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Background: High-sensitivity troponin T (hs-TnT) reflects the severity of ongoing myocardial damage. In acute heart failure (AHF), its additive prognostic value over B-type natriuretic peptides is unclear., Methods: Individual data of 1499 AHF patients with admission hs-TnT were collected from 3 cohorts., Results: Patients (78 ± 10 years, 51% men, N-terminal fragment of pro-B-type natriuretic peptide - NT-proBNP - 5660 [2693-12,466], hs-TnT 43 ng/L [26-69]) experiencing in-hospital death (n = 187, 13%) had significantly higher hs-TnT and NT-proBNP on admission (both p < 0.001). Patients with hs-TnT ≥43 ng/L and NT-proBNP ≥5660 ng/L had a 2.7-fold higher risk of in-hospital death (relative risk - RR 2.7, 95% confidence interval - CI 1.7-4.5). Among discharged patients, 1024 deaths (81%) occurred over 11 months (4-22). In the whole population, hs-TnT ≥43 ng/L predicted all-cause death at 6, 12 and 24 months independently from NT-proBNP ≥5660 ng/L. The best NT-proBNP cut-off for in-hospital mortality (4382 ng/L) independently predicted this endpoint, while the best hs-TnT cut-off (55 ng/L) did not. Patients with NT-proBNP ≥4382 ng/L and hs-TnT ≥55 ng/L had a 12-fold higher risk of in-hospital death (RR 11.7, 95% CI 6.9-19.7). The best hs-TnT cut-offs independently predicted all post-discharge outcomes., Conclusions: The best NT-proBNP cut-off (4382 ng/L) independently predicts outcome, while the best hs-TnT (55 ng/L) does not; patients with both biomarkers ≥best cut-offs have a 12-fold higher risk of in-hospital mortality. Admission hs-TnT ≥43 ng/L and the best hs-TnT cut-offs hold independent prognostic significance for post-discharge outcome, while hs-TnT seems less predictive than NT-proBNP when considering absolute values., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Relative hypochromia of erythrocytes defined as a reduced mean corpuscular hemoglobin concentration (MCHC) is a surrogate of iron deficiency. We aimed to evaluate the prevalence and prognostic impact of relative hypochromia in acute heart failure (AHF)., Methods: We prospectively characterized 1574 patients presenting with an adjudicated diagnosis of AHF to the emergency department. Relative hypochromia was defined as a MCHC ≤330 g/l and determined at presentation. The presence of AHF was adjudicated by two independent cardiologists. All-cause mortality and AHF-rehospitalization were the primary prognostic end-points., Results: Overall, 455 (29%) AHF patients had relative hypochromia. Patients with relative hypochromia had higher hemodynamic cardiac stress as quantified by NT-proBNP concentrations (p < 0.001), more extensive cardiomyocyte injury as quantified by high-sensitive cardiac troponin T (hs-cTnT) concentrations (p < 0.001), and lower estimated glomerular filtration rate (eGFR; p < 0.001) as compared to AHF patients without hypochromia. Cumulative incidences for all-cause mortality and AHF-rehospitalization at 720-days were 50% and 55% in patients with relative hypochromia as compared to 33% and 39% in patients without hypochromia, respectively (both p < 0.0001). The association between relative hypochromia and increased mortality (HR 1.7, 95% CI 1.4-2-0) persisted after adjusting for anemia (HR 1.5, 95% CI 1.3-1.8), and after adjusting for hemodynamic cardiac stress (HR 1.46, 95% CI 1.21-1.76) and eGFR (HR 1.5, 95% CI 1.3-1.8, p < 0.001)., Conclusions: Relative hypochromia is common and a strong and independent predictor of increased mortality in AHF. Given the direct link to diagnostic (endoscopy) and therapeutic interventions to treat functional iron deficiency, relative hypochromia deserves increased attention as an inexpensive and universally available biomarker., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The clinical availability of high-sensitivity cardiac troponin (hs-cTn) has enabled the development of several innovative strategies for the rapid rule-out of acute myocardial infarction (AMI). Due to the lack of direct comparisons, selection of the best strategy for clinical practice is challenging., Methods: In a prospective international multicenter diagnostic study enrolling 3696 patients presenting with suspected AMI to the emergency department, we compared the safety and efficacy of 14 different hs-cTn-based strategies: hs-cTn concentrations below the limit of detection (LoD), dual-marker combining hs-cTn with copeptin, ESC 0 h/1 h-algorithm, 0 h/2 h-algorithm, 2 h-ADP-algorithm, NICE-algorithm, and ESC 0 h/3 h-algorithm, each using either hs-cTnT or hs-cTnI. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations., Results: AMI was the final diagnosis in 16% of patients. Using hs-cTnT, safety quantified by the negative predictive value (NPV) and sensitivity was very high (99.8-100% and 99.5-100%) and comparable for all strategies, except the dual-marker approach (NPV 98.7%, sensitivity 96.7%). Similarly, using hs-cTnI, safety quantified by the NPV and sensitivity was very high (99.7-100% and 98.9-100%) and comparable for all strategies, except the dual-marker approach (NPV 96.9%, sensitivity 90.4%) and the NICE-algorithm (NPV 99.1%, sensitivity 94.7%). Efficacy, quantified by the percentage of patients eligible for rule-out, differed markedly, and was lowest for LoD-algorithm (15.7-26.8%)., Conclusion: All rapid rule-out algorithms, except the dual-marker strategy and the NICE-algorithm using hs-cTnI, favorably combine safety and efficacy, and can be considered for routine clinical practice., Clinical Trial Registration: NCT00470587, http://clinicaltrials.gov/show/NCT00470587., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The value of the 12-lead ECG in the diagnosis of non-ST-elevation myocardial infarction (NSTEMI) is limited due to insufficient sensitivity and specificity of standard ECG criteria. The QRS-T angle reflects depolarization-repolarization heterogeneity and might assist in detecting patients with a NSTEMI (diagnosis) as well as predicting patients with an increased mortality risk (prognosis)., Methods: We prospectively enrolled 2705 consecutive patients with symptoms suggestive of NSTEMI. The QRS-T angle was automatically derived from the standard 10 s 12-lead ECG recorded at presentation to the ED. Patients were followed up for all-cause mortality for 2 years., Results: NSTEMI was the final diagnosis in 15% (n = 412) of patients. QRS-T angles were significantly greater in patients with NSTEMI compared to those without (p < 0.001). The use of the QRS-T angle in addition to standard ECG criteria indicative of ischemia improved the diagnostic accuracy for NSTEMI as quantified by the area under the ROC curve from 0.68 to 0.72 (p < 0.001). An algorithm for the combined use of standard ECG criteria and the QRS-T angle improved the sensitivity of the ECG for NSTEMI from 45% to 78% and the specificity from 86% to 91% (p < 0.001 for both comparisons). The 2-year survival rates were 98%, 97% and 87% according to QRS-T angle tertiles (p < 0.001)., Conclusion: In patients with suspected NSTEMI, the QRS-T angle derived from the standard 12-lead ECG provides incremental diagnostic accuracy on top of standard ECG criteria indicative of ischemia, and independently predicts all-cause mortality during 2 years of follow-up., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Various scores have been derived for the assessment of syncope patients in the emergency department (ED) but stay inconsistently validated. We aim to compare their performance to the one of a common, easy-to-use CHADS 2 score., Methods: We prospectively enrolled patients ≥ 40 years old presenting with syncope to the ED in a multicenter study. Early clinical judgment (ECJ) of the treating ED-physician regarding the probability of cardiac syncope was quantified. Two independent physicians adjudicated the final diagnosis after 1-year follow-up. Major cardiovascular events (MACE) and death were recorded during 2 years of follow-up. Nine scores were compared by their area under the receiver-operator characteristics curve (AUC) for death, MACE or the diagnosis of cardiac syncope., Results: 1490 patients were available for score validation. The CHADS 2 -score presented a higher or equally high accuracy for death in the long- and short-term follow-up than other syncope-specific risk scores. This score also performed well for the prediction of MACE in the long- and short-term evaluation and stratified patients with accuracy comparative to OESIL, one of the best performing syncope-specific risk score. All scores performed poorly for diagnosing cardiac syncope when compared to the ECJ., Conclusions: The CHADS 2 -score performed comparably to more complicated syncope-specific risk scores in the prediction of death and MACE in ED syncope patients. While better tools incorporating biochemical and electrocardiographic markers are needed, this study suggests that the CHADS 2 -score is currently a good option to stratify risk in syncope patients in the ED., Trial Registration: NCT01548352., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Exercise ECG stress testing is the most widely available method for evaluation of patients with suspected myocardial ischemia. Its major limitation is the relatively poor accuracy of ST-segment changes regarding ischemia detection. Little is known about the optimal method to assess ST-deviations., Methods: A total of 1558 consecutive patients undergoing bicycle exercise stress myocardial perfusion imaging (MPI) were enrolled. Presence of inducible myocardial ischemia was adjudicated using MPI results. The diagnostic value of ST-deviations for detection of exercise-induced myocardial ischemia was systematically analyzed 1) for each individual lead, 2) at three different intervals after the J-point (J+40ms, J+60ms, J+80ms), and 3) at different time points during the test (baseline, maximal workload, 2min into recovery)., Results: Exercise-induced ischemia was detected in 481 (31%) patients. The diagnostic accuracy of ST-deviations was highest at +80ms after the J-point, and at 2min into recovery. At this point, ST-amplitude showed an AUC of 0.63 (95% CI 0.59-0.66) for the best-performing lead I. The combination of ST-amplitude and ST-slope in lead I did not increase the AUC. Lead I reached a sensitivity of 37% and a specificity of 83%, with similar sensitivity to manual ECG analysis (34%, p=0.31) but lower specificity (90%, p<0.001)., Conclusion: When using ECG stress testing for evaluation of patients with suspected myocardial ischemia, the diagnostic accuracy of ST-deviations is highest when evaluated at +80ms after the J-point, and at 2min into recovery., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The V-index is an ECG marker quantifying spatial heterogeneity of ventricular repolarization. We prospectively assessed the diagnostic and prognostic values of the V-index in patients with suspected non-ST-elevation myocardial infarction (NSTEMI)., Methods: We prospectively enrolled 497 patients presenting with suspected NSTEMI to the emergency department (ED). Digital 12-lead ECGs of five-minute duration were recorded at presentation. The V-index was automatically calculated in a blinded fashion. Patients with a QRS duration >120ms were ruled out from analysis. The final diagnosis was adjudicated by two independent cardiologists. The prognostic endpoint was all-cause mortality during 24months of follow-up., Results: NSTEMI was the final diagnosis in 14% of patients. V-index levels were higher in patients with AMI compared to other causes of chest pain (median 23ms vs. 18ms, p<0.001). The use of the V-index in addition to conventional ECG-criteria improved the diagnostic accuracy for the diagnosis of NSTEMI as quantified by area under the ROC curve from 0.66 to 0.73 (p=0.001) and the sensitivity of the ECG for AMI from 41% to 86% (p<0.001). Cumulative 24-month mortality rates were 99.4%, 98.4% and 88.3% according to tertiles of the V-index (p<0.001). After adjustment for age and important ECG and clinical parameters, the V-index remained an independent predictor of death., Conclusions: The V-index, an ECG marker quantifying spatial heterogeneity of ventricular repolarization, significantly improves the accuracy and sensitivity of the ECG for the diagnosis of NSTEMI and independently predicts mortality during follow-up., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The novel high-sensitivity cardiac troponin (hs-cTn) 0h/1h-algorithm substantially improves the early triage of patient's assigned "rule-out" or "rule-in" of acute myocardial infarction (AMI), while diagnostic uncertainty remains in that 25-30% of patients assigned to "observe". We aimed to better characterize these patients., Methods: In a prospective multicenter diagnostic study, we applied the hs-cTnT 0h/1h-algorithm in 2213 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists using all available information. Survival at 720-days was the prognostic endpoint. Findings were validated using a hs-cTnI 0h/1h-algorithm., Results: Twenty-four percent (n=523) of patients were assigned to "observe" by the hs-cTnT 0h/1h-algorithm. These patients differed significantly in multiple characteristics from "rule-out" and "rule-in" patients: they were older, in 75% male, and very often (57%) had pre-existing coronary artery disease (CAD). Diagnostic uncertainty for the presence of an AMI/UA was high. Only 39% of patients were suitable for coronary computed tomography angiography (CCTA). The most common final adjudicated diagnoses were non-cardiac disease (38%), non-coronary cardiac disease (24%), unstable angina (UA, 21%), and AMI (15%). Absolute hs-cTnT-changes within 3h had the highest diagnostic accuracy for AMI (AUC 0.86). Cumulative 720-day survival rate was 86%, which was significantly lower as compared to "rule-out" (p<0.001) and comparable to "rule-in" (p=ns). Findings were similar for the hs-cTnI "observe" zone., Conclusion: "Observe" patients are typically elderly men with pre-existing CAD and high long-term mortality. Absolute hs-cTn-changes within 3h, functional stress imaging and coronary angiography are the key diagnostic modalities., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)