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.
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.
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).
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.
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.
Objectives The aim of this study was to test the hypothesis that strain echocardiography might improve arrhythmic risk stratification in patients after myocardial infarction (MI). Background ...Prediction of ventricular arrhythmias after MI is challenging. Left ventricular ejection fraction (LVEF) <35% is the main parameter for selecting patients for implantable cardioverter-defibrillator therapy. Methods In this prospective, multicenter study, 569 patients >40 days after acute MI were included, 268 of whom had ST-segment elevation MIs and 301 non–ST-segment elevation MIs. By echocardiography, global strain was assessed as average peak longitudinal systolic strain from 16 left ventricular segments. Time from the electrocardiographic R-wave to peak negative strain was assessed in each segment. Mechanical dispersion was defined as the standard deviation from these 16 time intervals, reflecting contraction heterogeneity. Results Ventricular arrhythmias, defined as sustained ventricular tachycardia or sudden death during a median 30 months (interquartile range: 18 months) of follow-up, occurred in 15 patients (3%). LVEFs were reduced (48 ± 17% vs. 55 ± 11%, p < 0.01), global strain was markedly reduced (−14.8 ± 4.7% vs. −18.2 ± 3.7%, p = 0.001), and mechanical dispersion was increased (63 ± 25 ms vs. 42 ± 17 ms, p < 0.001) in patients with arrhythmias compared with those without. Mechanical dispersion was an independent predictor of arrhythmic events (per 10-ms increase, hazard ratio: 1.7; 95% confidence interval: 1.2 to 2.5; p < 0.01). Mechanical dispersion and global strain were markers of arrhythmias in patients with non–ST-segment elevation MIs (p < 0.05 for both) and in those with LVEFs >35% (p < 0.05 for both), whereas LVEF was not (p = 0.33). A combination of mechanical dispersion and global strain showed the best positive predictive value for arrhythmic events (21%; 95% confidence interval: 6% to 46%). Conclusions Mechanical dispersion by strain echocardiography predicted arrhythmic events independently of LVEF in this prospective, multicenter study of patients after MI. A combination of mechanical dispersion and global strain may improve the selection of patients after MI for implantable cardioverter-defibrillator therapy, particularly in patients with LVEFs >35% who did not fulfill current implantable cardioverter-defibrillator indications.
Results on the association between P-wave duration and the risk of atrial fibrillation (AF) are conflicting.
The purpose of this study was to obtain a detailed description of the relationship between ...P-wave duration and the risk of AF.
Using computerized analysis of electrocardiograms from a large primary care population, we evaluated the association between P-wave duration and the risk of AF. Secondary end-points were death from cardiovascular causes and putative ischemic stroke. Data on drug use, comorbidity, and outcomes were collected from administrative registries.
A total of 285,933 individuals were included. During median follow-up period of 6.7 years, 9550 developed AF, 9371 died of a cardiovascular cause, and 8980 had a stroke. Compared with the reference group (100-105 ms), individuals with very short (≤89 ms; hazard ratio HR 1.60, 95% confidence interval CI 1.41-1.81), intermediate (112-119 ms; HR 1.22, 95% CI 1.13-1.31), long (120-129 ms; HR 1.50, 95% CI 1.39-1.62), and very long P-wave duration (≥130 ms; HR 2.06, 95% CI 1.89-2.23) had an increased risk of incident AF. With respect to death from cardiovascular causes, we found an increased risk for very short (≤89 ms; HR 1.20, 95% CI 1.06-1.34), long (120-129 ms; HR 1.11, 95% CI 1.04-1.19), and very long P-wave duration (≥130 ms; HR 1.30, 95% CI 1.21-1.40) compared with the reference group (106-111 ms). Similar but weaker associations were found between P-wave duration and the risk of putative ischemic stroke.
In a large primary care population we found both short and long P-wave duration to be robustly associated with an increased risk of AF.
The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence ...for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT).
In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.
After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval CI, 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29).
In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).
A family history of atrial fibrillation constitutes a substantial risk of developing the disease, however, the pathogenesis of this complex disease is poorly understood. We perform whole-exome ...sequencing on 24 families with at least three family members diagnosed with atrial fibrillation (AF) and find that titin-truncating variants (TTNtv) are significantly enriched in these patients (P = 1.76 × 10
). This finding is replicated in an independent cohort of early-onset lone AF patients (n = 399; odds ratio = 36.8; P = 4.13 × 10
). A CRISPR/Cas9 modified zebrafish carrying a truncating variant of titin is used to investigate TTNtv effect in atrial development. We observe compromised assembly of the sarcomere in both atria and ventricle, longer PR interval, and heterozygous adult zebrafish have a higher degree of fibrosis in the atria, indicating that TTNtv are important risk factors for AF. This aligns with the early onset of the disease and adds an important dimension to the understanding of the molecular predisposition for AF.
Abstract
Aims
Left atrial (LA) volume and function impose significant impact on cardiovascular pathogenesis if compromised. We aimed at investigating the genetic architecture of LA volume and ...function using cardiac magnetic resonance imaging data.
Methods and results
We used the UK Biobank, which is a large prospective population study with available phenotypic and genetic data. On a subset of 35 658 European individuals, we performed genome-wide association studies on five volumetric and functional LA variables, generated using a machine learning algorithm. In total, we identified 18 novel genetic loci, mapped to genes with known roles in cardiomyopathy (e.g. MYO18B, TTN, DSP, ANKRD1) and arrhythmia (e.g. TTN, CASQ2, MYO18B, C9orf3). We observed high genetic correlation between LA volume and function and stroke, which was most pronounced for LA passive emptying fraction (rg = 0.40, P = 4 × 10−6). To investigate whether the genetic risk of atrial fibrillation (AF) is associated with LA traits that precede overt AF, we produced a polygenetic risk score for AF. We found that polygenetic risk for AF is associated with increased LA volume and decreased LA function in participants without AF LAmax 0.25 (mL/m2)/standard deviation (SD), 95% confidence interval (CI) (0.15; 0.36), P = 5.13 × 10−6; LAmin 0.21 (mL/m2)/SD, 95% CI (0.15; 0.28), P = 1.86 × 10−10; LA active emptying fraction −0.35%/SD, 95% CI (−0.43; −0.26), P = 3.14 × 10−14.
Conclusion
We report on 18 genetic loci associated with LA volume and function and show evidence for several plausible candidate genes important for LA structure.
Graphical Abstract
Genome-wide association study on left atrial volume and function based on cardiac magnetic resonance imaging. Imaging data from 35 658 individuals were exposed to machine learning algorithms to annotate five left atrial traits. A total of 18 novel genetic loci were associated with left atrial volume and function. Of these, 15 constituted unique loci. Genes marked with bold have previously been associated with cardiomyopathy.
Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these ...strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1-2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial ...genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized for many years. Presently, mutations in 25 genes have been associated with AF. However, the complexity of monogenic AF is illustrated by the recent finding that both gain- and loss-of-function mutations in the same gene can cause AF. Genome-wide association studies (GWAS) have indicated that common single-nucleotide polymorphisms (SNPs) have a role in the development of AF. Following the first GWAS discovering the association between PITX2 and AF, several new GWAS reports have identified SNPs associated with susceptibility of AF. To date, nine SNPs have been associated with AF. The exact biological pathways involving these SNPs and the development of AF are now starting to be elucidated. Since the first GWAS, the number of papers concerning the genetic basis of AF has increased drastically and the majority of these papers are for the first time included in a review. In this review, we discuss the genetic basis of AF and the role of both common and rare genetic variants in the susceptibility of developing AF. Furthermore, all rare variants reported to be associated with AF were systematically searched for in the Exome Sequencing Project Exome Variant Server.
The aim of this study was to use a 12-lead electrocardiogram obtained immediately post–transcatheter aortic valve replacement (TAVR) to identify predictors of late high-degree conduction defect ...(HD-CD) within 30 days after TAVR.
There are limited data on risk factors for the development of late HD-CD and the need to retain the temporary pacemaker after TAVR.
A single-center study was conducted including 467 consecutive patients, without pre-procedural pacemakers, undergoing TAVR.
Self-expandable, mechanical, or balloon-expandable heart valves were implanted in 328 (70%), 61 (13%), and 78 (17%) patients, respectively. For patients in sinus rhythm without right bundle branch block, late HD-CD developed in 0 of 70 patients (0%; 95% confidence interval CI: 0% to 5.1%) with PR interval <200 ms and QRS interval <120 ms and in 5 of 109 patients (4.6%; 95% CI: 1.5% to 10.4%; all with sufficient escape rhythm) with PR interval <240 ms and QRS interval <150 ms. Late HD-CD developed in 14 of 101 patients (13.9%; 95% CI: 7.8% to 22.2%; 6 with insufficient escape rhythm 5.9%; 95% CI: 2.2% to 12.5%) with PR interval ≥240 ms or QRS interval ≥150 ms. Furthermore, late HD-CD developed in 3 of 49 patients (6.1%; 95% CI: 1.3% to 16.9%; all with sufficient escape rhythm) and in 3 of 30 patients (10.0%; 95% CI: 2.1% to 26.5%; 2 with insufficient escape rhythm 6.7%; 95% CI: 0.8% to 22.1%) with atrial fibrillation and no right bundle branch block with QRS interval <140 and ≥140 ms, respectively.
On the basis of immediate post-TAVR 12-lead electrocardiography, removing the temporary pacemaker immediately following TAVR is potentially safe in patients without right bundle branch block who are: 1) in sinus rhythm with PR interval <240 ms and QRS interval <150 ms; or 2) in atrial fibrillation with a QRS interval <140 ms.
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