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

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. CONCLUSIONS: 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. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02036450.

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

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.

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 screen-detected atrial fibrillation merits anticoagulation. FUNDING: Innovation Fund Denmark, The Research Foundation for the Capital Region of Denmark, The Danish Heart Foundation, Aalborg University Talent Management Program, Arvid Nilssons Fond, Skibsreder Per Henriksen, R og Hustrus Fond, The AFFECT-EU Consortium (EU Horizon 2020), Læge Sophus Carl Emil Friis og hustru Olga Doris Friis' Legat, and Medtronic.

Targeted potassium levels to decrease arrhythmia burden in high risk patients with cardiovascular diseases (POTCAST): Study protocol for a randomized controlled trial.

BACKGROUND: Low plasma potassium (p-K) is associated with increased risk of malignant arrhythmia and observational studies indicate protective effects of p-K in the upper reference level. However, randomized clinical studies are needed to document whether actively increasing p-K to high-normal levels is possible and safe and improves cardiovascular outcomes. OBJECTIVE: To investigate if increased p-K reduces the risk of malignant arrhythmia and all-cause death in high-risk patients with a cardiovascular disease treated with an implantable cardioverter defibrillator (ICD) for primary or secondary preventive causes. Secondly, to investigate whether high-normal p-K levels can be safely reached and maintained using already available medications and potassium-rich dietary guidance. METHODS: This is a prospective, randomized, and open-labelled study enrolling patient at high-risk of malignant arrhythmias. According to sample size calculations, 1,000 patients will be randomized 1:1 to either an investigational regiment that aims to increase and maintain p-K at high-normal levels (4.5-5.0 mmol/L) or to usual standard of care and followed for an expected four years. The trial will run until a total of 291 events have occurred providing an α = 0.05 and 1-ß = 0.80. The composite primary endpoint includes ventricular tachycardia >125 bpm lasting >30 seconds, any appropriate ICD-therapy, and all-cause mortality. At present, 739 patients have been randomized. CONCLUSIONS: We present the rationale for the design of the POTCAST trial. The inclusion was initiated 2019 and is expected to be finished 2022. The study will show if easily available treatments to increase p-K may be a new treatment modality to protect against malignant arrythmias.

Left Atrial Remodeling and Cerebrovascular Disease Assessed by Magnetic Resonance Imaging in Continuously Monitored Patients.

BACKGROUND: Atrial remodeling is associated with future atrial fibrillation (AF) and stroke. AF has been associated with cognitive impairment and cerebral white matter lesions. We wished to investigate the possible direct association between atrial remodeling and cerebrovascular disease in patients with and without AF documented by implantable loop recorder (ILR). METHODS: Cardiac and cerebral magnetic resonance imaging were acquired in a cross-sectional study, including participants ≥70 years of age with stroke risk factors without known AF. Cerebrovascular disease was visually rated using the Fazekas scale and number of lacunar strokes. Left atrial (LA) and ventricular volumes and function were analyzed. Associations between atrial remodeling and cerebrovascular disease were assessed with logistic regression models. The analyses were stratified according to sinus rhythm or any AF during 3 months of continuous ILR monitoring to account for subclinical AF. RESULTS: Of 200 participants investigated, 87% had a Fazekas score ≥1 and 45% had ≥1 lacunar infarct. Within 3 months of ILR monitoring, AF was detected in 28 (14%) participants. For participants with sinus rhythm (n = 172), lower LA passive emptying fraction was associated with Fazekas score after multivariable adjustment (OR [95% CI]: 0.51 [0.27; 0.86] p = 0.02), and increased LA maximum (OR [95% CI]: 1.38 [1.07; 1.82] p = 0.01) and minimum volumes (OR [95% CI]: 1.48 [1.03; 2.17] p = 0.04) were associated with lacunar infarcts. There were no significant associations in patients with AF. CONCLUSION: In AF-free patients, as documented by ILR monitoring, we found an independent association between LA passive emptying fraction and Fazekas score and between atrial volumes and lacunar infarcts.

Day-to-day measurement of physical activity and risk of atrial fibrillation.

AIMS: The aim of this study was to investigate the association between within-individual changes in physical activity and onset of atrial fibrillation (AF). METHODS AND RESULTS: A total of 1410 participants from the general population (46.2% women, mean age 74.7 ± 4.1 years) with risk factors but with no prior AF diagnosis underwent continuous monitoring for AF episodes along with daily accelerometric assessment of physical activity using an implantable loop recorder during ≈3.5 years. The combined duration of monitoring was ≈1.6 million days, where 10 851 AF episodes lasting ≥60 min were detected in 361 participants (25.6%) with a median of 5 episodes (2, 25) each. The median daily physical activity was 112 (66, 168) min/day. A dynamic parameter describing within-individual changes in daily physical activity, i.e. average daily activity in the last week compared to the previous 100 days, was computed and used to model the onset of AF. A 1-h decrease in average daily physical activity was associated with AF onset the next day [odds ratio 1.24 (1.18-1.31)]. This effect was modified by overall level of activity (P < 0.001 for interaction), and the signal was strongest in the tertile of participants with lowest activity overall [low: 1.62 (1.41-1.86), mid: 1.27 (1.16-1.39), and high: 1.10 (1.01-1.19)]. CONCLUSIONS: Within-individual changes in physical activity are associated with the onset of AF episodes as detected by continuous monitoring in a high-risk population. For each person, a 1-h decrease in daily physical activity during the last week increased the odds of AF onset the next day by ≈25%, while the strongest association was seen in the group with the lowest activity overall. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02036450.

Comprehensive Evaluation of Rhythm Monitoring Strategies in Screening for Atrial Fibrillation: Insights From Patients at Risk Monitored Long Term With an Implantable Loop Recorder.

BACKGROUND: Stroke is an increasing health problem worldwide. Atrial fibrillation (AF) is a major risk factor for stroke, and the attention given to AF screening is rising, as new monitoring technologies emerge. We aimed to evaluate the performance of a large panel of screening strategies and to assess population characteristics associated with diagnostic yield. METHODS: Individuals with stroke risk factors but without AF were recruited from the general population to undergo screening with an implantable loop recorder. New-onset AF lasting ≥6 minutes was adjudicated by senior cardiologists. After continuous monitoring for >3 years, complete day-to-day heart rhythm data sets were reconstructed for every participant, including exact time of onset and termination of all AF episodes. Random sampling was applied to assess the sensitivity and negative predictive value of screening with various simulated screening strategies compared with the implantable loop recorder. The diagnostic yield across strategies and population subgroups was compared by use of nonparametric tests. RESULTS: The rhythm data sets comprised 590 participants enduring a total of 659 758 days of continuous monitoring and 20 110 AF episodes. In these data, a single 10-second ECG yielded a sensitivity (and negative predictive value) of 1.5% (66%) for AF detection, increasing to 8.3% (67%) for twice-daily 30-second ECGs during 14 days and to 11% (68%), 13% (68%), 15% (69%), 21% (70%), and 34% (74%) for a single 24-hour, 48-hour, 72-hour, 7-day, or 30-day continuous monitoring, respectively. AF detection further improved when subsequent screenings were performed or when the same monitoring duration was spread over several periods compared with a single period (eg, three 24-hour monitorings versus one 72-hour monitoring; P<0.0001 for all comparisons). The sensitivity was consistently higher among participants with age ≥75 years, male sex, CHADS2 score >2, or NT-proBNP (N-terminal pro-B-type natriuretic peptide) ≥40 pmol/L and among participants with underlying ≥24-hour AF episodes compared with shorter AF (P<0.0001 for all screening strategies). CONCLUSIONS: In screening for AF among participants with stroke risk factors, the diagnostic yield increased with duration, dispersion, and number of screenings, although all strategies had low yield compared with the implantable loop recorder. The sensitivity was higher among participants who were older, were male, or had higher NT-proBNP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Atrial fibrillation burden and cognitive decline in elderly patients undergoing continuous monitoring.

AIMS: To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors. METHODS: Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated. RESULTS: A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden <0.25%), and AFhigh, (AF burden >0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (P = .03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA <26 at 3 years found no association to AF diagnosis or burden. CONCLUSIONS: In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a 3-year period.

Incidence and predictors of atrial fibrillation episodes as detected by implantable loop recorder in patients at risk: From the LOOP study.

BACKGROUND: Recent studies have suggested a high prevalence of subclinical atrial fibrillation (AF) in various patient populations, and interest in AF screening has increased. However, knowledge about episode duration is scarce, and risk factors for short or long subclinical AF episodes have yet to be recognized. The aim of the study was to assess AF by long-term continuous screening and to investigate predictors of episodes lasting ≥6 minutes, ≥5.5 hours, or ≥24 hours, respectively. METHODS: A total of 597 patients aged ≥70 years and diagnosed with ≥1 of hypertension, diabetes, previous stroke, or heart failure were recruited from the general population to receive implantable loop recorder with remote monitoring. Exclusion criteria included history of AF or cardiac implantable electronic device. AF episodes were adjudicated by senior cardiologists. RESULTS: During 40 (37; 42) months of continuous monitoring, AF was detected in 209 (35%) of the patients. The cumulative incidences at 3 years were 33.8% (30.2%-37.8%), 16.1% (13.4%-19.4%), and 5.7% (4.1%-7.9%) for AF episodes lasting ≥6 minutes, ≥5.5 hours, and ≥24 hours, respectively. Slower resting sinus rate and higher body mass index, N-terminal prohormone of brain natriuretic peptide, and troponin T at baseline were independently associated with AF detection. Addition of these markers to a model of sex, age, and comorbidities improved prediction of AF episodes ≥24 hours (time-dependent area under the receiver operating characteristic curve 79% vs 65%, P = .037). CONCLUSIONS: A considerable burden of previously unknown AF was detected when long-term monitoring was applied in at-risk patients. Biomarkers were associated with AF incidence and improved prediction of long AF episodes.

Left atrial volume and function assessed by cardiac magnetic resonance imaging are markers of subclinical atrial fibrillation as detected by continuous monitoring.

AIMS: We aimed to investigate whether left atrial (LA) markers from cardiovascular magnetic resonance (CMR) were able to predict atrial fibrillation (AF) in elderly patients with risk factors for stroke. METHODS AND RESULTS: At baseline, 203 participants with stroke risk factors but without history of AF underwent advanced CMR and received an implantable loop recorder. During a median of 40 (37-42) months of continuous monitoring, incident AF was detected in 79 patients (39%). With regards to CMR markers, a steep increase in incidence rate of AF was seen with LA maximum volume (LAmax) above 55 mL/m2, LA minimum volume (LAmin) above 30 mL/m2, LA total emptying fraction (LA TEF) below 45%, LA active emptying fraction (LA AEF) below 37%, LA strain S below 25%, LA strain A below 17%, and LA strain rate A above -1.7 s-1. After multivariate adjustment, the above-mentioned CMR markers remained associated with AF incidence: hazard ratio (95% confidence interval) 1.25 (1.06-1.48) and 1.51 (1.22-1.87) per 10 mL/m2 increase of LAmax and LAmin, respectively, 1.49 (1.26-1.76) and 1.46 CI (1.25-1.71) per 5% decrease in LA TEF and LA AEF, respectively, 1.23 (1.05-1.44) and 1.56 (1.18-2.06) per 5% decrease in LA strain S and A, respectively, and 2.06 (1.31-3.23) per s-1 increase in LA strain rate A. In prediction analyses, LA functional indices increased area under the receiver operating characteristic curve significantly. CONCLUSION: The risk of AF, including asymptomatic AF, increases significantly with increasing LA volumes and worsening LA function.

Atrial fibrillation detected by continuous electrocardiographic monitoring using implantable loop recorder to prevent stroke in individuals at risk (the LOOP study): Rationale and design of a large randomized controlled trial.

Atrial fibrillation (AF) increases the rate of stroke 5-fold, and AF-related strokes have a poorer prognosis compared with non-AF-related strokes. Atrial fibrillation and stroke constitute an intensifying challenge, and health care organizations are calling for awareness on the topic. Previous studies have demonstrated that AF is often asymptomatic and consequently undiagnosed. The implantable loop recorder (ILR) allows for continuous, long-term electrocardiographic monitoring with daily transmission of arrhythmia information, potentially leading to improvement in AF detection and stroke prevention. METHODS: The LOOP study is an investigator-initiated, randomized controlled trial with 6,000 participants randomized 3:1 to a control group or to receive an ILR with continuous electrocardiographic monitoring. Participants are identified from Danish registries and are eligible for inclusion if 70years or older and previously diagnosed as having at least one of the following conditions: hypertension, diabetes mellitus, heart failure, or previous stroke. Exclusion criteria include history of AF and current oral anticoagulation treatment. When an AF episode lasting ≥6minutes is detected, oral anticoagulation will be initiated according to guidelines. Expected follow-up is 4years. The primary end point is time to stroke or systemic embolism, whereas secondary end points include time to AF diagnosis and death. CONCLUSION: The LOOP study will evaluate health benefits and cost-effectiveness of ILR as a screening tool for AF to prevent stroke in patients at risk. Secondary objectives include identification of risk factors for the development of AF and characterization of arrhythmias in the population. The trial holds the potential to influence the future of stroke prevention.

Single lead atrial vs. dual chamber pacing in sick sinus syndrome: extended register-based follow-up in the DANPACE trial.

AIMS: The DANPACE trial randomized patients with sick sinus syndrome (SSS) to single lead atrial (AAIR) or dual chamber (DDDR) pacemaker (PM). After 5 years follow-up, no difference in overall survival, stroke or heart failure (HF) was observed, whereas risk of atrial fibrillation (AF) and PM reoperation were increased in the AAIR group. The present study aimed to investigate very long term risk of death, AF hospitalization, stroke, HF and rate of change in pacing mode using national register-based data. METHODS AND RESULTS: The study population consisted of all 1384 patients included at Danish PM centres in the DANPACE trial randomized to AAIR (n = 696) or DDDR (n = 688). Long-term follow-up data was obtained from Danish national registers. Analysis was intention-to-treat. results: During mean follow-up of 8.9 years, 413 patients (59.3%) died in the AAIR-group compared to 367 (53.3%) in the DDDR-group (adjusted hazard ratio 1.03; 95% confidence interval 0.90-1.19; P = 0.65). We observed no difference in risk of AF hospitalization, stroke or HF. During extended follow-up, annual rate of pacing mode change to DDDR in the AAIR group was 4.5%, and higher than the 2.3% observed during trial conduct. CONCLUSION: This register-based long-term follow-up study indicates that there is no difference in mortality among patients with SSS randomized to AAIR or DDDR pacing, even with very long follow-up. Nor is there any difference in risk of AF hospitalization, stroke or HF. The higher rate of pacing mode-change to DDDR in the AAIR group suggests a different management of patients with an AAIR PM after the DANPACE trial.

Flow measurement at the aortic root - impact of location of through-plane phase contrast velocity mapping.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is considered the gold standard of cardiac volumetric measurements. Flow in the aortic root is often measured at the sinotubular junction, even though placing the slice just above valve level may be more precise. It is unknown how much flow measurements vary at different levels in the aortic root and which level corresponds best to left ventricle volumetry. METHODS: All patients were older than 70 years presenting with at least one of the following diagnoses: diabetes, hypertension, prior stroke and/or heart failure. Patients with arrhythmias during CMR and aortic stenosis were excluded from the analyses. Stroke volumes were measured volumetrically (SVref) from steady-state free precision short axis images covering the entire left ventricle, excluding the papillary muscles and including the left ventricular outflow tract. Flow sequences (through-plane phase contrast velocity mapping) were obtained at valve level (SVV) and at the sinotubular junction (SVST). Firstly, SVV and SVST were compared to each other and secondly, after excluding patients with mitral regurgitations to ensure that stroke volumes measured volumetrically would theoretically be equal to flow measurements, SVV and SVST were compared to SVref. RESULTS: Initially, 152 patients were included. 22 were excluded because of arrhythmias during scans and 9 were excluded for aortic stenosis. Accordingly, data from 121 patients were analysed and of these 63 had visually evident mitral regurgitation on cine images. On average, stroke volumes measured with flow at the sinotubular junction was 13-16 % lower than when measured at valve level (70.0 mL ±13.8 vs. 81.8 mL ±15.5). This was in excess of the expected difference caused by the outflow to the coronary arteries. In the 58 patients with no valvulopathy, stroke volumes measured at valve level (79.0 mL ±12.4) was closest to the volumetric measurement (85.4 mL ±12.0) but still significantly lower (p < 0.001). Flow measured at the ST-junction (68.1 mL ±11.6) was significantly lower than at valve level and the volumetric measurements. The mean difference between SVref-SVV (6.4 mL) and SVref-SVST (18.2 mL) showed similar variances (SD 7.4 vs. 8.1 respectively) and hence equal accuracy. CONCLUSIONS: Aortic flow measured at valve level corresponded best with volumetric measurements and on average flow measured at the sinotubular junction underestimated flow approximately 15 % compared to valve level. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02036450 . Registered 08/01/2014.

Suicide attempt by complete self-removal of a 12-year-old permanent pacemaker system: case report.

INTRODUCTION: Psychological adaption after pacemaker implantation can be challenging in patients with psychiatric disease. Suicide by self-removal of a permanent pacemaker system is a rare phenomenon described in a few cases in patients with psychiatric disorders. METHODS AND RESULTS: We describe a case of attempted suicide by complete self-removal of a 12-year-old permanent pacemaker system in a 70-year-old male patient with a bipolar disorder and a history of previous suicide attempts. CONCLUSIONS: Suicide attempt by self-removal of a permanent pacemaker system is very rare. In patients with a history of psychiatric disease and previous suicide attempts, careful information about the function of a pacemaker should be given.

Anticoagulation-Associated Bleeding in Patients Screened for Atrial Fibrillation versus Usual Care-A Post Hoc Analysis from the LOOP Study.

Background Atrial fibrillation (AF) prevalence is rising; however, data on the bleeding risks associated with the detection of subclinical AF are needed. Objective Our objective was to determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared with usual care. Methods This post hoc study utilized LOOP trial data from 6,004 elderly patients with stroke risks randomized to either ILR ( n = 1,503) or usual care ( n = 4,503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OACs), determined by time-dependent cox regression. Second, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelet treatment and in subgroups. Results OAC was initiated in 1,019 participants with a mean age (years) of 78.8 (± 4.67) in control versus 77.0 (± 4.84) in ILR, p < 0.0001. Altogether did 202 participants end or pause OAC treatment. Among AF patients (n = 910) had 40 (28%) completely ended OAC and 105 (72%) temporarily paused OAC during follow-up. Major bleeding events totaled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1,019 participants (4.6%); 26 versus 21 events in the control and ILR groups, respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared with before initiation was 2.08 (1.50-2.90) p < 0.0001 overall, 2.81 (1.82-4.34) p < 0.0001 for control and 1.32 (0.78-2.23) p = 0.31 for the ILR group ( p = 0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p = 0.09. For OAC users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared with 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared with 1.64 (0.82-2.93) for an age <75 years. Conclusion The individual risk of major bleeding increased twofold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared with those in usual care. Trial Registration: The LOOP study is registered at ClinicalTrials.gov, identifier: NCT020364 50.

Epicardial adipose tissue and subclinical incident atrial fibrillation as detected by continuous monitoring: a cardiac magnetic resonance imaging study.

Epicardial adipose tissue (EAT) has endocrine and paracrine functions and has been associated with metabolic and cardiovascular disease. This study aimed to investigate the association between EAT, determined by cardiac magnetic resonance imaging (CMR), and incident atrial fibrillation (AF) following long-term continuous heart rhythm monitoring by implantable loop recorder (ILR). This study is a sub-study of the LOOP study. In total, 203 participants without a history of AF received an ILR and underwent advanced CMR. All participants were at least 70 years of age at inclusion and had at least one of the following conditions: hypertension, diabetes, previous stroke, or heart failure. Volumetric measurements of atrial- and ventricular EAT were derived from CMR and the time to incident AF was subsequently determined. A total of 78 participants (38%) were diagnosed with subclinical AF during a median of 40 (37-42) months of continuous monitoring. In multivariable Cox regression analyses adjusted for age, sex, and various comorbidities, we found EAT indexed to body surface area to be independently associated with the time to AF with hazard ratios (95% confidence intervals) up to 2.93 (1.36-6.34); p = 0.01 when analyzing the risk of new-onset AF episodes lasting ≥ 24 h. Atrial EAT assessed by volumetric measurements on CMR images was significantly associated with the incident AF episodes as detected by ILR.

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

BACKGROUND: 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. METHODS AND RESULTS: 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 the ABC-stroke score as a continuous variable. CONCLUSIONS: 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. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT02036450.

Long-term Rate of Ventricular Arrhythmia in Autoimmune Disease.

AIMS: Although selected autoimmune diseases (AIDs) have been linked to an increased risk of ventricular arrhythmias (VAs), data on the long-term rate of VAs across the spectrum of AIDs are lacking. The aim of our study was to investigate the long-term rate of VAs (a composite of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest) in individuals with a history of 28 different AIDs. METHODS: Individuals diagnosed with an AID (2005-2018) were identified through Danish nationwide registries. Each patient with AID was matched with four individuals from the background population by age and sex. Multivariable Cox regression was used to compare the rate of VAs between the AIDs and background population, overall and according to individual AIDs. RESULTS: In total, 186,733 patients diagnosed with AIDs were matched with 746,932 individuals without AIDs (median age 55 years; 63% female; median follow-up 6.0 years). The 5-year cumulative incidence of VAs was 0.5% for patients with AIDs and 0.3% for matched individuals. Patients with any AIDs had a higher associated rate of VAs than matched individuals (HR 1.39 [95% CI, 1.29-1.49]). The highest HR was observed in patients with systemic sclerosis (3.86 [95% CI, 1.92-7.75]). The higher rate of VAs in patients with AIDs, compared with individuals from the background population, was more pronounced in patients without ischemic heart disease or heart failure/cardiomyopathy compared to those with these conditions (Pinteraction < 0.05). CONCLUSIONS: Despite a low cumulative incidence, patients with a history of AIDs had a higher relative rate of VAs than matched individuals.

In a large Danish nationwide study, we examined the risk of ventricular arrhythmias, which are serious and potentially life-threatening conditions, in patients with and without a history of autoimmune diseases. Patients with a history of any autoimmune disease had a higher risk of experiencing ventricular arrhythmias compared with age- and sex-matched individuals from the background population. This association was observed for most of the autoimmune diseases when examined individually. The higher rate of ventricular arrhythmias in patients with autoimmune diseases, compared with individuals from the background population, was relatively more pronounced in patients without a history of ischemic heart disease or heart failure/cardiomyopathy compared with individuals with a history of these conditions.

Left Atrial Strain Predicts Subclinical Atrial Fibrillation Detected by Long-term Continuous Monitoring in Elderly High-Risk Individuals.

BACKGROUND: Left atrial (LA) speckle tracking provides detailed information on atrial function. Its utility for predicting subclinical atrial fibrillation (SCAF) is unclear. Therefore, we sought to investigate whether LA strain measures could predict SCAF detected by long-term continuous rhythm monitoring. METHODS: This was an echocardiographic substudy of the LOOP study, where elderly at risk of stroke were randomized to receive a loop recorder (Reveal LINQ) or control. Participants who received a loop recorder were included in this analysis. Echocardiography included LA reservoir, conduit, and contraction strain. Participants were followed with continuous rhythm monitoring for SCAF (≥6 minutes). Cox proportional hazards regression was applied to adjust for atrial fibrillation risk factors. RESULTS: In total, 956 participants were eligible for analysis. Median continuous rhythm monitoring was 35 months (IQR, 20-40 months), during which 278 (29%) were diagnosed with SCAF. The mean age was 74 years, 56% were male, median CHA2DS2-VASc-score was 4. LA reservoir strain was an independent predictor of SCAF after multivariable adjustments (HR, 1.04 [1.02-1.05], per 1% decrease) and so was contraction strain. The findings were unchanged in competing risk analyses and in participants with normal LA size and diastolic function. Participants with low reservoir strain (<33%) had a significantly higher risk of SCAF compared with those with high reservoir strain (incidence rate, 14.5 [12.4-16.9] versus 9.8 [8.2-11.8] events/100 person-years). The same was noted for low versus high contraction strain. CONCLUSIONS: LA reservoir and contraction strain are independent predictors of SCAF in elderly at risk of stroke. This also applies to individuals with normal LA size and diastolic function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Osteoclastogenesis is influenced by modulation of gap junctional communication with antiarrhythmic peptides.

Osteoclasts are formed by the fusion of mononuclear precursor cells of the monocyte-macrophage lineage. Among several putative mechanisms, gap-junctional intercellular communication (GJC) has been proposed to have a role in osteoclast fusion and bone resorption. We examined the role of GJC in osteoclastogenesis and in vitro bone resorption with mouse bone marrow hematopoietic stem cells and RAW 264.7 cells. Blocking of gap junctions with 18-α-glycyrrhetinic acid (18GA) led to inhibition of osteoclastogenesis and in vitro bone resorption. Similarly, the GJC inhibitor GAP27 inhibited osteoclast formation. GJC modulation with the antiarrhythmic peptides (AAPs) led to increased amounts of multinuclear RAW 264.7 osteoclasts as well as increased number of nuclei per multinuclear cell. In the culture of bone marrow hematopoietic stem cells in the presence of bone marrow stromal cells AAP reduced the number of osteoclasts, and coculture of MC3T3-E1 preosteoblasts with RAW 264.7 macrophages prevented the action of AAPs to promote osteoclastogenesis. The present data indicate that AAPs modulate the fusion of the pure culture of cells of the monocyte-macrophage lineage. However, the fusion is influenced by GJC in cells of the osteoblast lineage.