Using the C₂HEST score for predicting postoperative atrial fibrillation after cardiac surgery: A report from the Western Denmark Heart Registry, the Danish National Patient Registry, and the Danish National Prescription Registry

ObjectivesNew-onset postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. A targeted approach is necessary for prophylactic handling of the complication. The authors tested the performance of the C2HEST score to predict POAF in patients undergoing cardiac surgery.DesignRegister-based cohort study.SettingThree cardiothoracic centers.ParticipantsAll adult patients undergoing cardiac surgery in Western Denmark between January 1, 2010, and December 31, 2018, were included. Data on patient comorbidities before surgery were obtained from the Western Denmark Heart Registry, the Danish National Patient Registry, and the Danish National Prescription Registry.InterventionsThe C2HEST score (C2: Coronary Artery Disease/Chronic Obstructive Pulmonary Disease [1 point each]; H: Hypertension; E: Elderly [Age ≥75, 2 points]; S: Systolic Heart Failure [2 points]; T: Thyroid disease [hyperthyroidism]) was calculated for each patient. The primary outcome was POAF within the primary hospital stay. The C2HEST score's discriminative ability was evaluated and compared with an age-stratified version (mC2HEST) as well as 2 validated clinical risk models (CHADS2 and CHA2DS2-VASc).Measurements and main resultsAmong the 14,279 patients included, 4,298 (30.1%) developed POAF. The C2HEST score's performance was not significantly better than the CHADS2 and CHA2DS2-VASc scores (area under the curve [AUC] 0.553 [95% confidence interval {CI} 0.543; 0.563] v 0.543 [95% CI 0.535; 0.552] and 0.565 [95% CI 0.555; 0.574], respectively). The age-modified (mC2HEST) score showed only modest improvement in the risk model, with an AUC of 0.580 (95% CI 0.570; 0.590).ConclusionThe discriminative ability of the C2HEST score, measured by the AUC, was limited in this population, and was not proven to be superior to the CHADS2, CHA2DS2-VASc, and mC2HEST scores in predicting POAF after cardiac surgery

Prediction of postoperative atrial fibrillation with postoperative epicardial electrograms

Objectives. New-onset postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. The arrhythmia often entails a longer hospital stay, greater risk of other complications, and higher mortality both short- and long-term. An investigation of the use of early atrial electrograms in predicting POAF in cardiac surgery was performed. Design. In this prospective observational study, a total of 99 consecutive adult patients undergoing coronary artery bypass grafting, valve surgery or both were included. On the first postoperative morning, standard 12-lead electrograms (ECG), unipolar atrial electrograms (aEG), and vital values were recorded. The outcome was new-onset POAF within one month postoperatively. Results. Three multivariable prediction models for POAF were formed using measurements derived from the ECG, aEG, and patient characteristics. Age, body mass index, and two unipolar electrogram measurements quantifying local activation time and fractionation were strongly associated with the outcome POAF. The performance of the POAF prediction models was assessed through receiver operating curve characteristics with cross-validation, and discrimination using the leave-one-out-method to internally validate the models. The cross-validated area under the receiver operating characteristic curve (AUC) was improved in a prediction model using atrial-derived electrogram variables (AUC 0.796, 95% CI 0.698-0.894), compared with previous ECG and clinical models (AUC 0.716, 95% CI 0.606-0.826 and AUC 0.718, 95% CI 0.613-0.822, respectively). Conclusions. This study found that easily obtainable measurements from atrial electrograms may be helpful in identifying patients at risk of POAF in cardiac surgery

Adipose tissue arachidonic acid content is associated with the expression of 5-lipoxygenase in atherosclerotic plaques

BACKGROUND: The content of arachidonic acid in adipose tissue is positively associated with the risk of myocardial infarction, whereas the content of eicosapentaenoic acid in adipose tissue has been reported to be negatively associated with the risk of myocardial infarction. Both arachidonic acid and eicosapentaenoic acid are substrates for the synthesis of pro-inflammatory leukotrienes and leukotrienes derived from eicosapentaenoic acid are generally much less potent. In this study we hypothesized that a high content of arachidonic acid in adipose tissue would reflect a high formation of arachidonic acid derived leukotrienes and a high expression of 5-lipoxygenase in atherosclerotic plaques. Likewise, we hypothesized that a high content of eicosapentaenoic acid in adipose tissue would reflect a low formation of arachidonic acid derived leukotrienes and a low expression of 5-lipoxygenase in plaques. METHODS: In a cross sectional study we included 45 consecutive subjects undergoing femoral thrombendarterectomy. The expression of 5-lipoxygenase in plaques was assessed by a semi-automated image analysis computer programme after immunohistochemical staining with mono-clonal 5-lipoxygenase antibodies. Leukotriene B(4) and cysteinyl leukotriene formation from stimulated femoral artery plaques was quantified using ELISA methods. The fatty acid content of adipose tissue biopsies from the thigh was analyzed using gas chromatography. Associations between variables were assessed by Pearson correlations and were further explored in a multivariable linear regression model adjusting for potential confounders. RESULTS: A high content of arachidonic acid in adipose tissue was associated with a higher expression of 5-lipoxygenase in plaques (r = 0.32, p = 0.03), but no significant associations with leukotriene B(4) (r = 0.22, p = 0.14) and cysteinyl leukotriene (r = −0.11, p = 0.46) formation was seen. No significant associations were found between the content of eicosapentaenoic acid in adipose tissue and 5-lipoxygenase expression or leukotriene formation in plaque. CONCLUSIONS: Adipose tissue arachidonic acid contents correlated positively with the expression of 5-lipoxygenase in plaques. This association might represent a causal link between adipose tissue arachidonic acid and the risk of myocardial infarction but confirmatory studies are needed

Risk and Subtypes of Stroke Following New-Onset Postoperative Atrial Fibrillation in Coronary Bypass Surgery:A Population-Based Cohort Study

BACKGROUND: New‐onset postoperative atrial fibrillation (POAF) develops in approximately one‐third of patients undergoing cardiac surgery and is associated with a higher incidence of ischemic stroke and increased mortality. However, it remains unknown to what extent ischemic stroke events in patients with POAF are cardioembolic and whether anticoagulant therapy is indicated. We investigated the long‐term risk and pathogenesis of postoperative stroke in patients undergoing coronary artery bypass grafting experiencing POAF. METHODS AND RESULTS: This was a register‐based cohort study. Data from the WDHR (Western Denmark Heart Registry) were linked with the DNPR (Danish National Patient Register), the Danish National Prescription Register, and the Cause of Death Register. All stroke diagnoses were verified, and ischemic stroke cases were subclassified according to pathogenesis. Furthermore, investigations of all‐cause mortality and the use of anticoagulation medicine for the individual patient were performed. A total of 7813 patients without a preoperative history of atrial fibrillation underwent isolated coronary artery bypass grafting between January 1, 2010, and December 31, 2018, in Western Denmark. POAF was registered in 2049 (26.2%) patients, and a postoperative ischemic stroke was registered in 195 (2.5%) of the patients. After adjustment, there was no difference in the risk of ischemic stroke (hazard ratio [HR], 1.08 [95% CI, 0.74–1.56]) or all‐cause mortality (HR, 1.09 [95% CI, 0.98–1.23]) between patients who developed POAF and non‐POAF patients. Although not statistically significant, patients with POAF had a higher incidence rate (IR; per 1000 patient‐years) of cardioembolic stroke (IR, 1 [95% CI, 0.6–1.6] versus IR, 0.5 [95% CI, 0.3–0.8]), whereas non‐POAF patients had a higher incidence rate of large‐artery occlusion stroke (IR, 1.1 [95% CI, 0.8–1.5] versus IR, 0.7 [95% CI, 0.4–1.4]). Early initiation of anticoagulation medicine was not associated with a lower risk of ischemic stroke. However, patients with POAF were more likely to die of cardiovascular causes than non‐POAF patients (P<0.001). CONCLUSIONS: We found no difference in the adjusted risk of postoperative stroke or all‐cause mortality in POAF versus non‐POAF patients. Patients with POAF after coronary artery bypass grafting presented with a higher, although not significant, proportion of ischemic strokes of the cardioembolic type

Agents intervening against delirium in the intensive care unit trial-Protocol for a secondary Bayesian analysis

Background Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID-ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients. Methods This protocol describes the secondary, pre-planned Bayesian analyses of the primary and secondary outcomes up to day 90 of the AID-ICU trial. We will use Bayesian linear regression models for all count outcomes and Bayesian logistic regression models for all dichotomous outcomes. We will adjust for stratification variables (site and delirium subtype) and use weakly informative priors supplemented with sensitivity analyses using sceptical priors. We will present results as absolute differences (mean differences and risk differences) and relative differences (ratios of means and relative risks). Posteriors will be summarised using median values as point estimates and percentile-based 95% credibility intervals. Probabilities of any benefit/harm, clinically important benefit/harm and clinically unimportant differences will be presented for all outcomes. Discussion The results of this secondary, pre-planned Bayesian analysis will complement the primary frequentist analysis of the AID-ICU trial and facilitate a nuanced and probabilistic interpretation of the trial results.Peer reviewe

Agents intervening against delirium in the intensive care unit (AID-ICU) - Protocol for a randomised placebo-controlled trial of haloperidol in patients with delirium in the ICU

Background Delirium among patients in the intensive care unit (ICU) is a common condition associated with increased morbidity and mortality. Haloperidol is the most frequently used pharmacologic intervention, but its use is not supported by firm evidence. Therefore, we are conducting Agents Intervening against Delirium in the Intensive Care Unit (AID‐ICU) trial to assess the benefits and harms of haloperidol for the treatment of ICU‐acquired delirium. Methods AID‐ICU is an investigator‐initiated, pragmatic, international, randomised, blinded, parallel‐group, trial allocating adult ICU patients with manifest delirium 1:1 to haloperidol or placebo. Trial participants will receive intravenous 2.5 mg haloperidol three times daily or matching placebo (isotonic saline 0.9%) if they are delirious. If needed, a maximum of 20 mg/daily haloperidol/placebo is given. An escape protocol, not including haloperidol, is part of the trial protocol. The primary outcome is days alive out of the hospital within 90 days post‐randomisation. Secondary outcomes are number of days without delirium or coma, serious adverse reactions to haloperidol, usage of escape medication, number of days alive without mechanical ventilation; mortality, health‐related quality‐of‐life and cognitive function at 1‐year follow‐up. A sample size of 1000 patients is required to detect a 7‐day improvement or worsening of the mean days alive out of the hospital, type 1 error risk of 5% and power 90%. Perspective The AID‐ICU trial is based on gold standard methodology applied to a large sample of clinically representative patients and will provide pivotal high‐quality data on the benefits and harms of haloperidol for the treatment ICU‐acquired delirium