Additional Stroke Risk Factors Research Articles

A polygenic risk score predicts future atrial fibrillation-related stroke/systemic embolism

Abstract Background Novel strategies to identify patients at risk of stroke/systemic embolism (SSE) earlier before development of clinical atrial fibrillation (AF) might be useful. We examined whether the AF polygenic risk score (PRS) added to a clinical risk model would improve prediction of AF-related SSE in people without prevalent AF. Methods A total of 62,145 individuals (≥65 years) without prevalent AF who had additional risk factors for stroke (hypertension, diabetes, heart failure, myocardial infarction, stroke or transient ischemic attack, and peripheral artery disease) were included from the UK Biobank. The primary endpoint was AF-related SSE and the secondary endpoint was incident AF. SSE event was considered AF-related when previously undiagnosed AF was identified at the time of SSE or up to 1-year after the SSE. Results For a median of 11.5 (10.6-12.4) years, 334 AF-related SSE and 7,428 incident AF events developed. After adjusting for the clinical risk model, AF-PRS identified a significant gradient for AF-related SSE and incident AF with a 4.59-fold (HR 4.59, 95% CI 3.12-6.75, p<0.001) and 3.14-fold (HR 3.14, 95% CI 2.90-3.40, p<0.001) higher risk in the top quintile of the AF-PRS. The number needed for 5-years of AF screening at the index age of 75 years to find 1 AF-related SSE and incident AF was 91 and 10 for high AF-PRS and 500 and 22 for low AF-PRS, respectively. AF-PRS added to a clinical risk model resulted in a significant improvement in C-statistics for AF-related SSE (C-index; 0.66 to 0.72, p for difference in C-index <0.001) and incident AF (C-index; 0.65 to 0.68, p for difference in C-index <0.001). Conclusions AF screening strategy based on AF-PRS added to a clinical risk model might detect and potentially prevent more cases of AF-related SSE.

Effects of long-term continuous screening for atrial fibrillation on heart failure events - results from the randomized LOOP Study

Abstract Background Previous research established a solid link between atrial fibrillation (AF) and heart failure (HF). However, while two landmark trials have assessed AF screening for stroke prevention, the potential impact of AF screening on HF remains unclear. Purpose This secondary analysis of the LOOP Study aimed to investigate the effects of AF screening on HF events. Methods The LOOP Study was a randomized clinical trial evaluating long-term continuous AF screening with implantable loop recorder (ILR) in individuals aged 70-90 years and with ≥1 of arterial hypertension, diabetes mellitus, HF, and/or prior stroke. At inclusion, study participants were randomized 1:3 to either ILR screening or usual care. Anticoagulation was recommended upon AF detection, whereas other treatment was left to the discretion of the treating physician. In this secondary analysis, a cause-specific Cox regression model was applied to explore the effects of AF screening vs usual care on 1) time-to-first HF event and 2) total HF events, with the latter performed using the Andersen-and-Gill extension. HF event was defined as newly diagnosed HF with left ventricular ejection fraction ≤40% or any HF hospitalization in participants with prior diagnosis of HF with reduced ejection fraction. Results In total, 6004 participants were enrolled in the LOOP Study: 1501 in the ILR group vs 4503 in the Control group. The study population had a mean age of 75 years and slightly more males than females (53% vs 47%), whereas 266 (4.4%) were previously diagnosed with HF at baseline. During a median follow-up of 5.4 years, a total of 208 HF events were reported in 175 (2.9%) participants: 37 events among 34 (2.3%) participants in the ILR group vs 171 events among 141 (3.1%) participants in the Control group. For time-to-first HF event, the annualized event rate was 0.44%/year [95% confidence interval (CI): 0.30-0.62] vs 0.61%/year [95% CI: 0.51-0.72] for ILR vs Control, corresponding to a hazard ratio (HR) of 0.72 [95% CI: 0.50-1.05]. When assessing total HF events, a significantly lower event rate was observed in the ILR group (0.47%/year [95% CI: 0.33-0.65]) compared with the Control group (0.73%/year [95% CI: 0.62-0.84]), resulting in a HR of 0.65 [95% CI: 0.44-0.97]. Conclusions Among elderly individuals with additional stroke risk factors, long-term continuous AF screening led to a significantly reduced risk of total HF events, compared with usual care. This should be considered as hypothesis-generating and warrants further investigation.Cumulative incidence of HF event

Screening for Atrial Fibrillation by Digital Health Technology in Older People in Homecare Settings: A Feasibility Trial.

Users of homecare services are often excluded from clinical trials due to advanced age, multimorbidity, and frailty. Atrial fibrillation (AF) is a common and frequently undiagnosed arrhythmia in the elderly and is associated with severe mortality, morbidity, and healthcare costs. Timely identification prevents associated complications through evidence-based treatment. This study is aimed at assessing the feasibility of AF screening using new digital health technology in older people in a homecare setting. Users of homecare services ≥ 65 years old with at least one additional risk factor for stroke in two Norwegian municipalities were assessed for study participation by nurses. Participants performed a continuous prolonged ECG recording using a patch ECG device (ECG247 Smart Heart Sensor). A total of 144 individuals were assessed for study participation, but only 18 (13%) were included. The main reasons for noninclusion were known AF and/or anticoagulation therapy (25%), severe cognitive impairment (26%), and lack of willingness to participate (36%). The mean age of participants performing the ECG test was 81 (SD ± 7) years, and 9 (50%) were women. All ECG tests were interpretable; the mean ECG monitoring time was 104 hours (IQR 34-338 hours). AF was detected in one individual (6%). This feasibility study highlights the challenges of enrolling older people receiving homecare services in clinical trials. However, all included participants performed an interpretable and prolonged continuous ECG recording with a digital ECG patch device. This trial is registered with NCT04700865.

The ABC-Stroke Risk Score and Effects of Atrial Fibrillation Screening on Stroke Prevention: Results From the Randomized LOOP Study.

The ABC-stroke score is a risk scheme for prediction of stroke or systemic embolism (SE) in atrial fibrillation (AF). This study sought to examine whether the score could be useful in predicting stroke in AF-naïve individuals and risk stratifying for AF screening. The LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study randomized 6004 AF-naïve individuals aged 70 to 90 years with stroke risk factors to either screening with an implantable loop recorder and anticoagulation upon detection of new-onset AF episodes ≥6 minutes, or usual care. A total of 5781 participants had available ABC-stroke score at baseline and were included in this secondary analysis: 4170 (72.1%) with an estimated stroke/SE risk ≤1%/year versus 1611 (27.9%) with an estimated stroke/SE risk >1%/year. Having an annual ABC-stroke risk >1% was associated with stroke/SE, stroke/SE/cardiovascular death, and all-cause death (hazard ratio, 1.82 [95% CI, 1.44-2.21], 2.17 [95% CI, 1.80-2.62], and 2.19 [95% CI, 1.87-2.56], respectively). For screening with implantable loop recorder versus usual care, no significant reduction in these study outcomes was obtained in any ABC-stroke risk groups (P>0.0500 for all), with no signal toward interaction (Pinteraction>0.2500 for all). Similar findings were yielded when assessing theABC-stroke score as a continuous variable. In an elderly, AF-naïve population with additional stroke risk factors, a higher ABC-stroke score could identify individuals with increased stroke risk. However, this risk score may not be useful in pinpointing those more likely to benefit from AF screening and subsequent preventive treatment. These findings should be considered as hypothesis generating and warrant further study. URL: https://www.clinicaltrials.gov; unique identifier: NCT02036450.

Antithrombotic Adherence to guideline-directed therapy and risk profile among Non-Valvular Atrial fibrillation patients

Introduction: Patients with Atrial fbrillation (AF) are at fivefold higher risk for Ischemic stroke than in the general population. Although the current therapeutic guidelines recommend the use of anticoagulants for thromboembolic prophylaxis in patients with nonvalvular AF (NVAF) with additional risk factor(s) for stroke, the global registry data show non-adherence to guidelines for the management of stroke in diferent regions of the world. The current study conducted at the tertiary referral cardiac center of Nepal for addressing the risk profle of stroke based on the current risk scores and the use of antithrombotic agents NVAF patients. Methodology: This was a descriptive observational cross sectional study conducted at Shahid Gangalal National Heart Centre (SGNHC), Kathmandu, Nepal from December 2020 to June 2020 which included patients with Nonvalvular AF. The main objective of the study was to study the clinical characteristics, stroke risk profle based on CHA ₂DS₂-VaSc score and risk of bleeding based on HAS-BLED score and the patterns of use of antithrombotic agents in NVAF patients. Results: A total of 79 cases of NVAF were included with 48(60.8%) males and 31(39.2%) females. The mean CHA₂DS₂-VaSc and HAS-BLED score were 2.44±1.2 and 1.51±1.4 respectively. The majority patients 38% had permanent AF followed by 25.5% had paroxysmal AF. Majority of patients were symptomatic with 67.1% presented with palpitation while 32.9% presented with shortness of breath (SOB). Based on the European Heart Rhythm Association (EHRA) AF related symptoms score, 41.8% had EHRA 2a and 2b while 1.3% had EHRA 4 score. The use of anticoagulants in patients with Nonvalvular AF was 41.6%, with NOACS in 33 % and warfarin used in 8.9% cases. The majority of patients 51.8% of study population were using anti-platelet agents with aspirin in 49.3 % and clopidogrel in 2.5 % cases while no medication in 6.3% of cases. Although 70.8% patients had CHA₂DS₂-VaSc score of 2 or more but the use of anticoagulants was only 58.9% with 46.4% NOACS and 12.5% using warfarin among this group of patients. Conclusion: Although the use of anticoagulant with NOACS in patients with higher risk of stroke is increasing, it is still underused in the majority of cases .There is a need of nationwide AF registry and the need of adoption of the current recommended guidelines to increase use of Anticoagulants in patients with Nonvalvular AF patients for the prevention of stroke .

Atrial Fibrillation In Patients With Stroke Attributed to Large- or Small-Vessel Disease

The STROKE AF study found that in patients with prior ischemic stroke attributed to large-artery atherosclerotic disease (LAD) or small-vessel occlusive disease (SVD), 12% developed AF over 1 year when monitored with an insertable cardiac monitor (ICM). The occurrence over subsequent years is unknown. To compare the rates of AF detection through 3 years of follow-up between an ICM vs site-specific usual care in patients with prior ischemic stroke attributed to LAD or SVD. This multicenter, randomized (1:1) clinical trial took place at 33 sites in the US with enrollment between April 2016 and July 2019 and 3-year follow-up through July 2022. Eligible patients were aged 60 years or older, or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index ischemic stroke attributed to LAD or SVD within 10 days prior to ICM insertion. Of the 496 patients enrolled, 492 were randomized and 4 were excluded. ICM monitoring vs site-specific usual care. The prespecified long-term outcome of the trial was AF detection through study follow-up (up to 3 years). AF was defined as an episode lasting more than 30 seconds, adjudicated by an expert committee. In total, 492 patients were randomized and included in the analyses (median [IQR] age, 66 [60-74] years; 307 men [62.4%] and 185 women [37.6%]), of whom 314 completed 3-year follow-up (63.8%). The incidence rate of AF at 3 years was 21.7% (46 patients) in the ICM group vs 2.4% (5 patients) in the control group (hazard ratio, 10.0; 95% CI, 4.0-25.2; P < .001). Patients with ischemic stroke attributed to LAD or SVD face an increasing risk of AF over time and most of the AF occurrences are not reliably detected by standard medical monitoring methods. One year of negative monitoring should not reassure clinicians that patients who have experienced stroke will not develop AF over the next 2 years. ClinicalTrials.gov Identifier: NCT02700945.

Electrocardiographic Morphology-Voltage-P-Wave-Duration (MVP) Score to Select Patients for Continuous Atrial Fibrillation Screening to Prevent Stroke

Morphology-voltage-P-wave-duration (MVP) score combining P-wave duration (PWD), P-wave voltage in lead I (PWVI), and interatrial block (IAB) has been demonstrated to predict atrial fibrillation (AF). Therefore, this study aimed to examine MVP score and its P-wave components as potential predictors of AF screening effects on stroke prevention. This was a secondary analysis of the LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) which randomized older persons (aged 70 to 90years) with additional stroke risk factors to either continuous monitoring with implantable loop recorder and anticoagulation upon detection of AF episodes ≥6minutes (the intervention group), or usual care. A total of 5,759 participants were included in the present analysis, where PWD, PWVI, and IAB were determined through a computerized analysis of 12-lead electrocardiogram and further employed to calculate baseline MVP score (0 to 6) for each participant. In total, 305 (5.3%) had stroke or systemic embolism during follow-up, with a higher risk in the group with MVP score 5 to 6 than those having score 0 to 2 (hazard ratio (HR) 1.54 [95% confidence interval (CI) 1.01 to 2.35]). This risk increase was mainly upheld by participants with IAB (HR 1.62 [95% CI 1.11 to 2.36] for IAB vs no IAB) and with longer PWD (HR 1.37 [95% CI 1.07 to 1.75] for >110 vs ≤110ms). Compared with usual care, implantable loop recorder screening did not significantly reduce the risk of stroke or systemic embolism in any MVP risk categories (HR 0.80 [95% CI 0.60 to 1.08] for MVP score 0 to 2, 0.54 [95% CI 0.16 to 1.85] for MVP score 3 to 4, and 0.89 [95% CI 0.35 to 2.25] for MVP score 5 to 6; pinteraction=0.78). In conclusion, a higher MVP score was associated with an increased stroke risk, but it did not demonstrate an association with effects of AF screening on stroke prevention. These findings should be considered hypothesis-generating and warrant further study.

Atrial fibrillation screening to prevent stroke in patients with high NT-proBNP - a post-hoc analysis of the randomized LOOP study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Innovation Fund Denmark Background and aims Stroke is a leading cause of mortality and disability, and atrial fibrillation (AF) is an important and potentially modifiable risk factor for stroke. AF screening can substantially increase the amount of patients diagnosed and treated, but randomized trials have yet to demonstrate a significant decrease in strokes following screening. N-terminal prohormone of brain natriuretic peptide (proBNP) is an established biomarker for AF and could potentially be used to select patients for screening. We a used randomized trial of AF screening vs usual care to investigated the usefulness of proBNP as a tool to select patients for screening to prevent outcomes. Methods The LOOP Study randomized AF-naïve individuals aged &amp;gt;70 years with additional stroke risk factors in a 1:3 ratio to either continuous AF screening using implantable loop recorder (ILR) with initiation of anticoagulation upon detection of AF, or usual care. In this post-hoc analysis, study participants with a baseline measurement of proBNP were included, and the effect of screening vs usual care was compared in groups according to proBNP tertiles. Results Of 6004 participants randomized, 5819 (97%) had proBNP measured. The tertiles of proBNP were at &amp;lt;11, 11-22, and 22 pmol/L (Figure 1). A total of 1014 participants (17.4%) were diagnosed with AF (ILR 32.1% vs Control 12.5%), and 310 (5.3%) endured a stroke or systemic arterial embolism (SAE) (ILR 4.5% vs Control 5.6%). In the lower two tertiles of proBNP, 13% were diagnosed with AF (ILR 26.6% vs Control 8.3%), and 4.6% endured a stroke or SAE (ILR 4.6% vs Control 4.6%), whereas in the highest tertile of proBNP, 25.9% were diagnosed with AF (ILR 42.9% vs 20.3%), and 6.73% endured a stroke or SAE (ILR 4.4% vs Control 7.5%). In the lower two tertiles of proBNP, there was no protective effect from AF screening as compared with usual care (hazard ratio (HR) 1.00 (95% CI 0.71-1.41), p=0.999), whereas in the highest tertile of proBNP there was a significant effect of screening (HR 0.59 (95% CI 0.37-0.93), p=0.021) (Figure 2). More details including proBNP cutoffs, and the impact on stroke subtypes, disability and mortality will be presented at the Congress. Conclusions In a population at increased risk of stroke, proBNP pose a useful biomarker to select individuals for AF screening to prevent stroke. In persons with increased proBNP, the effect of screening could be significant, whereas there is no signal towards effects from screening in people with normal proBNP levels.

Morphology-Voltage-P-wave-duration (MVP) score to select patients for continuous atrial fibrillation screening to prevent stroke

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The LOOP Study was funded by Innovation Fund Denmark [grant number 12-1352259], The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation [grant number 11-04-R83-A3363-22625], Aalborg University Talent Management Program, Arvid Nilssons Fond, Skibsreder Per Henriksen, R og Hustrus Fond, the European Union’s Horizon 2020 program [grant number 847770], Læge Sophus Carl Emil Friis og hustru Olga Doris Friis’ Legat, and an unrestricted grant from Medtronic. Background It is well known that atrial fibrillation (AF) confers a substantially increased risk of ischemic stroke, but data on health benefits from AF screening are scarce. The newly proposed MVP risk score combining the duration, voltage and morphology of P-wave has been demonstrated to be predictive of AF and might therefore also be useful in risk-stratifying individuals for AF screening and subsequent treatment. Purpose The present study sought to examine MVP risk score and its P-wave components for prediction of AF screening effects. Methods The LOOP Study randomized AF-naïve individuals aged 70-90 years with additional stroke risk factors to either continuous AF screening with implantable loop recorder (ILR) and subsequent anticoagulation initiation upon detection of AF episode ≥6 minutes, or usual care. In this secondary analysis, the LOOP participants with a baseline 12-lead electrocardiogram (ECG) suitable for P-wave measurement were included. Results Of 5759 participants included, 265 (4.6%) had had ischemic stroke during follow-up: 213 (4.9%) of 4311 in the control group versus 64 (3.6%) of 1448 in the ILR group. Among the participants in the control group, a significantly increased risk of ischemic stroke was observed for MVP score 5-6 versus score 0-2 (hazard ratio (HR) 1.66 [95% confidence interval (CI): 1.01-2.75]) and for the presence of interatrial block (IAB) versus no IAB (HR 1.85 [95% CI: 1.19-2.86]), whereas a P-wave voltage in lead I (PWVI) &amp;lt;100 µV was associated with risk reduction compared to higher voltage (HR 0.65 [95% CI: 0.45-0.93]). Further spline analysis revealed longer P-wave duration (PWD) to also be correlated with higher stroke risk (HR 1.49 [95% CI: 1.11-2.00] for &amp;gt;110 versus ≤110 ms). Compared with usual care, ILR screening did not significantly reduce the stroke risk regardless of MVP risk score, PWD, PWVI, or IAB pattern at baseline. Conclusions In an elderly population with additional stroke risk factors, both the P-wave parameters and the combined MVP risk score based on 12-lead ECG were associated with ischemic stroke, but these did not successfully demonstrate an association with effects of AF screening on stroke prevention.

Electrocardiographic markers of subclinical atrial fibrillation detected by implantable loop recorder

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The LOOP Study was funded by Innovation Fund Denmark [grant number 12-1352259], The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation [grant number 11-04-R83-A3363-22625], Aalborg University Talent Management Program, Arvid Nilssons Fond, Skibsreder Per Henriksen, R og Hustrus Fond, the European Union’s Horizon 2020 program [grant number 847770], Læge Sophus Carl Emil Friis og hustru Olga Doris Friis’ Legat, and an unrestricted grant from Medtronic. Background Atrial fibrillation (AF) is a well-known and treatable risk factor for stroke, which has sparked a substantial interest in AF screening. However, further insights into subclinical AF development are warranted to inform strategies of screening and subsequent clinical management upon AF detection. Purpose This study sought to identify 12-lead electrocardiogram (ECG) parameters associated with the onset, burden and progression of subclinical AF detected by long-term continuous monitoring. Methods We included AF-naïve individuals aged 70-90 years with ≥1 additional stroke risk factors (hypertension, diabetes, heart failure, or prior stroke) who underwent implantable loop recorder (ILR) monitoring in the LOOP Study. Using data from daily ILR recordings and computerized analysis of baseline ECG, we studied empirically selected ECG parameters for AF detection (≥6 minutes), cumulative AF burden, long-lasting AF (≥24 hours), and AF progression. Results Of 1370 individuals included, 419 (30.6%) developed AF during follow-up, with a mean cumulative AF burden of 1.5% [95% confidence interval (CI): 1.2-1.8%]. Several P-wave-related and ventricular ECG parameters were associated with new-onset AF as well as with cumulative AF burden in AF patients. P-wave duration (PWD), P-wave terminal force in lead V1, and interatrial block (IAB) further demonstrated significant associations with the risk of AF episode ≥24 hours. Among AF patients, we observed an overall reduction in cumulative AF burden over time (incidence rate ratio 0.70 [95% CI: 0.51-0.96]), whereas IAB was related to an increased risk of progression to AF episodes ≥24 hours (hazard ratio 1.86 [95% CI: 1.02-3.39]). Further spline analysis revealed longer PWD to also be associated with this progression in AF duration. Conclusions We identified several ECG parameters associated with new-onset AF detected by ILR. Especially PWD and IAB were robustly related to the onset and the burden of subclinical AF as well as progression over time.

Electrocardiographic markers of subclinical atrial fibrillation detected by implantable loop recorder: insights from the LOOP Study.

Insights into subclinical atrial fibrillation (AF) development are warranted to inform the strategies of screening and subsequent clinical management upon AF detection. Hence, this study sought to characterize the onset and progression of subclinical AF with respect to 12-lead electrocardiogram (ECG) parameters. We included AF-naïve individuals aged 70-90 years with additional stroke risk factors who underwent implantable loop recorder (ILR) monitoring in the LOOP Study. Using data from daily ILR recordings and the computerized analysis of baseline ECG, we studied empirically selected ECG parameters for AF detection (≥6 min), cumulative AF burden, long-lasting AF (≥24 h), and AF progression. Of 1370 individuals included, 419 (30.6%) developed AF during follow-up, with a mean cumulative AF burden of 1.5% [95% CI: 1.2-1.8]. Several P-wave-related and ventricular ECG parameters were associated with new-onset AF and with cumulative AF burden in AF patients. P-wave duration (PWD), P-wave terminal force in Lead V1, and interatrial block (IAB) further demonstrated significant associations with long-lasting AF. Among AF patients, we observed an overall reduction in cumulative AF burden over time (IRR 0.70 [95% CI: 0.51-0.96]), whereas IAB was related to an increased risk of progression to AF ≥24 h (HR 1.86 [95% CI: 1.02-3.39]). Further spline analysis also revealed longer PWD to be associated with this progression in AF duration. We identified several ECG parameters associated with new-onset subclinical AF detected by ILR. Especially PWD and IAB were robustly related to the onset and the burden of AF as well as progression over time.

Effects of Systematic Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: a Secondary Analysis of the Randomized LOOP Study.

Research suggests N-terminal pro-B-type natriuretic peptide (NT-proBNP) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. This study aimed to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention. In the LOOP Study, 6004 AF-naïve individuals aged 70-90 years with additional stroke risk factors were randomized 1:3 to either continuous screening with implantable loop recorder (ILR) and anticoagulation initiation upon detection of AF episodes ≥6 minutes, or usual care (Control). This post-hoc analysis included the study participants with available NT-proBNP measurement at baseline. A total of 5819 participants were included (mean age 74.7 years (standard deviation, 4.1), 47.5%females). The median NT-proBNP level was 15 pmol/L [interquartile range: 9-28], corresponding to 125 pg/mL [interquartile range: 76-233]. NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio (HR) 1.84 [95% confidence interval (CI): 1.51-2.25]) and the Control group (HR 2.79 [95% CI: 2.30-3.40]). Participants with NT-proBNP above median were also at higher risk of clinical events compared with those having lower levels (HR 1.21 [95% CI: 0.96-1.54] for stroke or systemic embolism (SE), 1.60 [95% CI: 1.32-1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI: 1.61-2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (HR 0.60 [95% CI: 0.40-0.90] and 0.70 [95% CI: 0.53-0.94], respectively), but not among those with lower levels (pinteraction=0.029 for stroke/SE and 0.045 for stroke/SE/cardiovascular death). No risk reduction in all-cause death was observed in either NT-proBNP subgroup for ILR versus Control (pinteraction=0.68). Analyzing NT-proBNP as a continuous variable yielded similar findings. In an elderly population with additional stroke risk factors, ILR screening for AF was associated with a significant reduction in stroke risk among individuals with higher NT-proBNP levels, but not among those with lower levels. These findings should be considered hypothesis-generating and warrant further study before clinical implementation.

Fully digital self-screening for atrial fibrillation with patch electrocardiogram.

Atrial fibrillation (AF) is the most common arrhythmia worldwide. The AF is associated with severe mortality, morbidity, and healthcare costs, and guidelines recommend screening people at risk. However, screening methods and organization still need to be clarified. The current study aimed to assess the feasibility of a fully digital self-screening procedure and to assess the prevalence of undetected AF using a continuous patch electrocardiogram (ECG) monitoring system. Individuals ≥65 years old with at least one additional risk factor for stroke from the general population of Norway were invited to a fully digital continuous self-screening for AF using a patch ECG device (ECG247 Smart Heart Sensor). Participants self-reported clinical characteristics and usability online, and all participants received digital feedback of their results. A total of 2118 individuals with a mean CHA2DS2-VASc risk score of 2.6 (0.9) were enrolled in the study [74% women; mean age 70.1 years (4.2)]. Of these, 1849 (87.3%) participants completed the ECG self-screening test, while 215 (10.2%) did not try to start the test and 54 (2.5%) failed to start the test. The system usability score was 84.5. The mean ECG monitoring time was 153 h (87). Atrial fibrillation was detected in 41 (2.2%) individuals. This fully digitalized self-screening procedure for AF demonstrated excellent feasibility. The number needed to screen was 45 to detect one unrecognized case of AF in subjects at risk for stroke. Randomized studies with long-term follow-up are needed to assess whether self-screening for AF can reduce the incidence of AF-related complications. NCT04700865.

Mechanisms and Clinical Manifestations of Cognitive Decline in Atrial Fibrillation Patients: Potential Implications for Preventing Dementia.

Atrial fibrillation (AF) patients face an approximate 1.5-fold increased risk of cognitive decline compared with the general population. Among poststroke AF patients, the risk of cognitive decline is even higher with an estimated threefold increase. This article provides a narrative review on the current evidence and highlights gaps in knowledge and areas for future research. Although earlier studies hypothesized that the association between AF and cognitive decline is mainly a consequence of previous ischemic strokes, more recent evidence also suggests such an association in AF patients without a history of clinical stroke. Because AF and cognitive decline mainly occur among elderly individuals, it is not surprising that both entities share multiple risk factors. In addition to clinically overt ischemic strokes, silent brain infarcts and other brain injury are likely mechanisms for the increased risk of cognitive decline among AF patients. Oral anticoagulation for stroke prevention in AF patients with additional stroke risk factors is one of the only proven therapies to prevent brain injury. Whether a broader use of oral anticoagulation, or more intense anticoagulation in some patients are beneficial in this context needs to be addressed in future studies. Although direct studies are lacking, it is reasonable to recommend optimal treatment of comorbidities and risk factors for the prevention of cognitive decline and dementia.

Thromboembolism in the Complications of Long COVID-19.

SARS-CoV-2 is a +ssRNA helical coronavirus responsible for the global pandemic caused by coronavirus disease 19 (COVID-19). Classical clinical symptoms from primary COVID-19 when symptomatic include cough, fever, pneumonia or even ARDS; however, they are limited primarily to the respiratory system. Long-COVID-19 sequalae is responsible for many pathologies in almost every organ system and may be present in up to 30% of patients who have developed COVID-19. Our review focuses on how long-COVID-19 (3 -24 weeks after primary symptoms) may lead to an increased risk for stroke and thromboembolism. Patients who were found to be primarily at risk for thrombotic events included critically ill and immunocompromised patients. Additional risk factors for thromboembolism and stroke included diabetes, hypertension, respiratory and cardiovascular disease, and obesity. The etiology of how long-COVID-19 leads to a hypercoagulable state are yet to be definitively elucidated. However, anti-phospholipid antibodies and elevated D-dimer are present in many patients who develop thromboembolism. In addition, chronic upregulation and exhaustion of the immune system may lead to a pro-inflammatory and hypercoagulable state, increasing the likelihood for induction of thromboembolism or stroke. This article provides an up-to-date review on the proposed etiologies for thromboembolism and stroke in patients with long-COVID-19 and to assist health care providers in examining patients who may be at a higher risk for developing these pathologies.

Screening for atrial fibrillation to prevent stroke in elderly individuals with or without preexisting cardiovascular disease: A post hoc analysis of the randomized LOOP Study

BackgroundAn evidence-based approach for risk stratification of subclinical atrial fibrillation (AF) and hereby AF screening is lacking. This study aimed to investigate whether established cardiovascular diseases (CVD) could help to identify the population more likely to benefit from AF screening. MethodsThe LOOP Study randomized AF-naïve individuals aged ≥70 years and with additional stroke risk factors to either screening with implantable loop recorder (ILR) and subsequent anticoagulation upon detection of new-onset AF episodes ≥6 min, or usual care. In this sub-study, all participants were divided into two risk groups according to the presence/absence of CVD (defined as ischemic heart disease, heart failure, previous stroke, valvular heart disease, or peripheral artery disease). ResultsA total of 1997 (33.3%) had CVD at baseline and experienced higher incidences of stroke or systemic arterial embolism (SAE), ischemic stroke, stroke/SAE/cardiovascular death, and all-cause death (adjusted HR 1.34 [1.06–1.69], 1.31 [1.02–1.69], 1.49 [1.23–1.79], and 1.59 [1.36–1.85], respectively) than those without. For ILR screening versus usual care, there was no decrease in stroke/SAE, ischemic stroke, or stroke/SAE/cardiovascular death among participants with CVD (adjusted p-values >0.05), whereas significant reductions in these outcomes were obtained by screening among those without CVD (adjusted HR 0.64 [0.44–0.93], 0.54 [0.35–0.82], 0.64 [0.46–0.87], respectively); adjusted p-values for interaction ≤0.05. ConclusionsIn an elderly, at-risk population, ILR screening did not prevent stroke significantly in individuals with CVD, whereas screening was associated with approximately 40% stroke risk reduction among those without CVD. However, these findings should be considered as hypothesis-generating and warrant further study.

Screening for atrial fibrillation to prevent stroke in elderly individuals with or without preexisting cardiovascular disease

Abstract Background Previous research has showed that various cardiovascular diseases (CVD) are associated with increased risks of atrial fibrillation (AF) and stroke. However, data on the interaction between CVD and AF screening efficacy are lacking. Purpose To evaluate the influence of preexisting CVD on the effects of AF screening with long-term continuous monitoring. Methods The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) randomized AF-naïve individuals aged ≥70 years and with additional stroke risk factors to either long-term screening with implantable loop recorder (ILR) and subsequent anticoagulation initiation upon detection of AF episodes ≥6 minutes, or usual care (the control group). In the current study, all participants from the LOOP Study were divided into two risk groups according to the presence of CVD (defined as ischemic heart disease, heart failure, previous stroke, valvular heart disease, or peripheral artery disease). The relative risks of outcomes in groupwise comparisons, as indicated by hazard ratio (HR), were assessed in the cause-specific Cox proportional-hazards model with death as competing risk. Results Of 6004 participants included, 1997 (33.3%) had ≥1 CVD at baseline. Compared with no CVD, the presence of CVD was associated with increased risks of AF diagnosis in the ILR group (adjusted HR 1.32 [1.09–1.59]) and of stroke or systemic arterial embolism in the entire study cohort (adjusted HR 1.34 [1.06–1.69]). For ILR screening versus usual care, there was no decrease in stroke or systemic arterial embolism among participants with preexisting CVD (adjusted HR 1.13 [0.76–1.68]), whereas a significant risk reduction was obtained by screening among those without CVD (adjusted HR 0.64 [0.44–0.93]). The interaction was significant (adjusted p-value for interaction 0.041). Conclusions In an elderly, high-risk population, ILR screening did not prevent stroke significantly in individuals with preexisting CVD, but it was associated with an approximately 40% risk reduction among those without CVD. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The LOOP Study was funded by Innovation Fund Denmark [grant number 12-1352259], The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation [grant number 11-04-R83-A3363-22625], Aalborg University Talent Management Program, Arvid Nilssons Fond, Skibsreder Per Henriksen, R og Hustrus Fond, the European Union's Horizon 2020 program [grant number 847770], Læge Sophus Carl Emil Friis og hustru Olga Doris Friis' Legat, and an unrestricted grant from Medtronic.

Systolic Blood Pressure and Effects of Screening for Atrial Fibrillation With Long-Term Continuous Monitoring (a LOOP Substudy).

Background:Hypertension is a well-known risk factor for atrial fibrillation (AF) and stoke, but data on the interaction between systolic blood pressure (SBP) and effects of AF screening are lacking.Methods:The LOOP Study randomized AF-naïve individuals aged 70 to 90 years with additional stroke risk factors to either screening with implantable loop recorder (ILR) and anticoagulation initiation upon detection of AF episodes ≥6 minutes, or usual care. In total, 5997 participants with available baseline SBP measurements were included in this substudy. Outcomes were analyzed according to the time-to-first-event principle using cause-specific Cox models.Results:The hazard ratio of stroke or systemic arterial embolism for ILR versus control decreased with increasing SBP. ILR screening yielded a 44% risk reduction of stroke or systemic arterial embolism among participants with SBP ≥150 mm Hg (adjusted hazard ratio, 0.56 [0.37–0.83]). Within the ILR group, SBP≥150 mm Hg was associated with a higher incidence of AF episodes ≥24 hours than lower SBP (adjusted hazard ratio, 1.70 [1.08–2.69]) but not with the overall occurrence of AF (adjusted P>0.05).Conclusions:The impact of AF screening on thromboembolic events increased with increasing blood pressure. SBP≥150 mm Hg was associated with a >1.5-fold increased risk of AF episodes ≥24 hours, along with an almost 50% risk reduction of stroke or systemic arterial embolism by ILR screening compared to lower blood pressure. These findings should be considered hypothesis-generating and warrant further study.Registration:URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02036450.

Frequency of cardioversions as an additional risk factor for stroke in atrial fibrillation – the FinCV-4 study

Background Patients with atrial fibrillation (AF) are selected for oral anticoagulation based on individual patient characteristics. There is little information on how clinical AF burden associates with the risk of ischaemic stroke or systemic embolism (SSE). The aim of this study was to explore the association of the frequency of cardioversions (CV) as a measure of clinical AF burden on the long-term SSE risk, with a focus on patients at intermediate stroke risk based on CHA2DS2-VASc score. For these patients, additional SSE risk stratification by assessing CV frequency may aid in the decision on whether to initiate oral anticoagulation. Methods This retrospective analysis of FinCV Study from years 2003–2010 included 2074 patients who were not using any oral anticoagulation (long term or temporary) after CVs and undergoing a total of 6534 CVs for AF from emergency departments of three hospitals. Two study groups were formed: high CV frequency (mean interval between CVs ≤12 months and low frequency (>12 months). Results A total of 107 SSEs occurred during a mean follow-up of 5.4 years. The event rates per 100 patient-years were 1.82 and 0.67 in high versus low CV frequency groups, respectively. After adjustment for CHA2DS2-VASc score, CV frequency independently predicted SSE (HR, 2.87 [95% CI, 1.47 to 5.64]; p = .002) at 3 years. Competing risk analysis also identified CV frequency (sHR, 2.70 [95% CI, 1.38–5.31]; p = .004) as an independent predictor for SSE. In patients with CHA2DS2-VASc score 1 and low CV frequency, the SSE risk was only 0.08 per 100 patient-years. Conclusions Frequency of CVs for symptomatic AF episodes provides additional information on stroke risk in AF patients with CHA2DS2-VASc score 1. Key messages This retrospective study offers a unique opportunity to observe the natural course of AF patients with infrequent episodes of clinical arrhythmia when they were not using OAC (before introduction of CHA2DS2-VASc score). Stroke or systemic embolism rate was very low (0.08 per 100 patient-years) in patients with one CHA2DS2-VASc point who visited the emergency room for cardioversion less than once a year. Frequency of cardioversions can be used for additional risk stratification in patients at intermediate risk of stroke based on CHA2DS2-VASc score.

Extrasystolic arrhythmia: is it an additional risk factor of cryptogenic stroke?

Aim to study the development of ischemic stroke (IS) or transient ischemic attack (TIA) in patients with extrasystoles (ES), depending on the moment of ES ventricular systole occurrence in cardiocycle.&#x0D; Material and methods. The study group included 440 patients with ES 700 per day; the control group consisted of 88 patients with ES 700 per day. The following instrumental and laboratory methods were used: echocardiography, Doppler ultrasound of brachiocephalic arteries, 24-hours ECG monitoring, digital sphygmography of common carotid arteries; CT or MRI of the brain; lipid spectrum. The study group was divided into two subgroups according to the moment of ES ventricular systole occurrence in cardiocycle, regardless of ectopia: subgroup 1 120 patients with ES before the transmitral blood flow peak; subgroup 2 320 patients with ES after the transmitral blood flow peak. We analyzed the development of stroke or TIA during 1 year.&#x0D; Results. For most parameters, subgroups 1, 2 and the control group were identical. The important differences were registered in the hemodynamic and kinetic parameters of common carotid arteries. The earlier the ES ventricular systole occurred in cardiocycle, the higher increase of the parameters was observed. During one year of follow-up, stroke and TIA occurred more frequently in subgroup 1.&#x0D; Conclusion. ES is an additional risk factor for stroke. The most dangerous is ES with ventricular systole occurrence before transmitral blood flow peak. The wave of the 1st post-extrasystolic contraction causes additional trauma of arterial wall and can become a key factor for instability of atherosclerotic plaques with their defragmentation, embolism and stroke.