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Objectives: The aim was to investigate the prognostic accuracy of admission ECG and its usefulness in determining the population at the highest risk of worse outcomes., Background: Fast and accurate assessment of chest pain patients remains a challenge for clinicians. Electrocardiogram (ECG) is performed in each case of suspicion of the cardiac origin of chest pain., Methods: Consecutive adult chest pain patients with suspicion of acute myocardial infarction (AMI) were enrolled in the study. The prognostic value of admission ECG changes alone and in combination with other clinical variables (cardiac troponin, diagnosis of AMI) were analyzed for the incidence of major adverse cardiac events (MACE) in a one‑year observation., Results: The ischemic pattern on admission ECG was a single risk factor of MACE (HR 2.996 95% CI 1.31-6.86, p = 0.009), contrary to the single admission high-sensitivity cardiac troponin T assay (hs-cTnT) (HR 1.79 95% CI 0.695-4.61). The highest risk of MACE was identified in case of the presence of both ischemic-ECG and positive hs-cTnT (HR 3.19 95% CI 1.496-6.81, p = 0.003)., Conclusions: The presence of ischemic changes in ECG in chest pain population with AMI suspicion increases the risk of MACE. The group at highest risk of MACE can by identified by the additional stratification with the admission single hs-TnT measurement (Tab. 2, Fig. 4, Ref. 40). Text in PDF www.elis.sk Keywords: acute coronary syndromes, cardiac troponin, electrocardiogram, emergency department, chest pain.

The diagnosis ofcoronary artery disease, which is one of the most common causes of death and disability worldwide, still remains a significant problem for clinicians. High‑sensitivity cardiac troponin (hs‑cTn) assays became the cornerstone in the diagnostic workup of acute myocardial infarction. Nowadays, they take an important position in diagnostic algorithms. However, there are still some unexplained issues in this field.This review summarizes and emphasizes the crucial role of hs‑cTn in acute coronary syndromes. The 0/1‑hour hs‑cTn algorithm was mentioned for the first time in the 2015 official European Society of Cardiology guidelines on non-ST‑segment‑elevation acute coronary syndromes. It was derived, validated, and implemented for all clinically‑available assays since then. In this review, troponin‑based strategies for rapid rule‑out or rule‑in of non-ST‑segment elevation myocardial infarction are gathered and compared with the update on the official European Society of Cardiology 0/1‑hour pathway with the most recent values of hs‑cTn. The document also focuses on the problem of possible analytic confounders (false‑‑positive and false‑negative results) and compares the usefulness of cTn to other diagnostic techniques (eg, magnetic resonance imaging). The review is divided into short, easy‑to‑read sections emphasizing 6 key messages on how to use and interpret hs‑cTn base algorithms in clinical practice at the emergency department.

Objective: Patients with suspected acute myocardial infarction (AMI) in the setting of left bundle branch block (LBBB) present an important diagnostic and therapeutic challenge to the clinician., Methods: We prospectively evaluated the incidence of AMI and diagnostic performance of specific ECG and high-sensitivity cardiac troponin (hs-cTn) criteria in patients presenting with chest discomfort to 26 emergency departments in three international, prospective, diagnostic studies. The final diagnosis of AMI was centrally adjudicated by two independent cardiologists according to the universal definition of myocardial infarction., Results: Among 8830 patients, LBBB was present in 247 (2.8%). AMI was the final diagnosis in 30% of patients with LBBB, with similar incidence in those with known LBBB versus those with presumably new LBBB (29% vs 35%, p=0.42). ECG criteria had low sensitivity (1%-12%) but high specificity (95%-100%) for AMI. The diagnostic accuracy as quantified by the receiver operating characteristics (ROC) curve of hs-cTnT and hs-cTnI concentrations at presentation (area under the ROC curve (AUC) 0.91, 95% CI 0.85 to 0.96 and AUC 0.89, 95% CI 0.83 to 0.95), as well as that of their 0/1-hour and 0/2-hour changes, was very high. A diagnostic algorithm combining ECG criteria with hs-cTnT/I concentrations and their absolute changes at 1 hour or 2 hours derived in cohort 1 (45 of 45(100%) patients with AMI correctly identified) showed high efficacy and accuracy when externally validated in cohorts 2 and 3 (28 of 29 patients, 97%)., Conclusion: Most patients presenting with suspected AMI and LBBB will be found to have diagnoses other than AMI. Combining ECG criteria with hs-cTnT/I testing at 0/1 hour or 0/2 hours allows early and accurate diagnosis of AMI in LBBB., Trial Registration Number: APACE: NCT00470587; ADAPT: ACTRN12611001069943; TRAPID-AMI: RD001107;Results., Competing Interests: Competing interests: CM has received research grants from the Swiss National Science Foundation and the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, 8sense, Abbott, Alere, AstraZeneca, Beckman Coulter, bioMerieux, BRAHMS, Critical Diagnostics, Nanosphere, Roche, Siemens, Singulex and the University Hospital Basel, as well as speaker or consulting honoraria from Abbott, Alere, AstraZeneca, BG Medicine, bioMerieux, BMS, Boehringer Ingelheim, BRAHMS, Cardiorentis, Daiichi Sankyo, Novartis, Roche, Sanofi, Singulex and Siemens. LC reports grants from Roche and from Abbott, during the conduct of the study, grants from Roche, grants and personal fees from Abbott Diagnostics, grants from Siemens, grants from Radiometer, personal fees from AstraZeneca, and grants from Alere, outside the submitted work. BL has served as a consultant for Roche Diagnostics, Beckman Coulter, Siemens Healthcare Diagnostics, Radiometer Medical, bioMérieux Clinical Diagnostics, Philips Healthcare and Fiomi Diagnostics. TR has received research grants from the Swiss National Science Foundation (PASMP3-136995), the Swiss Heart Foundation, the University of Basel, the Professor Max Cloetta Foundation, and the Department of Internal Medicine, University Hospital Basel, as well as speaker’s honoraria from BRAHMS and Roche. EG has received honoraria for lectures from Roche Diagnostics, BRAHMS, Thermo Fisher and Mitsubishi Chemical Europe. MC has received research support and speaking honoraria from Roche, Thermo Fisher and Novartis. RT reports speaker honoraria from BRAHMS and Roche. WP reports grants from Roche and from Abbott, during the conduct of the study, and grants from Roche, grants and personal fees from Abbott Diagnostics, grants from Siemens, grants from Radiometer, personal fees from AstraZeneca, non-financial support from Bayer, personal fees from Hospira and grants from Alere, outside the submitted work. MRG has received speaking honoraria from Abbott and a research grant from the Swiss Heart Foundation. JB has received speaking honoria from Siemens. GB is an employee of Roche Diagnostics. JWP is supported by a Senior Research Fellowship from the Canterbury Medical Research Foundation, Emergency Care Foundation and Canterbury District Health. All other authors declare that they have no conflict of interest with this study., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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: We desired to determine cardiac troponin (cTn) concentrations necessary to achieve a positive predictive value (PPV) of ≥75% for acute myocardial infarction (AMI) to justify immediate admission of patients to a monitored unit and, in general, early coronary angiography., Methods: In a prospective multicenter diagnostic study enrolling patients presenting to the emergency department with symptoms suggestive of AMI, final diagnoses were adjudicated by 2 independent cardiologists based on clinical information including cardiac imaging. cTn concentrations were measured using 5 different sensitive and high-sensitivity cTn (hs-cTn) assays in a blinded fashion at presentation and serially thereafter. The diagnostic end point was PPV for rule-in of AMI of initial cTn concentrations alone and in combination with early changes., Results: Among 3828 patients, 616 (16%) had an AMI. At presentation, 7% to 14% of patients had cTnT/I concentrations associated with a PPV of ≥75%. Adding absolute or relative changes did not significantly further increase the PPV. PPVs increased from 46.5% (95% CI, 43.6-49.4) for hs-cTnT at presentation >14 ng/L to 78.9% (95% CI, 74.7-82.5) for >52 ng/L ( P < 0.001), whereas PPVs in higher hs-cTnT strata remained largely unchanged [e.g., 82.4% (95% CI, 77.5-86.7) for >80 ng/L vs 83.9% (95% CI, 76.0-90.1) for >200 ng/L ( P = 0.72)]. The addition of early changes in hs-cTnT further increased the PPV up to 60 ng/L, but not for higher concentrations., Conclusions: Serial sampling does not seem necessary for predicting AMI and concurrent decision-making in about 10% of patients, as it only marginally increases the PPV for AMI and not in a statistically or clinically significant way., Clinicaltrialsgov Identifier: NCT00470587., (© 2018 American Association for Clinical Chemistry.)

Background: Clinical short-term risk stratification is a recommended approach in patients with chest pain and possible acute myocardial infarction (AMI) to further improve high safety of biomarker-based rule-out algorithms. The study aim was to assess clinical performance of baseline concentrations of high-sensitivity cardiac troponin T (hs-TnT) and copeptin and the modified HEART score (mHS) in early presenters to the emergency department with chest pain., Methods: This cohort study included patients with chest pain with onset maximum of 6 h before admission and no persistent ST-segment elevation on electrocardiogram. hs-TnT, copeptin, and the mHS were assessed from admission data. The diagnostic and prognostic value for three baseline rule-out algorithms: (1) single hs-TnT < 14 ng/l, (2) hs-TnT < 14 ng/l/mHS ≤ 3, and (3) hs-TnT < 14 ng/l/mHS ≤ 3/copeptin < 17.4 pmol/l, was assessed with sensitivity and negative predictive value. Primary diagnostic endpoint was the diagnosis of AMI. Prognostic endpoint was death and/or AMI within 30 days., Results: Among 154 enrolled patients, 44 (29%) were classified as low-risk according to the mHS; AMI was diagnosed in 105 patients (68%). For ruling out AMI, the highest sensitivity and NPV from all studied algorithms were observed for hs-TnT/mHS/copeptin (100%, 95% CI 96.6-100, and 100%, 95% CI 75.3-100). At 30 days, the highest event-free survival was achieved in patients stratified with hs-TnT/mHS/copeptin algorithm (100%) with 100% (95% CI 75.3-100) NPV and 100% (95% CI 96.6-100) sensitivity., Conclusions: The combination of baseline hs-TnT, copeptin, and the mHS has an excellent sensitivity and NPV for short-term risk stratification. Such approach might improve the triage system in emergency departments and be a bridge for inclusion to serial blood sampling algorithms.

Aims: We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific to older patients., Methods and Results: We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.5-99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767)., Conclusion: While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587 and NCT02355457 (BACC).

Background: High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI)., Methods: Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters., Results: Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect; 0.91 vs 0.94 for s-cTnI Ultra; 0.89 vs 0.94 for s-cTnI Accu; 0.91 vs 0.94 for hs-cTnI Accu)., Conclusions: Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation., Clinical Trial Registration: NCT00470587, http://clinicaltrials.gov/show/NCT00470587., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction., Methods: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms., Results: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng 2 /L 2 ) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0-99.9%]; product: NPV 99.4% [95% CI, 98.8-99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2-100%]; NPV validation cohort 99.5% [95% CI, 98.9-99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6-78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7-87.6%])., Conclusions: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction., Clinical Trial Registration: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.

Background: Clinical performance of the novel high-sensitivity cardiac troponin I (Siemens-hs-cTnI-Centaur) assay is unknown. We aimed to clinically validate the Siemens-hs-cTnI-Centaur assay and develop 0/1-h and 0/2-h algorithms., Methods: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists including all clinical information twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis); second, using hs-cTnI (Abbott-Architect, secondary analysis) measurements in addition to the clinically applied (hs)-cTn. Siemens-hs-cTnI-Centaur was measured at presentation, 1 h, and 2 h. The primary objective was a direct comparison of diagnostic accuracy, quantified by the area under the ROC curve (AUC), of Siemens-hs-cTnI-Centaur vs the 2 established hs-cTn assays (Roche-hs-cTnT-Elecsys, Abbott-hs-cTnI-Architect). Secondary objectives included the development of Siemens-hs-cTnI-Centaur-specific 0/1-h and 0/2-h algorithms., Results: AMI was the final diagnosis in 318 of 1755 (18%) patients (using Roche-hs-cTnT-Elecsys for adjudication). The AUC at presentation for Siemens-hs-cTnI-Centaur was 0.94 (95% CI, 0.92-0.96) and comparable with 0.95 (95% CI, 0.93-0.97) for Roche-hs-cTnT-Elecsys and 0.93 (95% CI, 0.90-0.96) for Abbott-hs-cTnI-Architect. Applying the derived Siemens-hs-cTnI-Centaur 0/1-h algorithm to the validation cohort, 46% of patients were ruled out (sensitivity, 99.1%; 95% CI, 95.3-100), and 18% of patients were ruled in (specificity, 94.1%; 95% CI, 91.8-95.9). The Siemens-hs-cTnI-Centaur 0/2-h algorithm ruled out 55% of patients (sensitivity, 100%; 95% CI, 94.1-100), and ruled in 18% of patients (specificity, 96.0%; 95% CI, 93.1-97.9). Findings were confirmed in the secondary analyses using serial measurements of Abbott-hs-cTnI-Architect for adjudication., Conclusions: Diagnostic accuracy and clinical utility of the novel Siemens-hs-cTnI-Centaur assay are high and comparable with the established hs-cTn assays. ClinicalTrials.gov Identifier: NCT00470587., (© 2018 American Association for Clinical Chemistry.)

Background: The safety of the European Society of Cardiology (ESC) 0/1-h algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin (hs-cTn) has been questioned., Objectives: This study aimed to validate the diagnostic performance of the 0/1-h algorithm in a large multicenter study., Methods: The authors prospectively enrolled unselected patients in 6 countries presenting to the emergency department with symptoms suggestive of NSTEMI. Final diagnosis was centrally adjudicated by 2 independent cardiologists. Hs-cTnT and hs-cTnI blood concentrations were measured at presentation and after 1 h. Safety of rule-out was quantified by the negative predictive value (NPV) for NSTEMI, accuracy of rule-in by the positive predictive value (PPV), and overall efficacy by the proportion of patients triaged towards rule-out or rule-in within 1 h., Results: Prevalence of NSTEMI was 17%. Among 4,368 patients with serial hs-cTnT measurements available, safety of rule-out (NPV 99.8%, 2,488 of 2,493), accuracy of rule-in (PPV 74.5%, 572 of 768), and overall efficacy were high by assigning three-fourths of patients either to rule-out (57%, 2,493 to 4,368) or rule-in (18%, 768 to 4,368). Similarly, among 3,500 patients with serial hs-cTnI measurements, safety of rule-out (NPV 99.7%, 1,528 of 1,533), accuracy of rule-in (PPV 62.3%, 498 of 800), and overall efficacy were high by assigning more than two-thirds of patients either to rule-out (44%, 1,533 of 3,500) or rule-in (23%, 800 of 3,500). Excellent safety was confirmed in multiple subgroup analyses including patients presenting early (≤3 h) after chest pain onset., Conclusions: The ESC 0/1-h algorithm using hs-cTnT and hs-cTnI is very safe and effective in triaging patients with suspected NSTEMI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587; and Biomarkers in Acute Cardiac Care [BACC]; NCT02355457)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: While prolongation of QRS duration and QTc interval during acute myocardial infarction (AMI) has been reported in animals, limited data is available for these readily available electrocardiography (ECG) markers in humans., Methods: Diagnostic and prognostic value of QRS duration and QTc interval in patients with suspected AMI in a prospective diagnostic multicentre study were prospectively assessed. Digital 12-lead ECGs were recorded at presentation. QRS duration and QTc interval were automatically calculated in a blinded fashion. Final diagnosis was adjudicated by two independent cardiologists. The prognostic endpoint was all-cause mortality during 24 months of follow-up., Results: Among 4042 patients, AMI was the final diagnosis in 19% of patients. Median QRS duration and median QTc interval were significantly greater in patients with AMI compared to those with other final diagnoses (98 ms [IQR 88-108] vs. 94 ms [IQR 86-102] and 436 ms [IQR 414-462] vs. 425 ms [IQR 407-445], p < 0.001 for both comparisons). The diagnostic value of both ECG signatures however was only modest (AUC 0.56 and 0.60). Cumulative mortality rates after 2 years were 15.9% vs. 5.6% in patients with a QRS > 120 ms compared to a QRS duration ≤ 120 ms (p < 0.001), and 11.4% vs. 4.3% in patients with a QTc > 440 ms compared to a QRS duration ≤ 440 ms (p < 0.001). After adjustment for age and important ECG and clinical parameters, the QTc interval but not QRS duration remained an independent predictor of mortality., Conclusions: Prolongation of QRS duration > 120 ms and QTc interval > 440 ms predict mortality in patients with suspected AMI, but do not add diagnostic value.

Introduction: High-sensitivity cardiac troponin assays have significantly improved the sensitivity of myocardial infarction detection by using cutoff values and early absolute changes. However, variation in repeated measures also depends on biological variability. This study aimed to assess the potential circadian component of this biological variability., Methods: 17 healthy volunteers were recruited, and standardized conditions for physical activity, meals, exposure to light and duration of sleep were imposed. Blood samples were collected every 4 h and high-sensitivity troponin T assay with a limit of detection of 3 ng/l and a 99th percentile of 14 ng/l were used. Circadian variations were analyzed using the cosinor method., Results: Statistically significant circadian variations were observed for body temperature, heart rate, and systolic/diastolic arterial blood pressures (p < 0.01 using both a non-adjusted cosinor model and a gender- and BMI-adjusted cosinor model). The amplitudes of the circadian variations were 18.93, 6, 15.35, and 1.92%, respectively. A statistically significant circadian biological variation of troponin blood concentrations was evidenced (p < 0.01 in both the non-adjusted cosinor model and the gender- and BMI-adjusted cosinor), with an amplitude of 20.5% (average: 4.39 ng/l; amplitude: 0.9 ng/l; peak at 06:00 and nadir at 18:00)., Discussion: This study demonstrates a circadian biological variation in blood troponin concentration in a healthy population. The amplitude of this variation challenges the cutoff value for instant rule-out of the rapid rule-in/rule-out of the recent European guidelines for the management of acute coronary syndromes. These findings deserve further investigation in a population at risk of myocardial infarction.

Background: Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI., Methods: Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality., Results: Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L, P <0.001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.924), hs-cTnT (AUC, 0.927), and hs-cTnI (AUC, 0.922) and superior to cTnI measured by a contemporary sensitivity assay (AUC, 0.909). The combination of cMyC with hs-cTnT or standard-sensitivity cTnI (but not hs-cTnI) led to an increase in AUC to 0.931 ( P <0.0001) and 0.926 ( P =0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categories: Net Reclassification Improvement +0.149 versus hs-cTnT, +0.235 versus hs-cTnI ( P <0.001). In early presenters (chest pain <3 h), the improvement in rule-in/rule-out classification with cMyC was larger compared with hs-cTnT (Net Reclassification Improvement +0.256) and hs-cTnI (Net Reclassification Improvement +0.308; both P <0.001). Comparing the C statistics, cMyC was superior to hs-cTnI and standard sensitivity cTnI ( P <0.05 for both) and similar to hs-cTnT at predicting death at 3 years., Conclusions: cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587., (© 2017 The Authors.)

Background: Uncertainties regarding the most appropriate definition and treatment of type 2 myocardial infarction (T2MI) due to supply-demand mismatch have contributed to inconsistent adoption in clinical practice., Objectives: This study sought a better understanding of the effect of the definition of T2MI on its incidence, treatment, and event-related mortality, thereby addressing an important unmet clinical need., Methods: The final diagnosis was adjudicated in patients presenting with symptoms suggestive of myocardial infarction by 2 independent cardiologists by 2 methods: 1 method required the presence of coronary artery disease, a common interpretation of the 2007 universal definition (T2MI 2007 ); and 1 method did not require coronary artery disease, the 2012 universal definition (T2MI 2012 )., Results: Overall, 4,015 consecutive patients were adjudicated. The incidence of T2MI based on the T2MI 2007 definition was 2.8% (n = 112). The application of the more liberal T2MI 2012 definition resulted in an increase of T2MI incidence of 6% (n = 240), a relative increase of 114% (128 reclassified patients, defined as T2MI 2012reclassified ). Among T2MI 2007 , 6.3% of patients received coronary revascularization, 22% dual-antiplatelet therapy, and 71% high-dose statin therapy versus 0.8%, 1.6%, and 31% among T2MI 2012reclassified patients, respectively (all p < 0.01). Cardiovascular mortality at 90 days was 0% among T2MI 2012reclassified , which was similar to patients with noncardiac causes of chest discomfort (0.2%), and lower than T2MI 2007 (3.6%) and type 1 myocardial infarction (T1MI) (4.8%) (T2MI 2012reclassified vs. T2MI 2007 and T1MI: p = 0.03 and 0.01, respectively)., Conclusions: T2MI 2012reclassified has a substantially lower event-related mortality rate compared with T2MI 2007 and T1MI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The early diagnosis of acute myocardial infarction (AMI) in patients with mild elevations of high-sensitivity cardiac troponin (hs-cTn) is a challenge. It is unclear whether copeptin, a marker of endogenous stress, or 1h-hs-cTn changes are better suited to address this important unmet clinical need., Methods: We prospectively enrolled patients presenting with symptoms suggestive of AMI to the emergency department (ED). Two independent cardiologists adjudicated the final diagnosis. Mild hs-cTn elevations were defined as 26.2 ng/L (99th percentile) to 75 ng/L for hs-cTnI, and 14 ng/L (99th percentile) to 50 ng/L (biological-equivalent to 75 ng/L for hs-cTnI) for hs-cTnT., Results: Among 1356 patients, 80 (6%) had mild hs-cTnI elevations at presentation. Within this group, AMI was the final diagnosis in 39 patients (49%). The diagnostic accuracy for the diagnosis of AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0.51 (95% CI 0.39-0.64) for hs-cTnI at presentation, 0.58 (95% CI 0.45-0.71) for copeptin at presentation, and 0.78 (95% CI 0.68-0.88) for 1h-hs-cTnI changes, which was significantly higher as compared to copeptin (p = 0.02) or hs-cTnI alone (p < 0.001). The additional use of 1h-hs-cTnI changes, but not of copeptin, improved diagnostic accuracy of hs-cTnI at presentation (AUC 0.80, 95% CI 0.70-0.90; p = 0.002 for comparison). Similar findings regarding copeptin and 1h-hs-cTnT/I changes were obtained for mild hs-cTnT elevations., Conclusions: About 6-22% of patients presenting with suggestive AMI to the ED have mild hs-cTnT/I elevations at presentation. In contrast to copeptin, the addition of 1h-hs-cTn changes substantially improves the early diagnosis of AMI.

Background: Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application., Methods: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI-based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm., Results: Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%-100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%-98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction P =0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies ( P <0.01 for LOD versus each of the other strategies)., Conclusions: All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587., (© 2017 American Heart Association, Inc.)

Importance: It is currently unknown whether the uniform (universal clinical practice for more than 2 decades) or 2 sex-specific cutoff levels are preferable when using high-sensitivity cardiac troponin T (hs-cTnT) levels in the diagnosis of acute myocardial infarction (AMI)., Objective: To improve the management of suspected AMI in women by exploring sex-specific vs uniform cutoff levels for hs-cTnT., Design, Setting, and Participants: In an ongoing prospective, diagnostic, multicenter study conducted at 9 emergency departments, the present study evaluated patients enrolled from April 21, 2006, through June 5, 2013. The participants included 2734 adults presenting with suspected AMI. Duration of follow-up was 2 years, and data analysis occurred from June 5 to December 21, 2015., Interventions: The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including measurements of serial hs-cTnT blood concentrations twice: once using the uniform 99th percentile cutoff value level of 14 ng/L and once using sex-specific 99th percentile levels of hs-cTnT (women, 9 ng/L; men, 15.5 ng/L)., Main Outcomes and Measures: Diagnostic reclassification in women and men using sex-specific vs the uniform cutoff level in the diagnosis of AMI., Results: Of the 2734 participants, 876 women (32%) and 1858 men (68%) were included. Median (interquartile range) age was 68 (55-77) and 59 (48-71) years, respectively. With the use of the uniform cutoff value, 127 women (14.5%) and 345 men (18.6%) received a final diagnosis of AMI. Among these, at emergency department presentation, levels of hs-cTnT were already above the uniform cutoff value in 427 patients (sensitivity, 91.3% [95% CI, 85%-95.6%] in women vs 90.7% [95% CI, 87.1%-93.5% in men]; specificity, 79.2% [95% CI, 76.1%-82.1%] in women vs 78.5% [95% CI, 76.4%-80.6%] in men). After readjudication using sex-specific 99th percentile levels, diagnostic reclassification regarding AMI occurred in only 3 patients: 0.11% (95% CI, 0.02-0.32) of all patients and 0.6% (95% CI, 0.13-1.85) of patients with AMI. The diagnosis in 2 women was upgraded from unstable angina to AMI, and the diagnosis in 1 man was downgraded from AMI to unstable angina. These diagnostic results were confirmed when using 2 alternative pairs of uniform and sex-specific cutoff values., Conclusions and Relevance: The uniform 99th percentile should remain the standard of care when using hs-cTnT levels for the diagnosis of AMI.

Background: There are sparse data on the performance of different types of drug-eluting stents (DES) in acute and real-life setting., Objective: The aim of the study was to compare the safety and efficacy of first- versus second-generation DES in patients with acute coronary syndromes (ACS)., Methods: This all-comer registry enrolled consecutive patients diagnosed with ACS and treated with percutaneous coronary intervention with the implantation of first- or second-generation DES in one-year follow-up. The primary efficacy endpoint was defined as major adverse cardiac and cerebrovascular event (MACCE), a composite of all-cause death, nonfatal myocardial infarction, target-vessel revascularization and stroke. The primary safety outcome was definite stent thrombosis (ST) at one year., Results: From the total of 1916 patients enrolled into the registry, 1328 patients were diagnosed with ACS. Of them, 426 were treated with first- and 902 with second-generation DES. There was no significant difference in the incidence of MACCE between two types of DES at one year. The rate of acute and subacute ST was higher in first- vs. second-generation DES (1.6% vs. 0.1%, p < 0.001, and 1.2% vs. 0.2%, p = 0.025, respectively), but there was no difference regarding late ST (0.7% vs. 0.2%, respectively, p = 0.18) and gastrointestinal bleeding (2.1% vs. 1.1%, p = 0.21). In Cox regression, first-generation DES was an independent predictor for cumulative ST (HR 3.29 [1.30-8.31], p = 0.01)., Conclusions: In an all-comer registry of ACS, the one-year rate of MACCE was comparable in groups treated with first- and second-generation DES. The use of first-generation DES was associated with higher rates of acute and subacute ST and was an independent predictor of cumulative ST.

Background: Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry., Methods: This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods., Results: 6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00., Discussion: As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.

Objectives: To test if the time of day significantly influences the occurrence of type 4A myocardial infarction in elective patients undergoing percutaneous coronary intervention (PCI)., Background: Recent studies have suggested an influence of circadian rhythms on myocardial infarction size and mortality among patients with ST-elevation myocardial infarction. The aim of the study is to investigate whether periprocedural myocardial infarction (PMI) is influenced by the time of day in elective patients undergoing PCI., Methods: All consecutive patients undergoing elective PCI between 2007 and 2011 at our institutions with known post-interventional troponin were retrospectively included. Patients (n = 1021) were divided into two groups according to the starting time of the PCI: the morning group (n = 651) between 07:00 and 11:59, and the afternoon group (n = 370) between 12:00 and 18:59. Baseline and procedural characteristics as well as clinical outcome defined as the occurrence of PMI were compared between groups. In order to limit selection bias, all analyses were equally performed in 308 pairs using propensity score (PS) matching., Results: In the overall population, the rate of PMI was statistically lower in the morning group compared to the afternoon group (20% vs. 30%, p < 0.001). This difference remained statistically significant after PS-matching (21% vs. 29%, p = 0.03). Multivariate analysis shows that being treated in the afternoon independently increases the risk for PMI with an odds ratio of 2.0 (95%CI: 1.1-3.4; p = 0.02)., Conclusions: This observational PS-matched study suggests that the timing of an elective PCI influences the rate of PMI.

The aim of the study was to compare the course of myocardial infarction in women versus men in Upper Silesia, an industrial region in the south of Poland. The study comprised 1003 patients with either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). The patients were divided into group 1 (300 females) and group 2 (control, 703 males). The groups differed significantly with respect to age, incidence of hypertension, diabetes, and smoking. In group 1 STEMI occurred significantly less frequently than NSTEMI. Taking this into account, we divided the studied cohort into group A (STEMI patients) and group B (NSTEMI patients), each subdivided into women and men. In the 30 day long follow-up, group 1 patients had significantly lower creatine kinase activity, higher occurrence of ventricular tachycardia, lower percentage of intra-aortic balloon pump use, and longer hospital stay compared with group 2. Group 1 was characterized by significantly higher mortality and target lesion reocclusion (TLR). The medical course of myocardial infarction in women is similar to that in men, as is the treatment of acute coronary syndrome. In our study, patients from both groups underwent invasive examination with consecutive interventional treatment with similar frequency. However, this finding is not reflected in the outcomes. Women had higher risks of death and TLR in 30 day follow-up. Taking this into consideration, we should attempt to identify the factors responsible for this situation by expanding the analysis to a larger population to allow firm conclusions to be drawn.