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Importance: The Apixaban for the Reduction of Thromboembolism in Patients With Device-Detected Subclinical Atrial Fibrillation (ARTESiA) randomized clinical trial showed that in patients with subclinical atrial fibrillation (SCAF) apixaban, compared with aspirin, reduced stroke/systemic embolism but increased major bleeding. Objectives: To characterize major bleeding events (site and severity) and identify factors associated with major bleeding. Design, Setting, and Participants: This was a prespecified subanalysis of the ARTESiA population who received treatment. This was an international, double-blind, double-dummy randomized clinical trial. Included were patients with 1 or more episodes of SCAF lasting 6 minutes to 24 hours with stroke risk factors (CHA2DS2-VASc score ≥3) or prior stroke without other risk factors. Study data were analyzed from August to November 2024. Interventions: Apixaban, 5 mg, twice daily (2.5 mg twice daily when indicated) or aspirin, 81 mg, once daily. Main Outcomes and Measures: Major bleeding adjudicated by a blinded committee according to International Society on Thrombosis and Hemostasis criteria. Results: A total of 3961 patients (mean [SD] age, 76.8 [7.6] years; 2535 male [64%]) were included in this analysis. After a mean (SD) follow-up of 3.5 (1.8) years, 1 or more major bleeding episodes occurred in 133 patients, 86 of 1989 taking apixaban and 47 of 1972 taking aspirin (1.71 vs 0.94 per 100-patient-years; hazard ratio [HR], 1.80; 95% CI, 1.26-2.57). The rates of intracranial (0.33 vs 0.40 per 100 patient-years; HR, 0.82; 95% CI, 0.43-1.57) and fatal (0.10% vs 0.16% per 100 patient-years; HR, 0.63; 95% CI, 0.20-1.91) bleeding were similar in the apixaban and aspirin groups, whereas the rate of gastrointestinal bleeding was higher in the apixaban group (0.89% vs 0.40% per 100 patient-years; HR, 2.23; 95% CI, 1.32-3.78). Among 133 index major bleeding events, those that occurred with apixaban were less likely to occur at critical sites (27.9% [24 of 86] vs 46.8% [22 of 47]; P = .03) including intracranial (18.6% [16 of 86] vs 42.6% [20 of 47]; P = .003). Most major bleeding events were nonemergencies characterized by decreased hemoglobin greater than or equal to 2 g/dL. Factors associated with major bleeding included nonsteroidal anti-inflammatory drug (NSAID) use (HR, 10.25; 95% CI, 6.57-15.99), cancer (HR, 2.87; 95% CI, 1.49-5.53), randomization to apixaban (HR, 1.84; 95% CI, 1.29-2.63), and age (HR, 1.47; 95% CI, 1.28-1.67, per 5-year increase). Conclusions and Relevance: Results of this subanalysis of the ARTESiA randomized clinical trial found that although the rate of major gastrointestinal bleeding was higher in patients with SCAF who were treated with apixaban vs aspirin, rates of fatal and intracranial bleeding were not different. Most major bleeding events were nonemergencies characterized by a decrease in hemoglobin level greater than or equal to 2 g/dL. NSAID use, cancer, randomization to apixaban, and increasing age were associated with an increased risk of major bleeding. Trial Registration: ClinicalTrials.gov Identifier: NCT01938248.

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BACKGROUND: Approximately one-third-of patients with transient new-onset atrial fibrillation (AF) during hospitalization for noncardiac surgery or medical illness will have recurrent AF within 1 year when assessed using two 14-day ECG monitors. The proportion of patients that would be diagnosed with recurrent AF with less monitoring is unknown. METHODS: We used data from a prospective cohort of participants with transient new-onset AF while hospitalized for noncardiac surgery or medical illness, who wore one or two 14-day ECG monitors. We calculated the proportion of patients that would be diagnosed with recurrent AF with different durations of ECG monitoring and the median time-to-detection of recurrent AF lasting ≥30 s. RESULTS: A total of 139 participants (41.0 % female, median CHA2DS2-VASc 3) wore an ECG monitor a median of 1.5 months following hospital discharge; 83 (59.7 %) wore a second monitor at median of 5.8 months after the first monitor. Recurrent AF was detected in 5.0 % of participants by 1 day, 5.8 % by 2 days, 6.5 % by 3 days, 12.2 % by 7 days, 21.6 % by 14 days and in 28.8 % by the end of the second 14-day monitor. Median monitoring time to recurrent AF was 5.3 (IQR 1.4-9.7) days. CONCLUSIONS: In patients with transient new-onset AF during hospitalization for another reason, the rate of detection of recurrent AF increased with longer monitoring durations. Approximately 80 % of diagnoses were made after 2 days of monitoring; the likelihood of capturing recurrent AF was 4 times higher with 14 days of monitoring compared to 2 days.

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Background: For patients with perioperative atrial fibrillation (POAF) after noncardiac surgery, earlier conversion to sinus rhythm might improve outcomes. The efficacy of a rhythm vs rate control strategy for the acute management of POAF remains uncertain. Methods: We searched databases for randomized controlled trials (RCTs) and observational studies that included patients with POAF after noncardiac surgery and reported outcomes for patients acutely treated with a rhythm control strategy vs either a rate control or no treatment strategy. Studies were pooled using random effects models. Results: Of the observational studies, a rhythm control strategy was associated with higher conversion rates to sinus rhythm compared with a rate control or no treatment strategy (risk ratio [RR], 1.93; 95% confidence interval [CI], 1.25-2.97; 9 studies; N = 591). Compared with a rate control or no treatment strategy, a rhythm control strategy was not associated with differences in length of hospital stay (mean difference, -1.67 days; 95% CI, -7.10 to 3.76; 2 studies), length of intensive care stay (mean difference, -1.90 days; 95% CI, -7.62 to 3.82; 1 study), or all-cause mortality (RR, 1.12; 95% CI, 0.62-2.00; 5 studies). In an RCT that compared amiodarone vs magnesium, the RR was 0.56 for conversion to sinus rhythm (95% CI, 0.31-1.03; N = 34). Conclusions: A rhythm control strategy was associated with greater success rates for conversion to sinus rhythm compared with a rate control or no treatment strategy. However, the observational studies were of low quality and only 1 small RCT was identified, and few data were available for other outcomes.

Contexte: Chez les patients présentant une fibrillation auriculaire périopératoire (FAPO) après une intervention chirurgicale non cardiaque, une conversion plus précoce en rythme sinusal pourrait améliorer les résultats cliniques. L'efficacité d'une stratégie de contrôle du rythme par rapport au contrôle de la fréquence pour la prise en charge aiguë de la FAPO reste incertaine. Méthodes: Nous avons recherché dans les bases de données les essais contrôlés randomisés (ECR) et les études observationnelles qui incluaient des patients atteints de FAPO après une chirurgie non cardiaque et qui rapportaient les résultats pour les patients traités en phase aiguë avec une stratégie de contrôle du rythme par rapport à une stratégie de contrôle de la fréquence ou à l'absence de traitement. Les études ont été regroupées à l'aide de modèles à effets aléatoires. Résultats: Parmi les études observationnelles, une stratégie de contrôle du rythme était associée à des taux de conversion en rythme sinusal plus élevés par rapport à une stratégie de contrôle de la fréquence ou d'absence de traitement (risque relatif [RR], 1,93; intervalle de confiance [IC] à 95 %, 1,25-2,97; 9 études ; N = 591). Par rapport à une stratégie de contrôle de la fréquence ou d'absence de traitement, une stratégie de contrôle du rythme n'a pas été associée à des différences en termes de durée d'hospitalisation (différence moyenne, -1,67 jours; IC à 95 %, -7,10 à 3,76; 2 études), de durée de séjour en soins intensifs (différence moyenne, -1,90 jours; IC à 95 %, -7,62 à 3,82; 1 étude) ou de mortalité toutes causes confondues (RR, 1,12; IC à 95 %, 0,62 à 2,00; 5 études). Dans un ECR comparant l'amiodarone au magnésium, le RR était de 0,56 pour la conversion en rythme sinusal (IC à 95 %, 0,31-1,03; N = 34). Conclusions: Une stratégie de contrôle du rythme a été associée à de meilleurs taux de réussite pour la conversion en rythme sinusal par rapport à une stratégie de contrôle de la fréquence ou d'absence de traitement. Cependant, les études d'observation étaient de faible qualité et seul un ECR de petite taille a été identifié, tandis que les données disponibles pour d'autres critères d'évaluation étaient limitées.

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There is conflicting literature on sex differences and clinical outcomes in patients who develop atrial fibrillation (AF) post-cardiac surgery. Our aim was to compare clinical outcomes between females and males with post-cardiac surgery AF. A systematic search was conducted for studies published until 27 September 2024 in MEDLINE, Embase, and CENTRAL. Included studies compared mortality and stroke in females vs. males who developed AF after cardiac surgery. Outcomes of interest were mortality and stroke. Pooled prevalence was used to compare comorbidities. Raw event rates were used to calculate odds ratios (ORs), which were pooled with a fixed-effects model. 10 422 studies were identified and 5 studies met inclusion criteria. 14 970 patients who developed AF after cardiac surgery were included, of whom 3748 were females. The length of follow-up was up to 10 years. The weighted average age was 70.4 ± 2.9 years in females and 66.7 ± 2.4 years in males (P = 0.32). At baseline, females had a higher prevalence of hypertension, diabetes, dyslipidemia, stroke, and peripheral vascular disease. The odds of in-hospital mortality among females were higher compared to males (5.5 vs. 3.0%; OR 2.04, 95% CI 1.42-2.91, P < 0.001, I 2 = 57%). There were no significant differences in post-discharge mortality (45.6 vs. 42.9%; OR 1.05, 95% CI 0.97-1.15, P = 0.23, I 2 = 0%) or in-hospital stroke (2.5 vs. 1.9%; OR 1.30, 95% CI 0.79-2.13, P = 0.30, I 2 = 57%) in females vs. males. In conclusion, females with post-cardiac surgery AF had a higher prevalence of comorbidities at baseline. The odds of in-hospital mortality were twice as high among females. There were no significant differences in post-discharge mortality or in-hospital stroke. Future studies are warranted to understand the mechanisms of increased in-hospital mortality in females and to develop effective monitoring strategies and interventions.

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BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is the most prevalent vascular complication following surgical procedures. Although the revised cardiac risk index (RCRI) is widely used to predict postoperative cardiovascular complications, its predictive accuracy is suboptimal. OBJECTIVES: Considering genetic influences may improve risk prediction. The authors propose integrating polygenic risk scores (PRS) with the RCRI to enhance MINS prediction. Identification of PRS associated with MINS could provide pathophysiological insights. METHODS: This is a case-control study nested within the Vascular Events in Noncardiac Surgery Participants Cohort Evaluation cohort, including patients aged 45 and above who underwent noncardiac surgery. Daily troponin levels were measured preoperatively and on days 1, 2, and 3 postoperatively. PRS was computed for MINS risk factors using publicly available summary statistics. Logistic regression models were used to assess the association between each PRS and MINS. PRS discrimination was assessed independently and in combination with RCRI. RESULTS: A total of 253 MINS cases were matched with 253 controls, adjusted for age, sex, and limited to individuals of European ancestry (ntotal = 506). The type II diabetes (T2D) PRS (OR: 1.26; 95% CI: 1.00-1.58; P = 0.047) and the HbA1c PRS (OR: 1.26; 95% CI: 1.03-1.54; P = 0.026) were associated with MINS. No other PRS, including those for coronary artery disease, stroke, and lipid biomarkers, showed significant associations. CONCLUSIONS: The T2D PRS and the HbA1c PRS were associated with an increased risk of MINS. The findings may reflect the multifactorial pathophysiology of MINS. Larger genetic studies and trials evaluating perioperative glucose management warrant consideration.

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We developed a survey to describe current practice on the detection and management of new-onset postoperative atrial fibrillation (POAF) occurring after coronary artery bypass grafting (CABG) or non-cardiac surgery. We e-mailed an online anonymous questionnaire of 17 multiple choice or rank questions to an international network of healthcare professionals. Between June 2023 and June 2024, 158 participants from 25 countries completed the survey. For CABG patients, 62.7% of respondents reported use of telemetry to detect POAF on the ward until discharge, and 40% reported no dedicated methods for monitoring AF recurrences during follow-up. The largest number (46%) reported prescribing oral anticoagulants (OACs) at discharge if patients were at risk according to CHA2DS2-VASc/CHA2DS2-VA scores, and the most common duration of OAC therapy was 3 months to 1 year (43%). For non-cardiac surgery patients, POAF detection methods varied, with 29% using periodic 12-lead ECG and 27% using telemetry followed by periodic ECGs. For monitoring AF recurrence, 33% reported planned cardiology visits with ECG. Regarding OAC prescription during follow-up, 51% reported they prescribe OACs only for patients who are at risk of stroke, and 42% prescribe OACs for an interval of 3 months to 1 year. The most commonly reported barrier to OAC prescription was the lack of randomized controlled trial data. For both CABG and non-cardiac surgery, the reported methods for POAF detection and recurrences monitoring were heterogeneous and prescription patterns for OACs varied greatly. The most frequently reported concern about long-term anticoagulation was lack of randomized data, indicating the urgent need for sound studies that inform daily clinical practice.

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AIMS: The left atrial appendage (LAA) produces natriuretic peptides and its removal or occlusion might increase the risk of heart failure (HF). We aimed to investigate the incidence of HF after LAA occlusion or removal (LAAO) in the Left Atrial Appendage Occlusion Study (LAAOS III). METHODS AND RESULTS: Patients (n = 4811) with atrial fibrillation (AF) and a CHA2DS2-VASc score ≥2, who were having cardiac surgery for another indication, were randomized to undergo surgical LAAO or not. We compared the composite outcome of HF-related hospitalizations and HF death between the two groups. HF assessment required clinical and radiographic evidence of HF. Analyses included a landmark analysis before and after 30 days and subgroups. Mean age was 71.2 years, 67.5% were male and 57.0% had prior HF. Over a mean follow-up of 3.8 years, 396 (8.3%) patients met the composite HF outcome: 209 (8.8%) with LAAO (n = 2379) and 187 (7.8%) without LAAO (n = 2391) (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.92-1.37, p = 0.25). There was no difference between the two groups in the first 30 days (1.6% vs. 1.1%; p = 0.12) and thereafter (7.6% vs. 7.1%; p = 0.57). Subgroups based on age, sex, body mass index, AF type, prior HF, cardiac rhythm or left ventricular ejection fraction showed consistent results. There was no difference in HF outcomes with LAAO between the cut-and-sew (HR 0.93, 95% CI 0.70-1.23, p = 0.62) versus other closure methods (HR 1.05, 95% CI 0.77-1.41, p = 0.77). CONCLUSIONS: Left atrial appendage occlusion or removal at the time of cardiac surgery does not appear to alter the risk of HF-related hospitalization or death. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01561651.

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OBJECTIVES: Atrial fibrillation is the most common complication of cardiac surgery and occurs frequently in patients without a history of the arrhythmia. We conducted a systematic review and meta-analysis of randomized controlled trials to assess whether prophylactic ablation during cardiac surgery in patients without a history of atrial fibrillation prevents atrial fibrillation. METHODS: We searched CENTRAL, MEDLINE and Embase from inception to August 2024. We included randomized trials of adults without a history of atrial fibrillation undergoing cardiac surgery. The intervention of interest was ablation during surgery. We pooled data using random-effects models. The primary outcome was new-onset early postoperative atrial fibrillation within 30 days following surgery. The key secondary outcome was incident clinical atrial fibrillation at follow-up (minimum 6 months). We assessed risk of bias using the Cochrane Collaboration's risk of bias tool v.2 and evidence quality using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: We included 7 trials (n = 687). The intervention was pulmonary vein isolation in 6 trials and ganglion plexi ablation in 1. Patients who received prophylactic ablation were less likely to have early postoperative atrial fibrillation (21% vs 37%, risk ratio [RR] 0.5, 95% confidence interval 0.3-0.8, I2 = 64%) and incident clinical atrial fibrillation at longest follow-up (range 6 months-2 years; 3% vs 10%, RR 0.3, 95% confidence interval 0.2-0.7, I2 = 0%). The quality of evidence was low. CONCLUSIONS: Prophylactic ablation during cardiac surgery may prevent atrial fibrillation in patients without a history of the arrhythmia. A definitive randomized trial is needed to confirm effects and safety.

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Background: Clinically important perioperative atrial fibrillation (POAF) is a common cardiac complication after noncardiac surgery. Little is known about how patients with POAF are managed acutely and whether practices have changed over time. Methods: We conducted an observational substudy of patients who had POAF, were at elevated cardiovascular risk, and were enrolled in the PeriOperative Ischemic Evaluation (POISE)-1, 2 and 3 trials between 2002 and 2021. POAF was defined as new, clinically important atrial fibrillation occurring within 30 days after surgery. We assessed the use of rhythm-control and anticoagulation treatment in response to POAF, at hospital discharge and at 30 days after surgery. We assessed for temporal trends using multivariable logistic regression. Results: Of the 27,896 patients included, 545 (1.9%) developed clinically important POAF. Patients received rhythm-control treatment in 48.6% of cases. The level of use of rhythm-control treatment increased over the course of the trials (POISE-1 vs POISE-2 vs POISE-3; 40.9% vs 49.5% vs 59.1%). A later randomization date was associated independently with use of rhythm-control treatment (odds ratio, 1.05 per year; 95% confidence interval, 1.01-1.09). Anticoagulation treatment was prescribed in 21% of POAF cases. The level of anticoagulation treatement use was higher in POISE-3, compared to that in the 2 previous trials (POISE-1 vs POISE-2 vs POISE-3-16.4% vs 16.5% vs 33.6%). A later randomization date was associated independently with use of anticoagulation treatment (odds ratio, 1.06 per year; 95% confidence interval, 1.02-1.11). Conclusions: Despite the absence of randomized controlled trials, the level of use of rhythm-control and anticoagulation treatment for POAF is rising. High-quality trials are needed urgently to determine whether these interventions are safe and effective in this population.

Contexte: En chirurgie non cardiaque, la fibrillation auriculaire postopératoire (FAPO) d'importance clinique est une complication cardiaque fréquente. La prise en charge ponctuelle des patients présentant une FAPO est mal connue et on ne sait pas précisément si les pratiques ont évolué au fil du temps. Méthodologie: Nous avons mené une sous-étude d'observation auprès de patients ayant présenté une FAPO et dont le risque cardiovasculaire était élevé, et qui avaient participé aux études 1, 2 ou 3 du programme d'essais cliniques POISE (PeriOperative Ischemic Evaluation) entre 2002 et 2021. La FAPO était définie comme un nouvel épisode de fibrillation auriculaire (FA) d'importance clinique au cours des 30 jours suivant une intervention chirurgicale. Nous avons évalué l'utilisation d'un traitement visant à régulariser le rythme cardiaque et de l'anticoagulothérapie dans la prise en charge d'une FAPO, au moment du congé de l'hôpital, puis 30 jours après l'intervention chirurgicale. Nous avons procédé à l'évaluation des tendances temporelles par régression logistique multivariée. Résultats: Sur les 27 896 patients inclus dans l'analyse, 545 (1,9 %) ont présenté une FAPO d'importance clinique. Dans 48,6 % des cas, les patients ont reçu un traitement visant à régulariser le rythme cardiaque. Le taux d'utilisation d'un traitement visant à régulariser le rythme cardiaque a augmenté d'une étude à l'autre (étude POISE-1 vs étude POISE-2 vs étude POISE-3; 40,9 % vs 49,5 % vs 59,1 %, respectivement). Une date plus tardive de la répartition aléatoire était un facteur indépendant de l'utilisation d'un traitement visant à régulariser le rythme cardiaque (rapport de cotes = 1,05 par an; intervalle de confiance [IC] à 95 % : 1,01-1,09). Une anticoagulothérapie a été prescrite à 21 % des patients ayant présenté une FAPO. Le taux d'utilisation d'une anticoagulothérapie était plus élevé dans l'étude POISE-3, comparativement aux deux essais précédents (étude POISE-1 vs étude POISE-2 vs étude POISE-3; ­ 16,4 % vs 16,5 % vs 33,6 %, respectivement). Une date plus tardive de la répartition aléatoire était un facteur indépendant d'utilisation d'une anticoagulothérapie (rapport de cotes = 1,06 par an; IC à 95 % : 1,02-1,11). Conclusions: Malgré l'absence d'essais comparatifs avec répartition aléatoire, le taux d'utilisation d'un traitement visant à régulariser le rythme cardiaque ou d'une anticoagulothérapie chez les patients présentant une FAPO est en augmentation. Il existe un besoin urgent de réaliser des études cliniques de grande qualité afin de déterminer si ces interventions sont sûres et efficaces dans cette population de patients.

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Background/Objectives: New-onset atrial fibrillation (AF) after cardiac surgery is associated with patient-important outcomes. Uncertainty persists regarding its prevention, detection, and management. This review seeks to identify, compile, and describe ongoing registered research studies involving patients with or at risk for post-operative AF (POAF) after cardiac surgery. Methods: We searched clinical trial registries in January 2023 for studies focusing on POAF prediction, prevention, detection, or management. We extracted data from each record and performed descriptive analyses. Results: In total, 121 studies met the eligibility criteria, including 82 randomized trials. Prevention studies are the most common (n = 77, 63.6%), followed by prediction (n = 21, 17.4%), management (n = 16, 13.2%), and detection studies (n = 7, 5.8%). POAF after cardiac surgery is an area of active research. Conclusions: There are many ongoing randomized prevention studies. However, two major clinical gaps persist; future randomized trials should compare rate and rhythm control in patients who develop POAF, and long-term follow-up studies should investigate strategies to monitor for AF recurrence in patients with POAF.

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BACKGROUND: Mounting evidence indicates that even device-detected subclinical atrial fibrillation is associated with a higher risk of heart failure (HF). However, the potential impact of atrial fibrillation screening on HF remains unknown. METHODS: The LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) evaluated the effects of atrial fibrillation screening on stroke prevention using an implantable loop recorder (ILR) versus usual care in older individuals with additional stroke risk factors. In this secondary analysis, we explored the following HF end points: (1) HF event or cardiovascular death; (2) HF event; (3) event with HF with reduced ejection fraction (HFrEF); and (4) HFrEF event or cardiovascular death. Outcomes were assessed in a Cox model both as time-to-first events and as total (first and recurrent) events analyzed using the Andersen-and-Gill method. RESULTS: Of 6004 participants (mean age 74.7 and 52.7% men), 1501 were randomized to ILR screening and 4503 to the control group. In total, 77 (5.1%) in the ILR group versus 295 (6.6%) in the control group experienced the primary outcome of an HF event or cardiovascular death. Compared with usual care, ILR screening was associated with a nonsignificant reduction in the primary outcome for the time-to-first event analysis (hazard ratio, 0.78 [95% CI, 0.61-1.01]) and the total event analysis (hazard ratio, 0.77 [95% CI, 0.59-1.01]). Similar results were obtained for the HF event. A significant risk reduction in total events was observed in the ILR group for the composite of HFrEF event or cardiovascular death and for HFrEF event (hazard ratio, 0.74 [95% CI, 0.56-0.98] and 0.65 [95% CI, 0.44-0.97], respectively). CONCLUSIONS: In an older population with additional stroke risk factors, ILR screening for atrial fibrillation tended to be associated with a lower rate of total HF events and cardiovascular death, particularly those related to HFrEF. These findings should be considered hypothesis-generating and warrant further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

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BACKGROUND: Polyphosphate (polyP), a procoagulant released from platelets, activates coagulation via the contact system and modulates cardiomyocyte viability. High-dose intravenous polyP is lethal in mice, presumably because of thrombosis. Previously, we showed that HRG (histidine-rich glycoprotein) binds polyP and attenuates its procoagulant effects. In this study, we investigated the mechanisms responsible for the lethality of intravenous polyP in mice and the impact of HRG on this process. METHODS: The survival of wild-type or HRG-deficient mice given intravenous synthetic or platelet-derived polyP in doses up to 50 mg/kg or saline was compared. To determine the contribution of thrombosis, the effect of FXII (factor XII) knockdown or enoxaparin on polyP-induced fibrin deposition in the lungs was examined. To assess cardiotoxicity, the ECG was continuously monitored, the levels of troponin I and the myocardial band of creatine kinase were quantified, and the viability of a cultured murine cardiomyocyte cell line exposed to polyP in the absence or presence of HRG was determined. RESULTS: In HRG-deficient mice, polyP was lethal at 30 mg/kg, whereas it was lethal in wild-type mice at 50 mg/kg. Although FXII knockdown or enoxaparin administration attenuated polyP-induced fibrin deposition in the lungs, neither affected mortality. PolyP induced dose-dependent ECG abnormalities, including heart block and ST-segment changes, and increased the levels of troponin and myocardial band of creatine kinase, effects that were more pronounced in HRG-deficient mice than in wild-type mice and were attenuated when HRG-deficient mice were given supplemental HRG. Consistent with its cardiotoxicity, polyP reduced the viability of cultured cardiomyocytes in a dose-dependent manner, an effect attenuated with supplemental HRG. CONCLUSIONS: High-dose intravenous polyP is cardiotoxic in mice, and HRG modulates this effect.

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BACKGROUND: Elevated heart rate (HR) predicts cardiovascular disease and mortality, but there are no established normal limits for ambulatory HR. We used data from the Swedish CArdioPulmonary Imaging Study to determine reference ranges for ambulatory HR in a middle-aged population. We also studied clinical correlates of ambulatory HR. METHODS: A 24-hour ECG was registered in 5809 atrial fibrillation-free individuals, aged 50-65 years. A healthy subset (n=3942) was used to establish reference values (excluding persons with beta-blockers, cardiovascular disease, hypertension, heart failure, anaemia, diabetes, sleep apnoea or chronic obstructive pulmonary disease).Minimum HR was defined as the lowest 1-minute HR. Reference ranges are reported as means±SDs and 2.5th-97.5th percentiles. Clinical correlates of ambulatory HR were analysed with multivariable linear regression. RESULTS: The average mean and minimum HRs were 73±9 and 48±7 beats per minute (bpm) in men and 76±8 and 51±7 bpm in women; the reference range for mean ambulatory HR was 57-90 bpm in men and 61-92 bpm in women. Average daytime and night-time HRs are also reported. Clinical correlates, including age, sex, height, body mass index, physical activity, smoking, alcohol intake, diabetes, hypertension, haemoglobin level, use of beta-blockers, estimated glomerular filtration rate, per cent of predicted forced expiratory volume in 1 s and coronary artery calcium score, explained <15% of the interindividual differences in HR. CONCLUSION: Ambulatory HR varies widely in healthy middle-aged individuals, a finding with relevance for the management of patients with a perception of tachycardia. Differences in ambulatory HR between individuals are largely independent of common clinical correlates.

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One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

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BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

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Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with poor clinical outcomes. The objective of this systematic review and meta-analysis was to assess the performance of risk scores to predict POAF in cardiac surgery patients. We searched MEDLINE, Embase, and Cochrane CENTRAL for studies that developed/evaluated a POAF risk prediction model. Pairs of reviewers independently screened studies and extracted data. We pooled area under the receiver operating curves (AUCs), sensitivity and specificity, and adjusted odds ratios from multivariable regression analyses using the generic inverse variance method and random effects models. Forty-three studies (n = 63,847) were included in the quantitative synthesis. Most scores were originally developed for other purposes but evaluated for predicting POAF. Pooled AUC revealed moderate POAF discrimination for the EuroSCORE II (AUC 0.59, 95% confidence interval [CI] 0.54 to 0.65), Society of Thoracic Surgeons (AUC 0.60, 95% CI 0.56 to 0.63), EuroSCORE (AUC 0.63, 95% CI 0.58 to 0.68), CHADS2 (AUC 0.66, 95% CI 0.57 to 0.75), POAF Score (AUC 0.66, 95% CI 0.63 to 0.68), HATCH (AUC 0.67, 95% CI 0.57 to 0.75), CHA2DS2-VASc (AUC 0.68, 95% CI 0.60 to 0.75) and SYNTAX scores (AUC 0.74, 95% CI 0.71 to 0.78). Pooled analyses at specific cutoffs of the CHA2DS2-VASc, CHADS2, HATCH, and POAF scores demonstrated moderate-to-high sensitivity (range 46% to 87%) and low-to-moderate specificity (range 31% to 70%) for POAF prediction. In conclusion, existing clinical risk scores offer at best moderate prediction for POAF after cardiac surgery. Better models are needed to guide POAF risk stratification in cardiac surgery patients.

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PURPOSE: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Although the evidence suggests that beta blockers prevent POAF, they often cause hypotension. Landiolol, an ultra-short-acting ß1 blocker, may prevent POAF, without adverse hemodynamic consequences. SOURCE: We searched MEDLINE, CENTRAL, Embase, and trial registries between January 1970 and March 2022. We included randomized controlled trials (RCTs) that evaluated the effect of landiolol for the prevention of POAF after cardiac surgery. Two reviewers independently assessed eligibility, extracted data, and assessed risk of bias using the Risk of Bias 2.0 tool. We pooled data using random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess certainty of evidence. PRINCIPAL FINDINGS: Nine RCTs including 868 participants met the eligibility criteria. Patients randomized to landiolol (56/460) had less POAF compared with controls (133/408) with a relative risk (RR) of 0.40 (95% confidence interval [CI], 0.30 to 0.54; I2 = 0%;) and an absolute risk of 12.2% vs 32.6% (absolute risk difference, 20.4%; 95% CI, 15.0 to 25.0). Landiolol resulted in a shorter hospital length-of-stay (LOS) (268 patients; mean difference, -2.32 days; 95% CI, -4.02 to -0.57; I2 = 0%). We found no significant difference in bradycardia (RR, 1.11; 95% CI, 0.48 to 2.56; I2 = 0%). No hypotension was reported with landiolol. We judged the certainty of evidence as moderate for POAF (because of indirectness as outcomes were not clearly defined) and low for LOS (because of imprecision and concern of reporting bias). CONCLUSION: In patients undergoing cardiac surgery, landiolol likely reduces POAF and may reduce LOS. A definitive large RCT is needed to confirm these findings. STUDY REGISTRATION: PROSPERO (CRD42021262703); registered 25 July 2021.

RéSUMé: OBJECTIF: La fibrillation auriculaire postopératoire (FAPO) est une complication fréquente après une chirurgie cardiaque. Bien que les données probantes suggèrent que les bêta-bloqueurs préviennent la FAPO, ces agents provoquent souvent une hypotension. Le landiolol, un ß1-bloqueur à action ultra-courte, pourrait prévenir la FAPO sans conséquences hémodynamiques indésirables. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, CENTRAL et Embase, et dans les registres d'études publiées entre janvier 1970 et mars 2022. Nous avons inclus les études randomisées contrôlées (ERC) évaluant l'effet du landiolol pour la prévention de la FAPO après une chirurgie cardiaque. Deux personnes ont indépendamment révisé l'éligibilité, extrait les données et évalué le risque de biais à l'aide de l'outil Risque de biais 2.0. Nous avons regroupé les données à l'aide de modèles à effets aléatoires. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Neuf ERC incluant 868 personnes remplissaient les critères d'éligibilité. Les patient·es randomisé·es dans le groupe landiolol (56/460) présentaient moins de FAPO que les témoins (133/408), avec un risque relatif (RR) de 0,40 (intervalle de confiance [IC] à 95 %, 0,30 à 0,54; I2 = 0 %) et un risque absolu de 12,2 % vs 32,6 % (différence de risque absolue, 20,4 %; IC 95 % 95 %, 15,0 à 25,0). Le landiolol a entraîné une durée de séjour hospitalier plus courte (268 patient·es; différence moyenne, −2,32 jours; IC 95 %, −4,02 à −0,57; I2 = 0 %). Nous n'avons trouvé aucune différence significative en matière de bradycardie (RR, 1,11; IC 95 %, 0,48 à 2,56; I2 = 0 %). Aucune hypotension n'a été rapportée avec le landiolol. Nous avons jugé que la certitude des données probantes était modérée pour la FAPO (en raison du caractère indirect car les critères d'évaluation n'étaient pas clairement définis) et faible pour la durée de séjour hospitalier (en raison de l'imprécision et de questionnements concernant le biais de déclaration). CONCLUSION: Chez les patient·es bénéficiant d'une chirurgie cardiaque, le landiolol réduit probablement la FAPO et peut réduire la durée de séjour hospitalier. Une ERC définitive à grande échelle est nécessaire pour confirmer ces résultats. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262703); enregistrée le 25 juillet 2021.

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BACKGROUND: Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Long-term risks for AF recurrence in these patients are unclear. OBJECTIVE: To estimate risk for AF recurrence in patients with new-onset AF during a hospitalization for noncardiac surgery or medical illness compared with a matched population without AF. DESIGN: Matched cohort study. (ClinicalTrials.gov: NCT03221777). SETTING: Three academic hospitals in Hamilton, Ontario, Canada. PARTICIPANTS: The study enrolled patients hospitalized for noncardiac surgery or medical illness who had transient new-onset AF. For each participant, an age- and sex-matched control participant with no history of AF from the same hospital ward was recruited. All participants left the hospital in sinus rhythm. MEASUREMENTS: 14-day electrocardiographic (ECG) monitor at 1 and 6 months and telephone assessment at 1, 6, and 12 months. The primary outcome was AF lasting at least 30 seconds on the monitor or captured by ECG 12-lead during routine care at 12 months. RESULTS: Among 139 participants with transient new-onset AF (70 patients with medical illness and 69 surgical patients) and 139 matched control participants, the mean age was 71 years (SD, 10), the mean CHA2DS2-VASc score was 3.0 (SD, 1.5), and 59% were male. The median duration of AF during the index hospitalization was 15.8 hours (IQR, 6.4 to 49.6 hours). After 1 year, recurrent AF was detected in 33.1% (95% CI, 25.3% to 40.9%) of participants in the transient new-onset AF group and 5.0% (CI, 1.4% to 8.7%) of matched control participants; after adjustment for the number of ECG monitors worn and for baseline clinical differences, the adjusted relative risk was 6.6 (CI, 3.2 to 13.7). After exclusion of participants who had electrical or pharmacologic cardioversion during the index hospitalization (n = 40) and their matched control participants and limiting to AF events detected by the patch ECG monitor, recurrent AF was detected in 32.3% (CI, 23.1% to 41.5%) of participants with transient new-onset AF and 3.0% (CI, 0% to 6.4%) of matched control participants. LIMITATIONS: Generalizability is limited, and the study was underpowered to evaluate subgroups and clinical predictors. CONCLUSION: Among patients who have transient new-onset AF during a hospitalization for noncardiac surgery or medical illness, approximately 1 in 3 will have recurrent AF within 1 year. PRIMARY FUNDING SOURCE: Peer-reviewed grants.