Redefinition Of Acute Myocardial Infarction Research Articles

The Perils, Pitfalls and Opportunities of Using High Sensitivity Cardiac Troponin

Cardiac troponins (cTn) are considered to be the 'gold standard' biomarker for the diagnosis of acute coronary syndrome (ACS); a pathological spectrum which includes cardiac ischemia, angina, myocardial infarction and ultimately cardiac failure. The growing evidence base for the diagnostic and prognostic use of cTn in ACS has resulted in a universal redefinition of acute myocardial infarction (AMI). Recently a number of immunoassays with claims of superior sensitivity have been produced. The analytical and clinical performance of these assays require appropriate evaluation. Sensitive assays can be used for diagnosis in the first few hours after an ischemic episode. Early elevations in cTn are prognostic. A single time point for cTn testing may be useful for rule out, however such a strategy does not detect the rising and falling pattern required for diagnosis as suggested in the universal definition of AMI. The newer assays demonstrate low level cTn positivity in apparently healthy people. In addition, the sensitive assays detect more cTn positive patients who do not have a final diagnosis of ACS. It is unknown if such mild elevations in cTn detected by sensitive assays are of clinical concern. What is certain is that AMI remains a clinical not a biochemical diagnosis and interpretation of cTn concentrations should be made according to the clinical context. This review highlights the development of the sensitive assays, documents their analytical and clinical performance and reviews the usefulness of cTn elevation in non-ACS conditions.

Reply to Letter Regarding Article, “High-Sensitivity Troponin T Concentrations in Acute Chest Pain Patients Evaluated With Cardiac Computed Tomography”

We appreciate the very insightful comments by Drs Lippi and Cervellin regarding our study1 and agree that the exceptional analytic sensitivity of the novel high-sensitivity (hs) troponin (hsTn) assays raises several very important questions about their optimal use in the evaluation of patients with suspected or proven acute coronary syndrome (ACS), including those with acute myocardial infarction (MI). The tension created today by the hsTn assays is rather reminiscent of that when original cardiac troponin (cTn) methods were released nearly 20 years ago. Indeed, with the initial use of first-generation cardiac-specific cTnT or cTnI assays, it was immediately evident that these tests were more sensitive for acute MI than creatine kinase-MB (CK-MB); this led to confusion about the correct nomenclature of a cTn-positive/CK-MB–negative event. Subsequent studies demonstrated patients with such a syndrome had a risk comparable to that of an acute MI,2 and the biochemical redefinition of acute MI was changed to a cTn …

Sensitive Cardiac Troponin Assays: Myth and Magic or a Practical Way Forward?

Sensitive Cardiac Troponin Assays: Myth and Magic or a Practical Way Forward?Cardiac troponins (cTn) are considered to be the ‘gold standard’ biomarkers for the diagnosis of acute coronary syndrome (ACS) a pathological spectrum which includes cardiac ischemia, angina, myocardial infarction and ultimately cardiac failure. The growing evidence base for the diagnostic and prognostic use of cTn in ACS has resulted in a universal redefinition of acute myocardial infarction (AMI). A diagnosis of AMI includes the detection of an elevated cTn (or CK-MB) with at least one measurement within 24 hours of the cardiac episode being >upper 99th percentile of a reference population, in conjunction with evidence of myocardial ischemia. A number of high sensitivity immunoassays with claims of superior imprecision and a definable 99th percentile have been produced. Clinically, these have two important impacts. First, there is a drive to change the values into whole numbers by the application of a unit change which carries the scope for confusion. Secondly, the near-normal Gaussian distribution of sensitive cTn in healthy subjects will increase the frequency of cTn positivity in the non-ACS population. The problem is to decipher if such minor elevations in cTn are of clinical concern. What is certain is that AMI remains a clinical not a biochemical diagnosis and the interpretation of cTn concentrations should be made according to the clinical context.

10 years of data collected in the Berlin Myocardial Infarction Registry (BMIR) – Changes in treatment and outcome for patients with acute myocardial infarction

Background: Over a decade of years, from 1999–2008, guidelines for treatment of patients with myocardial infarction (MI) have been regularly updated and new definitions for acute MI have been established. Aim of the present study was to investigate the changes in treatment and hospital mortality over this 10-year period in acute MI-patients under the influence of the implementation of guideline-based therapy and the redefinition of acute myocardial infarction in Berlin, Germany. Methods: In the BMIR, data of patients with acute myocardial infarction (AMI) have been collected prospectively since 1999. We analyzed data from 1.1.1999–1.4.2008 of 11 hospitals continuously participating in the BMIR. We consecutively included 9830 MI patients. Demographic data, data on reperfusion therapy and discharge medication, and on hospital mortality were analyzed. Results:

Cardiac Troponin in Cerebral Injury: Understanding your Laboratory Reports

Cardiac troponin (cTn) is now the ‘gold standard’ biochemical test for the diagnosis of acute coronary syndrome (ACS). This clinical spectrum of ischemic heart disease includes stable and unstable angina through to acute myocardial infarction (AMI). The growing evidence base for the diagnostic and prognostic use of cTn in ACS has resulted in the redefinition of AMI [1]. With increasing popularity owing to ease of measurement, the presence of a tick box on a laboratory request form and a reduction in test price, cTn is a common request in many clinical scenarios outside the remit of ACS. This has resulted in the identification of a plethora of elevated cTn in other conditions, often creating clinical confusion. With the redefinition of AMI, many emergency physicians could not adequately distinguish between a primary acute coronary syndrome and secondary ischemic or nonischemic disease states [2], plainly from ignoring the clinical history. A common misconception is that elevated cTn indicates AMI. It does not. All cTn elevations indicate myocardial cell necrosis [3] but not the pathological mechanism of release. Anecdotal data from a London teaching hospital demonstrate as many as 30% of all medical noncardiac admissions with elevated serum cTn do not have a final diagnosis of ACS [2]. Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are expressed in the cardiac myocyte. A small circulating pool exists in the cytosol, but greater than 90% is bound to the thin filament of the contractile apparatus. The cardiac isoforms are distinctly different in amino acid sequence from those expressed in skeletal muscle. Monoclonal antibodies have been raised against cTnT and cTnI and form the basis of immunoassay tests that have been in commercial use since the early 1990s [4]. Patients presenting to the emergency department with an acute cerebral injury may be cognitively impaired or exhibit severe speech

Development of the Cardiac Troponin T Immunoassay

Featured Article: Katus HA, Looser S, Hallermayer K, Remppis A, Scheffold T, Borgya A, et al. Development and in vitro characterization of a new immunoassay of cardiac troponin T. Clin Chem 1992;38:386–93.1 This paper was the first report on the development and analytical characterization of an immunoassay for cardiac troponin T (cTnT)2 that was useful for large-scale clinical chemistry testing. Preceding methods we had generated for measurement of cTnT using a pilot immunoassay yielded promising clinical data in patients with chest pain, indicating a higher diagnostic sensitivity and specificity than measurement of cardiac enzymes for detection of myocardial injury. Whereas the pilot assay used polyclonal antisera, the novel sandwich assay employed 2 preselected monoclonal antibodies with high cardiospecificity, thereby decreasing cross-reactivity with skeletal muscle troponin T to <0.5%. This cTnT assay allowed measurement of cTnT in only 90 min with a between-run precision below 5%. The assay was manufactured by Boehringer Mannheim (Enzymun-Test System) and provided sufficient analytical sensitivity and precision to be employed in large multicenter trials, which ultimately led to the redefinition of acute myocardial infarction (AMI). This report …

Intraoperative myocardial infarction in non-cardiac surgery: is a universal definition feasible?

Diagnostic criteria for the redefinition of acute myocardial infarction (AMI) have been recently published.1 In this new classification, intraoperative (IPEMI) or post-operative (POMI) AMI, in the setting of non-cardiac surgery, were not included. It is well known that this category of AMI occurs under particular circumstances while the diagnostic criteria have not been fully elucidated.2 Patients with pre-operative cardiac risk undergoing intermediate or high surgical risk operations are more prone to IPEMI and POMI. …

The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: Lessons from the Global Registry of Acute Coronary Events (GRACE)

The impact and prognostic value of the redefinition of myocardial infarction (MI) with more sensitive markers have not been evaluated prospectively in a large, less selected population with acute coronary syndrome (ACS). We evaluated the attack and case-fatality rates of MI based on initial and/or peak creatine kinase (CK), creatine kinase-MB (CK-MB), and cardiac troponin (the upper limit of normal [ULN] was defined according to the local hospital's standard) in a prospective observational registry of 26,267 patients with ACS admitted to 106 hospitals in 14 countries. The addition of cardiac troponin-positive status to CK status as a criterion for the diagnosis of MI resulted in as many as 1 in 4 additional patients meeting the redefined criteria. Compared with patients without elevated levels of CK and cardiac troponin, the crude odds for dying during hospitalization were significantly higher for patients with elevated troponin but not CK levels of greater than or equal to the ULN (odds ratio [OR] 2.2, 95% CI 1.6-2.9), those without CK levels >2 times the ULN (OR 2.8, 95% CI 2.2-3.5), and those with nonelevated levels of CK-MB (OR 2.1, 95% CI 1.4-3.2). The addition of cardiac troponin-positive status significantly increased the multivariable-adjusted odds for hospital death in patients with CK < or =2 times the ULN (OR 1.6, 95% CI 1.2-2.1) but not for patients without elevated levels of CK or CK-MB. The prognostic value of cardiac troponin, beyond that supplied by CK status or important baseline characteristics, assists in the identification of patients with ACS who are at increased risk for death.

The role of cardiac troponin in the recent redefinition of acute myocardial infarction.

1. Alan HB Wu, PhD[⇑][1] 1. is at Hartford Hospital, Hartford CT 1. Address for correspondence: Alan HB Wu PhD, Department of Pathology and Laboratory Medicine, Hartford Hospital, 80 Seymour St, Hartford CT 06102. (860) 545-5221, (860) 545-3733 (fax). awu{at}harthosp.org 1. Describe the structure and function of the three troponin proteins. 2. Explain the release of cardiac troponins following an acute myocardial infarction. 3. Discuss the clinical utility of troponin T versus troponin I. 4. Describe the impact of troponin assays on the redefinition of acute myocardial infarction. 5. Explain the issues surrounding lower cutoff concentrations for troponin assays. Troponin is a complex of three proteins (troponins T, I, and C) that bind to the thin filament (actin) of striated muscle. Its major regulatory function is to bind calcium and regulate muscle contraction. Following injury to muscle cells (heart or skeletal muscles) the intact troponin complex along with free troponin subunits are released into blood. Although troponin is found in both skeletal muscles and the myocardium, the amino acid sequences for cardiac troponin T (cTnT) and I (cTnI) isoforms are significantly different from their skeletal muscle counterparts. This is not the case for troponin C, where the subunits from these tissues are identical. Commercial assays have been constructed for measurement of cTnT and cTnI in blood that have been shown to have high specificity for cardiac disease. These assays also have high sensitivity, because the tissue concentrations of cardiac troponin T and I are higher than for other cardiac markers such as myoglobin and creatine kinase. Moreover, the normal concentrations of these cardiac proteins are much lower than for myoglobin and CK, as these proteins are also released from normal skeletal muscle turnover.1 Following acute myocardial infarction (AMI), cardiac troponins are released into blood from two subcellular pools. The initial rise within the first six hours after disease onset is due to the free cytosolic pool, estimated to be about 6% to 8% for cTnT and 3% to 4% for cTnI.2 There is a second, continual increase of cardiac troponin that is due to the gradual breakdown of myofibrils… ABBREVIATIONS: AMI = acute myocardial infarction; cTnI = cardiac troponin I; cTnT = cardiac troponin T. 1. Describe the structure and function of the three troponin proteins. 2. Explain the release of cardiac troponins following an acute myocardial infarction. 3. Discuss the clinical utility of troponin T versus troponin I. 4. Describe the impact of troponin assays on the redefinition of acute myocardial infarction. 5. Explain the issues surrounding lower cutoff concentrations for troponin assays. [1]: #corresp-1

The Clinical Significance of Redefinition of Acute Myocardial Infarction by ESC/ACC

Background and Objectives:Epidemiologic studies and clinical trials require a more precise definition of acute myocardial infarction (AMI). The advent of sensitive and specific serologic biomarkers can identify those patients with small areas of myocardial necrosis. Acute myocardial infarction was redefined and approved by the ESC/ACC on September, 2000. To investigate the clinical implications of the revised criteria, the clinical features, the in-hospital outcomes and the 18 months outcomes were compared between the AMI patients who were diagnosed using the definition of the WHO criteria and those AMI patients added by the revised criteria. Subjects and Methods:One hundred and seventy four consecutive patients diagnosed as AMI by the new criteria were included in the study. These patients with positive cardiac enzymes and ischemic symptoms or signs (n=174) were divided into two groups. The patients of group 1 (n=105) were the patients who were diagnosed with AMI by the WHO criteria, and the patients of group 2 (n=69), were the additional patients who were diagnosed with AMI only by the new criteria. Results:The new criteria of AMI by ESC/ACC increased the numbers of AMI by 66%. As compared with group 1, women and patients with hypertension and a past history of ischemic heart disease were more common in group 2 (p<0.05). Percutaneous coronary intervention (PCI) was used less frequently and Angiotensin converting enzyme inhibitors (ACEIs), beta blockers and aspirin were prescribed less frequently in group 2. The total cardiac events and cumulative survival rate in group 1 were higher than in Group 2 (12.3% vs 7.2%, 89% vs 94%, respectively) but these differences were not statistically significant. Conclusion:The new criteria results in a substantial increase in the diagnosis of AMI, and the new criteria helps identify patients who were missed by the old criteria. The patients with AMI who were added by the new criteria had a similar risk of adverse outcome. (Korean Circulation J 2004;34(12):1188-1193)

Cardiac biomarkers and acute coronary syndromes--the Euro Heart Survey of Acute Coronary Syndromes Experience.

AMIS: To examine the application of the redefinition of acute myocardial infarction (AMI) published on 4 September 2000. The Euro Heart Survey of Acute Coronary Syndromes (ACS) prospectively surveyed 10484 patients in 103 hospitals across 25 European and Mediterranean basin countries during 4 September 2000 to 15 May 2001. We evaluated the use of cardiac troponin assays and whether the diagnosis of unstable angina (UA) or AMI was in accordance with the results of biomarker assays (cardiac troponins, CK-MB mass, CK-MB%, or CK). Troponin assays were used in 6036 (63.3%) of the 9538 patients with available biomarker levels; of whom elevated troponin levels were recorded in 648 of 2307 (28.1%) patients with UA and in 2957 of 3729 (79.3%) patients with AMI. Of the 8871 patients with available creatine kinase values, levels above the upper limit of normal were recorded in 848 of 3625 (23.4%) patients with UA and in 3948 of 5246 (75.3%) patients with AMI. Cardiac troponin assays are still not universally available for the evaluation of ACS patients. A substantial proportion of ACS patients receive a diagnosis of UA or AMI, irrespective of the result of biomarker assays, indicating that the redefinition of AMI has not yet been universally adopted, and that additional efforts are warranted to ensure its appropriate implementation.