northeast DR 200 monitor, programmed for detecting AF, was used. Auto-triggered and patient-activated recordings obtained during two consecutive 15-day monitoring periods were assessed. Either 3-day serial ECG or ≥24h Holter monitor was also completed in 119/181 patients. The primary outcome was patient compliance with 30 days of monitoring. Secondary outcomes included detection of any duration of AF within the two monitoring periods. Results: The compliance rate for the full 30-day monitoring period was 98.9% (179/181). AF was detected on 30-day monitor in 11.6% (21/181) of patients. Of the patients who received both 3-day serial ECG or ≥24h Holter and 30-day monitoring, AF was only detected in 0.84% (1/119) with 3-day serial ECG and/or Holter monitoring vs. 14.3% (17/119) with 30-day monitoring. AF was detected in 76.2% (16/21) of patients in the first 15 day period. 14 patients had AF lasting longer than 6 minutes, 5 had AF lasting between 30 secs - 6 min and 2 had AF &lt; 30 secs. Of patients who completed the 30-day monitoring, 38.8% had AF recurring through the 30 days. 85.7% (18/21) of patients were switched to a novel oral anticoagulant (NOAC), while 3 patients died and thus could not be switched to a NOAC. In conclusion, 30-day cardiac monitoring is feasible in a community setting with high compliance rates, yields similar AF detection rates as seen in clinical trials and positively impacts patient management. There are missed opportunities for secondary stroke prevention in the community without 30-day monitoring.

Introduction: Although current guidelines indicate that the clinical benefit of prolonged cardiac monitoring for atrial fibrillation (AF) detection in ischemic stroke (IS) patients remains uncertain, clinical trials suggest that implantable cardiac monitors (ICMs) substantially increase AF detection due to prolonged monitoring duration. Methods: In the present systematic review and meta-analysis we sought to investigate the association of ICM duration with the yield of AF detection in IS patients. We also assessed whether IS subtype, individual patient characteristics and elapsed time between IS onset and CM implantation may also impact the probability of AF detection. We included studies reporting AF detection rates by ICM in IS patients with negative initial AF screening. We excluded studies reporting prolonged cardiac monitoring with devices other than ICM, not providing AF detection rates or monitoring duration and reporting overlapping data for the same population. Random-effects model was used to calculate the pooled estimates in all subgroup and univariate meta-regression analyses. Results: We included 28 studies (4531 patients; mean age:65 years; 52% men). In meta-regression analyses the proportion of AF detection by ICM was independently associated with monitoring duration (coefficient=0.015,95%CI:0.005-0.024) and mean patient age (coefficient=0.009, 95%CI:0.003-0.015). No association was detected with other patient characteristics, including IS subtype (cryptogenic vs. embolic stroke of undetermined source) or time from IS onset to CM implantation. In subgroup analyses significant differences (p&lt;0.001) in the AF detection rates were documented according to ICM duration (&lt;6 months: 4%, 95%CI: 3%-6%; ≥6 months &amp; ≤12 months: 20%, 95%CI: 17%-24%; &gt;12 months &amp; ≤24 months: 26%, 95%CI: 23%-30%; &gt;24 months: 34%, 95%CI: 30%-39%). Conclusion: Extended duration of ICM monitoring appears to be the only factor that increases substantially the yield of AF detection in patients with IS and initial negative AF screening. IS subtype and individual patients characteristics, except age, are not related to the probability of AF detection.

INTRODUCTION: Prolonged cardiac monitoring is frequently used to detect atrial fibrillation (AF) in high-risk populations, with the goal of preventing thromboembolic events. We sought to determine the impact of prolonged cardiac monitoring on the incidence of stroke and systemic embolism (SSE) or transient ischemic attack (TIA) METHODS: We performed a systematic review and meta-analysis of randomized trials evaluating prolonged monitoring versus usual care (PROSPERO #CRD42021277611). Studies were identified through CENTRAL, MEDLINE, and Embase. We included studies with ≥100 participants and ≥30 days follow-up. The primary outcome was a composite of SSE/TIA, as reported in the original trials. Secondary outcomes included AF detection, oral anticoagulation (OAC) initiation, and major bleeding. Sensitivity analysis examining the impact of monitoring device, and indication for monitoring were performed. Meta-analyses were performed with R using a random-effects model. RESULTS: From 1411 records, we included 9 RCTs (n = 10,205). Mean age was 70 years, 40% were female, and mean CHADS2 score was 4.0. Studies used implantable cardiac monitors (n = 4), external cardiac monitors (n = 3), or handheld ECG devices (n = 2). Study populations included post-stroke (n = 5), high risk for AF or stroke (n = 2), and post-cardiac surgery (n = 1). Mean follow-up was 16 months (range 3-65). Extended monitoring did not significantly reduce the primary outcome (Figure, random effects risk ratio [RR] 0.87, 95% confidence interval [CI] 0.72-1.06, I2 = 0%) or its individual components. Extended monitoring increased AF detection (RR 4.56, 95% CI 3.01-6.92, I2 = 65%) and OAC usage (RR 2.25, 95% CI 2.01-2.53, I2 = 0%), but did not impact major bleeding (RR 1.23, 95% CI 0.84-1.82, I2 = 0%). CONCLUSION: Prolonged monitoring was associated with increased AF detection and OAC use, without significantly reducing the occurrence of thromboembolic events.

BackgroundGuidelines recommend a confirmed diagnosis of atrial fibrillation (AF) to initiate oral anticoagulation in cryptogenic stroke (CS) patients. However, the intermittent nature of AF can make detection challenging with intermittent short-term cardiac monitoring.ObjectiveThe purpose of this retrospective cohort study was to examine post-CS utilization of cardiac monitoring and associated clinical outcomes.MethodsAdults with incident hospitalization for CS were identified in the Optum® claims database and assessed for cardiac monitoring received poststroke. Patient were stratified into those with a long-term insertable cardiac monitor (ICM) vs external cardiac monitor (ECM) only. The timing of ICM placement poststroke was treated as a time-dependent covariate. The clinical outcomes of interest were time to AF diagnosis, oral anticoagulation usage, and all-cause mortality.ResultsA total of 12,994 patients met selection criteria for the analysis, of whom 1949 (15%) received an ICM and 11,045 (85%) received ECM only. In those who had received an ECM as their first monitoring modality, only 4.4% moved on to receive an ICM for longer-term monitoring. Use of ECM before ICM was associated with a longer time to AF diagnosis (median 336 vs 194 days). Compared to those with ECM only, ICM patients had a significantly lower rate of death (hazard ratio [HR] 0.70; P = .004), and faster time to AF diagnosis (HR 1.50; P <.0001) and anticoagulation initiation (HR 1.57; P <.0001) during follow-up of up to 5 years after CS.ConclusionIn a real-world study of CS patients, prolonged cardiac monitoring was associated with higher rates of AF detection and treatment, and higher odds of survival.