Background Atrial fibrillation is an independent risk factor for the development of cognitive impairments. Regular coffee consumption has shown cognitive benefits in healthy individuals. Whether regular consumption reduces cognitive decline in vulnerable patients is controversial. We investigated the association in elderly people with atrial fibrillation. Methods and Results Daily coffee consumption was assessed using a structured nutrition questionnaire, and cognitive function was evaluated by a detailed neurocognitive‐test‐battery, including the Montreal Cognitive Assessment, Trail‐Making Test, semantic fluency, and Digit‐Symbol‐Substitution Test. The cognitive construct score combines all neurocognitive tests mentioned and provides an overall cognitive performance indicator. Hs‐CRP (high‐sensitivity C‐reactive protein) and IL‐6 (interleukin‐6) were measured to explore an association with inflammation. Results were estimated using linear mixed‐effects‐models with detailed adjustments for confounders. The <1 cup/day consumers (reference group) reached a cognitive construct score of −0.24 (95% CI, –0.27 to –0.16), and the group with the highest consumption (>5 cups/day) was at −0.10 (95% CI, –0.10 to 0.04; p =0.048). Montreal Cognitive Assessment score in the reference group was 24.58 (95% CI, 24.58–25.32); the group with the highest intake achieved 25.25 (95% CI, 24.98–26.85; p =0.163). Inflammatory markers decreased with higher coffee consumption (hs‐CRP with 5 compared with <1 cup/day by factor 0.78 [95% CI, 0.54–1.13], p = 0.188, IL‐6 significantly by factor 0.73 [95% CI, 0.57–0.95], p =0.017). Conclusions Coffee consumption in patients with atrial fibrillation may be associated with improved cognitive performance and reduced inflammatory markers. Further research is needed to confirm these findings and to consider implementation in dietary counseling for atrial fibrillation management. Registration URL: https://www.clinicaltrials.gov ; Identifier: NCT02105844.

Atrial fibrillation (AF) increases the risk of adverse cardiovascular events, yet the underlying biological mechanisms remain unclear. We evaluate a panel of 12 circulating biomarkers representing diverse pathophysiological pathways in 3817 AF patients to assess their association with adverse cardiovascular outcomes. We identify 5 biomarkers including D-dimer, growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTropT) that independently predict cardiovascular death, stroke, myocardial infarction, and systemic embolism, significantly enhancing predictive accuracy. Additionally, GDF-15, insulin-like growth factor-binding protein-7 (IGFBP-7), NT-proBNP, and hsTropT predict heart failure hospitalization, while GDF-15 and IL-6 are associated with major bleeding events. A biomarker model improves predictive accuracy for stroke and major bleeding compared to established clinical risk scores. Machine learning models incorporating these biomarkers demonstrate consistent improvements in risk stratification across most outcomes. In this work, we show that integrating biomarkers related to myocardial injury, inflammation, oxidative stress, and coagulation into both conventional and machine learning-based models refine prognosis and guide clinical decision-making in AF patients.

Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci. Furthermore, we assayed chromatin accessibility using assay for transposase-accessible chromatin with sequencing and histone H3 lysine 4 trimethylation in stem cell-derived atrial cardiomyocytes. We observed a marked increase in chromatin accessibility for our sentinel variants and prioritized genes in atrial cardiomyocytes. Finally, a polygenic risk score (PRS) based on our updated effect estimates improved AF risk prediction compared to the CHARGE-AF clinical risk score and a previously reported PRS for AF. The doubling of known risk loci will facilitate a greater understanding of the pathways underlying AF.

BACKGROUND:Noncardiac surgery is associated with an inflammatory response. Whether increased inflammation in the perioperative period is associated with subsequent morbidity and mortality is unknown. METHODS:MEDLINE, EMBASE, and CENTRAL were systematically searched from date of inception until May 2023. Longitudinal studies were included if they reported multivariable adjusted associations of biomarkers measured preoperatively and/or within 10 days after surgery with at least one prespecified adverse outcome in noncardiac surgery patients. Data were extracted independently and in duplicate. Risk estimates were pooled using DerSimonian-Laird random-effects models and reported as summary odds ratios (ORs) with 95% CIs. The outcomes were all-cause mortality and major adverse cardiovascular events. RESULTS:Fifty-two studies with a total of 121,849 patients were included. The median follow-up was 56 [IQR, 28-63] months and the average age was 57 (±3) years. Elevated preoperative C-reactive protein (CRP) levels were associated with a higher risk of mortality (OR 1.57, 95% CI 1.29-1.90, I2 = 93%, 28 studies). This association was stronger in non-cancer surgery populations (OR 2.10, 95% CI 1.92-2.31, I2 = 0%, 4 studies) when compared to cancer surgery populations (OR 1.51, 95% CI 1.26-1.81, I2 = 83%, 24 studies) (p for subgroup difference = 0.001). Similarly, higher postoperative CRP levels were associated with all-cause mortality (OR 1.61, 95% CI 1.17-2.20, I2 = 90%, 7 studies). Higher preoperative CRP levels were associated with major cardiovascular events (OR 2.11, 95% CI 1.51-2.94, I2 = 0%, 2 studies). Other preoperatively measured biomarkers associated with all-cause mortality were fibrinogen (OR 1.48, 95% CI 1.05-2.09, I2 = 52%, 5 studies), interleukin-6 (OR 1.17, 95% CI 1.07-1.28, I2 = 27%, 3 studies), and tumour necrosis factor-alpha (OR 1.37, 95% CI 1.16-1.61, I2 = 0%, 2 studies). CONCLUSION AND RELEVANCE:Inflammatory biomarker levels in the perioperative period were associated with all-cause mortality and adverse cardiovascular events in patients undergoing noncardiac surgery.

Introduction: Atrial fibrillation (AF) adversely impacts right ventricular (RV) and right atrial (RA) structure and function. There are limited data on these changes after electrical cardioversion (ECV) and the relative contribution of heart rate to evaluate the immediate (1–2 h) and short-term (4–6 weeks) changes in right cardiac chamber dimensions and RV function after ECV in patients with persistent AF. Methods: Right cardiac chamber dimensions and RV function were measured in 64 patients using transthoracic echocardiography 1–2 h before, immediately after, and 4–6 weeks after ECV. Associations between changes in right-heart measures and rhythm status at follow-up were assessed using linear regression models. Results: For patients who remained in sinus rhythm 4–6 weeks after ECV (n = 48), median fractional area change (FAC) at baseline, immediately after ECV, and 4–6 weeks after ECV were 39 (Q1:35, Q3:42) %, 42 (Q1:39, Q3:46) %, 46 (Q1:43, Q3:49) % (p < 0.01); median tricuspid annular plane systolic excursion (TAPSE) values at the same time points were 18 (Q1:17, Q3:20) mm, 20 (Q1:18, Q3:23) mm, and 24 (Q1:22, Q3:26) mm (p < 0.01), respectively. There was no significant difference in RV end systolic area and RA volume index before and after ECV. However, RV end systolic area and RA volume index decreased significantly after 4–6 weeks from a median of 10 (Q1:8, Q3:13) cm2 to 8 (Q1:7, Q3:10) cm2 (p < 0.01), and from a median of 30 (Q1:24, Q3:36) mL/m2 to 24 (Q1:20, Q3:27) mL/m2 (p < 0.01). Changes in TAPSE were significantly associated with sinus rhythm at follow-up (p = 0.027), changes in FAC showed a strong trend to association with sinus rhythm (p = 0.053), and this was not true for RA measures (p = 0.64). Conclusions: Among AF patients who remained in sinus rhythm after ECV, RV function improved immediately after ECV with further improvement at 4–6 weeks following sinus rhythm restoration.

The use of oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF) increases their risk of bleeding. The prognosis of AF patients who experience a bleeding event is not well studied.

Abstract Aims We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients. Methods and results We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [−0.12 (−0.22; −0.07)] than patients without new brain infarcts [0.07 (−0.09; 0.25)]. New WML or Mb were not associated with cognitive decline. Conclusion In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844

Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF). In this study we sought to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up. Significant between-group changes were observed for bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were − 10.4%, − 62.0% and − 25.6% in patients with sinus rhythm, and 3.1%, 1.1% and − 9.4% in patients with recurrent AF, for a between-group difference of − 13.5% (95% confidence interval [CI] − 19.3% to − 7.6%; P < 0.001), − 63.1% (95% CI − 76.6% to − 49.6%; P < 0.001) and − 16.3% (95% CI − 27.9% to − 4.7%; P = 0.007). In multivariable models, the reductions of BMP10 and NT-proBNP were significantly associated with follow-up rhythm status (β coefficient per 1 − SD decrease, − 3.85; 95% CI − 6.34 to − 1.35; P = 0.003 for BMP10 and − 5.84; 95% CI − 10.22 to − 1.47; P = 0.009 for NT-proBNP. In conclusion, changes in BMP10 und NT-proBNP levels were independently associated with rhythm status after cardioversion, suggesting that these markers may be dependent on the actual heart rhythm.

Sustained forms of atrial fibrillation (AF) may be associated with a higher risk of adverse outcomes, but few if any long-term studies took into account changes of AF type and co-morbidities over time. We prospectively followed 3843 AF patients and collected information on AF type and co-morbidities during yearly follow-ups. The primary outcome was a composite of stroke or systemic embolism (SE). Secondary outcomes included myocardial infarction, hospitalization for congestive heart failure (CHF), bleeding and all-cause mortality. Multivariable adjusted Cox proportional hazards models with time-varying covariates were used to compare hazard ratios (HR) according to AF type. At baseline 1895 (49%), 1046 (27%) and 902 (24%) patients had paroxysmal, persistent and permanent AF and 3234 (84%) were anticoagulated. After a median (IQR) follow-up of 3.0 (1.9; 4.2) years, the incidence of stroke/SE was 1.0 per 100 patient-years. The incidence of myocardial infarction, CHF, bleeding and all-cause mortality was 0.7, 3.0, 2.9 and 2.7 per 100 patient-years, respectively. The multivariable adjusted (a) HRs (95% confidence interval) for stroke/SE were 1.13 (0.69; 1.85) and 1.27 (0.83; 1.95) for time-updated persistent and permanent AF, respectively. The corresponding aHRs were 1.23 (0.89, 1.69) and 1.45 (1.12; 1.87) for all-cause mortality, 1.34 (1.00; 1.80) and 1.30 (1.01; 1.67) for CHF, 0.91 (0.48; 1.72) and 0.95 (0.56; 1.59) for myocardial infarction, and 0.89 (0.70; 1.14) and 1.00 (0.81; 1.24) for bleeding. In this large prospective cohort of AF patients, time-updated AF type was not associated with incident stroke/SE.

AIMS:To determine the risk of subsequent adverse clinical outcomes in anticoagulated patients with atrial fibrillation (AF) who experienced a new bleeding event.METHODS AND RESULTS:Anticoagulated AF patients were followed in two prospective cohort studies. Information on incident bleeding was systematically collected during yearly follow-up visits and events were adjudicated as major bleeding or clinically relevant non-major bleeding (CRNMB) according to the International Society on Thrombosis and Haemostasis guidelines. The primary outcome was a composite of stroke, myocardial infarction (MI), or all-cause death. Time-updated multivariable Cox proportional-hazards models were used to compare outcomes in patients with and without incident bleeding. Median follow-up was 4.08 years [interquartile range (IQR): 2.93-5.98]. Of the 3277 patients included (mean age 72 years, 28.5% women), 646 (19.7%) developed a new bleeding, 297 (9.1%) a major bleeding and 418 (12.8%) a CRNMB. The incidence of the primary outcome was 7.08 and 4.04 per 100 patient-years in patients with and without any bleeding [adjusted hazard ratio (aHR): 1.36, 95% confidence interval (CI): 1.16-1.61; P < 0.001; median time between a new bleeding and a primary outcome 306 days (IQR: 23-832)]. Recurrent bleeding occurred in 126 patients [incidence, 8.65 per 100 patient-years (95% CI: 7.26-10.30)]. In patients with and without a major bleeding, the incidence of the primary outcome was 11.00 and 4.06 per 100 patient-years [aHR: 2.04, 95% CI: 1.69-2.46; P < 0.001; median time to a primary outcome 142 days (IQR: 9-518)], and 59 had recurrent bleeding [11.61 per 100 patient-years (95% CI: 8.99-14.98)]. The incidence of the primary outcome was 5.29 and 4.55 in patients with and without CRNMB [aHR: 0.94, 95% CI: 0.76-1.15; P = 0.53; median time to a composite outcome 505 days (IQR: 153-1079)], and 87 had recurrent bleeding [8.43 per 100 patient-years (95% CI: 6.83-10.40)]. Patients who had their oral anticoagulation (OAC) discontinued after their first bleeding episode had a higher incidence of the primary composite than those who continued OAC (63/89 vs. 159/557 patients; aHR: 4.46, 95% CI: 3.16-6.31; P < 0.001).CONCLUSION:In anticoagulated AF patients, major bleeding but not CRNMB was associated with a high risk of adverse outcomes, part of which may be explained by OAC discontinuation. Most events occurred late after the bleeding episode, emphasizing the importance of long-term follow-up in these patients.

BACKGROUND: Perioperative atrial fibrillation is associated with an increased risk of stroke, myocardial infarction, and death after noncardiac surgery. Anticoagulation therapy is effective for stroke prevention in nonsurgical atrial fibrillation, but its efficacy and safety in perioperative atrial fibrillation are unknown. METHODS: We searched MEDLINE, EMBASE, and CENTRAL from database inception until January 2022. We included studies comparing anticoagulation versus no anticoagulation use in patients with perioperative atrial fibrillation after noncardiac surgery. Our study outcomes included stroke ± systemic embolism, bleeding, mortality, myocardial infarction, and venous thromboembolism. We pooled studies using fixed-effects models. We reported summary risk ratios (RRs) for studies reporting multivariable-adjusted results. RESULTS: Seven observational studies but no randomised trials were included. Of the 27,822 patients, 29.1% were prescribed therapeutic anticoagulation. Anticoagulation use was associated with a lower risk of stroke ± systemic embolism (RR 0.73; 95% CI, 0.62–0.85; I2 = 81%; 3 studies) but a higher risk of bleeding (RR 1.14; 95% CI, 1.04–1.25; 1 study). There was a lower risk of mortality associated with anticoagulation use (RR 0.45; 95% CI, 0.40–0.51; I2 = 80%; 2 studies). There was no difference in the risk of myocardial infarction (RR 2.19; 95% CI, 0.97–4.96; 1 study). The certainty of the evidence was very low across all outcomes. CONCLUSION: Anticoagulation is associated with a reduced risk of stroke and death but an increased risk of bleeding. The quality of the evidence is very poor. Randomised trials are needed to better determine the effects of anticoagulation use in this population.

Evidence for the association of atrial fibrillation (AF) present on the ECG and cardiovascular outcomes in AF patients is limited.

The association of blood pressure (BP) and hypertension with the presence of different types of brain lesions in patients with atrial fibrillation is unclear. BP values were obtained in a multicenter cohort of patients with atrial fibrillation. Systolic and diastolic BP was categorized in predefined groups. All patients underwent brain magnetic resonance imaging and neurocognitive testing. Brain lesions were classified as large noncortical or cortical infarcts, small noncortical infarcts, microbleeds, or white matter lesions. White matter lesions were graded according to the Fazekas scale. Overall, 1738 patients with atrial fibrillation were enrolled in this cross-sectional analysis (mean age, 73 years, 73% males). Mean BP was 135/79 mm Hg, and 67% of participants were taking BP-lowering treatment. White matter lesions Fazekas ≥2 were found in 54%, large noncortical or cortical infarcts in 22%, small noncortical infarcts in 21%, and microbleeds in 22% of patients, respectively. Compared with patients with systolic BP <120 mm Hg, the adjusted odds ratios (95% CI) for Fazekas≥2 was 1.25 (0.94–1.66), 1.41 (1.03–1.93), and 2.54 (1.65–3.95) among patients with systolic BP of 120 to 140, 140 to 160, and ≥160 mm Hg ( P for linear trend<0.001). Per 5 mm Hg increase in systolic and diastolic BP, the adjusted β-coefficient (95% CI) for log-transformed white matter lesions was 0.04 (0.02–0.05), P <0.001 and 0.04 (0.01–0.06), P =0.004. Systolic BP was associated with small noncortical infarcts (odds ratios [95% CI] per 5 mm Hg 1.05 [1.01–1.08], P =0.006), microbleeds were associated with hypertension, but large noncortical or cortical infarcts were not associated with BP or hypertension. After multivariable adjustment, BP and hypertension were not associated with neurocognitive function. Among patients with atrial fibrillation, BP is strongly associated with the presence and extent of white matter lesions, but there is no association with large noncortical or cortical infarcts. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02105844.

BACKGROUND: Little is known about the association between alcohol consumption and risk of cardiovascular events in patients with established atrial fibrillation (AF). The main aim of the current study was to investigate the associations of regular alcohol intake with incident stroke or systemic embolism in patients with established AF. METHODS: To assess the association between alcohol consumption and cardiovascular events in patients with established AF, we combined data from 2 comparable prospective cohort studies that followed 3852 patients with AF for a median of 3.0 years. Patients were grouped into 4 categories of daily alcohol intake (none, > 0 to < 1, 1 to < 2 and ≥ 2 drinks/d). The primary outcome was a composite of stroke and systemic embolism. Secondary outcomes were all-cause mortality, myocardial infarction, hospital admission for acute heart failure, and a composite of major and clinically relevant nonmajor bleeding. Associations were assessed using time-updated, multivariable-adjusted Cox proportional hazards models. RESULTS: Mean age (± standard deviation) was 71 ± 10 years (28% were women and 84% were on oral anticoagulants). We observed 136 confirmed strokes or systemic emboli. Compared with nondrinkers, adjusted hazard ratios for the primary outcome event were 0.87, 95% confidence interval (CI) 0.55–1.37 for > 0 to < 1 drinks/d; 0.70, 95% CI 0.39–1.25 for 1 to < 2 drinks/d; and 0.96, 95% CI 0.56–1.67 for ≥ 2 drinks/d (p for linear [quadratic] trend 0.71 [0.22]). There was no significant association between alcohol consumption and bleeding, but there was a nonlinear association with heart failure (p for quadratic trend 0.01) and myocardial infarction (p for quadratic trend 0.007). INTERPRETATION: In patients with AF, we did not find a significant association between low to moderate alcohol intake and risk of stroke or other cardiovascular events. Our findings do not support special recommendations for patients with established AF with regard to alcohol consumption. Trial registration: ClinicalTrials.gov, no. NCT02105844

Purpose: Silent brain infarcts (SBI) are frequently detected in patients with atrial fibrillation (AF), but it is unknown whether SBI are linked to autonomic dysfunction. We aimed to explore the association of autonomic dysfunction with SBI in AF patients. Methods: 1,358 AF patients without prior stroke or TIA underwent brain MRI and 5-min resting ECG. We divided our cohort into AF patients who presented in sinus rhythm (SR-group, n = 816) or AF (AF-group, n = 542). HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, mean heart rate, root mean square root of successive differences of normal-to-normal intervals, 5-min total power and power in the low frequency, high frequency and very low frequency range were calculated. Primary outcome was presence of SBI in the SR group, defined as large non-cortical or cortical infarcts. Secondary outcomes were SBI volumes and topography. Results: Mean age was 72 ± 9 years, 27% were female. SBI were detected in 10.5% of the SR group and in 19.9% of the AF group ( p < 0.001). HRVI <15 was the only HRV parameter associated with the presence of SBI after adjustment for clinical covariates in the SR group [odds ratio (OR) 1.67; 95% confidence interval (CI): 1.03–2.70; p = 0.037]. HRVI <15 was associated with larger brain infarct volumes [β (95% CI) −0.47 (−0.84; −0.09), p = 0.016] in the SR group and was more frequently observed in patients with right- than left-hemispheric SBI ( p = 0.017). Conclusion: Impaired HRVI is associated with SBI in AF patients. AF patients with autonomic dysfunction might undergo systematic brain MRI screening to initiate intensified medical treatment. Clinical Trials Gov Identifier: NCT02105844.

BACKGROUND:Atrial fibrillation (AF) is frequently reported as a complication of noncardiac surgery. It is unknown whether new-onset perioperative AF is associated with an increased risk of stroke and death beyond the perioperative period. We performed a systematic review and meta-analysis to assess the long-term risks of stroke and mortality associated with new-onset perioperative AF after noncardiac surgery.METHODS:MEDLINE and EMBASE were searched from inception to March 2020 for studies reporting on the association between perioperative AF and the risk of stroke and death occurring beyond 30 days after noncardiac surgery. Reference screening, study selection, data extraction, and quality assessment were performed in duplicate. Data were pooled using inverse variance-weighted random-effects models and presented as risk ratios (RRs).RESULTS:From 7344 citations, we included 31 studies (3,529,493 patients). The weighted mean incidence of perioperative AF was 0.7%. During a mean follow-up of 28.1 ± 9.4 months, perioperative AF was associated with an increased risk of stroke (1.5 vs 0.9 strokes per 100 patient-years; RR: 2.9, 95% confidence interval [CI]: 2.1-3.9, I2 = 78%). Perioperative AF was also associated with a significantly higher risk of all-cause mortality (21.0 vs 7.6 deaths per 100 patient-years; RR: 1.8, 95% CI: 1.5-2.2, I2 = 94%). The pooled adjusted hazard ratios for stroke and all-cause mortality were 1.9 (95% CI: 1.6-2.2, I2 = 31%) and 1.5 (95% CI: 1.3-1.7, I2 = 20%), respectively.CONCLUSIONS:Patients who had perioperative AF after noncardiac surgery had a higher long-term risk of stroke and mortality compared with patients who did not. Whether this risk is modifiable with oral anticoagulation therapy should be investigated.

Abstract Background Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. We aimed to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. Methods Patients with persistent AF undergoing elective electrical cardioversion were enrolled. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up using multivariable logistic regression models. Results Of the 100 patients included (mean [SD] age 66 (10) years, 25% women), 28 (28%) had an AF recurrence. Of the 21 biomarkers assessed, 4 reached the predefined between group significance of p<0.01. The most significant ones were bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were -10.4%, -62.0% and -25.6% in patients with sinus rhythm, and 3.1%, 1.1% and -9.4% in patients with recurrent AF, for a between group difference of -13.5% (95% confidence interval [CI], -19.3% to -7.6%; P<0.001), -63.1% (95% CI, -76.6% to -49.6%; P<0.001) and -16.3 (95% CI, -27.9% to -4.7%; P=0.007). In age and sex adjusted models, reductions of BMP10 and NT-proBNP were significantly associated with rhythm status at follow-up (β coefficient per 1-SD decrease, -2.03; 95% CI, -3.06 to -1.00; P<0.001 and -3.98; 95% CI, -5.75 to -2.22; P<0.001, respectively). After additional adjustment for demographic characteristics, risk factors for AF, and changes in clinical measures, the β coefficients per 1-SD were -3.85 (95% CI, -6.34 to -1.35; P=0.003) for BMP10 and -5.84 (95% CI, -10.22 to -1.47; P=0.009) for NT-proBNP. Conclusions Changes in BMP10 und NT-proBNP levels were strongly associated with rhythm status after electrical cardioversion, suggesting that these markers may be dependent on the actual heart rhythm.

AIMS To develop and externally validate a risk score for all-cause hospital admissions in patients with atrial fibrillation. METHODS AND RESULTS We used a prospective cohort of 2387 patients with established atrial fibrillation as derivation cohort. Independent risk factors were selected from a broad range of variables using the least absolute shrinkage and selection operator method fit to a Cox model. The risk score was validated in a separate prospective cohort of 1300 atrial fibrillation patients. The incidence of all-cause hospital admission was 19.1 per 100 person-years in the derivation cohort and it was 26.1 per 100 person-years in the validation cohort. The most important predictors for admission were age (75-79 years: adjusted hazard ratio (aHR), 1.34; 95% confidence interval (CI), 1.01-1.78; 80-84 years: aHR, 1.50; 95% CI, 1.11-2.03; ≥85 years: aHR, 1.88; 95% CI, 1.36-2.62), prior pulmonary vein isolation (aHR, 0.72; 95% CI, 0.58-0.88), hypertension (aHR, 1.16; 95% CI, 0.99-1.36), diabetes (aHR, 1.38; 95% CI, 1.17-1.62), coronary heart disease (aHR, 1.17; 95% CI, 1.02-1.36), prior stroke/transient ischaemic attack (aHR, 1.26; 95% CI, 1.18-1.47), heart failure (aHR, 1.19; 95% CI, 1.03-1.39), peripheral artery disease (aHR, 1.35; 95% CI, 1.08-1.67), cancer (aHR, 1.33; 95% CI, 1.12-1.57), renal failure (aHR, 1.17; 95% CI, 0.99-1.37) and previous falls (aHR, 1.40; 95% CI, 1.13-1.74). A risk score with these variables was well calibrated, and achieved a C-index of 0.64 in the derivation and 0.59 in the validation cohort. CONCLUSIONS Multiple risk factors were associated with hospital admissions in atrial fibrillation patients. This prediction tool selects high-risk patients who may benefit from preventive interventions.