Cardiac troponins in renal insufficiency: review and clinical implications

Patients with renal insufficiency may have increased serum troponins even in the absence of clinically suspected acute myocardial ischemia. While cardiovascular disease is the most common cause of death in patients with renal failure, we are just beginning to understand the clinical meaning of serum troponin elevations. Serum troponin T is increased more frequently than troponin I in patients with renal failure, leading clinicians to question its specificity for the diagnosis of myocardial infarction. Many large-scale trials demonstrating the utility of serum troponins in predicting adverse events and in guiding therapy and intervention in acute coronary syndromes have excluded patients with renal failure. Despite persistent uncertainty about the mechanism of elevated serum troponins in patients with reduced renal function, data from smaller groups of renal failure patients have suggested that troponin elevations are associated with added risk, including an increase in mortality. It is possible that increases in serum troponin from baseline in patients with renal insufficiency admitted to hospital with acute coronary syndrome may signify myocardial necrosis. Further studies are needed to clarify this hypothesis.     

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.     

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.     

Elevated Serum Cardiac Troponin in Non‐acute Coronary Syndrome

Cardiac troponins (CTn) are the most sensitive and specific biochemical markers of myocardial injury and risk stratification. The assay for troponin T (cTnI) is standardized, and results obtained from different institutions are comparable. This is not the case with troponin I (cTnT), and clinicians should be aware that each institution must analyze and standardize its own results. Elevated cTn levels indicate cardiac injury, but do not define the mechanical injury. The differentiation of cTn elevation caused by coronary events from those not related to an acute coronary syndrome (ACS) is tiresome, at times vexing, and often costly. Elevation of cTn in non‐ACS is a marker of increased cardiac and all‐cause morbidity and mortality. The cause of these elevations may involve serious medical conditions that require meticulous diagnostic evaluation and aggressive therapy. At present, there are no guidelines to treat patients with elevated troponin levels and no coronary disease. The current strategy of treatment of patients with elevated troponin and non‐ACS involves treating the underlying causes. Copyright © 2009 Wiley Periodicals, Inc.     

Abnormal troponin I levels after supraventricular tachycardia

Elevated troponin I in the absence of angiographically visible coronary lesions is seen in up to 10-15% of those undergoing angiography for suspected coronary artery disease. Serum troponin-I is a sensitive indicator of myocardial damage but abnormal troponin I levels have been also reported without acute coronary syndrome and without cardiac damage. Cardiac troponin I is released from myocytes in both reversible and irreversible myocardial injury. The changes in myocyte membrane permeability resulting from the injury could be enough for the release of cardiac troponins from the free cytosolic pool of myocytes without structural damage. It has been reported that the presence of tachycardia sufficient to warrant hospital admission also can raise troponin. We present a case of troponin I positive in a 49-year-old Italian woman admitted to the hospital with supraventricular tachycardia. Also this case focuses attention on the importance of a correct evaluation of abnormal troponin I levels.     

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.     

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.     

Troponins in patients with acute coronary syndromes: biologic,diagnostic, and therapeutic implications

The cardiac troponins have expanded the spectrum of detectable myocardial injury and enhanced the clinician's ability to identify patients with acute coronary syndromes who are at higher risk for death or recurrent ischemic events. Based on available data, it appears most likely that any reliably detected troponin elevation results from myocyte necrosis. This notion has served as the basis for the recent revision of diagnostic criteria for acute myocardial infarction based on cardiac troponin. Nevertheless, further research is necessary to conclusively refute the possibility that the release of cardiac troponins may also occur in the setting of reversible myocyte injury resulting from cellular ischemia. Such an investigation establishing biologic correlates of troponin elevation is likely to prove valuable in guiding diagnostic terminology as well as in therapy. For example, clinical research finding cardiac troponin elevation to be predictive of intracoronary throumbus and distal microvascular obstruction has been important to the evaluation of troponis for targeting powerful antiplatelet and antithrombin therapies. Whether related to irreversible or reversible injury, the cardiac troponins have blurred the traditional boundaries between unstable angina and myocardial infarction and have evolved as powerful tools for risk stratification and therapeutic decision-making.     

Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides

Myocardial dysfunction, which is characterized by transient biventricular impairment of intrinsic myocardial contractility, is a common complication in patients with sepsis. Left ventricular systolic dysfunction is reflected by a reduced left ventricular stroke work index or, less accurately, by an impaired left ventricular ejection fraction (LVEF). Early recognition of myocardial dysfunction is crucial for the administration of the most appropriate therapy. Cardiac troponins and natriuretic peptides are biomarkers that were previously introduced for diagnosis and risk stratification in patients with acute coronary syndrome and congestive heart failure, respectively. However, their prognostic and diagnostic impact in critically ill patients warrants definition. The elevation of cardiac troponin levels in patients with sepsis, severe sepsis, or septic shock has been shown to indicate left ventricular dysfunction and a poor prognosis. Troponin release in this population occurs in the absence of flow-limiting coronary artery disease, suggesting the presence of mechanisms other than thrombotic coronary artery occlusion, probably a transient loss in membrane integrity with subsequent troponin leakage or microvascular thrombotic injury. In contrast to the rather uniform results of studies dealing with cardiac troponins, the impact of raised B-type natriuretic peptide (BNP) levels in patients with sepsis is less clear. The relationship between BNP and both LVEF and left-sided filling pressures is weak, and data on the prognostic impact of high BNP levels in patients with sepsis are conflicting. Mechanisms other than left ventricular wall stress may contribute to BNP release, including right ventricular overload, catecholamine therapy, renal failure, diseases of the CNS, and cytokine up-regulation. Whereas cardiac troponins may be integrated into the monitoring of myocardial dysfunction in patients with severe sepsis or septic shock to identify those patients requiring early and aggressive supportive therapy, the routine use of BNP and other natriuretic peptides in this setting is discouraged at the moment.     

Risk stratification in acute coronary syndrome

BACKGROUND: The spectrum of symptoms of patients with active ischemic heart disease ranges from silent ischemia to acute myocardial infarction and the extent of myocardial damage from reversible myocardial injury to extensive necrosis. The term "acute coronary syndrome" comprises this continuum. In particular the evaluation of patients without ST-segment elevation is difficult, for clinical symptoms, ECG criteria and CK-MB measurements appear insufficient for appropriate risk stratification. TROPONIN MEASUREMENT: Serial measurements of either troponin T or I reliably detect minor myocardial damage in those patients, who are known to be at a higher risk for adverse cardiac events comparable to the risk of patients with acute myocardial infarction. Hence determination of troponins allow superior risk stratification contributing to early triage and therapeutic decision making. Without elevation of troponins the cardiac risk for death or myocardial infarction will not exceed 1%. CONCLUSION: Patients with elevated troponins should be early hospitalized and further evaluated in order to begin efficacious therapy as soon as possible. These patients represent a high-risk subgroup of patients clinically classified as unstable angina, who might benefit from potential antithrombotic treatment such as low-molecular weight heparin or glycoprotein IIb/IIIa antagonists without or with revascularization strategies.     

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.     

Prognostic value of troponin T in hospitalized patients with angina or non-ST-segment elevation myocardial infarction

INTRODUCTION AND OBJECTIVES: Cardiac troponins are highly specific and sensitive for detecting minimal myocardial damage. The aim of our study was to determine the prognostic value of troponin T levels in patients hospitalized for suspected angina or myocardial infarction without ST-segment elevation. PATIENTS AND METHOD: We recorded the frequency of death, acute myocardial infarction, heart failure, or need for coronary revascularization in the three months after the onset of symptoms in 346 consecutive patients admitted for suspected acute coronary syndrome, excluding those who developed myocardial infarction with persistent ST-segment elevation. RESULT:. Serum troponin T levels were > or = 0.1 ng/ml in 133 patients (troponin T positive group) and lower in 213 patients (troponin T negative group). The relative risk (RR) and 95 percent confidence intervals (95% CI) of individual and grouped events for the troponin T positive group were 3.2 (95% CI, 1.4-7.3; p = 0.006) for death; 2.8 (95% CI, 1.43-5.51; p = 0.003) for death or myocardial infarction; and 2.8 (95% CI, 1.6-5.0; p < 0.001) for death, myocardial infarction or heart failure. Diabetes mellitus and troponin T levels > or = 0.1 ng/ml had independent prognostic value after adjusting for age, sex, and electrocardiographic changes; with RR 2.5 (95% CI, 1.01-5.9) for death, myocardial infarction or heart failure. CONCLUSIONS: The prognosis of patients hospitalized for chest pain who do not immediately develop transmural necrosis depends on serum troponin T levels at hospital admission. Troponin T levels > or = 0.1 ng/ml almost triple the risk of major events in the three months after the acute episode. The prognostic value of troponin T is independent of age, sex, presence of diabetes mellitus, and electrocardiographic changes.     

Physical activity,exercise and cardiac troponins: Clinical implications

Cardiac troponins constitute essential components of the cardiac contractile apparatus and are released into the bloodstream following cardiomyocyte injury. Because of their cardiac specificity, cardiac troponin I or T are the recommended biomarkers for diagnosing acute myocardial infarction. However, cardiac troponin concentrations also frequently increase acutely after strenuous prolonged exercise, making the interpretation of cardiac troponin test results in patients presenting with acute chest pain challenging. This acute troponin response following exercise is commonly considered to be physiological and without adverse long-term consequences, but the possibility of exercise-induced, minor myocardial injury that may become clinically relevant if repeated over decades, has not been ruled out. Attempts to biochemically differentiate between physiological cardiac troponin release versus release after acute ischemic myocardial injury has so far proved largely unsuccessful, but future measurement of specific troponin fragments could be promising. Cardiac troponins also provide strong prognostic information across the spectrum of cardiovascular (CV) disease (CVD). In the chronic setting, low-level elevation of cardiac troponins has been associated with adverse outcome, and concentrations even within the normal range provide independent information concerning risk of developing heart failure (HF) and CVD death. Exercise exerts many beneficial effects on the CV system, and longitudinal observational data from epidemiological studies suggest that higher physical activity (PA) is associated with lower concentrations of cardiac troponins. Conversely, a sedentary life-style has been associated with higher cardiac troponin concentrations and a parallel increase in the risk of HF. Serial measurement of cardiac troponins using high sensitivity assays for monitoring the effect of life-style intervention, including PA appears promising.     

Acute coronary syndrome: biochemical strategies in the troponin era

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.     

Biomarkers of myocardial ischemia in the emergency room: cardiospecific troponin and beyond

A timely and efficient diagnosis is critical in patients with chest pain, to optimize the efficacy of myocardial revascularization in those with an acute coronary syndrome, and offset the increasing overcrowding in the emergency room by early discharge of subjects without myocardial ischemia. Although cardiospecific troponins remain the biochemical gold standards for diagnosing an acute coronary syndrome, several additional biomarkers have been proposed. As a general rule, there are important issues that should be addressed when combining an innovative diagnostic test with troponin, including a benchmark evaluation of diagnostic performance, the impact on throughput and turnaround time, along with the analytical features of the assay and the cost to benefit ratio of a multi-marker approach. Despite a considerable amount of data has been published, there is insufficient analytical and clinical evidence to support the use of most of these novel biomarkers as surrogates or in combination with troponin for diagnosing ischemic heart disease, especially when the latter is assessed with the novel highly-sensitive immunoassays.     

Elevated troponin levels in absence of coronary artery disease after supraventricular tachycardia

Generally speaking elevated troponin levels are consistent with the diagnosis of acute coronary syndrome and haemodynamically relevant coronary artery stenosis. However, they may also point to minor myocardial injury in other circumstances. Four patients with elevated troponin levels after supraventricular tachycardia without evidence of coronary artery disease and very low risk scores for acute coronary syndrome are described and discussed.     

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.     

Cardiac troponins in the elderly: interpretation of elevated levels

Elderly patients with myocardial infarction commonly present with symptoms other than chest pain. The clinician evaluation of the elderly may rely on laboratory methods more so than in younger patients. Fortunately,advances in laboratory science have brought newer biomarkers of cardiac injury to the clinical arena including cardiac troponins I and T(cTnI,cTnT) . These regulatory components of the contractile apparatus are sensitive indicators of myocardial injury. Their central role in the current definition of acute myocardial infarction highlights their utility in the diagnosis of acute myocardial ischemic syndromes. The troponins are also released in some clinical situations where thrombotic complications of coronary artery disease and resultant acute myocardial infarction have not occurred. Examples of these conditions include conditions like myocarditis,pulmonary embolism,sepsis,and acute stroke. Elevated troponins in these conditions are thought to emanate from injured myocardial cells and in most circumstances have been associated with adverse outcomes. Interpretation of elevated troponin in the elderly requires consideration of other possible conditions.     

Elevated cardiac troponin levels in patients with submassive pulmonary embolism.

BACKGROUND: Cardiac troponins are reliable markers of myocardial injury that are being used increasingly in patients presenting with undifferentiated chest pain or dyspnea to diagnose an acute coronary syndrome. If elevated cardiac troponin levels also occur in patients with pulmonary embolism because of right ventricular dilation and myocardial injury, such patients could be misdiagnosed. We performed a prospective cohort study to determine the prevalence of elevated cardiac troponin I (cTnI) levels in patients with submassive pulmonary embolism. METHODS: Consecutive patients with objectively confirmed submassive pulmonary embolism and no previous history of ischemic heart disease, other cardiac disease, or renal insufficiency were included. Creatine kinase and cTnI levels were measured within 24 hours of clinical presentation on 2 occasions 8 to 12 hours apart. RESULTS: Of 24 patients with submassive pulmonary embolism, 5 (20.8%) had elevated cTnI levels of 0.4 microg/L or higher (95% confidence interval, 7.1-42.2%). One of these patients had a cTnI level higher than 2.3 microg/L that was suggestive of myocardial infarction. CONCLUSION: Pulmonary embolism should be considered in the differential diagnosis of patients presenting with undifferentiated chest pain or dyspnea and an elevated cardiac troponin level.     

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.