scholarly journals Quantifying the Release of Biomarkers of Myocardial Necrosis from Cardiac Myocytes and Intact Myocardium

2017 ◽  
Vol 63 (5) ◽  
pp. 990-996 ◽  
Author(s):  
Jack Marjot ◽  
Thomas E Kaier ◽  
Eva D Martin ◽  
Shiney S Reji ◽  
O'Neal Copeland ◽  
...  

AbstractBACKGROUNDMyocardial infarction is diagnosed when biomarkers of cardiac necrosis exceed the 99th centile, although guidelines advocate even lower concentrations for early rule-out. We examined how many myocytes and how much myocardium these concentrations represent. We also examined if dietary troponin can confound the rule-out algorithm.METHODSIndividual rat cardiac myocytes, rat myocardium, ovine myocardium, or human myocardium were spiked into 400-μL aliquots of human serum. Blood was drawn from a volunteer after ingestion of ovine myocardium. High-sensitivity assays were used to measure cardiac troponin T (cTnT; Roche, Elecsys), cTnI (Abbott, Architect), and cardiac myosin-binding protein C (cMyC; EMD Millipore, Erenna®).RESULTSThe cMyC assay could only detect the human protein. For each rat cardiac myocyte added to 400 μL of human serum, cTnT and cTnI increased by 19.0 ng/L (95% CI, 16.8–21.2) and 18.9 ng/L (95% CI, 14.7–23.1), respectively. Under identical conditions cTnT, cTnI, and cMyC increased by 3.9 ng/L (95% CI, 3.6–4.3), 4.3 ng/L (95% CI, 3.8–4.7), and 41.0 ng/L (95% CI, 38.0–44.0) per μg of human myocardium. There was no detectable change in cTnI or cTnT concentration after ingestion of sufficient ovine myocardium to increase cTnT and cTnI to approximately 1 × 108 times their lower limits of quantification.CONCLUSIONSBased on pragmatic assumptions regarding cTn and cMyC release efficiency, circulating species, and volume of distribution, 99th centile concentrations may be exceeded by necrosis of 40 mg of myocardium. This volume is much too small to detect by noninvasive imaging.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T.R Johannessen ◽  
D Atar ◽  
O.M Vallersnes ◽  
A.C.K Larstorp ◽  
I Mdala ◽  
...  

Abstract Background Patients presenting with acute chest pain outside of hospitals represent a diagnostic challenge. Purpose We aimed to validate whether a single high-sensitivity cardiac troponin T (hs-cTnT) safely can rule out acute myocardial infarction (AMI) in a primary care emergency setting. In addition, we aimed to investigate if the hs-HEART (History, Electrocardiogram (ECG), Age, Risk factors, and hs-Troponin) score would add valuable diagnostic information. Methods This is a secondary analysis from a prospective diagnostic study, including 1711 patients with acute non-specific chest pain presenting to a primary care emergency clinic from November 2016 to October 2018. The European Society of Cardiology (ESC) 0/1-hour algorithm triages patients towards direct rule-out if the 0-hour hs-cTnT is below 5 ng/L, combined with a normal ECG and a 3-hour symptom duration. The hs-HEART score (0–10 points) was calculated retrospectively, and a score ≤3 points was considered low-risk. In addition, a modified hs-HEART score, with more comparable hs-cTnT cut-off values, was applied. The primary endpoint was AMI during the index episode; the secondary the 90-day incidence of AMI (including index) and all-cause death. Results Among 1711 patients, 61 (3.6%) had an AMI, and 525 (30.7%) were assigned towards direct rule-out. With no AMIs in this group, the rule-out safety was high (negative predictive value (NPV) and sensitivity 100%). The hs-HEART score triaged more patients (n=966) as low-risk, but missed six AMIs (NPV 99.4% and sensitivity 90.2%). The modified hs-HEART score (n=707, AMI=3) increased the low-risk sensitivity to 95.1%. The 90-day incidence of AMI and all-cause death in the direct rule-out, low-risk hs-HEART, and modified hs-HEART group, were 0.0%, 0.7%, and 0.4%, respectively. Conclusions The ESC direct rule-out approach, with a single hs-cTnT below 5 ng/L, combined with a normal ECG, and a 3-hour symptom duration, is superior to the two hs-HEART scores in ruling out AMI in a primary care emergency setting. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Norwegian Research Fund for General Practice


Author(s):  
Chen Dongxu ◽  
Zhou Yannan ◽  
Yang Yilin ◽  
Yao Chenling ◽  
Gu Guorong ◽  
...  

Abstract Objectives A rapid 0 h/1 h algorithm using high-sensitivity cardiac troponin T (hs-cTnT) for rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) is recommended by the European Society of Cardiology. We aim to prospectively evaluate the diagnostic performance of the algorithm in Chinese Han patients with suspected NSTEMI. Methods In this prospective diagnostic cohort study, 577 patients presenting to the emergency department with suspected NSTEMI and recent (<12 h) onset of symptoms were enrolled. The levels of serum hs-cTnT were measured on admission, 1 h later and 4–14 h later. All patients underwent the initial clinical assessment and were triaged into three groups (rule-out, rule-in and observe) according to the 0 h/1 h algorithm. The major cardiovascular events (MACE) were evaluated at the 7-day and 30-day follow-ups. Results Among 577 enrolled patients, NSTEMI was the final diagnosis for 106 (18.4%) patients. Based on the hs-cTnT 0 h/1 h algorithm, 148 patients (25.6%) were classified as rule-out, 278 patients (48.2%) as rule-in and 151 patients (26.2%) were assigned to the observe group. The rule-out approach resulted in a sensitivity of 100% and negative predictive value of 100%. The rule-in approach resulted in a specificity of 62.9% [95% CI (58.5–67.2%)] and positive predictive value of 37.1% [95%CI (31.3–42.8%)]. No MACE was observed in the rule-out group within 30-day follow-up. Conclusions The hs-cTnT 0 h/1 h algorithm is a safe tool for early rule-out of NSTEMI, while probably not an effective strategy for accurate rule-in of NSTEMI in Chinese Han population.


2015 ◽  
Vol 187 (8) ◽  
pp. E243-E252 ◽  
Author(s):  
Tobias Reichlin ◽  
Raphael Twerenbold ◽  
Karin Wildi ◽  
Maria Rubini Gimenez ◽  
Nathalie Bergsma ◽  
...  

Cardiology ◽  
2020 ◽  
Vol 145 (11) ◽  
pp. 685-692
Author(s):  
Arash Mokhtari ◽  
Ardavan Khoshnood ◽  
Jakob Lundager Forberg ◽  
Caroline Hård af Segerstad ◽  
Ulf Ekström ◽  
...  

Chest pain is one of the most common complaints at the emergency department (ED), and it is commonly the perceived likelihood of acute coronary syndrome (ACS) that drives management. Guidelines from the European Society of Cardiology (ESC) recommend the use of a 0-/1-h high-sensitivity cardiac troponin T (hs-cTnT) protocol to rule out or in ACS, but this is mostly based on observational studies. The aim of the ESC-TROP trial is to determine the safety and effectiveness of the ESC 0-/1-h hs-cTnT protocol when implemented in routine care. Adult chest pain patients at 5 EDs in the Skåne Region, Sweden, are included in the trial. The 0-/1-h hs-cTnT ESC protocol supplemented with clinical assessment and electrocardiography (ECG) is implemented at 3 EDs, and the other 2 EDs act as concurrent controls. Outcomes will be evaluated during the 10 months after the implementation and the corresponding 10 months of the previous year. The 2 co-primary outcomes are (a) acute myocardial infarction (AMI) and all-cause death within 30 days in patients discharged from the ED, and (b) ED length of stay of the same patients. Secondary outcomes include the proportion of chest pain patients discharged from the ED and the number of ruled-out patients undergoing objective testing within 30 days. The ESC-TROP trial will determine the performance and applicability of the 0-/1-h hs-cTnT ESC protocol supplemented with clinical assessment and ECG when implemented in routine ED care. It will provide evidence whether 0-/1-h hs-cTnT testing is safe, effective, and feasible, and whether widespread implementation as recommended by ESC guidelines should be supported.


2019 ◽  
Vol 9 (1) ◽  
pp. 14-22 ◽  
Author(s):  
M Arslan ◽  
A Dedic ◽  
E Boersma ◽  
EA Dubois

Aims: The purpose of this study was to determine (a) the ability of serial high-sensitivity cardiac troponin T measurements to rule out acute myocardial infarction and (b) the ability of a single high baseline high-sensitivity cardiac troponin T measurement to rule in acute myocardial infarction in patients presenting to the emergency department with acute chest pain. Methods and results: Embase, Medline, Cochrane, Web of Science and Google scholar were searched for prospective cohort studies that evaluated parameters of diagnostic accuracy of serial high-sensitivity cardiac troponin T to rule out acute myocardial infarction and a single baseline high-sensitivity cardiac troponin T value>50 ng/l to rule in acute myocardial infarction. The search yielded 21 studies for the systematic review, of which 14 were included in the meta-analysis, with a total of 11,929 patients and an overall prevalence of acute myocardial infarction of 13.0%. For rule-out, six studies presented the sensitivity of serial measurements <14 ng/l. This cut-off classified 60.1% of patients as rule-out and the summary sensitivity was 96.7% (95% confidence interval: 92.3–99.3). Three studies presented the sensitivity of a one-hour algorithm with a baseline high-sensitivity cardiac troponin T value<12 ng/l and delta 1 hour <3 ng/l. This algorithm classified 60.2% of patients as rule-out and the summary sensitivity was 98.9% (96.4–100). For rule-in, six studies reported the specificity of baseline high-sensitivity cardiac troponin T value>50 ng/l. The summary specificity was 94.6% (91.5–97.1). Conclusion: Serial high-sensitivity cardiac troponin T measurement strategies to rule out acute myocardial infarction perform well, and a single baseline high-sensitivity cardiac troponin T value>50 ng/l to rule in acute myocardial infarction has a high specificity.


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