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Background: Intravenous digoxin is still used in emergency departments (EDs) to treat patients with acute heart failure (AHF), especially in those with rapid atrial fibrillation. Nonetheless, many emergency physicians are reluctant to use intravenous digoxin in patients with advanced age, impaired renal function, and potassium disturbances due to its potential capacity to increase adverse outcomes., Objective: We investigated whether intravenous digoxin used to treat rapid atrial fibrillation in patients with AHF may influence mortality in patients with specific age, estimated glomerular filtration rate (eGFR), and serum potassium classes., Design: A secondary analysis of patients included in in the Spanish EAHFE cohort, which includes patients diagnosed with AHF in the ED., Setting: 45 Spanish EDs., Participants: Two thousand one hundred ninety-four patients with AHF and rapid atrial fibrillation (heart rate ≥100 bpm) not receiving digoxin at home, divided according to whether they were or were not treated with intravenous digoxin in the ED., Outcome: The relationships between age, eGFR, and potassium with 30-day mortality were investigated using restricted cubic spline (RCS) models adjusted for relevant patient and episode variables. The impact of digoxin use on such relationships was assessed by checking interaction., Main Results: The median age of the patients was 82 years [interquartile range (IQR) = 76-87], 61.4% were women, 65.2% had previous episodes of atrial fibrillation, and the median heart rate at ED arrival was 120 bpm (IQR = 109-135). Digoxin and no digoxin groups were formed by 864 (39.4%) and 1330 (60.6%) patients, respectively. There were 191 deaths within the 30-day follow-up period (8.9%), with no differences between patients receiving or not receiving digoxin (8.5 vs. 9.1%, P  = 0.636). Although analysis of RCS curves showed that death was associated with advanced age, worse renal function, and hypo- and hyperkalemia, use of intravenous digoxin did not interact with any of these relationships ( P  = 0.156 for age, P  = 0.156 for eGFR; P  = 0.429 for potassium)., Conclusion: The use of intravenous digoxin in the ED was not associated with significant changes in 30-day mortality, which was confirmed irrespective of patient age or the existence of renal dysfunction or serum potassium disturbances., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: We aimed to test the hypothesis if combining coronary artery calcium score (Ca-score) as a quantitative anatomical marker of coronary atherosclerosis with high-sensitivity cardiac troponin as a quantitative biochemical marker of myocardial injury provided incremental value in the detection of functionally relevant coronary artery disease (fCAD) and risk stratification., Methods and Results: Consecutive patients undergoing myocardial perfusion single-photon emission computed tomography (MPS) without prior CAD were enrolled. The diagnosis of fCAD was based on the presence of ischaemia on MPS and coronary angiography; fCAD was centrally adjudicated in the diagnostic and prognostic domain. Diagnostic accuracy was evaluated using the area under the receiver-operating characteristic curve (AUC). The composite of cardiovascular death and non-fatal acute myocardial infarction (AMI) within 730 days was the primary prognostic endpoint. Among 1715 patients eligible for the diagnostic analysis, 399 patients had fCAD. The combination of Ca-score and high-sensitivity cardiac troponin T (hs-cTnT) had good diagnostic accuracy for the diagnosis of fCAD (AUC 0.79, 95% confidence interval (CI) 0.77-0.81), but no incremental value compared with the Ca-score alone (AUC 0.79, 95% CI 0.77-0.81, P = 0.965). Similar results were observed using high-sensitivity cardiac troponin I (AUC 0.80, 95% CI 0.77-0.82) instead of hs-cTnT. Among 1709 patients (99.7%) with available follow-up, 59 patients (3.5%) suffered the composite primary prognostic endpoint (non-fatal AMI, n = 34; CV death, n = 28). Both Ca-score and hs-cTnT had independent prognostic value. Increased risk was restricted to patients with elevation in both markers., Conclusion: The combination of the Ca-score with hs-cTnT increases the prognostic accuracy for future events but does not provide incremental value vs. the Ca-score alone for the diagnosis of fCAD., Study Registration: Clinical trial registration: NCT00470587., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Digoxin is commonly used to treat acute heart failure (AHF), especially in patients with concurrent atrial fibrillation (AF). Nonetheless, there is little consensus about in which patients digoxin should be given, the proper time for digoxin initiation, and whether digoxin initiation is associated with improved outcomes. We investigated factors related to digoxin initiation after an episode of AHF and whether patients receiving digoxin presented better short-term outcomes. We analyzed digoxin-naïve AHF patients from a Spanish and Swiss database, who were dichotomized into cohorts based on their receipt of digoxin treatment at discharge. The relationship between digoxin initiation and 23 additional patient covariates, including chronic treatment, was investigated, as well as its association with 90-day combined adverse events (defined as all-cause death or AHF hospitalization). Of 13,105 patients (10,600/2505 from the Spanish/Swiss cohorts, respectively), the median (interquartile range) age was 83 (74.87) years, and 51% were women. Of these, 484 (3.7%) received digoxin at discharge, which was associated with AF, female sex, left ventricular ejection fraction (LVEF) < 50%, and coming from the Spanish cohort. Parameters inversely associated with receiving digoxin at discharge included some chronic treatments, diabetes mellitus (DM), and chronic kidney disease (CKD). Digoxin initiation was not association with 90-day adverse events, adjusted hazard ratio (aHR) = 0.939 (0.769-1.146), but there was an interaction for CKD, aHR = 1.390 (0.831-2.325) vs. 0.854 (0.682-1.183), p = 0.039, and for cohort pertinence, with higher risk in the Swiss cohort; aHR = 1.405 (0.827-2.386) vs. 0.862 (0.689-1.077), p = 0.046. Digoxin initiation after an AHF episode was more frequent in the Spanish cohort and was associated with certain patient characteristics (AF, female sex, reduced LVEF, no DM, no CKD), but had no effect on 90-day outcomes., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Aims: We hypothesized that the current gold standard for risk stratification of patients with acute heart failure (AHF), the Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF (MEESSI-AHF) risk score, can be further improved by adding systemic inflammation as quantified by C-reactive protein (CRP)., Methods and Results: In a prospective multicentre diagnostic study (BASEL V), AHF was centrally adjudicated by two independent cardiologists. The MEESSI-AHF risk score was calculated using an established reduced and recalibrated model containing 12 independent risk factors. Model extension was performed by refitting and adding CRP in the logistic regression model with 30-day mortality as binary outcome. Discrimination, calibration and clinical usefulness were used to assess the performance of the extended Multiple Estimation of risk based on the Emergency department Spanish Score In patients (MEESSI) model. Validation was performed in an independent, retrospective and single-centre AHF cohort. Among 1208 AHF patients with complete data allowing calculation of the recalibrated MEESSI and the extended MEESSI models, the prognostic accuracy for 30-day mortality of the extended MEESSI model (c-statistic 0.83, 95% confidence interval [CI] 0.79-0.87) was significantly higher compared to the recalibrated model (c-statistic 0.79, 95% CI 0.75-0.83, p = 0.013). The extended model allowed to stratify a higher percentage of patients into the lowest risk group compared to the recalibrated model (33.1% vs. 20.3%). Demonstrating a calibration plot's slope of 1.00 (95% CI 0.81-1.19) and an intercept of 0.0 (95% CI -0.22 to 0.22), the extended MEESSI model achieved excellent and improved calibration. Results were confirmed in the independent validation cohort (n = 575)., Conclusions: Quantifying inflammation using CRP concentration provided incremental value in AHF risk stratification using the established MEESSI model., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Functionally relevant coronary artery disease (fCAD) can result in premature death or nonfatal acute myocardial infarction. Its early detection is a fundamentally important task in medicine. Classical detection approaches suffer from limited diagnostic accuracy or expose patients to possibly harmful radiation. Here we show how machine learning (ML) can outperform cardiologists in predicting the presence of stress-induced fCAD in terms of area under the receiver operating characteristic (AUROC: 0.71 vs. 0.64, p = 4.0E-13). We present two ML approaches, the first using eight static clinical variables, whereas the second leverages electrocardiogram signals from exercise stress testing. At a target post-test probability for fCAD of <15%, ML facilitates a potential reduction of imaging procedures by 15-17% compared to the cardiologist's judgement. Predictive performance is validated on an internal temporal data split as well as externally. We also show that combining clinical judgement with conventional ML and deep learning using logistic regression results in a mean AUROC of 0.74., (© 2024. The Author(s).)

Introduction: Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear., Methods: In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery. Cardiac complications were prospectively monitored and centrally adjudicated by two independent experts. The primary endpoint was perioperative myocardial infarction or injury attributable to a cardiac cause (cardiac PMI) within the first three postoperative days. The secondary endpoints were major adverse cardiac events (MACE), defined as a composite of myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death and all-cause death after 365 days. We used inverse probability of treatment weighting to account for differences between patients receiving beta-blockers and those who did not., Results: A total of 3839/10 272 (37.4%) patients (mean age 74 yr; 44.8% female) received beta-blockers before surgery. Patients on beta-blockers were older, and more likely to be male with established cardiorespiratory and chronic kidney disease. Cardiac PMI occurred in 1077 patients, with a weighted odds ratio of 1.03 (95% confidence interval [CI] 0.94-1.12, P=0.55) for patients on beta-blockers. Within 365 days of surgery, 971/10 272 (9.5%) MACE had occurred, with a weighted hazard ratio of 0.99 (95% CI 0.83-1.18, P=0.90) for patients on beta-blockers., Conclusion: Preoperative use of beta-blockers was not associated with decreased cardiac complications including cardiac perioperative myocardial infarction or injury and major adverse cardiac event. Additionally, preoperative use of beta-blockers was not associated with increased all-cause death within 30 and 365 days., Clinical Trial Registration: NCT02573532., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments., Methods: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324)., Results: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24-71) versus 33 (19-59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort., Conclusion: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Introduction: Atrial fibrillation (AF) and heart failure (HF) frequently coexist. Prediction of left ventricular ejection fraction (LVEF) recovery after catheter ablation (CA) for AF remains difficult., Objectives: To evaluate the value of biomarkers, alone and in conjunction with the Antwerp score to predict LVEF recovery after CA for AF., Methods: Patients undergoing CA for AF with depressed LVEF(<50%) were included. Plasma levels of 13 biomarkers were measured immediately prior to CA. Patients were categorized into "responders" and "non-responders" in similar fashion to the Antwerp score derivation and validation cohorts. The predictive power of the biomarkers alone and combined in outcome prediction was evaluated., Results: 208 patients with depressed LVEF were included (median age 63 years, 19% female, median LAVI 42 ml/m2, median LVEF 43%). At a median follow-up time of 30 months, 161 (77%) were responders and 47 (23%) were non-responders. Of 13 biomarkers, four (ANG2, GDF15, FGF23 and MyBPC3) were significantly different between responders and non-responders (p ≤0.001) and combined could predict the endpoint with an AUC of 0.72 (95%CI 0.64-0.81) overall, 0.69 (95%CI 0.59-0.78) in HFmrEF and 0.88 (95%CI 0.77-0.98) in HFrEF. Only ANG2 and GDF15 remained significantly associated with LVEF recovery after adjustment for age, sex and Antwerp score and significantly improved the accuracy of the Antwerp score predictions (p<0.001). The AUC of the Antwerp score in the outcome prediction improved from 0.75 (95% CI 0.67-0.83) to 0.78 (95% CI 0.70-0.86) CONCLUSION: A biomarker panel (ANG2, GDF15) significantly improved the accuracy of the Antwerp Score., (Copyright © 2024. Published by Elsevier Inc.)

Background: Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) is a validated clinical decision support tool that uses machine learning with or without serial cardiac troponin measurements at a flexible time point to calculate the probability of myocardial infarction (MI). How CoDE-ACS performs at different time points for serial measurement and compares with guideline-recommended diagnostic pathways that rely on fixed thresholds and time points is uncertain., Methods: Patients with possible MI without ST-segment-elevation were enrolled at 12 sites in 5 countries and underwent serial high-sensitivity cardiac troponin I concentration measurement at 0, 1, and 2 hours. Diagnostic performance of the CoDE-ACS model at each time point was determined for index type 1 MI and the effectiveness of previously validated low- and high-probability scores compared with guideline-recommended European Society of Cardiology (ESC) 0/1-hour, ESC 0/2-hour, and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome) pathways., Results: In total, 4105 patients (mean age, 61 years [interquartile range, 50-74]; 32% women) were included, among whom 575 (14%) had type 1 MI. At presentation, CoDE-ACS identified 56% of patients as low probability, with a negative predictive value and sensitivity of 99.7% (95% CI, 99.5%-99.9%) and 99.0% (98.6%-99.2%), ruling out more patients than the ESC 0-hour and High-STEACS (25% and 35%) pathways. Incorporating a second cardiac troponin measurement, CoDE-ACS identified 65% or 68% of patients as low probability at 1 or 2 hours, for an identical negative predictive value of 99.7% (99.5%-99.9%); 19% or 18% as high probability, with a positive predictive value of 64.9% (63.5%-66.4%) and 68.8% (67.3%-70.1%); and 16% or 14% as intermediate probability. In comparison, after serial measurements, the ESC 0/1-hour, ESC 0/2-hour, and High-STEACS pathways identified 49%, 53%, and 71% of patients as low risk, with a negative predictive value of 100% (99.9%-100%), 100% (99.9%-100%), and 99.7% (99.5%-99.8%); and 20%, 19%, or 29% as high risk, with a positive predictive value of 61.5% (60.0%-63.0%), 65.8% (64.3%-67.2%), and 48.3% (46.8%-49.8%), resulting in 31%, 28%, or 0, who require further observation in the emergency department, respectively., Conclusions: CoDE-ACS performs consistently irrespective of the timing of serial cardiac troponin measurement, identifying more patients as low probability with comparable performance to guideline-recommended pathways for MI. Whether care guided by probabilities can improve the early diagnosis of MI requires prospective evaluation., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00470587.