High-sensitive cardiac troponin T

Cardiac troponin is the preferred biomarker for the diagnosis of acute myocardial infarction (AMI). The recent development of a high-sensitive cardiac troponin T (hs-cTnT) assay permits detection of very low levels of cTnT. Using the hs-cTnT assay improves the overall diagnostic accuracy in patients with suspected AMI, while a negative result also has a high negative predictive value. The gain in sensitivity may be particularly important in patients with a short duration from symptom onset to admission. Measurement of cardiac troponin T with the hs-cTnT assay may provide strong prognostic information in patients with acute coronary syndromes, stable coronary artery disease, heart failure and even in the general population; however, increased sensitivity comes at a cost of decreased specificity. Serial testing, as well as clinical context and co-existing diseases, are likely to become increasingly important for the interpretation of hs-cTnT assay results.     

Coronary Computed Tomography Angiography for Evaluation of Chest Pain in the Emergency Department

Coronary computed tomography angiography has emerged as an important diagnostic modality for evaluation of acute chest pain in the emergency department for patients at low to intermediate risk for acute coronary syndromes. Several clinical trials have shown excellent negative predictive value of coronary computed tomography angiography to detect obstructive coronary artery disease. Cardiac biomarkers such as troponins and creatine kinase MB, along with history, electrocardiogram, age, risk factors, troponin score, and Thrombolysis in Myocardial Infarction score should be used in conjunction with coronary computed tomography angiography for safe and rapid discharge of patients from the emergency department. Coronary computed tomography angiography along with high-sensitivity troponin assays could be effective for rapid evaluation of acute chest pain in the emergency department, but high-sensitivity troponins are not always available. Emergency department physicians are not quite comfortable making clinical decisions, especially if the coronary stenosis is in the range of 50% to 70%. In these cases, further evaluation with functional testing, such as nuclear stress testing or stress echocardiogram, is a common approach in many centers; however, newer methods such as fractional flow reserve computed tomography could be safely incorporated in coronary computed tomography angiography to help with clinical decision-making in these scenarios.     

Impact of troponins on the evaluation and treatment of patients with acute coronary syndromes.

Cardiac troponins possess superior sensitivity and specificity for the detection of cardiac injury. They can be used successfully to replace measurements of MB isoenzyme of creatine kinase or lactate dehydrogenase for the retrospective diagnosis of myocardial infarction. Measurement of these proteins confers powerful prognostic information that can be used to triage patients. An increasing body of data suggests that measurement of troponin proteins can be useful to guide therapeutic decisions in patients with acute coronary artery syndromes, especially regarding treatment with low-molecular-weight heparin or IIB/IIIA inhibitors. The absence of troponins in the circulation does not necessarily indicate the absence of coronary artery disease. With current assays, a significant diagnostic difference does not appear to exist between cardiac troponin I and T in patients with acute coronary artery syndromes.     

Use and misuse of cardiac troponins in clinical practice

Cardiac troponins are very sensitive and specific markers of myocardial injury. Elevated troponin levels in the setting of acute coronary syndrome are diagnostic of acute myocardial infarction and provide guidance to clinicians with regard to appropriate use of intensive medical and revascularization therapies. However, elevated troponin levels are commonly seen in several noncoronary ischemia presentations and create considerable confusion among clinicians in these settings. In this review article, we discuss the utility of troponins in various clinical settings and present a "common sense" approach to interpreting troponin elevation outside the setting of acute coronary syndrome.     

C-reactive protein and other inflammatory biomarkers as predictors of outcome following acute coronary syndromes

Despite diagnostic and therapeutic advances, the rate of event recurrence is still relatively high and short- and long-term prediction of risk is necessary although extremely challenging to provide optimal treatment to patients with acute coronary syndromes. Available data recommend the use of C-reactive protein (CRP) as a prognostic marker in patients with acute coronary syndromes in addition to other prognostic factors including troponin levels. Evaluation of CRP levels at time of admission should be included in the evaluation of the patient's risk profile, including clinical data, associated diseases, markers of myocardial necrosis (especially troponin levels), left ventricle performance, and age. A cutoff level of 10 mg/L for CRP may be used as a marker of higher risk for death and possibly myocardial infarction in acute coronary syndromes, and a cutoff of 3 mg/L identifies a group of patients with intermediate risk and a high rate of recurrent events.     

Cardiac Troponins: Bench to Bedside Interpretation in Cardiac Disease

Cardiac troponins are the preferred biomarkers for the determination of acute myocardial necrosis. The high sensitivity of the available assays has significantly increased the detection of microscopic amounts of myocardial damage. Although compelling evidence indicates that elevated cardiac troponins are markers of poor prognosis and increased mortality, irrespective of the clinical scenario, small elevations can be seen in protean conditions and may confound the diagnosis of acute coronary syndromes. Emerging evidence suggests multiple different cellular mechanisms leading to cardiac troponin release, which challenge long held paradigms such as equivalency between troponin release into the circulation and irreversible cell death. Hence, knowledge of the physiology and pathophysiology of these cardiac biomarkers is essential for their accurate interpretation and consequent correct clinical diagnosis. Herein, the current relevant information about cardiac troponins is discussed, with special emphasis on pathophysiology and clinical correlates.     

Classification and risk stratification of patients with acute chest pain using a low discriminatory level of cardiac troponin T

BACKGROUND: Cardiac troponins are the biochemical markers of choice for the evaluation of acute coronary syndromes (ACS). Using the first-generation test, most studies related adverse outcome to > 0.20 or 0.10 microg/l cardiac troponin T (cTnT) levels. With the highly sensitive and specific second- and third-generation assays, cTnT is undetectable in most healthy individuals. HYPOTHESIS: We evaluated whether a lower cTnT level, within 24 h of admission, could indicate an increased risk of future complications. METHODS: During 1998-1999, clinical data were collected in 260 patients with ACS. Cardiac troponin T was measured at arrival, and 4, 8, and 12-24 h thereafter. The maximum cTnT value was then used to assess, over a 15-month follow-up period, the cumulative risk of death or myocardial infarction (MI), as well as rates of events according to quartiles of cTnT values. RESULTS: Patients with < or = 0.03 microg/l cTnT levels had the lowest rate of adverse events and the best Kaplan-Meier event-free survival curve. Increasing cTnT levels were associated with stepwise increases in mortality rates and with a constant 10-fold increase in MI rates during follow-up. CONCLUSIONS: A low threshold cTnT elevation is recommended to assess the risk of ACS. All cTnT elevations > 0.03 microg/l predict a higher risk of MI during follow-up, whereas increasing values predict mortality in relation to the amount of elevation.     

Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded

Current guidelines for the diagnosis of non-ST-segment elevation myocardial infarction are largely based on an elevated troponin level. While this rapid and sensitive blood test is certainly valuable in the appropriate setting, its widespread use in a variety of clinical scenarios may lead to the detection of troponin elevation in the absence of thrombotic acute coronary syndromes. Many diseases, such as sepsis, hypovolemia, atrial fibrillation, congestive heart failure, pulmonary embolism, myocarditis, myocardial contusion, and renal failure, can be associated with an increase in troponin level. These elevations may arise from various causes other than thrombotic coronary artery occlusion. Given the lack of any supportive data at present, patients with nonthrombotic troponin elevation should not be treated with antithrombotic and antiplatelet agents. Rather, the underlying cause of the troponin elevation should be targeted. However, troponin elevation in the absence of thrombotic acute coronary syndromes still retains prognostic value. Thus, cardiac troponin elevations are common in numerous disease states and do not necessarily indicate the presence of a thrombotic acute coronary syndrome. While troponin is a sensitive biomarker to "rule out" non-ST-segment elevation myocardial infarction, it is less useful to "rule in" this event because it may lack specificity for acute coronary syndromes.     

Does elevated cardiac troponin I in patients with unstable angina predict ischemia on stress testing?

To help guide physicians in their evaluation of patients with acute coronary syndromes, we investigated whether elevated cardiac troponin I in patients presenting with unstable angina predicts ischemia on stress testing. Elevated cardiac troponin I in patients who present with chest pain and normal creatine kinase levels is associated with ischemia on stress testing, as well as with future cardiac events.     

Prognostic Value of Continuous ST‐Segment Monitoring in Patients with Non‐ST‐Segment Elevation Acute Coronary Syndromes

Background: Patients with non‐ST‐segment elevation acute coronary syndromes constitute a heterogeneous group concerning prognosis. The 12‐lead ECG at rest is recommended for early risk stratification but is unable to reflect the dynamic nature of myocardial ischemia and coronary thrombosis. This study investigated whether continuous ST‐segment monitoring provides early prognostic information in such patients. Methods: We prospectively studied 183 patients admitted due to chest pain at rest suggestive of an acute coronary syndrome. ST‐segment monitoring was performed continuously for 24 hours from admission. Cardiac‐specific troponin I levels were determined on admission and every 6 hours for the first 24 hours. The endpoint was defined as death or nonfatal myocardial infarction, whichever occurred first by 30 days follow‐up. Results: ST episodes, defined as transient ST deviations of at least 0.1 mV, were detected in 50 patients 27.3%) and associated with worse 30‐day outcome: 22.0% endpoint rate compared to 6.8% for patients without ST episodes (P = 0.003). In a multivariate analysis, the presence of ST episodes hazard ratio, 3.07; 95% Cl, 1.26 to 7.46; P = 0.014) and peak troponin I levels > 0.2 μg/L (hazard ratio, 2.65; 95% Cl, 1.01 to 6.95; P = 0.048) were independent predictors of prognosis. The combination of ST‐segment monitoring and peak troponin I identified patients at low (2.5%, n = 79), intermediate (14.5%, n = 76), and high (25.0%, n = 28) risk for the 30‐day endpoint. Conclusions: In patients with non‐ST‐segment elevation acute coronary syndromes, continuous ST‐segment monitoring provides on‐line early prognostic information, in addition to troponin I levels. A.N.E. 2002;7(1):29–39     

The role of cardiac troponin t and other new biochemical markers in evaluation and risk stratification of patients with acute chest pain syndromes

Background and hypothesis: Increased serum creatinine kinase (CK) and CK-MB enzyme levels have been used for years to detect myocardial infarction (MI). However, serum myoglobin and CK-MB mass or protein levels may indicate MI earlier; cardiac troponin T is the most specific marker of myocardial injury and it can detect even minor myocardial necrosis. The diagnostic and prognostic utility of the traditional and new markers of cardiac injury in the emergency evaluation of patients with acute chest pain syndromes were therefore compared. Methods: One hundred and fifteen consecutive patients with an acute coronary syndrome, and 64 controls recruited during the same period, were examined. The time elapsed from onset of symptoms to blood collection was recorded. Cardiac markers were measured in specimens collected upon arrival (0 h), and 2 and 5–9 h, and later in cases of longer observation. The major cardiac events occurring up to 40 months after the index examination were recorded. Results: cTnT levels provided unique information: they were the most specific indicators of myocardial damage and identified unstable angina patients at high risk of future major events. Up to 6 h after the onset of chest pain, the new markers were elevated more frequently than the traditional ones and permitted earlier MI recognition. The worst prognosis (nonfatal myocardial infarction or death) was noted in subjects with chest pain at rest within 48 h before the index examination and elevated cTnT levels. Conclusions: The new markers, particularly cardiac troponin T, offer considerable advantages and they should be more widely used in the diagnosis and risk stratification of acute coronary syndromes.     

Abnormal troponin I levels in acute pulmonary embolism without abnormal concentrations of D-dimer at admission

Serum troponin I is a sensitive indicator of myocardial damage but abnormal troponin I levels have been reported without acute coronary syndrome and without cardiac damage. It has been reported that right ventricular overload and hypoxia in acute pulmonary embolism may lead to right ventricular myocardium injury reflected by elevated cardiac troponin levels and that in patients with acute central sub-massive or non-massive pulmonary embolism, even mild increase in troponin I >0.03 mug/L may provide relevant short-term prognostic information independent to clinical, laboratory and echocardiographic data. It has also been reported that patients with acute small pulmonary embolism might present with relatively low concentrations of D-dimer and it might have implications regarding the diagnostic yield of D-dimer in patients who are suspected of having an acute pulmonary embolism. We present a case of abnormal troponin I levels without abnormal concentrations of D-dimer at admission in a 26-year-old Italian man with acute pulmonary embolism. Also this case focuses attention on the importance of a correct evaluation of abnormal troponin I levels and not elevated D-dimer levels in acute pulmonary embolism.     

Stress testing and troponin in unstable coronary syndromes: the status trial-clinical outcomes and resource use

Cardiac troponins are markers used to diagnose acute myocardial infarction, but their value in guiding management in low- to intermediate-risk patients is not well established. Using a randomized design, the authors compared a strategy using stress testing with blinded troponins vs a troponin I-guided strategy for risk stratification and management of 241 patients with intermediate-risk unstable angina. Fewer stress-tested patients required coronary care unit admission and repeat hospitalization for acute coronary syndrome, at a lower cost. There was no significant difference in rates of death and myocardial infarction due to acute coronary syndrome at 6 months' follow-up. For patients with intermediate-risk acute coronary syndrome, stress testing is as safe as, and more cost-effective than, a troponin I-guided strategy. Patients with marginal troponin I elevations can safely undergo stress testing. Further studies combining stress testing and a troponin I-guided strategy are warranted.     

Cardiac troponin T in acute coronary syndrome with renal insufficiency

Cardiac troponin levels are frequently elevated in patients with chronic renal failure, hence diagnosis of myocardial necrosis is difficult. The prevalence of elevated serum troponin T was determined and its diagnostic value in acute coronary syndrome was assessed in patients with chronic renal insufficiency. A retrospective cross-sectional analysis was performed in 227 patients with chronic renal insufficiency and a diagnosis of unstable angina, non-ST or ST-segment elevation myocardial infarction. All patients had baseline serum troponin T levels measured at previous visits; the baseline troponin T level was raised in 53.3%. Cardiac troponin T levels did not correlate with creatinine levels, and were not affected by dialysis. Mortality after an acute coronary event was high (46.3%). Because of the elevated baseline cardiac troponin T levels, detection of acute coronary syndrome in patients with chronic renal failure requires evaluation of serial cardiac enzyme measurements and serial 12-lead electrocardiograms. Early and definitive cardiac interventions may contribute towards decreasing the mortality rate in this group of patients.     

L’élévation de la troponine en dehors des syndromes coronariens aigus

Cardiac troponins are the most sensitive and specific markers of myocardial injury. Cardiac troponin elevation are common in many diseases and do not necessarily indicate the presence of a thrombotic acute coronary syndrome. In clinical practice, interpretation of dynamic changes of troponin may be challenging. Troponin evaluation should be performed only if clinically indicated and must be interpreted in the context of clinical presentation, ECG changes, troponin level and kinetic. In the absence of thrombotic acute coronary syndrom, troponin retains a prognostic value. Its practical interest as a risk criteria is limited to a few situations like pulmonary embolism, pericarditis an myocarditis.     

Troponin elevation in patients with heart failure: on behalf of the third Universal Definition of Myocardial Infarction Global Task Force: Heart Failure Section

Cardiac troponin testing is commonly performed in patients with heart failure (HF). Despite being strongly linked to spontaneous (Type I) acute myocardial infarction (MI)-a common cause of acute HF syndromes-it is well recognized that concentrations of circulating troponins above the 99th percentile of a normal population in the context of both acute and chronic HF are highly prevalent, and frequently unrelated to Type I MI. Other mechanism(s) leading to troponin elevation in HF syndromes remain elusive in many cases but prominently includes supply-demand inequity (Type II MI), which may be associated with coronary artery obstruction and endothelial dysfunction, or may occur in the absence of coronary obstruction due to increased oxygen demand related to increased wall tension, anaemia, or other factors provoking subendocardial injury. Non-coronary triggers, such as cellular necrosis, apoptosis, or autophagy in the context of wall stress may explain the troponin release in HF, as can toxic effects of circulating neurohormones, toxins, inflammation, and infiltrative processes, among others. Nonetheless, across a wide spectrum of HF syndromes, when troponin elevation occurs, independent of mechanism, it is strongly predictive of an adverse outcome. Clinicians should be aware of the high frequency of troponin elevation when measuring the marker in patients with HF, should keep in mind the possible causes of this phenomenon, and, independent of a diagnosis of 'acute MI', should recognize the considerable ramifications of troponin elevation in this setting.     

La troponine et les autres marqueurs de souffrance myocardique,quelle signification en médecine interne ?

PURPOSE: Troponin is now the gold standard for the diagnosis of myocardial infarction. Aiming at improving the management of a patient suspect of an acute coronary syndrome, this article will point the interpretation of troponin dosages according to the clinical presentation and concomitant diseases. ACTUALITIES: First, the interest of troponin dosage as compared with other markers of myocardial ischemia will be underlined. Then, the literature available about troponin in cardiovascular diseases but also in extracardiac diseases will be analysed. Finally, the difficulties of assay will be discussed. PERSPECTIVES: The availability of a sensitive and specific marker such as troponin is definitively a progress in the management of patients with an acute coronary syndromes. But it remains a biological contribution to the global management of the patient. It is important to know the causes susceptible to increase the levels of troponin to avoid a wrong interpretation of the dosage, leading to diagnostic but also therapeutic mistakes.     

Troponins in acute coronary syndromes

Cardiac troponins have replaced creatine kinase-MB as the preferred biomarker for establishing the diagnosis of myocardial infarction (MI). Expert recommendations set the diagnostic decision-limit for each assay at the 99th percentile of troponin levels in an apparently healthy reference population, which due to a lack of standardization, will vary depending upon the manufacturer. Among patients presenting with an acute coronary syndrome (ACS), even low-level elevations of cardiac troponin T or I correlate with higher risk of death and recurrent ischemic events compared to patients with levels of troponin below the decision limit. Renal failure does not appear to diminish the prognostic value of troponins among patients with a high clinical probability of ACS. Moreover, patients with elevated levels of troponin derive the most benefit from more intense medical therapy with antithrombin and antiplatelet medications, as well as an early invasive management strategy. Whereas cardiac troponins are extremely specific for myocardial necrosis, they do not discriminate between ischemic and non-ischemic etiologies of myocardial injury. Clinicians must, therefore, determine whether a patient's presenting symptoms are consistent with ACS. Combining troponin with other cardiac biomarkers may offer complimentary information on the underlying pathobiology and prognosis in an individual patient. Future generations of troponin assays may detect specific posttranslational modifications of troponins that may increase the analytic sensitivity for myocardial damage and offer insight into the timing and mechanism of myocardial injury.     

循环微小RNA与急性心肌梗死早期诊断的研究进展

急性心肌梗死是常见的心血管急症,是造成急性死亡的主要原因.心肌损伤标志物可以反映心肌坏死程度,为急性心肌梗死的诊断和预后判断提供重要信息.肌钙蛋白敏感性和特异性高,是目前临床中应用最广泛的心肌损伤标志物.然而肌钙蛋白起峰偏晚,不利于急性心肌梗死极早期的诊断.寻找敏感性准确性更高、起峰更快的新型心肌损伤标志物是冠心病领域研究的热点.最近的研究发现,急性心肌梗死时循环血中心肌特异性的微小RNA升高,可能作为心肌梗死新的生化指标,现对此做简要综述.     

Troponins in acute coronary syndromes

Delivering superior clinical specificity and sensitivity for myocardial necrosis, cardiac troponin has replaced creatine kinase-MB as the preferred biomarker for establishing the diagnosis of myocardial infarction. On the basis of expert recommendations, present convention sets the diagnostic decision-limit for each assay at the 99th percentile of troponin levels in an apparently healthy reference population. Owing to a lack of standardization between different assays, this level, corresponding to the 99th percentile, will vary depending upon the manufacturer. Among patients presenting with an acute coronary syndrome (ACS), even low-level elevations of cardiac troponin T or I are associated with higher risk of death and recurrent ischemic events compared with patients with a troponin level below the appropriate decision limit. Renal failure does not appear to diminish the prognostic value of troponins among patients with a high clinical probability of ACS. In addition, patients with elevated levels of troponin appear to gain the most benefit from more aggressive medical therapy with antithrombin and antiplatelet medications as well as an early invasive management strategy. Cardiac troponins offer extremely high tissue specificity but do not discriminate between ischemic and nonischemic mechanisms of myocardial injury; thus, presently the clinician must assess whether a patient's presenting symptoms are consistent with ACS. It is possible that future generations of troponin assays will detect specific post-translational modifications of troponins that may increase the analytic sensitivity for myocardial damage and offer insight into the timing and mechanism of myocardial injury.