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Introduction: Pulmonary transit time (PTT) is the time it takes blood to pass from the right ventricle to the left ventricle via the pulmonary circulation, making it a potentially useful marker for heart failure. We assessed the association of PTT with diastolic dysfunction (DD) and mitral valve regurgitation (MVR). Methods: We evaluated routine stress perfusion cardiovascular magnetic resonance (CMR) scans in 83 patients including assessment of PTT with simultaneously available echocardiographic assessment. Relevant DD and MVR were defined as exceeding Grade I (impaired relaxation and mild regurgitation). PTT was determined from CMR rest perfusion scans. Normalized PTT (nPTT), adjusted for heart rate, was calculated using Bazett's formula. Results: Higher PTT and nPTT values were associated with higher grade DD and MVR. The diagnostic accuracy for the prediction of DD as quantified by the area under the ROC curve (AUC) was 0.73 (CI 0.61-0.85; p = 0.001) for PTT and 0.81 (CI 0.71-0.89; p < 0.001) for nPTT. For MVR, the diagnostic performance amounted to an AUC of 0.80 (CI 0.68-0.92; p < 0.001) for PTT and 0.78 (CI 0.65-0.90; p < 0.001) for nPTT. PTT values < 8 s rule out the presence of DD and MVR with a probability of 70% (negative predictive value 78%). Conclusion: CMR-derived PTT is a readily obtainable hemodynamic parameter. It is elevated in patients with DD and moderate to severe MVR. Low PTT values make the presence of DD and MVR-as assessed by echocardiography-unlikely., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Martin Segeroth et al.)

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.

Background: Infranodal conduction disorders are common after transcatheter aortic valve replacement (TAVR). Risk factors are incompletely understood., Objective: The purpose of this study was to assess the impact of valve implantation depth and calcium burden of the device landing zone on infranodal conduction intraprocedure pre- and post-TAVR., Methods: In all patients undergoing TAVR between June 2020 and June 2021, the His-ventricle (HV) interval was measured pre- and post-valve deployment. The difference between the 2 measurements defined delta HV, whereas infranodal conduction delay was defined as HV interval >55 ms. Valve implantation depth was measured as the distance between the aortic annular plane and the ventricular prosthesis end. Calcium burden was quantified as the volume of calcium in 6 regions of interest: the non-, right, and left coronary cusps (NCC, RCC, and LCC, respectively) and the corresponding regions of the left ventricular outflow tract (LVOT) underlying each cusp (LVOT NCC , LVOT RCC , LVOT LCC , respectively)., Results: Of 101 patients (mean age 81 ± 5.7 years; 47% women), 37 demonstrated infranodal conduction delay intraprocedure post-TAVR. Overall, mean implantation depth was 5 ± 3.1 mm, median calcium volume was 2080 mm 3 [interquartile range 632-2400]. Delta HV showed no correlation with implantation depth or calcium burden (r = -0.08 and r = 0.12, respectively). However, LVOT NCC calcification was a significant predictor for infranodal conduction delay post-valve deployment in a multivariable logistic regression model (odds ratio 1.62 per 100-mm 3 increase (95% confidence interval 1.06-2.69; P = .04)., Conclusion: Assessment of LVOT NCC calcification may identify patients at risk for infranodal conduction delay after TAVR, whereas implantation depth did not predict infranodal conduction delay., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

Study Objective: The diagnostic performance of T-wave amplitudes for the detection of myocardial infarction is largely unknown. We aimed to address this knowledge gap., Methods: T-wave amplitudes were automatically measured in 12-lead ECGs of patients presenting with acute chest discomfort to the emergency department within a prospective diagnostic multicenter study. The final diagnosis was centrally adjudicated by 2 independent cardiologists. Patients with left ventricular hypertrophy, complete left bundle branch block, or paced ventricular depolarization were excluded. The performance for lead-specific 95th-percentile thresholds were reported as likelihood ratios (lr), specificity, and sensitivity., Results: Myocardial infarction was the final diagnosis in 445 (18%) of 2457 patients. In most leads, T-wave amplitudes tended to be greater in patients without myocardial infarction than those with myocardial infarction, and T-wave amplitude exceeding the 95th percentile had positive and negative lr close to 1 or with confidence intervals (CIs) crossing 1. The exceptions were leads III, aVR, and V1, which had positive lrs of 3.8 (95% CI, 2.7 to 5.3), 4.3 (95% CI, 3.1 to 6.0) and 2.0 (95% CI, 1.4 to 2.9), respectively. These leads normally have inverted T waves, so T-wave amplitude exceeding the 95th percentile reflects upright rather than increased-amplitude hyperacute T waves., Conclusion: Hyperacute T waves, when defined as increased T-wave amplitude exceeding the 95th percentile, did not provide useful information in diagnosing myocardial infarction in this sample., (Copyright © 2022 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Aims: It has been demonstrated that several cardiac pathologies, including myocardial ischaemia, can be detected using smartwatch electrocardiograms (ECGs). Correct placement of bipolar chest leads remains a major challenge in the outpatient population., Methods and Results: In this feasibility trial, we propose an augmented reality-based smartphone app that guides the user to place the smartwatch in predefined positions on the chest using the front camera of a smartphone. A machine-learning model using MobileNet&#95;v2 as the backbone was trained to detect the bipolar lead positions V1-V6 and visually project them onto the user's chest. Following the smartwatch recordings, a conventional 10 s, 12-lead ECG was recorded for comparison purposes. All 50 patients participating in the study were able to conduct a 9-lead smartwatch ECG using the app and assistance from the study team. Twelve patients were able to record all the limb and chest leads using the app without additional support. Bipolar chest leads recorded with smartwatch ECGs were assigned to standard unipolar Wilson leads by blinded cardiologists based on visual characteristics. In every lead, at least 86% of the ECGs were assigned correctly, indicating the remarkable similarity of the smartwatch to standard ECG recordings., Conclusion: We have introduced an augmented reality-based method to independently record multichannel smartwatch ECGs in an outpatient setting., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Pulmonary transit time (PTT) is the time blood takes to pass from the right ventricle to the left ventricle via pulmonary circulation. We aimed to quantify PTT in routine cardiovascular magnetic resonance imaging perfusion sequences. PTT may help in the diagnostic assessment and characterization of patients with unclear dyspnoea or heart failure (HF)., Methods and Results: We evaluated routine stress perfusion cardiovascular magnetic resonance scans in 352 patients, including an assessment of PTT. Eighty-six of these patients also had simultaneous quantification of N-terminal pro-brain natriuretic peptide (NTproBNP). NT-proBNP is an established blood biomarker for quantifying ventricular filling pressure in patients with presumed HF. Manually assessed PTT demonstrated low inter-rater variability with a correlation between raters >0.98. PTT was obtained automatically and correctly in 266 patients using artificial intelligence. The median PTT of 182 patients with both left and right ventricular ejection fraction >50% amounted to 6.8 s (Pulmonary transit time: 5.9-7.9 s). PTT was significantly higher in patients with reduced left ventricular ejection fraction (<40%; P < 0.001) and right ventricular ejection fraction (<40%; P < 0.0001). The area under the receiver operating characteristics curve (AUC) of PTT for exclusion of HF (NT-proBNP <125 ng/L) was 0.73 (P < 0.001) with a specificity of 77% and sensitivity of 70%. The AUC of PTT for the inclusion of HF (NT-proBNP >600 ng/L) was 0.70 (P < 0.001) with a specificity of 78% and sensitivity of 61%., Conclusion: PTT as an easily, even automatically obtainable and robust non-invasive biomarker of haemodynamics might help in the evaluation of patients with dyspnoea and HF., Competing Interests: Conflict of interest None declared, (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: The objective of this study was to quantify secondary prevention care by creating a secondary prevention benchmark (2PBM) score for patients undergoing ambulatory cardiac rehabilitation (CR) after acute coronary syndrome (ACS)., Methods: In this observational cohort study, 472 consecutive ACS patients who completed the ambulatory CR program between 2017 and 2019 were included. Benchmarks for secondary prevention medication and clinical and lifestyle targets were predefined and combined in the comprehensive 2PBM score with maximum 10 points. The association of patient characteristics and achievement rates of components and the 2PBM were assessed using multivariable logistic regression analysis., Results: Patients were on average 62 ± 11 yr of age and predominantly male (n = 406; 86%). The types of ACS were ST-elevation myocardial infarction (STEMI) in 241 patients (51%) and non-ST-elevation myocardial infarction in 216 patients (46%). Achievement rates for components of the 2PBM were 71% for medication, 35% for clinical benchmark, and 61% for lifestyle benchmark. Achievement of medication benchmark was associated with younger age (OR = 0.979: 95% CI, 0.959-0.996, P = .021), STEMI (OR = 2.05: 95% CI, 1.35-3.12, P = .001), and clinical benchmark (OR = 1.80: 95% CI, 1.15-2.88, P = .011). Overall ≥8 of 10 points were reached by 77% and complete 2PBM by 16%, which was independently associated with STEMI (OR = 1.79: 95% CI, 1.06-3.08, P = .032)., Conclusions: Benchmarking with 2PBM identifies gaps and achievements in secondary prevention care. ST-elevation myocardial infarction was associated with the highest 2PBM scores, suggesting best secondary prevention care in patients after ST-elevation myocardial infarction., Competing Interests: O.P. received unrestricted grands from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Sanofi. The other authors reported no direct or indirect conflicts of interests for this research., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Self-reported exercise capacity is a well-established prognostic measure in stable ambulatory patients with cardiac and pulmonary disease., Objectives: The authors aimed to directly compare the prognostic accuracy of quantified self-reported exercise capacity using the Duke Activity Status Index (DASI) with the established objective disease-severity marker B-type natriuretic peptide (BNP) in patients presenting with acute dyspnea to the emergency department., Methods: The DASI was obtained in a prospective multicenter diagnostic study recruiting unselected patients presenting with acute dyspnea to the emergency department. The prognostic accuracy of DASI and BNP for 90-day and 720-day all-cause mortality was evaluated using C-index., Results: Among 1,019 patients eligible for this analysis, 75 (7%) and 297 (29%) patients died within 90 and 720 days after presentation, respectively. Unadjusted hazard ratios (HRs) and multivariable adjusted hazard ratios (aHRs) for 90- and 720-day mortality increased continuously from the fourth (best self-reported exercise capacity) to the first DASI quartile (worst self-reported exercise capacity). For 720-day mortality the HR of the first quartile vs the fourth was 9.1 (95% CI, 5.5-14.9) vs (aHR: 6.1, 95% CI: 3.7-10.1), of the second quartile 6.4 (95% CI: 3.9-10.6) vs (aHR: 4.4, 95% CI: 2.6-7.3), while of the third quartile the HR was 3.2 (95% CI: 1.9-5.5) vs (aHR: 2.4, 95% CI: 1.4-4.0). The prognostic accuracy of the DASI score was high, and higher than that of BNP concentrations (720-day mortality C-index: 0.67 vs 0.62; P  = 0.024)., Conclusions: Quantification of self-reported subjective exercise capacity using the DASI provides high prognostic accuracy and may aid physicians in risk stratification. (Basics in Acute Shortness of Breath EvaLuation [BASEL V] Study [BASEL V]; NCT01831115)., Competing Interests: This study was supported by research grants from the 10.13039/501100001711Swiss National Science Foundation, the 10.13039/501100004362Swiss Heart Foundation, the 10.13039/100008375University of Basel, the 10.13039/100016015University Hospital Basel, Critical Diagnostics, 10.13039/100000046Abbott, BRAHMS, 10.13039/100004337Roche and 10.13039/100016946Singulex. None of those supporters had any role in study design, the conduct of the study, the analysis of the data, or the decision to submit this manuscript for publication. Dr Breidthardt has received research grants from the Swiss National Science Foundation, the University Hospital Basel, the Department of Internal Medicine, University Hospital Basel, Abbott, and Roche. Dr Mueller has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the University Hospital Basel, the University of Basel, Abbott, Beckman Coulter, Biomerieux, BRAHMS, Ortho Clinical, Quidel, Novartis, Roche, Siemens, Singulex, and Sphingotec. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Aim: The presence of accompanying dyspnea is routinely assessed and common in patients presenting with acute chest pain/discomfort to the emergency department (ED). We aimed to assess the association of accompanying dyspnea with differential diagnoses, diagnostic work-up and outcome., Methods: We enrolled patients presenting to the ED with chest pain/discomfort. Final diagnoses were adjudicated by independent cardiologists using all information including cardiac imaging. The primary diagnostic endpoint was the final diagnosis. The secondary diagnostic endpoint was the performance of high-sensitivity cardiac troponin (hs-cTn) and the European Society of Cardiology (ESC) 0/1h-algorithms for the diagnosis of myocardial infarction (MI). The prognostic endpoints were cardiovascular and all-cause mortality at two years., Results: Among 6045 patients, 2892/6045 (48%) had accompanying dyspnea. The prevalence of ACS in patients with versus without dyspnea was comparable (MI 22.4% vs. 21.9%, p = 0.60, unstable angina 8.7% vs. 7.9%, p = 0.29). In contrast, patients with dyspnea more often had cardiac, non-coronary disease (15.3% vs. 10.2%, p < 0.001). Diagnostic accuracy of hs-cTnT/I concentrations was not affected by the presence of dyspnea (area under the curve 0.89-0.91 in both groups) and the safety of the ESC 0/1h-algorithms was maintained with negative predictive values >99.4%. Accompanying dyspnea was an independent predictor for cardiovascular and all-cause death at two years (Hazard Ratio [HR] 1.813 [95%CI, 1.453-2.261, p < 0.01])., Conclusion: Accompanying dyspnea was not associated with a higher prevalence of ACS but with cardiac, non-coronary disease. While the safety of the diagnostic work-up was not affected, accompanying dyspnea was an independent predictor for cardiovascular and all-cause death., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate the relationship between ambient temperature and atmospheric pressure (AP) and the severity of heart failure (HF) decompensations., Methods: We analysed patients coming from the Epidemioloy Acute Heart Failure Emergency (EAHFE) Registry, a multicentre prospective cohort study enrolling patients diagnosed with decompensated HF in 26 emergency departments (EDs) of 16 Spanish cities. We recorded patient and demographic data and maximum temperature (T max ) and AP (AP max ) the day before ED consultation. Associations between temperature and AP and severity endpoints were explored by logistic regression. We used restricted cubic splines to model continuous non-linear associations of temperature and AP with each endpoint., Results: We analysed 16,545 patients. Daily T max and AP max (anomaly) of the day before patient ED arrival ranged from 0.8 to 41.6° and from - 61.7 to 69.9 hPa, respectively. A total of 12,352 patients (75.2%) were hospitalised, with in-hospital mortality in 1171 (7.1%). The probability of hospitalisation by HF decompensation showed a U-shaped curve versus T max and an increasing trend versus AP max . Regarding temperature, hospitalisation significantly increased from 20 °C (reference) upwards (25 °C: OR = 1.12, 95% CI = 1.04-1.21; 40 °C: 1.65, 1.13-2.40) and below 5.4 °C (5 °C: 1.21, 1.01-1.46). Concerning the mean AP of the city (anomaly = 0 hPa), hospitalisation increased when AP max (anomaly) was above + 7.0 hPa (atmospheric anticyclone; + 10 hPa: 1.14, 1.05-1.24; + 30 hPa: 2.02. 1.35-3.03). The lowest probability of mortality also corresponded to cold-mild temperatures and low AP, with a significant increased risk only found for T max above 24.3 °C (25 °C: 1.13, 1.01-1.27; 40 °C: 2.05, 1.15-3.64) and AP max (anomaly) above + 3.4 hPa (+ 10 hPa: 1.21, 1.07-1.36; + 30 hPa: 1.73, 1.06-2.81). Sensitivity analysis confirmed the main analysis results., Conclusion: Temperature and AP are independently associated with the severity of HF decompensations, with possible different effects on the need for hospitalisation and in-hospital mortality., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Multiple smart devices capable to detect atrial fibrillation (AF) are presently available. Sensitivity and specificity for the detection of AF may differ between available smart devices, and this has not yet been adequately investigated., Objectives: The aim was to assess the accuracy of 5 smart devices in identifying AF compared with a physician-interpreted 12-lead electrocardiogram as the reference standard in a real-world cohort of patients., Methods: We consecutively enrolled patients presenting to a cardiology service at a tertiary referral center in a prospective, diagnostic study., Results: We prospectively analyzed 201 patients (31% women, median age 66.7 years). AF was present in 62 (31%) patients. Sensitivity and specificity for the detection of AF were comparable between devices: 85% and 75% for the Apple Watch 6, 85% and 75% for the Samsung Galaxy Watch 3, 58% and 75% for the Withings Scanwatch, 66% and 79% for the Fitbit Sense, and 79% and 69% for the AliveCor KardiaMobile, respectively. The rate of inconclusive tracings (the algorithm was unable to determine the heart rhythm) was 18%, 17%, 24%, 21%, and 26% for the Apple Watch 6, Samsung Galaxy Watch 3, Withings Scan Watch, Fitbit Sense, and AliveCor KardiaMobile (P < 0.01 for pairwise comparison), respectively. By manual review of inconclusive tracings, the rhythm could be determined in 955 (99%) of 969 single-lead electrocardiograms. Regarding patient acceptance, the Apple Watch was ranked first (39% of participants)., Conclusions: In this clinical validation of 5 direct-to-consumer smart devices, we found differences in the amount of inconclusive tracings diminishing sensitivity and specificity of the smart devices. In a clinical setting, manual review of tracings is required in about one-fourth of cases., Competing Interests: Funding Support and Author Disclosures Dr Knecht has received funding from the Stiftung für kardiovaskuläre Forschung. Dr Schaer has served on the Speakers Bureau for Medtronic. Dr Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the University Hospital Basel, the University of Basel, Abbott, Beckman Coulter, Brahms, Idorsia, Novartis, Ortho Diagnostics, Quidel, Roche, Siemens, Singulex, and Sphingotec, outside the submitted work; and speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Novartis, Osler, Roche, and Sanofi, all paid to the institution. Dr Kühne has received personal fees from Bayer, Boehringer Ingelheim, Pfizer BMS, Daiichi Sankyo, Medtronic, Biotronik, Boston Scientific, Johnson & Johnson, Roche; and grants from Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo, all outside the submitted work. Dr Sticherling has served on the advisory board for Medtronic Europe and Boston Scientitic Europe; received educational grants from Biosense Webster and Biotronik; received a research grant from the European Union’s FP7 program and Biosense Webster; and received lecture and consulting fees from Abbott, Medtronic, Biosense Webster, Boston Scientific, MicroPort, and Biotronik, all outside the submitted work. Dr Badertscher has received research funding from the University of Basel, the Stiftung für Herzschrittmacher und Elektrophysiologie, the Freiwillige Akademische Gesellschaft Basel, and Johnson & Johnson, all outside the submitted work; and received personal fees from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Aims: Systemic inflammation may be central in the pathophysiology of acute heart failure (AHF). We aimed to assess the possible role of systemic inflammation in the pathophysiology, phenotyping, and risk stratification of patients with AHF., Methods and Results: Using a novel Interleukin-6 immunoassay with unprecedented sensitivity (limit of detection 0.01 ng/L), we quantified systemic inflammation in unselected patients presenting with acute dyspnoea to the emergency department in a multicentre study. One-year mortality was the primary prognostic endpoint. Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF, 83.7% of whom had elevated interleukin-6 concentrations (>4.45 ng/L). Interleukin-6 was significantly higher in AHF patients compared to patients with other causes of dyspnoea (11.2 [6.1-26.5] ng/L vs. 9.0 [3.2-32.3] ng/L, p < 0.0005). Elevated interleukin-6 concentrations were independently predicted by increasing N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T, as well as the clinical diagnosis of infection. Among the different AHF phenotypes, interleukin-6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0-164.2] ng/L) and lowest in patients with hypertensive AHF (9.3 [4.8-21.6] ng/L, p = 0.001). Inflammation as quantified by interleukin-6 was a strong and independent predictor of 1-year mortality both in all AHF patients, as well as those without clinically overt infection at presentation (adjusted hazard ratio [95% confidence interval] 1.45 [1.15-1.83] vs. 1.48 [1.09-2.00]). The addition of interleukin-6 significantly improved the discrimination of the BIOSTAT-CHF risk score., Conclusion: An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation as quantified by interleukin-6, which seems to contribute to AHF phenotype and to the risk of death., (© 2023 European Society of Cardiology.)

Background and Objective: The prognosis of myocardial infarction in patients with rapid atrial fibrillation (RAF) is poorly known. We sought to ascertain if troponin concentrations are associated with a higher risk of major adverse cardiovascular events (MACE) in patients with RAF and chest discomfort suggestive of coronary origin., Methods: We retrospectively reviewed all consecutive patients attending an emergency department of a single-center (2008-2017) with chest pain suggestive of coronary origin who had RAF and at least one troponin determination. Patients were classified as having normal/increased troponin. They were followed until December 2019 to detect MACE (primary outcome), which included acute coronary syndrome (ACS), revascularization, stroke, or all-cause death. In addition to cardiovascular death and type I myocardial infarction, these were considered secondary outcomes. The adjusted risk was determined by Cox regression, and sensitivity analysis were run. Relationship between troponin as a continuous variable and outcomes was also evaluated, as well as interaction by sex., Results: We included 574 patients (median = 76.5 years, IQR = 14, women 56.8%, increased troponin 34.1%) followed by a median of 3.8 years (IQR = 4.8). MACE occurred in 200 patients (34.8%). Increased troponin was independently associated with MACE (adjusted hazard ratio, 1.502, 95% CI, 1.130-1.998), ACS (adjusted hazard ratio, 2.488, 95% CI, 1.256-4.928), type I myocardial infarction (adjusted hazard ratio, 2.771, 95% CI, 1.212-6.333) and stroke (adjusted hazard ratio, 3.580, 95% CI, 1.888-6.787) but not with death, cardiovascular death or revascularization. Sensitivity analyses were consistent with these results. There was no interaction by sex. When assessed continuously, an increase in troponin concentrations was lineally associated with a steady increase in the risk of MACE., Conclusions: In patients with RAF who complain of chest pain, increased troponin levels are related to adverse cardiovascular outcomes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In 2019 the European Society of Cardiology (ESC) lowered the target values for low-density lipoprotein cholesterol (LDL-C) from <1.8 mmol/L to <1.4 mmol/L for secondary prevention of cardiovascular disease (CVD). The aim of this study was to determine the clinical impact of the 2019 ESC/EAS dyslipidaemia guidelines on lipid-lowering therapies and achievement rates of LDL-C targets in a contemporary cohort of CAD patients participating in an ambulatory cardiac rehabilitation (CR) program.We conducted a retrospective analysis of prospectively collected data from the Swiss Secondary Prevention Registry (SwissPR) in patients with Coronary Artery Disease (CAD), who completed the ambulatory cardiovascular rehabilitation program (CR) of the University Hospital Basel, Switzerland from January 2017 to April 2021. To evaluate the impact of the guideline publication, the cohort was split into a pre-Guideline 2019 group (A) and a post-Guideline 2019 group (B). In total 1320 patients were screened leaving 875 patients for analysis. At discharge, more patients in group B were on maximal statin doses (20% vs. 9%, p < 0.0001) and on combination therapy with ezetimibe (51% vs. 17%, p < 0.0001) than in group A, which resulted in 53% of patients reaching the LDL-C target of <1.4 mmol/L in group B. Regression analysis revealed that dyslipidaemia and positive smoking history represent independent predictors for intensified lipid-lowering medication, whereas absolving CR after publication of the 2019 guidelines was the only significant predictor for reduced LDL-C at CR discharge. We found a significant difference in prescription rates of lipid-lowering medication, especially combination therapies and statin doses, after publication of the 2019 ESC/EAS dyslipidaemia guidelines resulting in an achievement rate of >50% of the LDL-C target <1.4 mmol/L in CAD patients participating in ambulatory CR.

Background: Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope., Objective: The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies., Methods: The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE)., Results: Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P <.01). Recommendations were discordant in ∼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P <.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines., Conclusion: ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

To investigate the relationship of ambient temperature and atmospheric pressure (AP) at patient discharge after an episode of acute heart failure (AHF) with very early post-discharge adverse outcomes. We analyzed 14,656 patients discharged after an AHF episode from 26 hospitals in 16 Spanish cities. The primary outcome was the 7-day post-discharge combined adverse event (emergency department -ED- revisit or hospitalization due to AHF, or all-cause death), and secondary outcomes were these three adverse events considered individually. Associations (adjusted for patient and demographic conditions, and length of stay -LOS- during the AHF index episode) of temperature and AP with the primary and secondary outcomes were investigated. We used restricted cubic splines to model the continuous non-linear association of temperature and AP with each endpoint. Some sensitivity analyses were performed. Patients were discharged after a median LOS of 5 days (IQR = 1-10). The highest temperature at discharge ranged from - 2 to 41.6 °C, and AP was from 892 to 1037 hPa. The 7-day post-discharge combined event occurred in 1242 patients (8.4%), with percentages of 7-day ED-revisit, hospitalization and death of 7.8%, 5.1% and 0.9%, respectively. We found no association between the maximal temperature and AP on the day of discharge and the primary or secondary outcomes. Similarly, there were no significant associations when the analyses were restricted to hospitalized patients (median LOS = 7 days, IQR = 4-11) during the index event, or when lag-1, lag-2 or the mean of the 3 post-discharge days (instead of point estimation) of ambient temperature and AP were considered. Temperature and AP on the day of patient discharge are not independently associated with the risk of very early adverse events during the vulnerable post-discharge period in patients discharged after an AHF episode., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Aims: Obese patients have lower natriuretic peptide concentrations. We hypothesized that adjusting the concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for obesity could further increase its clinical utility in the early diagnosis of acute heart failure (AHF)., Methods and Results: This hypothesis was tested in a prospective diagnostic study enrolling unselected patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists/internists centrally adjudicated the final diagnosis using all individual patient information including cardiac imaging. NT-proBNP plasma concentrations were applied: first, using currently recommended cut-offs; second, using cut-offs lowered by 33% with body mass index (BMI) of 30-34.9 kg/m 2 and by 50% with BMI ≥ 35 kg/m 2 . Among 2038 patients, 509 (25%) were obese, of which 271 (53%) had AHF. The diagnostic accuracy of NT-proBNP as quantified by the area under the receiver-operating characteristic curve was lower in obese versus non-obese patients (0.890 vs. 0.938). For rapid AHF rule-out in obese patients, the currently recommended cut-off of 300 pg/ml achieved a sensitivity of 96.7% (95% confidence interval [CI] 93.8-98.2%), ruling out 29% of patients and missing 9 AHF patients. For rapid AHF rule-in, the age-dependent cut-off concentrations (age <50 years: 450 pg/ml; age 50-75 years: 900 pg/ml; age >75 years: 1800 pg/ml) achieved a specificity of 84.9% (95% CI 79.8-88.9%). Proportionally lowering the currently recommended cut-offs by BMI increased sensitivity to 98.2% (95% CI 95.8-99.2%), missing 5 AHF patients; reduced the proportion of AHF patients remaining in the 'gray zone' (48% vs. 26%; p = 0.002), achieving a specificity of 76.5% (95% CI 70.7-81.4%)., Conclusions: Adjusting NT-proBNP concentrations for obesity seems to further increase its clinical utility in the early diagnosis of AHF., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Prompt differential diagnosis of wide QRS complex tachycardia (WCT) is crucial to patient management. However, distinguishing ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with wide QRS complexes remains problematic, especially for nonelectrophysiologists., Objectives: This study aimed to develop a simple-to-use algorithm with integration of clinical and electrocardiographic (ECG) parameters for the differential diagnosis of WCT., Methods: The 12-lead ECGs of 206 monomorphic WCTs (153 VT, 53 SVT) with electrophysiology-confirmed diagnoses were analyzed. In the novel Basel algorithm, VT was diagnosed in the presence of at least 2 of the following criteria: 1) clinical high risk features; 2) lead II time to first peak >40 ms; and 3) lead aVR time to first peak >40 ms. The algorithm was externally validated in 203 consecutive WCT cases (151 VT, 52 SVT). Its' diagnostic performance and clinical applicability were compared with those of the Brugada and Vereckei algorithms., Results: The Basel algorithm showed a sensitivity, specificity, and accuracy of 92%, 89%, and 91%, respectively, in the derivation cohort and 93%, 90%, and 93%, respectively, in the validation cohort. There were no significant differences in the performance characteristics between the 3 algorithms. The evaluation of the clinical applicability of the Basel algorithm showed similar diagnostic accuracy compared with the Brugada algorithm (80% vs 81%; P = 1.00), but superiority compared with the Vereckei algorithm (72%; P = 0.03). The Basel algorithm, however, enabled a faster diagnosis (median 36 seconds vs 105 seconds for the Brugada algorithm [P = 0.002] and 50 seconds for the Vereckei algorithm [P = 0.02])., Conclusions: The novel Basel algorithm based on simple clinical and ECG criteria allows for a rapid and accurate differential diagnosis of WCT., Competing Interests: Funding Support and Author Disclosures Dr Schaer has received personal fees from Medtronic. Dr Kühne has received grants from the Swiss National Science Foundation, the Swiss Heart Foundation, Daiichi-Sankyo, Bayer, Pfizer BMS, and Boston Scientific; and has received personal fees from Bayer, Boehringer Ingelheim, Pfizer BMS, Daiichi-Sankyo, Medtronic, Biotronik, Boston Scientific, and Johnson & Johnson, all outside the submitted work. Dr Henrikson has received fellowship support from Abbott, Boston Scientific, and Medtronic; and has served as chair of the clinical endpoints committee for Biotronik. Dr Sticherling has received grants from Biosense-Webster; and has received lecture fees from Abbott, Medtronic, Biosense-Webster, Boston Scientific, Microport, and Biotronik. Dr Reichlin has received speaker/consulting honoraria or travel support from Abbott/SJM, AstraZeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi-Sankyo, Medtronic, Pfizer BMS, and Roche, all for work outside the submitted study; and has received support for his institution’s fellowship program from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic for work outside the submitted study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics., Design: Individual patient level data meta-analysis and modelling study., Setting: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies., Participants: Individual patient level data for 10 369 patients with suspected acute heart failure were pooled for the meta-analysis to evaluate NT-proBNP thresholds. A decision support tool (Collaboration for the Diagnosis and Evaluation of Heart Failure (CoDE-HF)) that combines NT-proBNP with clinical variables to report the probability of acute heart failure for an individual patient was developed and validated., Main Outcome Measure: Adjudicated diagnosis of acute heart failure., Results: Overall, 43.9% (4549/10 369) of patients had an adjudicated diagnosis of acute heart failure (73.3% (2286/3119) and 29.0% (1802/6208) in those with and without previous heart failure, respectively). The negative predictive value of the guideline recommended rule-out threshold of 300 pg/mL was 94.6% (95% confidence interval 91.9% to 96.4%); despite use of age specific rule-in thresholds, the positive predictive value varied at 61.0% (55.3% to 66.4%), 73.5% (62.3% to 82.3%), and 80.2% (70.9% to 87.1%), in patients aged <50 years, 50-75 years, and >75 years, respectively. Performance varied in most subgroups, particularly patients with obesity, renal impairment, or previous heart failure. CoDE-HF was well calibrated, with excellent discrimination in patients with and without previous heart failure (area under the receiver operator curve 0.846 (0.830 to 0.862) and 0.925 (0.919 to 0.932) and Brier scores of 0.130 and 0.099, respectively). In patients without previous heart failure, the diagnostic performance was consistent across all subgroups, with 40.3% (2502/6208) identified at low probability (negative predictive value of 98.6%, 97.8% to 99.1%) and 28.0% (1737/6208) at high probability (positive predictive value of 75.0%, 65.7% to 82.5%) of having acute heart failure., Conclusions: In an international, collaborative evaluation of the diagnostic performance of NT-proBNP, guideline recommended thresholds to diagnose acute heart failure varied substantially in important patient subgroups. The CoDE-HF decision support tool incorporating NT-proBNP as a continuous measure and other clinical variables provides a more consistent, accurate, and individualised approach., Study Registration: PROSPERO CRD42019159407., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the British Heart Foundation, Medical Research Council, and Chief Scientist Office; Y-EC has received honorariums for lectures and presentations from Biomérieux, Roche Diagnostics, and Thermo Fisher; CdF has received consulting fees from Fuji Rebio, Ortho Diagnostics, Quidel, and Roche Diagnostics and a patent entitled “Methods for assessing differential risk for developing heart failure” (patent number: PCT/US2015/029838); SS has received a grant from Roche Diagnostics and a patent entitled “Methods for assessing differential risk for developing heart failure” (patent number: PCT/US2015/029838); ABG has received personal fees and non-financial support from Roche Diagnostics during the conduct of the study and personal fees from Abbott and AstraZeneca, grants, personal fees, and non-financial support from Boehringer-Ingelheim, and personal fees and non-financial support from Novartis and Vifor outside the submitted work. YP has received consulting fees from Roche Diagnostics, Pfizer, and Forbion and honorariums from CVOI and Daiichi Sankyo; HKG has received grants from Roche Diagnostics, Jana Care, Ortho Clinical, Novartis, Pfizer, Alnylam, and Akcea (IONIS), consulting fees from Amgen, Eko, Merck, and Pfizer, and stock in Eko; JCW works as a biostatistician at the biotech company BRAHMS GmbH, part of Thermo Fisher Scientific; MM has received grants from Health Care Research Projects and Biomarker Research and personal fees from Consulting outside the submitted work; ASVS has received speaker fees from Abbott Diagnostics outside the submitted work; AMR has received grants, personal fees, and non-financial support from Roche Diagnostics outside the submitted work; JJVM has received consulting fees from Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Dal-Cor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos, payments for advisory boards, symposiums, or lectures from Abbott, Alkem Metabolics, Canadian Medical and Surgical Knowledge Translation Research Group, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Servier, and the Corpus, has participated on a data safety monitoring board or advisory board for Cardialysis (MONITOR study) and Merck (VICTORIA trial), and works as company director for Global Clinical Trial Partners Ltd (GCTP) outside the submitted work; CM has received grants and non-financial support from several diagnostic companies during the conduct of the study and grants, personal fees, and non-financial support from several diagnostic companies outside the submitted work; JJ has received grants from Abbott Diagnostics, Innolife, and Novartis and consulting fees from Abbott, Jana Care, Novartis, Roche Diagnostics, Bristol-Myers Squibb, Janssen, and Prevencio; NLM has received grants from Siemens Healthineers, consulting fees from Roche Diagnostics and LumiraDx, and speaker fees from Abbott Diagnostics and Siemens Healthineers outside the submitted work; KKL, DD, and NLM are employed by the University of Edinburgh, which has filed a patent on the CoDE-HF score (patent reference: PCT/GB2021/051470); no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Cardiac myosin-binding protein C (cMyC) demonstrated high diagnostic accuracy for the early detection of non-ST-elevation myocardial infarction (NSTEMI). Its dynamic release kinetics may enable a 0/1h-decision algorithm that is even more effective than the ESC hs-cTnT/I 0/1 h rule-in/rule-out algorithm., Methods and Results: In a prospective international diagnostic study enrolling patients presenting with suspected NSTEMI to the emergency department, cMyC was measured at presentation and after 1 h in a blinded fashion. Modelled on the ESC hs-cTnT/I 0/1h-algorithms, we derived a 0/1h-cMyC-algorithm. Final diagnosis of NSTEMI was centrally adjudicated according to the 4th Universal Definition of Myocardial Infarction. Among 1495 patients, the prevalence of NSTEMI was 17%. The optimal derived 0/1h-algorithm ruled-out NSTEMI with cMyC 0 h concentration below 10 ng/L (irrespective of chest pain onset) or 0 h cMyC concentrations below 18 ng/L and 0/1 h increase <4 ng/L. Rule-in occurred with 0 h cMyC concentrations of at least 140 ng/L or 0/1 h increase ≥15 ng/L. In the validation cohort (n = 663), the 0/1h-cMyC-algorithm classified 347 patients (52.3%) as 'rule-out', 122 (18.4%) as 'rule-in', and 194 (29.3%) as 'observe'. Negative predictive value for NSTEMI was 99.6% [95% confidence interval (CI) 98.9-100%]; positive predictive value 71.1% (95% CI 63.1-79%). Direct comparison with the ESC hs-cTnT/I 0/1h-algorithms demonstrated comparable safety and even higher triage efficacy using the 0h-sample alone (48.1% vs. 21.2% for ESC hs-cTnT-0/1 h and 29.9% for ESC hs-cTnI-0/1 h; P < 0.001)., Conclusion: The cMyC 0/1h-algorithm provided excellent safety and identified a greater proportion of patients suitable for direct rule-out or rule-in based on a single measurement than the ESC 0/1h-algorithm using hs-cTnT/I., Trial Registration: ClinicalTrials.gov number, NCT00470587., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Trimethylamine N-oxide (TMAO) has been associated with cardiovascular outcomes. However, the diagnostic value of TMAO and its precursors have not been assessed for functionally relevant coronary artery disease (fCAD) and its prognostic potential in this setting needs to be evaluated., Methods: Among 1726 patients with suspected fCAD serum TMAO, and its precursors betaine, choline and carnitine, were quantified using liquid chromatography tandem mass spectrometry. Diagnosis of fCAD was performed by myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography blinded to marker concentrations. Incident all-cause death, cardiovascular death (CVD) and myocardial infarction (MI) were assessed during 5-years follow-up., Results: Concentrations of TMAO, betaine, choline and carnitine were significantly higher in patients with fCAD versus those without (TMAO 5.33 μM vs 4.66 μM, p < 0.001); however, diagnostic accuracy was low (TMAO area under the receiver operating curve [AUC]: 0.56, 95% CI [0.53-0.59], p < 0.001). In prognostic analyses, TMAO, choline and carnitine above the median were associated with significantly (p < 0.001 for all) higher cumulative events for death and CVD during 5-years follow-up. TMAO remained a significant predictor for death and CVD even in full models adjusted for renal function (HR = 1.58 (1.16, 2.14), p = 0.003; HR = 1.66 [1.07, 2.59], p = 0.025). Prognostic discriminative accuracy for TMAO was good and robust for death and CVD (2-years AUC for CVD 0.73, 95% CI [0.65-0.80])., Conclusion: TMAO and its precursors, betaine, choline and carnitine were significantly associated with fCAD, but with limited diagnostic value. TMAO was a strong predictor for incident death and CVD in patients with suspected fCAD., Clinical Trial Registration: NCT01838148., (© 2022. The Author(s).)

Background: Current guidelines recommend interpreting concentrations of NPs (natriuretic peptides) irrespective of the time of presentation to the emergency department. We hypothesized that diurnal variations in NP concentration may affect their diagnostic accuracy for acute heart failure., Methods: In a secondary analysis of a multicenter diagnostic study enrolling patients presenting with acute dyspnea to the emergency department and using central adjudication of the final diagnosis by 2 independent cardiologists, the diagnostic accuracy for acute heart failure of BNP (B-type NP), NT-proBNP (N-terminal pro-B-type NP), and MR-proANP (midregional pro-atrial NP) was compared among 1577 daytime presenters versus 908 evening/nighttime presenters. In a validation study, the presence of a diurnal rhythm in BNP and NT-proBNP concentrations was examined by hourly measurements in 44 stable individuals., Results: Among patients adjudicated to have acute heart failure, BNP, NT-proBNP, and MR-proANP concentrations were comparable among daytime versus evening/nighttime presenters (all P =nonsignificant). Contrastingly, among patients adjudicated to have other causes of dyspnea, evening/nighttime presenters had lower BNP (median, 44 [18-110] versus 74 [27-168] ng/L; P <0.01) and NT-proBNP (median, 212 [72-581] versus 297 [102-902] ng/L; P <0.01) concentrations versus daytime presenters. This resulted in higher diagnostic accuracy as quantified by the area under the curve of BNP and NT-proBNP among evening/nighttime presenters (0.97 [95% CI, 0.95-0.98] and 0.95 [95% CI, 0.93-0.96] versus 0.94 [95% CI, 0.92-0.95] and 0.91 [95% CI, 0.90-0.93]) among daytime presenters (both P <0.01). These differences were not observed for MR-proANP. Diurnal variation of BNP and NT-proBNP with lower evening/nighttime concentration was confirmed in 44 stable individuals ( P <0.01)., Conclusions: BNP and NT-proBNP, but not MR-proANP, exhibit a diurnal rhythm that results in even higher diagnostic accuracy among evening/nighttime presenters versus daytime presenters., Registration: URL: https://www., Clinicaltrials: gov; Unique identifiers: NCT01831115, NCT02091427, and NCT02210897.

Background: Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity., Methods: This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed., Results: Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57-2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001)., Conclusions: Quantifying the adrenomedullin's system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF., (© 2021. The Author(s).)

Background: The Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes not evident during emergency department (ED) evaluation., Objective: To externally validate the CSRS and compare it with another validated score, the Osservatorio Epidemiologico della Sincope nel Lazio (OESIL) score., Design: Prospective cohort study., Setting: Large, international, multicenter study recruiting patients in EDs in 8 countries on 3 continents., Participants: Patients with syncope aged 40 years or older presenting to the ED within 12 hours of syncope., Measurements: Composite outcome of serious clinical plus procedural events (primary outcome) and the primary composite outcome excluding procedural interventions (secondary outcome)., Results: Among 2283 patients with a mean age of 68 years, the primary composite outcome occurred in 7.2%, and the composite outcome excluding procedural interventions occurred in 3.1% at 30 days. Prognostic performance of the CSRS was good for both 30-day composite outcomes and better compared with the OESIL score (area under the receiver-operating characteristic curve [AUC], 0.85 [95% CI, 0.83 to 0.88] vs. 0.74 [CI, 0.71 to 0.78] and 0.80 [CI, 0.75 to 0.84] vs. 0.69 [CI, 0.64 to 0.75], respectively). Safety of triage, as measured by the frequency of the primary composite outcome in the low-risk group, was higher using the CSRS (19 of 1388 [0.6%]) versus the OESIL score (17 of 1104 [1.5%]). A simplified model including only the clinician classification of syncope (cardiac syncope, vasovagal syncope, or other) variable at ED discharge-a component of the CSRS-achieved similar discrimination as the CSRS (AUC, 0.83 [CI, 0.80 to 0.87] for the primary composite outcome)., Limitation: Unable to disentangle the influence of other CSRS components on clinician classification of syncope at ED discharge., Conclusion: This international external validation of the CSRS showed good performance in identifying patients at low risk for serious outcomes outside of Canada and superior performance compared with the OESIL score. However, clinician classification of syncope at ED discharge seems to explain much of the performance of the CSRS in this study. The clinical utility of the CSRS remains uncertain., Primary Funding Source: Swiss National Science Foundation & Swiss Heart Foundation.

Background: Perioperative myocardial infarction/injury (PMI) is a frequent, often missed and incompletely understood complication of noncardiac surgery. The aim of this study was to evaluate whether patient- or procedure-related factors are more strongly associated to the development of PMI in patients undergoing repeated noncardiac surgery., Methods: In this prospective observational study, patient- and procedure-related factors were evaluated for contribution to PMI using: 1) logistic regression modelling with PMI as primary endpoint, 2) evaluation of concordance of PMI occurrence in the first and the second noncardiac surgery (surgery 1 and 2). and 3) the correlation of the extent of cardiomyocyte injury quantified by high-sensitivity cardiac troponin T between surgery 1 and 2. The secondary endpoint was all-cause mortality associated with PMI reoccurrence in surgery 2., Results: Among 784 patients undergoing repeated noncardiac surgery (in total 1'923 surgical procedures), 116 patients (14.8%) experienced PMI during surgery 1. Among these, PMI occurred again in surgery 2 in 35/116 (30.2%) patients. However, the vast majority of patients developing PMI during surgery 2 (96/131, 73.3%) had not developed PMI during surgery 1 (phi-coefficient 0.150, p < 0.001). The correlation between the extent of cardiomyocyte injury occurring during surgery 1 and 2 was 0.153. All-cause mortality following a second PMI in surgery 2 was dependent on time since surgery (adjusted hazard ratio 5.6 within 30 days and 2.4 within 360 days)., Conclusions: In high-risk patients, procedural factors are more strongly associated with occurrence of PMI than patient factors, but patient factors are also contributors to the occurrence of PMI., (Copyright © 2022. Published by Elsevier B.V.)