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Competing Interests: Funding support and author disclosures Dr Pellikka receives research support from Ultromics, with money paid to her institution; is supported as the Betty Knight Scripps- George M. Gura, Jr. MD, Professor of Cardiovascular Diseases Clinical Research, Mayo Clinic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objective: To evaluate the diagnostic performance of the previously recommended baseline high-sensitivity cardiac troponin T (hs-cTnT) thresholds of 52 and 100 ng/L in identifying patients at high risk of acute myocardial infarction (AMI)., Patients and Methods: This study compared the positive predictive value (PPV) for index AMI of these high-risk hs-cTnT thresholds in adult patients in the emergency department undergoing hs-cTnT measurement., Results: The adjudicated MAyo Southwest Wisconsin 5th Gen Troponin T ImplementatiON cohort included 2053 patients, with 157 (7.6%) who received a diagnosis of AMI. The hs-cTnT concentrations of greater than 52 and greater than 100 ng/L resulted in PPVs of 41% (95% CI, 35%-48%) and 57% (95% CI, 48%-66%). In patients with chest discomfort, hs-cTnT concentrations greater than 52 ng/L resulted in a PPV of 66% (95% CI, 56%-76%) and hs-cTnT concentrations greater than 100 ng/L resulted in a PPV of 77% (95% CI, 65%-87%). The CV Data Mart Biomarker cohort included 143,709 patients, and 3003 (2.1%) received a diagnosis of AMI. Baseline hs-cTnT concentrations greater than 52 and greater than 100 ng/L resulted in PPVs of 12% (95% CI, 11%-12%) and 17% (95% CI, 17%-19%), respectively. In patients with chest pain and hs-cTnT concentrations greater than 52 ng/L, the PPV for MI was 17% (95% CI, 15%-18%) and in those with concentrations greater than 100 ng/L, only 22% (95% CI, 19%-25%)., Conclusion: In unselected patients undergoing hs-cTnT measurement, the hs-cTnT thresholds of greater than 52 and greater than 100 ng/L provide suboptimal performance for identifying high-risk patients. In patients with chest discomfort, an hs-cTnT concentration of greater than 100 ng/L, but not the European Society of Cardiology-recommended threshold of greater than 52 ng/L, provides an acceptable performance but should be used only with other clinical features., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations., Methods and Results: Observational US cohort study of emergency department patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase > 99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of ≥52, >100, >200, or >300 ng/L, positive predictive values (PPVs) for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89), and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82), and 54% (95% CI 25-81). In CKD patients with a 2 h hs-cTnT delta of ≥10, >20, or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96), and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86), and 75% (95% CI 58-88)., Conclusion: Diagnostic performance of standard baseline and serial 2 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values., Competing Interests: Conflict of interest: A.S.J. has consulted or presently consults for most of the major diagnostics companies, including Beckman-Coulter, Abbott, Siemens, ET Healthcare, Ortho Diagnostics, Roche, Radiometer, Sphingotec, Spinchip, and LumiraDx. He has stock in RCE Technologies. Y.S. has been on advisory boards or consults for Roche Diagnostics, Abbott. Diagnostics, Philips, GE, and Zoll. All other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The 2021 American College of Cardiology/American Heart Association chest pain guidelines recommend risk scores such as HEAR (History, Electrocardiogram, Age, Risk factors) for short-term risk stratification, yet limited data exist integrating them with high-sensitivity cardiac troponin T (hs-cTnT)., Methods: Retrospective, multicenter (n = 2), observational, US cohort study of consecutive emergency department patients without ST-elevation myocardial infarction who had at least one hs-cTnT (limit of quantitation [LoQ] <6 ng/L, and sex-specific 99th percentiles of 10 ng/L for women and 15 ng/L for men) measurement on clinical indications in whom HEAR scores (0-8) were calculated. The composite major adverse cardiovascular event (MACE) outcome was 30-day prognosis., Results: Among 1979 emergency department patients undergoing hs-cTnT measurement, 1045 (53%) were low risk (0-3), 914 (46%) intermediate risk (4-6), and 20 (1%) high risk (7-8) based on HEAR scores. HEAR scores were not associated with increased risk of 30-day MACE in adjusted analyses. Patients with quantifiable hs-cTnT (LoQ-99th) had an increased risk for 30-day MACE (3.4%) irrespective of HEAR scores. Those with serial hs-cTnT <99th percentile remained at low risk (range 0%-1.2%) across all HEAR score strata. Higher scores were not associated with long-term (2-year) events., Conclusions: HEAR scores are of limited value in those with baseline hs-cTnT 99 th percentile to define short-term prognosis. In those with baseline quantifiable hs-cTnT within the reference range (<99 th percentile), a higher risk (>1%) for 30-day MACE exists even in those with low HEAR scores. With serial hs-cTnT measurements, HEAR scores overestimate risk when hs-cTnT remains <99th percentile., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Differentiating type 2 myocardial infarction from myocardial injury can be difficult. In addition, the presence of objective evidence of myocardial ischemia may facilitate identification of high-risk type 2 myocardial infarction patients., Methods: This was an observational cohort study of adult emergency department patients undergoing high-sensitivity cardiac troponin T (hs-cTnT) measurement. Patients with ≥1 hs-cTnT >99th percentile were adjudicated following the Fourth Universal Definition of Myocardial Infarction. Patients were categorized as "subjective type 2 myocardial infarction" when ischemic symptoms were the lone criteria supporting type 2 myocardial infarction, or "objective type 2 myocardial infarction" when there was ≥1 objective clinical feature (electrocardiography, imaging, angiography) of acute myocardial ischemia. The primary outcome was mortality., Results: A total of 857 patients were included, among which 55 (6.4%) were classified as subjective type 2 myocardial infarction, 36 (4.2%) as objective type 2 myocardial infarction, and 702 (82%) as myocardial injury. Those with objective type 2 myocardial infarction had a higher risk of mortality during the index presentation (17% vs 1.7%, P < .0001; hazard ratio 11.1; 95% confidence interval, 3.7-33.4) and at 2-year follow-up (47% vs 31%, P = .04; hazard ratio 1.92; 95% confidence interval, 1.17-3.14) than those with myocardial injury. Objective type 2 myocardial infarction had a higher mortality than subjective type 2 myocardial infarction at index presentation (17% vs 2.0%, P = .01) and at 1 (25% vs 9.1%, P = .04) and 3 months (31% vs 13%, P = .04) follow-up. There were no mortality differences between subjective type 2 myocardial infarction and myocardial injury., Conclusion: In patients diagnosed with type 2 myocardial infarction, those with objective evidence of myocardial ischemia have significantly worse outcomes compared with those with myocardial injury and subjective type 2 myocardial infarction. A more rigorous type 2 myocardial infarction definition that emphasizes these criteria may facilitate diagnosis and risk-stratification., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Our goal was to evaluate a previously validated artificial intelligence-augmented electrocardiography (AI-ECG) screening tool for left ventricular systolic dysfunction (LVSD) in patients undergoing high-sensitivity-cardiac troponin T (hs-cTnT)., Methods and Results: Retrospective application of AI-ECG for LVSD in emergency department (ED) patients undergoing hs-cTnT. AI-ECG scores (0-1) for probability of LVSD (left ventricular ejection fraction ≤ 35%) were obtained. An AI-ECG score ≥0.256 indicates a positive screen. The primary endpoint was a composite of post-discharge major adverse cardiovascular events (MACEs) at two years follow-up. Among 1977 patients, 248 (13%) had a positive AI-ECG. When compared with patients with a negative AI-ECG, those with a positive AI-ECG had a higher risk for MACE [48 vs. 21%, P < 0.0001, adjusted hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.11-1.75]. This was largely because of a higher rate of deaths (32 vs. 14%, P < 0.0001; adjusted HR 1.26, 95% 0.95-1.66) and heart failure hospitalizations (26 vs. 6.1%, P < 0.001; adjusted HR 1.75, 95% CI 1.25-2.45). Together, hs-cTnT and AI-ECG resulted in the following MACE rates and adjusted HRs: hs-cTnT < 99th percentile and negative AI-ECG: 116/1176 (11%; reference), hs-cTnT < 99th percentile and positive AI-ECG: 28/107 (26%; adjusted HR 1.54, 95% CI 1.01-2.36), hs-cTnT > 99th percentile and negative AI-ECG: 233/553 (42%; adjusted HR 2.12, 95% CI 1.66, 2.70), and hs-cTnT > 99th percentile and positive AI-ECG: 91/141 (65%; adjusted HR 2.83, 95% CI 2.06, 3.87)., Conclusion: Among ED patients evaluated with hs-cTnT, a positive AI-ECG for LVSD identifies patients at high risk for MACE. The conjoint use of hs-cTnT and AI-ECG facilitates risk stratification., Competing Interests: Conflict of interest: Y.S.: advisory board/speaker for Roche Diagnostics and advisory board Abbott Diagnostics. Patent #20210401347. A.S.J. has consulted or presently consults for most of the major diagnostics companies, including Beckman-Coulter, Abbott, Siemens, ET Healthcare, Ortho Diagnostics, Roche, Radiometer, Sphingotec, RCE Technologies, and Amgen and Novartis. All other authors have nothing to disclose., (© 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.)

Background: Aminophylline, an adenosine antagonist, can be used to prevent adenosine-mediated bradyarrhythmias., Methods: Retrospective, observational, descriptive analysis of patients undergoing rotational atherectomy with intravenous (IV) aminophylline pretreatment during a 10-year period (2010-2020). The primary composite outcome was the occurrence of a documented bradyarrhythmia requiring pharmacologic intervention and/or temporary pacemaker (TPM) implantation., Results: A total of 296 patients received IV aminophylline pretreatment. The primary composite outcome occurred in 1.7% (n = 5) of patients. None of the patients required rescue TPM. Bradyarrhythmias were documented in 2.4% (n = 7) of patients. Pharmacologic interventions, typically with IV atropine, were used in 15% (n = 43) of patients. Per-vessel analyses demonstrated that patients undergoing atherectomy to the circumflex and right coronary arteries were more likely than those undergoing atherectomy to other vessels to have bradyarrhythmias requiring pharmacologic intervention (3.4% vs 0%, P = .01)., Conclusions: In this 10-year single-center experience using IV aminophylline pretreatment to prevent major bradyarrhythmias in patients undergoing coronary atherectomy, none of the patients required rescue TPM implantation. These data demonstrate that coronary atherectomy can be performed safely without prophylactic TPM, with aminophylline pretreatment and selective use of atropine representing an effective noninvasive approach., (© 2023 The Authors.)

Aims: Limited US outcome data exist among patients with myocardial injury and types 1 and 2 myocardial infarction (MI) evaluated with high-sensitivity cardiac troponin (hs-cTn)., Methods and Results: This is an observational US cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Post-discharge major adverse cardiovascular events (MACE) included death, MI, heart failure (HF) hospitalization, stroke or transient ischaemic attack, and new-onset atrial fibrillation or flutter during 2 years follow-up. Among 2002 patients, 857 (43%) had ≥1 hs-cTnT >99th percentile. Among these, 702 (81.9%) had myocardial injury, 64 (7.5%) had type 1 MI, and 91 (10.6%) had type 2 MI. Compared with patients without myocardial injury, type 2 MI [8.4 vs. 50%; adjusted hazard ratio (HR) 2.31, 95% confidence interval (CI) 1.49-3.58] and myocardial injury (8.4 vs. 47%; adjusted HR 3.13, 95% CI 2.39-4.09) had a higher risk of MACE, in large part because of death and HF hospitalizations. Compared with patients with type 1 MI, type 2 MI (23 vs. 50%; adjusted HR 2.24; 95% CI 1.23-4.10) and myocardial injury (23 vs. 47%; adjusted HR 2.02; 95% CI 1.20-3.40) also have a higher risk of MACE., Conclusion: Among unselected US ED patients undergoing hs-cTnT measurement, most increases are due to myocardial injury, and type 2 MI is more frequent than type 1 MI. Patients with myocardial injury and type 2 MI have morbid outcomes, in large part due to death and HF., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection of 5 ng/L to exclude acute myocardial infarction. Per the US Food and Drug Administration, hs-cTnT can only report to the limit of quantitation of 6 ng/L, a threshold for which there are limited data. Our goal was to determine whether a single hs-cTnT below the limit of quantitation of 6 ng/L is a safe strategy to identify patients at low risk for acute myocardial injury and infarction., Methods: The efficacy (proportion identified as low risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least 1 hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic ECG with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling out acute myocardial infarction and safety (myocardial infarction or death at 30 days) were evaluated., Results: A total of 85 610 patients were evaluated in the CV Data Mart Biomarker cohort, among which 24 646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% versus 20%, P <0.0001). Among 11 962 patients with baseline hs-cTnT<6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% CI, 98.6-99.0) and sensitivity of 99.6% (95% CI, 99.5-99.6). In the adjudicated cohort, a nonischemic ECG with hs-cTnT<6 ng/L identified 33% of patients (610/1849) as low risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for myocardial infarction or death., Conclusions: A single hs-cTnT below the limit of quantitation of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

Background: Limited data exist on high-sensitivity cardiac troponin (hs-cTn) for risk-stratification in COVID-19., Methods: We conducted a multicenter, retrospective, observational, US-based study of COVID-19 patients undergoing hs-cTnT. Outcomes included short-term mortality (in-hospital and 30-days post-discharge) and a composite of major adverse events, including respiratory failure requiring mechanical ventilation, cardiac arrest, and shock within the index presentation and/or mortality during the index hospitalization or within 30-days post-discharge., Results: Among 367 COVID-19 patients undergoing hs-cTnT, myocardial injury was identified in 46%. They had a higher risk for mortality (20% vs 12%, P < 0.0001; unadjusted HR 4.44, 95% CI 2.13-9.25, P < 0.001) and major adverse events (35% vs. 11%, P < 0.0001; unadjusted OR 4.29, 95% CI 2.50-7.40, P < 0.0001). Myocardial injury was associated with major adverse events (adjusted OR 3.84, 95% CI 2.00-7.36, P < 0.0001) but not mortality. Baseline (adjusted OR 1.003, 95% CI 1.00-1.007, P = 0.047) and maximum (adjusted OR 1.005, 95% CI 1.001-1.009, P = 0.0012) hs-cTnT were independent predictors of major adverse events. Most (95%) increases were due to myocardial injury, with 5% (n = 8) classified as type 1 or 2 myocardial infarction. A single hs-cTnT <6 ng/L identified 26% of patients without mortality, with a 94.9% (95% CI 87.5-98.6) negative predictive value and 93.1% sensitivity (95% CI 83.3-98.1) for major adverse events in those presenting to the ED., Conclusions: Myocardial injury is frequent and prognostic in COVID-19. While most hs-cTnT increases are modest and due to myocardial injury, they have important prognostic implications. A single hs-cTnT <6 ng/L at presentation may facilitate the identification of patients with a favorable prognosis., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Limited U.S. data exist regarding high-sensitivity cardiac troponin (cTn) implementation., Objectives: This study sought to evaluate the impact of high-sensitivity cardiac troponin T (cTnT) implementation., Methods: Observational U.S. cohort study of emergency department (ED) patients undergoing measurement of cTnT during the transition from 4th (pre-implementation March 12, 2018, to September 11, 2018) to 5th generation (Gen) cTnT (post-implementation September 12, 2018, to March 11, 2019). Diagnoses were adjudicated following the Fourth Universal Definition of Myocardial Infarction (MI). Resources evaluated included length of stay, hospitalizations, and cardiac testing., Results: In this study, 3,536 unique patients were evaluated, including 2,069 and 2,491 ED encounters pre- and post-implementation. Compared with 4th Gen cTnT, encounters with ≥1 cTnT >99th percentile increased using 5th Gen cTnT (15% vs. 47%; p < 0.0001). Acute MI (3.3% vs. 8.1%; p < 0.0001) and myocardial injury (11% vs. 38%; p < 0.0001) increased. Although type 1 MIs increased (1.7% vs. 2.9%; p = 0.0097), the overall MI increase was largely due to more type 2 MIs (1.6% vs. 5.2%; p < 0.0001). Women were less likely than men to have MI using 4th Gen cTnT (2.3% vs. 4.4%; p = 0.008) but not 5th Gen cTnT (7.7% vs. 8.5%; p = 0.46). Overall length of stay and stress testing were reduced, and angiography was increased (all p < 0.05). Among those without cTnT increases, there were more ED discharges and a reduction in length of stay, echocardiography, and stress tests (all p < 0.05)., Conclusions: High-sensitivity cTnT implementation resulted in a marked increase in myocardial injury and MI, particularly in women and patients with type 2 MI. Despite this, except for angiography, overall resource use did not increase. Among those without cTnT increases, there were more ED discharges and fewer cardiac tests., Competing Interests: Funding Support and Author Disclosures This publication was made possible in part by the Mayo Clinic CTSA through grant UL1TR002377 from the National Center for Advancing Translational Sciences, a component of the National Institutes of Health. Dr. Jaffe has consulted or presently consults for most of the major diagnostics companies, including Beckman, Abbott, Siemens, ET Healthcare, Roche, Radiometer, Sphingotec, Amgen, and Novartis. Dr. Sandoval has previously served on the Advisory Boards for Roche Diagnostics and Abbott Diagnostics without personal compensation; and has also been a speaker without personal financial compensation for Abbott Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)