Acute Coronary Syndrome: Biochemical Strategies in the Troponin Era

doi:10.1378/chest.122.4.1428

Chest

Volume 122, Issue 4, October 2002, Pages 1428-1435

https://doi.org/10.1378/chest.122.4.1428 Get rights and content

New biomarkers, such as cardiac troponins, have a major role to play for cost-effective management of individuals with acute chest pain and suspected coronary syndrome, and the laboratory is now poised to assume a vital role in assessing damage and determining prognosis. The redefined biochemical criterion proposed to classify acute coronary syndrome patients presenting with ischemic symptoms as patients with myocardial infarction is heavily predicated on an increased troponin concentration in blood. In an era of evidence-based medicine, we can no longer overlook the diagnostic and prognostic benefits provided by the measurement of these highly sensitive and specific proteins.

Section snippets

The Troponin Era

Considering these pitfalls in the traditional criteria for diagnosis of AMI and the excellent findings of several clinical trials using highly sensitive and specific markers of heart muscle damage that are not themselves enzymes, such as cardiac troponins, the Committee on Standardization of Markers of Cardiac Damage (C-SMCD) of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) made in 1999 a recommendation to expand on the enzyme diagnostic criteria for AMI to

The Biochemical Strategy

An important point concerns the selection of the most appropriate strategy for the use of new markers and the suggested sample frequency in patients with chest pain and without ECG evidence of AMI at hospital admission. In fact, the excitement of new applications in the use of biomarkers to improve routine patient care can be offset by angst regarding the appropriate selection and utilization of currently available and new assays.

Two strategies have competed in this area. The first relies on

Selection of Decision Limits for Troponin Use

One of the most important problems in the practical use of the cardiac-specific troponins is the right definition of decision limits. The basic question is, “How much necrosis is needed to make the diagnosis of AMI?”²⁹ In the purest physiologic sense, the answer is that any detectable necrosis is an AMI. Consequently, even small elevations of specific markers of myocardial damage, such as cardiac troponins, should be acknowledged as indicative of significant injury, reflecting the incremental

Biomarkers in ST-Segment Elevation of Myocardial Infarction

As previously stated, since the sensitivity of the initial ECG is only 60% for detecting AMI, the use of the new biochemical markers may significantly contribute to the early diagnosis and become relevant just when ECG is not diagnostic. Conversely, there is no need for the use of any biochemical marker when the clinical diagnosis of AMI is unequivocal. In these patients, biochemical marker testing is indeed unnecessary for diagnostic purposes, being the ECG changes, namely ST-segment elevation

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Cited by (67)

Death or revascularization among nonadmitted ED patients with low-positive vs negative troponin T results
2014, American Journal of Emergency Medicine
Citation Excerpt :
This of course implies that 1% of patients without acute myocardial injury have a result above this threshold. Initial enthusiasm about the specificity of troponin assays has given way to the realization that troponin can be elevated in conditions other than acute myocardial injury, including chronic renal failure, chronic heart disease, and skeletal muscle disease [1,3]. In such cases, a low-positive troponin result may be an important prognostic indicator for long-term serious outcomes due to causes other than coronary occlusion, but the relevance of this result during a “rule-out myocardial infarction (MI)” evaluation is poorly understood [4].
Compare outcomes among emergency department (ED) patients with low-positive (0.01-0.02 ng/mL) vs negative troponin T.
Retrospective cohort study of nonadmitted ED patients with troponin testing at a tertiary-care hospital. Trained research assistants used a structured tool to review charts from all nonadmitted ED patients with troponin testing, 12/1/2009 to 11/30/2010. Outcomes of death and coronary revascularization were assessed at 30 days and 6 months via medical record review, Social Security Death Index searches, and patient contact.
There were 57 596 ED visits; with 33 388 (58%) discharged immediately, 6410 (11%) assigned to the observation unit, and 17 798 (31%) admitted or other. Troponin was measured in 2684 (6.7%) of the nonadmitted cases. Troponin was negative in 2523 (94.0%), low positive in 78 (2.9%), and positive (≥ 0.03 ng/mL) in 83 (3.1%). Of troponin-negative cases, 0.8% (95% CI, 0.4-1.1%) died or were revascularized by 30 days, vs 2.8% (95% CI, 0.0-6.7%) of low-positive cases (risk difference [RD], 2.0%; 95% CI, − 1.8 to 5.9%). At 6 months, the rates were 1.7% (95% CI, 1.1-2.2%) and 12.9% (95% CI, 5.0-20.7%) (RD, 11%; 95% CI, 3.3-19.1%). Death alone at 30 days occurred in 0.4% (95% CI, 0.1-0.6%) vs 1.3% (95% CI, 0.0-3.8%) (RD, 0.9%; 95% CI, − 1.6 to 3.4%). Death at 6 months occurred in 1.2% (95% CI, 0.8-1.6%) vs 11.7% (95% CI, 4.5-18.9%) (RD, 10%; 95% CI, 3.3-17.7%).
Among patients not initially admitted, rates of death and coronary revascularization differed insignificantly at 30 days but significantly at 6 months. Detailed inspection of our results reveals that the bulk of the added risk at 6 months was due to non-cardiac mortality.
High-sensitivity troponin: A new tool for pathophysiological investigation and clinical practice
2009, Advances in Clinical Chemistry
Citation Excerpt :
First generation cTnT assays were, however, susceptible to false positivity due to cross-reactivity with skeletal TnT antibody [10]. Second generation immunoassay methods, designed using more highly specific antibodies, solved the interference problem with skeletal muscle isoforms and showed comparable results with cTnI assays [11–13]. Substantial data exist today that conclusively demonstrate that methods that rely on cTnI and cTnT detection share absolute specificity for myocardial damage.
At the dawn of the new century, the advent of more specific myocardial tissue markers, such as cardiac troponin I (cTnI) and T (cTnT), has led to a new definition of acute myocardial infarction (AMI) by international guidelines. If we accept the concept that AMI is the portion of acutely necrotic myocardial tissue (irrespective of size), some patients previously diagnosed with severe angina may be currently considered to present minimal (even microscopic) quantities of myocardial necrosis. Although increased cTnI or cTnT values always indicate myocardial tissue damage, a positive test is not able to identify the mechanism responsible for that cardiac damage (which could be not due to ischemia). New cTnI and cTnT immunoassays with increased analytical sensitivity may increase “false positive” results in patients with cardiovascular disease, especially those with advanced age, heart failure (HF), severe comorbidities (such as chronic renal insufficiency), or assuming potential cardiotoxic drugs. Hence, it may be not clear for most patients and physicians whether high-sensitivity cTnI and cTnT methods will lead to more clarity or confusion. The aim of this review is to update the present knowledge in the field of cTnI and cTnT with particular attention on the impact of immunoassays with increased analytical sensitivity on both laboratory and clinical practice.
Earlier detection of myocardial infarction by an improved cardiac TnI assay
2007, Clinical Biochemistry
The aim of this study was to establish the diagnostic sensitivity of combinations of well-selected monoclonal antibodies (mAbs) against cardiac troponin I (cTnI) to allow an earlier rule-in of acute coronary syndrome (ACS) patients.
Using several combinations of mAbs, four new experimental cTnI immunoassays were evaluated to analyze plasma samples from 62 patients suffering from angina (16/62), patients having a chest pain of extracardiovascular origin (19/62) and ACS without ST elevation (NSTE-ACS) (27/62).
Assay 2, which relies on a capture mAb directed against the central part of cTnI and two conjugated mAbs directed against the N-ter region, provided the best clinical sensitivity. In 11 out of 27 patients with NSTE-ACS, it detected an early rise of cTnI within 0 and 1 h upon admission, contributing to the detection of 53% of samples found to be negative by the reference AccuTnI Assay upon admission (Beckman Coulter), thereby reducing the delay in diagnosis.
Assay 2 can identify early cTnI elevation in NSTE-ACS, possibly facilitating the rule-in procedure for these patients once the assay is automated.
In vitro and in vivo examination of cardiac troponins as biochemical markers of drug-induced cardiotoxicity
2007, Toxicology
Cardiac troponin T (cTnT) and troponin I (cTnI) are becoming acknowledged as useful biochemical markers of drug-induced cardiotoxicity. In this study we examined the release kinetics of cTnT and cTnI using an in vitro model of isolated rat neonatal ventricular cardiomyocytes (NVCM, 72 h treatment with 0.1–3 μM of daunorubicin) and compared it with data from a rabbit model of chronic anthracycline-induced cardiomyopathy in vivo (3 mg/kg of daunorubicin weekly, 10 weeks). In cell-culture media, the cTnI and cTnT concentrations were concentration- and time-dependently increasing in response to daunorubicin exposure and were negatively exponentially related to cardiomyocyte viability. With 3 μM daunorubicin, the relative increase of AUC of cTnT and cTnI was 2.4- and 5.3-fold higher than the increase of LDH activity, respectively. In rabbits, the daunorubicin-induced cardiomyopathy was associated with progressive increase of both cTnT and cTnI. Although the correlation between cTnT and cTnI cumulative release (AUCs) was found (R = 0.81; P < 0.01) and both cardiac troponins corresponded well with the echocardiographically-assessed systolic dysfunction (R = 0.83 and 0.81 for cTnT and cTnI, respectively; P < 0.001), the first significant increase in cTnI levels was observed earlier (at a cumulative daunorubicin dose of 200 mg/m²) than with cTnT (350 mg/m²). In conclusion, our study has confirmed cTnT and cTnI as very sensitive and specific markers of anthracycline-induced cardiotoxicity. The troponins can become not only the bridge between the clinical and experimental studies of drug-induced cardiotoxicity but also the linkage between the preclinical experiments in vitro and in vivo.
From multi-omics approaches to personalized medicine in myocardial infarction
2023, Frontiers in Cardiovascular Medicine
Early diagnosis of brain natriuretic peptide (pro-BNP) and ischemia modified albumin (IMA) levels in acute coronary syndrome patients with ST segment elevation myocardial Infarction (STEMI) and non ST segment elevation myocardial Infarction (NSTEMI)
2020, Systematic Reviews in Pharmacy

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Chest

ReviewAcute Coronary Syndrome: Biochemical Strategies in the Troponin Era

Section snippets

The Troponin Era

The Biochemical Strategy

Selection of Decision Limits for Troponin Use

Biomarkers in ST-Segment Elevation of Myocardial Infarction

Am J Cardiol

Am J Cardiol

Clin Chim Acta

Clin Chim Acta

Am Heart J

Clin Biochem

Am J Cardiol

Clin Chim Acta

The challenge of evaluating the patient with chest pain

Arch Pathol Lab Med

Evaluation of the patient with acute chest pain

N Engl J Med

Optimizing classification of acute myocardial infarction: from diagnosis to prognosis

Eur Heart J

Nomenclature and criteria for diagnosis of ischemic heart disease: report of the Joint International Society and Federation of Cardiology/World Health Organization Task Force on Standardization of Clinical Nomenclature

Circulation

Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain

JAMA

Biochemical assessment of myocardial damage with new diagnostic tools

Cardiologia

Evaluation of the emergency department chest pain patients

Am J Cardiol

Missed diagnoses of acute cardiac ischemia in the emergency department

N Engl J Med

Use of biochemical markers in acute coronary syndromes. IFCC Scientific Division, Committee on Standardization of Markers of Cardiac Damage

Clin Chem Lab Med

It's time for a change to a troponin standard

Circulation

Cardiac troponin T composition in normal and regenerating human skeletal muscle

Clin Chem

Biochemical differences between cTnT and cTnI and their significance for diagnosis of acute coronary syndromes

Eur Heart J

International survey on the use of cardiac markers

Clin Chem

National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for the use of cardiac markers in coronary artery diseases

Clin Chem

Single-point troponin T measurement on the day of coronary unit discharge after myocardial infarction strongly correlates with ejection fraction and infarct size by nuclear imaging and with CK-MB release [abstract]

Clin Chem

Cardiac biochemical algorithms in the troponin era: audit of some care maps one year after their introduction

Biochim Clin

The sensitivity of cardiac markers: an evidence-based approach

Clin Chem Lab Med

Evidence based approach to practice guides and decision thresholds for cardiac markers

Scand J Clin Lab Invest

Strategies for the early diagnosis of acute myocardial infarction using biochemical markers

Am J Clin Pathol

Long-term experience with an accelerated protocol for diagnosis of chest pain

Arch Pathol Lab Med

Troponin T: role in altering patient management and enabling earlier discharge from a district general hospital

Ann Clin Biochem

Biochemical markers of cardiac damage: what is current, what is redundant?

Biochim Clin

Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease

N Engl J Med

Review
Acute Coronary Syndrome: Biochemical Strategies in the Troponin Era