Aims Undetected atrial fibrillation (AF) is a major health concern. Blood biomarkers associated with AF could simplify patient selection for screening and further inform ongoing research towards stratified prevention and treatment of AF. Methods and results Forty common cardiovascular biomarkers were quantified in 638 consecutive patients referred to hospital [mean ± standard deviation age 70 ± 12 years, 398 (62%) male, 294 (46%) with AF] with known AF or ≥2 CHA 2 DS 2 -VASc risk factors. Paroxysmal or silent AF was ruled out by 7-day ECG monitoring. Logistic regression with forward selection and machine learning algorithms were used to determine clinical risk factors, imaging parameters, and biomarkers associated with AF. Atrial fibrillation was significantly associated with age [bootstrapped odds ratio (OR) per year = 1.060, 95% confidence interval (1.04–1.10); P = 0.001], male sex [OR = 2.022 (1.28–3.56); P = 0.008], body mass index [BMI, OR per unit = 1.060 (1.02–1.12); P = 0.003], elevated brain natriuretic peptide [BNP, OR per fold change = 1.293 (1.11–1.63); P = 0.002], elevated fibroblast growth factor-23 [FGF-23, OR = 1.667 (1.36–2.34); P = 0.001], and reduced TNF-related apoptosis-induced ligand-receptor 2 [TRAIL-R2, OR = 0.242 (0.14–0.32); P = 0.001], but not other biomarkers. Biomarkers improved the prediction of AF compared with clinical risk factors alone (net reclassification improvement = 0.178; P < 0.001). Both logistic regression and machine learning predicted AF well during validation [area under the receiver-operator curve = 0.684 (0.62–0.75) and 0.697 (0.63–0.76), respectively]. Conclusion Three simple clinical risk factors (age, sex, and BMI) and two biomarkers (elevated BNP and elevated FGF-23) identify patients with AF. Further research is warranted to elucidate FGF-23 dependent mechanisms of AF.

In a European AF patients' cohort, a pure rate control strategy was associated with a higher risk for adverse events at 1-year follow-up, and partially adjusted analysis suggested that rate control independently increased the risk for all-cause death. A fully adjusted propensity score matched analysis found that this association was no longer statistically significant, suggesting an important role of comorbidities in determining the higher risk for all-cause death.

Introduction This X-VeRT (eXplore the efficacy and safety of once-daily oral riVaroxaban for the prevention of caRdiovascular events in patients with nonvalvular aTrial fibrillation scheduled for cardioversion) substudy evaluated the effects of treatment with rivaroxaban or a vitamin-K antagonist (VKA) on levels of biomarkers of coagulation (D-dimer, thrombin–antithrombin III complex [TAT] and prothrombin fragment [F1.2]) and inflammation (high sensitivity C-reactive protein [hs-CRP] and high-sensitivity interleukin-6 [hs-IL-6]) in patients with atrial fibrillation (AF) who were scheduled for cardioversion and had not received adequate anticoagulation at baseline (defined as, in the 21 days before randomization: no oral anticoagulant; international normalized ratio <2.0 with VKA treatment; or <80% compliance with non-VKA oral anticoagulant treatment). Methods Samples for biomarker analysis were taken at baseline (n = 958) and treatment completion (42 days after cardioversion; n = 918). The influence of clinical characteristics on baseline biomarker levels and the effect of treatment on changes in biomarker levels were evaluated using linear and logistic models. Results Baseline levels of some biomarkers were significantly associated with type of AF (D-dimer and hs-IL-6) and with history of congestive heart failure (hs-CRP, D-dimer, and hs-IL-6). Rivaroxaban and VKA treatments were associated with reductions from baseline in levels of D-dimer (−32.3 and −37.6%, respectively), TAT (−28.0 and −23.1%, respectively), hs-CRP (−12.5 and −17.9%, respectively), and hs-IL-6 (−9.2 and −9.8%, respectively). F1.2 levels were reduced from baseline in patients receiving a VKA (−53.0%) but not in those receiving rivaroxaban (2.7%). Conclusion Anticoagulation with rivaroxaban reduced levels of key inflammation and coagulation biomarkers to a similar extent as VKAs, with the exception of F1.2. Further investigation to confirm the value of these biomarkers in patients with AF is merited.

BackgroundLittle is known about the association of atrial fibrillation symptom burden with quality of life and outcomes.Methods and ResultsIn the Prevention of Thromboembolic Events–European Registry in Atrial Fibrillation (n=6196 patients with atrial fibrillation; mean±SD age, 71.8±10.4 years; 39.7% women), we assessed European Heart Rhythm Association score symptoms and calculated correlations with the standardized health status questionnaire (EQ‐5D‐5L). Patients were followed up for atrial fibrillation therapies and outcomes (stroke/transient ischemic attack/arterial thromboembolism, coronary events, heart failure, and major bleeding) over 1 year. Most individuals (92%) experienced symptoms. Correlations with health status and quality of life were modest. In multivariable‐adjusted regression models, the dichotomized European Heart Rhythm Association score (intermediate/frequent versus never/occasional symptoms) was associated with cardioversions (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.01–1.45) and catheter ablation (OR, 1.97; 95% CI, 1.44–2.69), and inversely related with heart rate control (OR, 0.80; 95% CI, 0.70–0.92) and heart failure incidence (OR, 1.65; 95% CI, 1.16–2.34). Anxiety was inversely related with stroke/transient ischemic attack/arterial thromboembolism (OR, 0.55; 95% CI, 0.32–0.93), whereas chest pain related positively with coronary events (OR, 2.45; 95% CI, 1.42–4.22). Fatigue (OR, 1.84; 95% CI, 1.30–2.60), dyspnea (OR, 2.33; 95% CI, 1.63–3.33), and anxiety (OR, 1.72; 95% CI, 1.16–2.55) were associated with heart failure incidence. Palpitations were positively associated with cardioversion (OR, 1.32; 95% CI, 1.08–1.61) and ablation therapy (OR, 2.02; 95% CI, 1.48–2.76).ConclusionsA higher symptom burden, in particular palpitations, predicted interventions to restore sinus rhythm. The score itself had limited predictive value, but its individual components were related to different and specific clinical events, and may thus be helpful to target patient management.

Background: There is increasing evidence that right ventricular ejection fraction (RVEF) may provide incremental value to left ventricular (LV) ejection fraction for the prediction of major adverse cardiovascular events. To date, generalizable utility for RVEF quantification in patients with cardiovascular disease has not been established. Using a large prospective clinical outcomes registry, we investigated the prognostic value of RVEF for the prediction of major adverse cardiovascular events- and heart failure-related outcomes. Methods: Seven thousand one hundred thirty-one consecutive patients with known or suspected cardiovascular disease undergoing cardiovascular magnetic resonance imaging were prospectively enrolled. Multichamber volumetric quantification was performed by standardized operational procedures. Patients were followed for the primary composite outcome of all-cause death, survived cardiac arrest, admission for heart failure, need for transplantation or LV assist device, acute coronary syndrome, need for revascularization, stroke, or transient ischemic attack. A secondary, heart failure focused outcome of heart failure admission, need for transplantation/LV assist device or death was also studied. Results: Mean age was 54±15 years. The mean LV ejection fraction was 55±14% (range 6%–90%) with a mean RVEF of 54±10% (range 9%–87%). At a median follow-up of 908 days, 870 (12%) patients experienced the primary composite outcome and 524 (7%) the secondary outcome. Each 10% drop in RVEF was associated with a 1.3-fold increased risk of the primary outcome ( P <0.001) and 1.5-fold increased risk of the secondary outcome ( P <0.001). RVEF was an independent predictor following comprehensive covariate adjustment, inclusive of LV ejection fraction. Patients with an RVEF<40% experienced a 3.1-fold risk of the primary outcome ( P <0.001) with a 1-year cumulative event rate of 22% versus 7% above this cutoff. Conclusions: RVEF is a powerful and independent predictor of major adverse cardiac events with broad generalizability across patients with known or suspected cardiovascular disease. These findings support migration towards biventricular phenotyping for the classification of risk in clinical practice. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04367220.

Background Natriuretic peptides are routinely quantified to diagnose heart failure (HF). Their concentrations are also elevated in atrial fibrillation (AF). To clarify their value in predicting future cardiovascular events, we measured natriuretic peptides in unselected patients with cardiovascular conditions and related their concentrations to AF and HF status and outcomes. Methods and Results Consecutive patients with cardiovascular conditions presenting to a large teaching hospital underwent clinical assessment, 7‐day ECG monitoring, and echocardiography to diagnose AF and HF. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) was centrally quantified. Based on a literature review, four NT‐proBNP groups were defined (<300, 300–999, 1000–1999, and ≥2000 pg/mL). Clinical characteristics and NT‐proBNP concentrations were related to HF hospitalization or cardiovascular death. Follow‐up data were available in 1616 of 1621 patients (99.7%) and analysis performed at 2.5 years (median age, 70 [interquartile range, 60–78] years; 40% women). HF hospitalization or cardiovascular death increased from 36 of 488 (3.2/100 person‐years) in patients with neither AF nor HF, to 55 of 354 (7.1/100 person‐years) in patients with AF only, 92 of 369 (12.1/100 person‐years) in patients with HF only, and 128 of 405 (17.7/100 person‐years) in patients with AF plus HF ( P <0.001). Higher NT‐proBNP concentrations predicted the outcome in patients with AF only (C‐statistic, 0.82; 95% CI, 0.77–0.86; P <0.001) and in other phenotype groups (C‐statistic in AF plus HF, 0.66; [95% CI, 0.61–0.70]; P <0.001). Conclusions Elevated NT‐proBNP concentrations predict future HF events in patients with AF irrespective of the presence of HF, encouraging routine quantification of NT‐proBNP in the assessment of patients with AF.

No abstract

ObjectivesProlonged ECG monitoring is clinically useful to detect unknown atrial fibrillation (AF) in stroke survivors. The diagnostic yield of prolonged ECG monitoring in other patient populations is less well characterised. We therefore studied the diagnostic yield of prolonged Holter ECG monitoring for AF in an unselected patient cohort referred from primary care or seen in a teaching hospital.MethodsWe analysed consecutive 7-day ECG recordings in unselected patients referred from different medical specialities and assessed AF detection rates by indication, age and comorbidities.ResultsSeven-day Holter ECGs (median monitoring 127.5 hours, IQR 116 to 152) were recorded in 476 patients (mean age 54.6 (SD 17.0) years, 55.9% female) without previously known AF, requested to evaluate palpitations (n=241), syncope (n=99), stroke or transient ischaemic attack (n=75), dizziness (n=29) or episodic chest pain (n=32). AF was newly detected in 42/476 (8.8%) patients. Oral anticoagulation was initiated in 40/42 (95.2%) patients with newly detected AF. Multivariate logistic regression, adjusted for age, sex and monitoring duration found four clinical parameters to be associated with newly detected AF: hypertension OR=2.54, (1.08 to 8.61) (adjusted OR (95% CI)), p=0.034; previous stroke or TIA OR=4.14 (1.81 to 13.01), p=0.001; left-sided valvular heart disease OR=5.07 (2.48 to 18.70), p<0.001 and palpitations OR=2.86, (1.33 to 10.44), p=0.015.ConclusionsOpen multispeciality access to prolonged ECG monitoring, for example, as part of integrated, cross-sector AF care, can accelerate diagnosis of AF and increase adequate use of oral anticoagulation, especially in older and symptomatic patients with comorbidities.