Browsing by Author "Krieger, Derk W."

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Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study
(2023) Krieger, Derk W.
Background: Research suggests NT-proBNP (N-terminal pro-B-type natriuretic peptide) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. The aim of this study was to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention. Methods: In the LOOP Study (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), 6004 AF-naïve individuals at least 70 years old and with additional stroke risk factors were randomized 1:3 to either screening with an implantable loop recorder (ILR) and initiation of anticoagulation upon detection of AF episodes lasting ≥6 minutes or usual care (control). This post hoc analysis included study participants with available NT-proBNP measurement at baseline. Results: A total of 5819 participants (96.9% of the trial population) were included. The mean age was 74.7 years (SD, 4.1 years) and 47.5% were female. The median NT-proBNP level was 15 pmol/L (interquartile range, 9–28 pmol/L) corresponding to 125 pg/mL (interquartile range, 76–233 pg/mL). NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio, 1.84 [95% CI, 1.51–2.25]) and the control group (hazard ratio, 2.79 [95% CI, 2.30–3.40]). Participants with NT-proBNP above the median were also at higher risk of clinical events compared with those having lower levels (hazard ratio, 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 (hazard ratio, 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. Conclusion: In an older 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.
Electrocardiographic markers of subclinical atrial fibrillation detected by implantable loop recorder: insights from the LOOP Study
(2023) Krieger, Derk W.
Aims: 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. Methods and results: 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. Conclusion: 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.
Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study): a randomised controlled trial
(2021) Krieger, Derk W.
Background: It is unknown whether screening for atrial fibrillation and subsequent treatment with anticoagulants if atrial fibrillation is detected can prevent stroke. Continuous electrocardiographic monitoring using an implantable loop recorder (ILR) can facilitate detection of asymptomatic atrial fibrillation episodes. We aimed to investigate whether atrial fibrillation screening and use of anticoagulants can prevent stroke in individuals at high risk. Methods: We did a randomised controlled trial in four centres in Denmark. We included individuals without atrial fibrillation, aged 70–90 years, with at least one additional stroke risk factor (ie, hypertension, diabetes, previous stroke, or heart failure). Participants were randomly assigned in a 1:3 ratio to ILR monitoring or usual care (control) via an online system in permuted blocks with block sizes of four or eight participants stratified according to centre. In the ILR group, anticoagulation was recommended if atrial fibrillation episodes lasted 6 min or longer. The primary outcome was time to first stroke or systemic arterial embolism. This study is registered with ClinicalTrials.gov, NCT02036450. Findings: From Jan 31, 2014, to May 17, 2016, 6205 individuals were screened for inclusion, of whom 6004 were included and randomly assigned: 1501 (25•0%) to ILR monitoring and 4503 (75•0%) to usual care. Mean age was 74•7 years (SD 4•1), 2837 (47•3%) were women, and 5444 (90•7%) had hypertension. No participants were lost to follow-up. During a median follow-up of 64•5 months (IQR 59•3–69•8), atrial fibrillation was diagnosed in 1027 participants: 477 (31•8%) of 1501 in the ILR group versus 550 (12•2%) of 4503 in the control group (hazard ratio [HR] 3•17 [95% CI 2•81–3•59]; p<0•0001). Oral anticoagulation was initiated in 1036 participants: 445 (29•7%) in the ILR group versus 591 (13•1%) in the control group (HR 2•72 [95% CI 2•41–3•08]; p<0•0001), and the primary outcome occurred in 318 participants (315 stroke, three systemic arterial embolism): 67 (4•5%) in the ILR group versus 251 (5•6%) in the control group (HR 0•80 [95% CI 0•61–1•05]; p=0•11). Major bleeding occurred in 221 participants: 65 (4•3%) in the ILR group versus 156 (3•5%) in the control group (HR 1•26 [95% CI 0•95–1•69]; p=0•11). Interpretation: In individuals with stroke risk factors, ILR screening resulted in a three-times increase in atrial fibrillation detection and anticoagulation initiation but no significant reduction in the risk of stroke or systemic arterial embolism. These findings might imply that not all atrial fibrillation is worth screening for, and not all screendetected atrial fibrillation merits anticoagulation.
Relationship between left atrial strain, diastolic dysfunction and subclinical atrial fibrillation in patients with cryptogenic stroke: the SURPRISE echo substudy
(2019) Krieger, Derk W.
Abstract: Paroxysmal atrial fibrillation (PAF) may be the cause of a substantial part of cryptogenic strokes (CS). Echocardiography could assist risk stratification for PAF to select patients in need of prolonged rhythm monitoring. We aimed to assess the value of left atrial (LA) strain and a revised diastolic dysfunction (DDF) model with LA strain for predicting PAF. This was a prospective study of 56 CS patients who had a cardiac monitor implanted for 3 year monitoring for PAF, and an echocardiogram performed prior to monitoring. Conventional echocardiography, global longitudinal strain (GLS) and LA strain were performed. LA speckle tracking provided the LA reservoir strain (LAs). Patients were stratified into high versus low LAs by ROC curves (28.2%), and this cut-off was used to refine DDF grading. During follow-up of median 20 months, 13 (23%) patients were diagnosed with PAF. No conventional echocardiographic parameters differed between patients who developed PAF and those without PAF. However, LAs was significantly impaired in PAF patients (LAs: 30 vs. 27% for non-PAF and PAF, p = 0.046). Low LAs significantly predicted PAF independent of LA volume and GLS [OR 5.88 (1.30; 26.55), p = 0.021]. Revised DDF grading significantly predicted PAF, even when adjusted for the CHADS2 risk-score (OR 1.88 [1.01;3.50], per increase in DDF grade, p for trend = 0.047), which was not the case for conventional DDF grading. In conclusion, LAs associates with PAF independent of GLS and LA size, and may be used to improve the performance of DDF grading for identifying PAF in CS patients.
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
(2022) Krieger, Derk W.
Background: An 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. Methods: The 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). Results: A 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. Conclusions: In 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.
Searching for Atrial Fibrillation Poststroke A White Paper of the AF-SCREEN International Collaboration
(2019) Krieger, Derk W.
Abstract: Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non– vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non– vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.