Association of bone morphogenetic protein 10 and recurrent atrial fibrillation after catheter ablation.

AIMS: Atrial remodelling, defined as a change in atrial structure, promotes atrial fibrillation (AF). Bone morphogenetic protein 10 (BMP10) is an atrial-specific biomarker released to blood during atrial development and structural changes. We aimed to validate whether BMP10 is associated with AF recurrence after catheter ablation (CA) in a large cohort of patients. METHODS AND RESULTS: We measured baseline BMP10 plasma concentrations in AF patients who underwent a first elective CA in the prospective Swiss-AF-PVI cohort study. The primary outcome was AF recurrence lasting longer than 30 s during a follow-up of 12 months. We constructed multivariable Cox proportional hazard models to determine the association of BMP10 and AF recurrence. A total of 1112 patients with AF (age 61 ± 10 years, 74% male, 60% paroxysmal AF) was included in our analysis. During 12 months of follow-up, 374 patients (34%) experienced AF recurrence. The probability for AF recurrence increased with increasing BMP10 concentration. In an unadjusted Cox proportional hazard model, a per-unit increase in log-transformed BMP10 was associated with a hazard ratio (HR) of 2.28 (95% CI 1.43; 3.62, P < 0.001) for AF recurrence. After multivariable adjustment, the HR of BMP10 for AF recurrence was 1.98 (95% CI 1.14; 3.42, P = 0.01), and there was a linear trend across BMP10 quartiles (P = 0.02 for linear trend). CONCLUSION: The novel atrial-specific biomarker BMP10 was strongly associated with AF recurrence in patients undergoing CA for AF. CLINICALTRIALS.GOV IDENTIFIER: NCT03718364; https://clinicaltrials.gov/ct2/show/NCT03718364.

Right Heart Structure and Function after Electrical Cardioversion for Atrial Fibrillation.

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.

Bleeding and ischaemic events after first bleed in anticoagulated atrial fibrillation patients: risk and timing.

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.

Silent brain infarcts impact on cognitive function in atrial fibrillation.

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.

Alcohol consumption and risk of cardiovascular outcomes and bleeding in patients with established atrial fibrillation.

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.

Aldosterone-to-renin ratio and blood pressure in young adults from the general population.

BACKGROUND: The effect of the renin angiotensin system on blood pressure (BP) values in young adults from the general population is not well studied. We investigated the relationship between the aldosterone-to-renin ratio (ARR) and various BP indices in this population. METHODS: We assembled a population-based sample of adults aged 25-41 years. Conventional and 24-hour BP recordings were obtained in all patients. Direct renin concentration and plasma aldosterone concentration were measured. Multivariable regression models were constructed to assess the relationships of ARR with BP and hypertension. RESULTS: We included 1,353 individuals (mean age 37 years, 56% women). The median (interquartile range) ARR, direct renin concentration, and plasma aldosterone concentration were 13.8 (8.7-22.9), 7.2 ng/L (4.4-11.0) and 94 ng/L (68-134). All BP indices were higher across sex-specific ARR quartiles. Per 1-unit increase in log-transformed ARR, the multivariable-adjusted ß-coefficients (95% CI) for conventional, 24-hour, daytime, and nighttime systolic BP were 1.68 (0.87-2.48), P < .0001; 2.40 (1.68-3.12), P < .0001; 2.23 (1.48-2.99), P < .0001; and 2.80 (2.03-3.58), P < .0001, respectively. Per 1-unit increase in log-transformed ARR, the multivariable-adjusted odds ratio (95% CI) for conventional, 24-hour, sustained and masked hypertension was 1.70 (1.17-2.28), P = .0004; 1.29 (1.06-1.56), P = .01; 1.82 (1.33-2.49), P = .002; and 1.14 (0.94-1.38), P = .20, respectively. CONCLUSIONS: In young adults, ARR was strongly associated with conventional and ambulatory BP. Our data suggest that an aldosterone-driven phenomenon occurs very early in the development of hypertension.

C-reactive protein for prediction of atrial fibrillation recurrence after catheter ablation.

BACKGROUND: Inflammation plays an important role in the initiation and progression of atrial fibrillation (AF), but data about the relationship between subclinical inflammation and recurrence of AF after catheter ablation remains poorly studied. We aimed to assess whether plasma levels of C-reactive protein (CRP) are associated with long-term AF recurrence following catheter ablation. METHODS: Prior to the intervention, plasma CRP concentrations were measured in patients who underwent first catheter ablation for AF. AF recurrence was evaluated after 12 months and defined as any AF episode longer than 30 s recorded on either 12-lead electrocardiogram, 24-h Holter or 7-day Holter monitoring. Multivariable adjusted Cox models were constructed to examine the association of CRP levels and AF recurrence. RESULTS: Of the 711 patients (mean age: 61 years, 25% women) included in this study, 247 patients (35%) experienced AF recurrence after ablation. Patients who were in the highest CRP quartile had a higher rate of recurrent AF compared to those who were in the lowest quartile (53.4 vs. 33.1% at 1 year of follow-up; P = 0.004). The adjusted hazard ratios (aHR) of recurrent AF across increasing quartiles of CRP were 1.0 (reference), 1.26 (95% confidence interval [CI], 0.86-1.84), 1.15 (95% CI, 0.78-1.70) and 1.60 (95% CI, 1.10-2.34) (P trend = 0.015). A similar effect was observed when CRP was analyzed as continuous variable (aHR per unit increase, 1.21; 95% CI, 1.05-1.39; P = 0.009). When a predefined CRP cut-off of 3 mg/l was applied, patients with CRP levels of 3 mg/l or above had a higher risk of AF recurrence than those with levels below (aHR, 1.44; 95% CI, 1.06-1.95; P = 0.019). CONCLUSIONS: Increasing pre-interventional CRP levels are associated with a higher risk of AF recurrence in patients undergoing catheter ablation for AF. TRAIL REGISTRATION: ClinicalTrials.gov identifier, NCT03718364.

Plasma levels of glucagon-like peptide 1 and markers of obesity among young and healthy adults.

OBJECTIVE: Glucagon-like peptide 1 (GLP-1)-related pathways may partially explain the strong relationship between obesity and type 2 diabetes. We therefore aimed to evaluate the relationships between fasting GLP-1 levels, body fat mass and other obesity markers in a large sample of young and healthy adults. DESIGN AND PATIENTS: Our population-based study included 2096 individuals aged 24-44. Exclusion criteria were prevalent cardiovascular disease, diabetes or a body mass index (BMI) >35 kg/m(2) . Body fat mass was obtained by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships of GLP-1 with various measures of body composition. RESULTS: Median age of our population was 37 years, median BMI 24·1 kg/m(2) and median body fat 25·1%. A strong positive correlation was observed in age-adjusted models between GLP-1 and fat mass in men (ß (95% confidence interval) 1·38 (0·69; 2·07), P < 0·001) and women (1·27 (0·65; 1·89), P < 0·001) as well as fully adjusted models including BMI in men [0·87 (0·27; 1·46), P < 0·01] but not women [0·29 (-0·07; 0·64), P = 0·11]. The relationships of GLP-1 with BMI for men and women [0·00 (-0·34; 0·34), P = 0·99] [-0·02 (-0·28; 0·25), P = 0·91] and waist circumference [0·43 (-0·45; 1·30), P = 0·34] [0·37 (-0·44; 1·18), P = 0·37], respectively, were not significant after multivariable adjustment including fat mass. CONCLUSION: Among young and healthy adults, GLP-1 levels are strongly and independently related to body fat mass especially in men but not BMI or waist circumference. These results raise the hypothesis that GLP-1 may be implicated in body fat mass regulation.

Associations of inflammatory biomarkers with morbidity and mortality after noncardiac surgery: A systematic review and meta-analysis.

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.

Anticoagulation use in perioperative atrial fibrillation after noncardiac surgery: a systematic review and meta-analysis.

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.

Associations of Inflammatory Biomarkers With the Risk of Morbidity and Mortality After Cardiac Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Although inflammatory biomarkers have been associated with cardiovascular events in nonsurgical settings, these associations have not been systematically addressed in patients undergoing cardiac surgery. This review aimed to evaluate the relationships of inflammatory markers with mortality and adverse cardiovascular events in patients undergoing cardiac surgery. METHODS: Medline, Embase, and Central databases were systematically searched for studies reporting pre- or postoperative levels of inflammatory biomarkers in patients undergoing cardiac surgery. Outcomes of interest were postoperative mortality, nonfatal myocardial infarction, stroke, congestive heart failure, and major adverse cardiovascular events (MACE). Studies reporting multivariable adjusted risk estimates were included. Risk estimates were pooled with the use of random-effects models and reported as summary odds ratios (ORs). RESULTS: Among 14,465 citations identified, 29 studies including 29,401 participants met the eligibility criteria. The average follow-up time after surgery was 31 months. Preoperative C-reactive protein (CRP) levels were associated with an increased risk of all-cause mortality (OR 1.88, 95% CI 1.60-2.20; I2 = 19%; 11 studies) and MACE (OR 1.73, 95% CI 1.34-2.24; I2 = 0%; 3 studies). CRP levels measured on postoperative day 6 (OR 7.4, 95% CI 2.90-18.88, 1 study) and day 10 (OR 11.8, 95% CI 3.50-39.78, 1 study) were associated with a higher risk of all-cause mortality. Less, but overall similar, information was available for other inflammatory biomarkers. CONCLUSIONS: In this large meta-analysis, inflammatory biomarkers measured before or after cardiac surgery were associated with mortality and adverse cardiovascular outcomes in patients undergoing cardiac surgery.

Biomarkers associated with rhythm status after cardioversion in patients with atrial fibrillation.

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 (ß 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.

Use of Anticoagulation Therapy in Patients With Perioperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-analysis.

Background: Perioperative atrial fibrillation (POAF) after cardiac surgery is associated with an increased risk of stroke. However, the efficacy and safety of using anticoagulation therapy in this population are unknown. Methods: We performed a systematic review and meta-analysis of studies comparing use of anticoagulation therapy vs no anticoagulation therapy in patients with POAF after cardiac surgery. Outcomes included arterial thromboembolism (ie, stroke ± systemic embolism) and bleeding. Data were pooled using fixed-effects models. We reported summary risk ratios (RRs) for studies with multivariable adjustment and estimated absolute risk differences with 95% confidence intervals (CIs). Results: Nine observational studies met eligibility criteria. No randomized trials were identified. Of the 254,200 POAF patients included, 27.3% received anticoagulation. Six studies reported outcomes after long-term follow-up (median 5.0 years; range 4.2-10.0). The risk of arterial thromboembolism was lower in patients receiving anticoagulation therapy (RR 0.83; 95% CI, 0.69-0.99; I2 = 57%; P = 0.04; 6 studies). The estimated short-term and long-term absolute risk reductions in arterial thromboembolism with use of anticoagulation therapy were 0.8% (95% CI, 0.4-1.4) and 2 events per 1000 person-years (95% CI, 0-4), respectively. The risk of bleeding was higher in patients receiving anticoagulation therapy (RR 3.22; 95% CI, 2.82-3.68; I2 = 98%; P < 0.001; 2 studies). The estimated short-term and long-term absolute risk increases in bleeding with use of anticoagulation therapy were 0.5% (95% CI, 0.4-0.6) and 42 events per 1000 person-years (95% CI, 35-51), respectively. Conclusions: Use of anticoagulation therapy is associated with a small reduction in the risk of arterial thromboembolism, but also an increased risk of bleeding. Randomized controlled trials are needed to address this issue.

Introduction: La fibrillation auriculaire périopératoire (FAPO) après l'intervention chirurgicale au cœur est associée à une augmentation du risque d'accident vasculaire cérébral (AVC). Toutefois, on ne connaît pas l'efficacité et l'innocuité de la l'anticoagulothérapie de cette population. Méthodes: Nous avons réalisé une revue systématique et une méta-analyse d'études qui comparaient l'utilisation de l'anticoagulothérapie vs l'absence d'anticoagulothérapie chez les patients atteints de FAPO après l'intervention chirurgicale au cœur. Les résultats étaient notamment la thromboembolie artérielle (c.-à-d. l'AVC ± l'embolie systémique) et les hémorragies. Nous avons regroupé les données à l'aide de modèles à effets fixes. Nous avons rapporté les risques relatifs (RR) sommaires d'études avec l'ajustement multivarié et l'estimation des différences du risque absolu avec des intervalles de confiance (IC) à 95 %. Résultats: Neuf études observationnelles répondaient aux critères d'admissibilité. Aucun essai à répartition aléatoire n'a été trouvé. Parmi les 254 200 patients atteints de FAPO sélectionnés, 27,3 % avaient reçu une anticoagulation. Six études révélaient des résultats après le suivi à long terme (médiane 5,0 ans ; fourchette 4,2-10,0). Le risque de thromboembolie artérielle était plus faible chez les patients qui avaient reçu une anticoagulothérapie (RR 0,83 ; IC à 95 %, 0,69-0,99 ; I2 = 57 % ; P = 0,04 ; six études). Les estimations de réduction du risque absolu à court terme et à long terme lors de thromboembolie artérielle avec l'utilisation de l'anticoagulothérapie étaient respectivement de 0,8 % (IC à 95 %, 0,4-1,4) et de deux événements par 1000 personnes-années (IC à 95 %, 0-4). Le risque d'hémorragie était plus élevé chez les patients qui avaient reçu une anticoagulothérapie (RR 3,22 ; IC à 95 %, 2,82-3,68 ; I2 = 98 % ; P < 0,001 ; deux études). Les estimations d'augmentation du risque absolu à court terme et à long terme des hémorragies avec l'utilisation de l'anticoagulothérapie étaient respectivement de 0,5 % (IC à 95 %, 0,4-0,6) et de 42 événements par 1000 personnes-années (IC à 95 %, 35-51). Conclusions: L'utilisation de l'anticoagulothérapie est associée à une réduction minime du risque de thromboembolie artérielle, mais aussi à une augmentation du risque d'hémorragie. Des essais cliniques à répartition aléatoire sont nécessaires pour aborder cette question.

Short-term and Long-term Risk of Stroke in Patients With Perioperative Atrial Fibrillation After Cardiac Surgery: Systematic Review and Meta-analysis.

BACKGROUND: Perioperative atrial fibrillation (POAF) after cardiac surgery has been associated with an increased risk of stroke in some studies. However, the exact magnitude of this association during short-term and long-term follow-up remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for the time period from database inception to October 2020. We included observational studies with ≥ 100 patients that reported data on short-term or long-term stroke risk in patients with and without POAF after cardiac surgery. Data were pooled using random-effects models. We reported summary risk ratios (RRs) for studies reporting multivariable adjusted results and calculated absolute risk differences (ARDs) with 95% confidence intervals (CIs). RESULTS: A total of 55 studies with 540,209 patients were included. POAF was associated with both an increased relative risk (RR 1.69; 95% CI, 1.41-2.03; I2 = 82%; 9 studies) and absolute risk of short-term stroke (4.5% vs 2.5%; ARD 2.0%; 95% CI, 1.28-2.89). POAF was associated with an increased relative risk (RR 1.20; 95% CI, 1.12-1.29; I2 = 16%; 10 studies) and absolute risk of long-term stroke (1.06 vs 0.88 per 100 patient-years; ARD 0.18 per 100 patient-years; 95% CI, 0.07-0.26). Sensitivity analyses of high-quality studies and studies reporting either ischemic or embolic strokes yielded similar findings. CONCLUSIONS: POAF after cardiac surgery was associated with an increased risk of both short-term and long-term stroke. However, the long-term stroke ARD was small, and whether these patients will benefit from long-term oral anticoagulation therapy is unclear.

CONTEXTE: La fibrillation auriculaire périopératoire (FAPO) après une chirurgie cardiaque a été associée à un risque accru d'accident vasculaire cérébral (AVC) dans certaines études. Cependant, l'ampleur exacte de cette association durant le suivi à court et à long terme reste incertaine. MÉTHODOLOGIE: Nous avons effectué des recherches dans les bases de données PubMed, Embase et CENTRAL (Cochrane Central Register of Controlled Trials) pour la période allant de la création de ces bases à octobre 2020. Nous avons inclus des études d'observation comptant ≥ 100 patients et rapportant des données sur le risque d'AVC à court ou à long terme chez les patients ayant présenté ou non une FAPO après une chirurgie cardiaque. Les données ont été regroupées à l'aide de modèles à effets aléatoires. Nous avons consigné les rapports de risque (RR) sommaires pour les études rapportant des résultats corrigés multivariables et calculé les différences de risque absolu (DRA) avec des intervalles de confiance (IC) à 95 %. RÉSULTATS: Au total, 55 études portant sur 540 209 patients ont été incluses. La FAPO était associée à une augmentation tant du risque relatif (RR : 1,69; IC à 95 % : 1,41 à 2,03; I2 = 82 %; 9 études) que du risque absolu d'AVC à court terme (4,5 % vs 2,5 %; DRA : 2,0 %; IC à 95 % : 1,28 à 2,89). La FAPO était également associée à une augmentation du risque relatif (RR : 1,20; IC à 95 % : 1,12 à 1,29; I2 = 16 %; 10 études) et du risque absolu d'AVC à long terme (1,06 vs 0,88 par 100 années-patients; DRA : 0,18 par 100 années-patients; IC à 95 % : 0,07 à 0,26). Les analyses de sensibilité des études de haute qualité et des études rapportant des AVC ischémiques ou emboliques ont donné des résultats similaires. CONCLUSIONS: La FAPO après une chirurgie cardiaque a été associée à un risque accru d'AVC à court et à long terme. Cependant, comme la différence de risque absolu d'AVC à long terme était faible, la possibilité qu'une anticoagulothérapie orale à long terme soit bénéfique pour ces patients est incertaine.

Long-term risk of adverse outcomes according to atrial fibrillation type.

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.

Insulin-like growth factor-binding protein 7 and risk of congestive heart failure hospitalization in patients with atrial fibrillation.

BACKGROUND: The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker. OBJECTIVE: The purpose of this study was to assess whether insulin-like growth factor-binding protein 7 (IGFBP-7), a marker of myocardial damage, identifies AF patients at high risk for this complication. METHODS: We analyzed 2 prospective multicenter observational cohort studies that included 3691 AF patients. Levels of IGFBP-7 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from frozen plasma samples at baseline. The primary endpoint was hospitalization for CHF. Multivariable adjusted Cox regression analyses were constructed. RESULTS: Mean patient age was 69 ± 12 years, 1028 (28%) were female, and 879 (24%) had a history of CHF. The incidence per 1000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32, and 85. The corresponding multivariable adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.0, 1.05 (0.63-1.77), 2.38 (1.50-3.79), and 4.37 (2.72-7.04) (P for trend <.001). In a subgroup of 2812 patients without pre-existing CHF at baseline, the corresponding aHRs were 1.0, 0.90 (0.47-1.72), 1.69 (0.94-3.04), and 3.48 (1.94-6.24) (P for trend <.001). Patients with IGFBP-7 and NT-proBNP levels above the biomarker-specific median had a higher risk of incident CHF hospitalization (aHR 5.20; 3.35-8.09) compared to those with only 1 elevated marker (elevated IGFBP-7 aHR 2.17; 1.30-3.60); elevated NT-proBNP aHR 1.97; 1.17-3.33); or no elevated marker (reference). CONCLUSION: Higher plasma levels of IGFBP-7 were strongly and independently associated with CHF hospitalization in AF patients. The prognostic information provided by IGFBP-7 was additive to that of NT-proBNP.

The Admit-AF risk score: A clinical risk score for predicting hospital admissions in patients with atrial fibrillation.

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.

Frailty to predict unplanned hospitalization, stroke, bleeding, and death in atrial fibrillation.

AIMS: Atrial fibrillation (AF) and frailty are common, and the prevalence is expected to rise further. We aimed to investigate the prevalence of frailty and the ability of a frailty index (FI) to predict unplanned hospitalizations, stroke, bleeding, and death in patients with AF. METHODS AND RESULTS: Patients with known AF were enrolled in a prospective cohort study in Switzerland. Information on medical history, lifestyle factors, and clinical measurements were obtained. The primary outcome was unplanned hospitalization; secondary outcomes were all-cause mortality, bleeding, and stroke. The FI was measured using a cumulative deficit approach, constructed according to previously published criteria and divided into three groups (non-frail, pre-frail, and frail). The association between frailty and outcomes was assessed using multivariable-adjusted Cox regression models. Of the 2369 included patients, prevalence of pre-frailty and frailty was 60.7% and 10.6%, respectively. Pre-frailty and frailty were associated with a higher risk of unplanned hospitalizations [adjusted hazard ratio (aHR) 1.82, 95% confidence interval (CI) 1.49-2.22; P < 0.001; and aHR 3.59, 95% CI 2.78-4.63, P < 0.001], all-cause mortality (aHR 5.07, 95% CI 2.43-10.59; P < 0.001; and aHR 16.72, 95% CI 7.75-36.05; P < 0.001), and bleeding (aHR 1.53, 95% CI 1.11-2.13; P = 0.01; and aHR 2.46, 95% CI 1.61-3.77; P < 0.001). Frailty, but not pre-frailty, was associated with a higher risk of stroke (aHR 3.29, 95% CI 1.2-8.39; P = 0.01). CONCLUSION: Over two-thirds of patients with AF are pre-frail or frail. These patients have a high risk for unplanned hospitalizations and other adverse events. These findings emphasize the need to carefully evaluate these patients. However, whether screening for pre-frailty and frailty and targeted prevention strategies improve outcomes needs to be shown in future studies. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier number: NCT02105844.

Association of psychosocial factors with all-cause hospitalizations in patients with atrial fibrillation.

BACKGROUND: A high burden of cardiovascular comorbidities puts patients with atrial fibrillation (AF) at high risk for hospitalizations, but the role of other factors is less clear. HYPOTHESIS: To determine the relationship between psychosocial factors and the risk of unplanned hospitalizations in AF patients. METHODS: Prospective observational cohort study of 2378 patients aged 65 or older with previously diagnosed AF across 14 centers in Switzerland. Marital status and education level were defined as social factors, depression and health perception were psychological components. The pre-defined outcome was unplanned all-cause hospitalization. RESULTS: During a median follow-up of 2.0 years, a total of 1713 hospitalizations occurred in 37% of patients. Compared to patients who were married, adjusted rate ratios (aRR) for all-cause hospitalizations were 1.28 (95% confidence interval [CI], 0.97-1.69) for singles, 1.31 (95%CI, 1.06-1.62) for divorced patients, and 1.02 (95%CI, 0.82-1.25) for widowed patients. The aRRs for all-cause hospitalizations across increasing quartiles of health perception were 1.0 (highest health perception), 1.15 (95%CI, 0.84-1.59), 1.25 (95%CI, 1.03-1.53), and 1.66 (95%CI, 1.34-2.07). No different hospitalization rates were observed in patients with a secondary or primary or less education as compared to patients with a college degree (aRR, 1.06; 95%CI, 0.91-1.23 and 1.05; 95%CI, 0.83-1.33, respectively). Presence of depression was not associated with higher hospitalization rates (aRR, 0.94; 95%CI, 0.68-1.29). CONCLUSIONS: The findings suggest that psychosocial factors, including marital status and health perception, are strongly associated with the occurrence of hospitalizations in AF patients. Targeted psychosocial support interventions may help to avoid unnecessary hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02105844.