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Cardiac Markers 

  • Author: Donald Schreiber, MD, CM; Chief Editor: Barry E Brenner, MD, PhD, FACEP  more...
Updated: Aug 24, 2015

Definition and Efficacy

Cardiac markers are used in the diagnosis and risk stratification of patients with chest pain and suspected acute coronary syndrome (ACS). The cardiac troponins, in particular, have become the cardiac markers of choice for patients with ACS. Indeed, cardiac troponin is central to the definition of acute myocardial infarction (MI) in the consensus guidelines from the European Society of Cardiology (ESC) and the American College of Cardiology (ACC).[1, 2, 3, 4]

For example, patients with elevated troponin levels but negative creatine kinase-MB (CK-MB) values who were formerly diagnosed with unstable angina or minor myocardial injury are now reclassified as non–ST-segment elevation MI (NSTEMI), even in the absence of diagnostic electrocardiogram (ECG) changes.

Similarly, only 1 elevated troponin level above the established cutoff is required to establish the diagnosis of acute MI, according to the ACC guidelines for NSTEMI.[4, 5, 6]

These changes were instituted following the introduction of increasingly sensitive and precise troponin assays. Up to 80% of patients with acute MI will have an elevated troponin level within 2-3 hours of emergency department (ED) arrival, versus 6-9 hours or more with CK-MB and other cardiac markers.

Accordingly, some have advocated relying solely on troponin and discontinuing the use of CK-MB and other markers.[7, 8, 9, 10, 11] Nevertheless, CK-MB and other markers continue to be used in some hospitals to rule out MI and to monitor for additional cardiac muscle injury over time.

Note that cardiac markers are not necessary for the diagnosis of patients who present with ischemic chest pain and diagnostic ECGs with ST-segment elevation. These patients may be candidates for thrombolytic therapy or primary angioplasty. Treatment should not be delayed to wait for cardiac marker results, especially since the sensitivity is low in the first 6 hours after symptom onset. ACC/American Heart Association (AHA) guidelines recommend immediate reperfusion therapy for qualifying patients with ST-segment elevation MI (STEMI), without waiting for cardiac marker results.[12, 13]

Go to Myocardial Infarction and Complications of Myocardial Infarction for more complete information on these topics.


Cardiac Troponins

The troponins are regulatory proteins found in skeletal and cardiac muscle. Three subunits have been identified: troponin I (TnI), troponin T (TnT), and troponin C (TnC). The genes that encode for the skeletal and cardiac isoforms of TnC are identical; thus, no structural difference exists between them. However, the skeletal and cardiac subforms for TnI and troponin TnT are distinct, and immunoassays have been designed to differentiate between them.

Two different reference ranges are used in troponin assays. The upper percentile reference limit gives the upper limit of what can be expected in a normal, healthy, adult population, while the coefficient of variation (CV) is the percent variation in assay results that can be expected when the same sample is repeatedly analyzed.

According to European Society of Cardiology (ESC)/American College of Cardiology Foundation (ACCF)/American Heart Association (AHA)/ World Heart Federation (WHF) guidelines, MI refers specifically to myocardial necrosis due to myocardial ischemia. However, although elevations in the serum levels of TnI, TnT, and CK-MB indicate the presence of injury-associated necrosis of myocardial cells, such elevations do not point to the underlying mechanism of the necrosis. While myocardial necrosis occurs in MI, it can also be a product of predominantly nonischemic myocardial injury, as occurs in association with heart failure, arrhythmia, myocarditis, renal failure, pulmonary embolism, and percutaneous or surgical coronary procedures.[1]

The sensitivity, specificity, and precision of the different commercially available troponin assays vary considerably. These differences are related to a lack of standardization, the use of different monoclonal antibodies, the presence of modified TnI and TnT in the serum, and variations in antibody cross-reactivity to the various detectable forms of TnI that result from its degradation.

Only one manufacturer produces the TnT assay, and its 99th percentile cutoffs and the 10% CV are well established. However, up to 20-fold variation has occurred in results obtained with the multitude of commercial TnI assays currently available, each with their own 99th percentile upper reference limits and 10% CV levels.

In the GUSTO IV study, a relatively insensitive point-of-care TnI assay was used to screen patients for study eligibility. In a subsequent study, the blood samples were reanalyzed using the 99th percentile cutoff of a far more sensitive central laboratory TnT assay. The more sensitive 99th percentile cutoff of this TnT assay identified an additional 96 (28%) of 337 patients with a positive TnT result but negative point-of-care TnI; these patients had higher rates of death or MI at 30 days.[14]

In a similar reanalysis of the TACTICS-TIMI 18 trial, 3 different TnI cutoffs were compared on 1821 patients to evaluate the 30-day risk of death or MI: the 99th percentile, 10% CV, and the World Health Organization (WHO) acute MI cutoffs. (The WHO cutoffs define acute MI using CK-MB and report troponin levels as either a higher “acute MI level” or a lower “intermediate level” that is correlated with “leak” or “minor myocardial injury.”)

Using the 10% CV cutoff identified, an additional 12% more cases were identified relative to the WHO acute MI cutoff. The 99th percentile cutoff identified an additional 10% of cases relative to the 10% CV cutoff, as well as a 22% increase in the number of cases over the WHO acute MI cutoff. Nevertheless, the odds ratios for the adverse cardiac event rates of death or MI at 30 days were similar for all 3 cutoffs, suggesting that the lower cutoffs detected more patients with cardiovascular risk without sacrificing specificity.[15, 16]

The National Academy of Clinical Biochemistry (NACB) working with the ACC/ESC guidelines has recommended adoption of the 99th percentile upper reference limit as the recommended cutoff for a positive troponin result. Ideally, the precision of the assay at this cutoff level should be measured by a CV that is less than 10%.

However, most TnI assays are imprecise at the 99th percentile reference limit.[17] Some have therefore recommended that the cutoff level be raised to the slightly higher 10% CV level instead of the 99th percentile reference limit to ensure adequate assay precision.

In addition, studies have shown that populations within the 99th percentile reference limit include patients with low troponin levels who nevertheless have an elevated cardiac risk, and that the true 99th percentile cutoff for a healthy patient population is actually a factor of 10-50 lower. Accordingly, these investigations suggest that higher sensitivity or ultrasensitive troponin assays are necessary.[16] The advantage of ultrasensitive troponins is based on the premise that lower cutoff levels achieve higher sensitivity that will allow earlier diagnosis, often within 90 minutes of presentation.

To optimize the assay’s use in the ED, it is important to be familiar with the particular troponin assay available in the laboratory and to know whether the cutoff is set at the 10% CV level or the 99th percentile upper reference limit.

Point-of-care assays

NACB recommendations specify that cardiac markers be available on an immediate basis 24 h/d, 7 d/wk, with a turnaround time of 1 hour.[18] Point-of-care (POC) devices that provide rapid results should be considered in hospitals whose laboratories cannot meet these guidelines.

POC assays for CK-MB, myoglobin, and the cardiac troponins TnI and TnT are available. Only qualitative TnT assays are available as POC tests, but both quantitative and qualitative POC TnI assays are currently marketed.

In a multicenter trial, the time to positivity was significantly faster for the POC device than for the local laboratory (2.5 h vs 3.4 h).[19]

In another multicenter study, which evaluated the i-STAT POC TnI assay in comparison with the central laboratory in 2000 patients with suspected ACS, POC testing reduced the length of stay by approximately 25 minutes for patients who were discharged from the ED.[20, 21] The sensitivity of current POC assays coupled with the benefit of rapid turnaround time make the POC assays attractive clinical tools in the ED.

Prognostic value of troponin

In addition to its use in the diagnosis of MI, an elevated troponin level can identify patients at high risk for adverse cardiac events.[22, 23] Specifically, data from a meta-analysis indicated that an elevated troponin level in patients without ST-segment elevation is associated with a nearly 4-fold increase in the cardiac mortality rate.[24] In patients without ST-segment elevation who were being considered for thrombolytic therapy, initial TnI levels on admission correlated with mortality at 6 weeks, but CK-MB levels were not predictive of adverse cardiac events and had no prognostic value.[22]

Other studies revealed that an elevated troponin level at baseline was an independent predictor of mortality, even in patients with chest pain and acute MI with ST-segment elevation who were eligible for reperfusion therapy.[25, 26]

Finally, the TIMI IIIB, GUSTO IIa, GUSTO IV ACS, and FRISC trial all demonstrated a direct correlation between the level of TnI or TnT and the mortality rate and adverse cardiac event rate in ACS.[22, 25, 27, 28, 29]


Creatine Kinase–MB

Prior to the introduction of cardiac troponins, the biochemical marker of choice for the diagnosis of acute MI was the CK-MB isoenzyme. The criterion most commonly used for the diagnosis of acute MI was 2 serial elevations above the diagnostic cutoff level or a single result more than twice the upper limit of normal. Although CK-MB is more concentrated in the myocardium, it also exists in skeletal muscle and false-positive elevations occur in a number of clinical settings, including trauma, heavy exertion, and myopathy.

CK-MB first appears 4-6 hours after symptom onset, peaks at 24 hours, and returns to normal in 48-72 hours. Its value in the early and late (>72 h) diagnosis of acute MI is limited. However, its release kinetics can assist in diagnosing reinfarction if levels rise after initially declining following acute MI.

In the CRUSADE registry, a review of almost 30,000 patients revealed that discordant troponin and CK-MB results occurred in 28% of patients. However, patients who were troponin negative but CK-MB positive had in-hospital mortality rates that were not significantly increased from patients who were negative for both biomarkers.[30]

Similarly, in a report of more than 10,000 patients with ACS from the multicenter GRACE registry, in-hospital mortality was highest when both troponin and CK-MB were positive, intermediate in troponin-positive/CK-MB-negative patients, and lowest in patients in whom both markers were negative and in those who were troponin-negative/CK-MB-positive.[31] Thus, an isolated CK-MB elevation has limited prognostic value in patients with a non-ST elevation ACS.

CK-MB/CK relative index

The relative index calculated by the ratio of CK-MB (mass) to total CK can assist in differentiating false-positive elevations of CK-MB arising from skeletal muscle. A ratio of less than 3 is consistent with a skeletal muscle source, while ratios greater than 5 are indicative of a cardiac source. Ratios between 3 and 5 represent a gray zone. No definitive diagnosis can be established without serial determinations to detect a rise.

The CK-MB/CK relative index was introduced to improve the specificity of CK-MB elevation for myocardial infarction. However, sensitivity for acute MI falls when concurrent cardiac injury and skeletal muscle injury is present. In an ED-based study to evaluate the CK-MB relative index compared with the absolute CK-MB, specificity was increased, but with a loss of sensitivity.[32]

The CK-MB/CK relative index is useful if patients have only an MI or only skeletal muscle injury, but not if they have both. Therefore, in the combined setting of acute MI and skeletal muscle injury (rhabdomyolysis, heavy exercise, polymyositis), the fall in sensitivity is significant.

Note that the diagnosis of acute MI must not be based on an elevated relative index alone, because the relative index may be elevated in clinical settings when either the total CK or the CK-MB is within normal limits. The relative index is only clinically useful when both the total CK and the CK-MB levels are increased.

CK-MB isoforms

The CK-MB isoenzyme exists as 2 isoforms: CK-MB1 and CK-MB2. Laboratory determination of CK-MB actually represents the simple sum of the isoforms CK-MB1 and CK-MB2. CK-MB2 is the tissue form and initially is released from the myocardium after MI. It is converted peripherally in serum to the CK-MB1 isoform rapidly after symptom onset.

Normally, the tissue CK-MB1 isoform predominates; thus, the CK-MB2/CK-MB1 ratio is typically less than 1. A result is positive if the CK-MB2 is elevated and the ratio is greater than 1.7.

CK-MB2 can be detected in serum within 2-4 hours after onset and peaks at 6-9 hours, making it an early marker for acute MI. Two large studies evaluating its use revealed a sensitivity of 92% at 6 hours after symptom onset, compared with 66% for CK-MB and 79% for myoglobin.[33, 34] The major disadvantage of this assay is that it is relatively labor intensive for the laboratory.



Myoglobin is a heme protein found in skeletal and cardiac muscle that has attracted considerable interest as an early marker of MI. Its low molecular weight accounts for its early release profile: myoglobin typically rises 2-4 hours after onset of infarction, peaks at 6-12 hours, and returns to normal within 24-36 hours.

Rapid myoglobin assays are available, but overall, they have a lack of cardiospecificity. Serial sampling every 1-2 hours can increase the sensitivity and specificity; a rise of 25-40% over 1-2 hours is strongly suggestive of acute MI. However, in most studies, myoglobin only achieved 90% sensitivity for acute MI, so the negative predictive value of myoglobin is not high enough to exclude the diagnosis of acute MI.

The original studies that evaluated myoglobin used the WHO definition of acute MI that was based on a CK-MB standard. With the adoption of a troponin standard for acute MI in the ACC/ESC definition, the sensitivity of myoglobin for acute MI is substantially reduced. This significantly diminishes its utility, and a number of studies have indicated that contemporary cardiac troponin assays render the use of myoglobin measurements unnecessary.[8, 10]


Testing Strategy

In patients with definite or possible ACS, serial evaluation of cardiac markers is essential to diagnosing acute MI.

The American College of Emergency Physicians (ACEP) recommends 3 different testing strategies for ruling out NSTEMI in the ED.[35] One strategy is to use a single negative CK-MB, TnI, or TnT measured 8-12 hours after symptom onset.

Another strategy is to use negative myoglobin in conjunction with a negative CK-MB mass or negative TnI measured at baseline and at 90 minutes in patients presenting less than 8 hours after symptom onset.

A third approach is to use a negative 2-hour delta CK-MB in conjunction with a negative 2-hour delta TnI in patients presenting less than 8 hours after symptom onset.

Note that ACEP does not specify whether to use the 99th percentile cutoff, the 10% CV cutoff, or the WHO acute MI cutoffs for troponin.

The 90-minute rule-out with myoglobin recommended by ACEP was based on a study that used myoglobin in conjunction with either CK-MB or TnI.[36] The CK-MB/myoglobin protocol yielded a sensitivity of 92% at 90 minutes, and the myoglobin/TnI combination yielded a sensitivity of 97% at 90 minutes.

ACEP acknowledges the relative lack of specificity for myoglobin and that many of the myoglobin studies did not define MI per the ACC/ESC guidelines. Nevertheless, it is difficult to comprehend the ACEP clinical policy that accepts a missed MI rate of 3-8%.

ACEP’s recommendations on the use of delta CK-MB and delta TnI are based on determining the change in the level of TnI or CK-MB on samples drawn 2 hours apart. However, the delta TnI evaluation is partially based on the use of older TnI assays and outdated WHO acute MI cutoffs in a retrospective study. Therefore, ACEP’s recommendation to use a delta TnI in conjunction with a delta CK-MB may not be generalizable to other commercially available troponin assays. Caution must be used when using ACEP’s recommendations in ED patients with chest pain and suspected ACS.

The following table outlines the recommended sampling frequency after ED admission for the different cardiac markers.

Table 1. Sampling Frequency of Cardiac Markers (Open Table in a new window)

  Baseline 3-4 h 6-9 h 12-24 h >24 h
CK-MB isoforms, myoglobin X X X    

(only if very high risk)

Late presenters

(TnI, TnT)


The sample time at 3-4 hours is useful in the ED or chest pain observation unit where rapid triage and early diagnosis are essential. In other patients admitted for ACS, biomarkers drawn at the 3- to 4-hour interval are not as important as they are at the 6- to 9-hour mark. The ACC/AHA guidelines for the treatment of patients with unstable angina and NSTEMI recommend a baseline sample upon ED arrival and a repeat sample 6-9 hours after presentation.

Few studies on the "time to positivity" have been performed, but serial samples that become positive in the 12- to 24-hour window are considered unlikely, unless the patient has ongoing symptoms of ischemia after admission. Acute MI can therefore be ruled out in patients with negative serial marker results through the 6- to 9-hour period after presentation.


Cardiac Markers in Therapeutic Management

Clinical trials have demonstrated the benefits of using cardiac markers as an indicator for specific therapeutic interventions in ACS. However, this use remains investigational; currently, no validated therapeutic algorithms are based on an isolated positive marker result in the absence of other clinical or ECG findings.

Subgroup analysis of trials with low molecular weight heparin (LMWH) showed a decreased cardiac event rate in patients with a positive result for TnT and who were treated with an LMWH.[37, 38]

Similarly, in the PRISM trial, patients with an elevated TnI who were treated with the glycoprotein (GP) IIb/IIIa inhibitor tirofiban (Aggrastat) demonstrated a significant decrease in cardiac events compared with patients without an elevated TnI level. No significant difference in outcomes was seen in patients without TnI elevations who were treated with tirofiban when compared with placebo.[39]

In the PURSUIT trial, patients who were treated with the GP IIb/IIIa inhibitor eptifibatide (Integrilin) within 6 hours of symptom onset obtained the greatest benefit, and subgroup analysis showed that patients with an elevated troponin level also had better responses to therapy than did those whose troponin result was negative.[40]

Finally, in the TACTICS-TIMI 18 trial, patients with elevations in TnI or TnT had a significant reduction in death, MI, or rehospitalization for ACS within 6 months after being treated with early invasive therapy consisting of aspirin, heparin, tirofiban, and catheterization/revascularization within 4-48 hours.[41, 42] Subset analysis noted that an elevation of CK-MB did not benefit the early invasive group when compared with the conservative management group. However, early invasive therapy did benefit the subgroup of patients with elevated troponin levels but normal CK-MB levels.[43]

These studies suggest that a positive troponin result alone is an independent predictor of high risk for adverse cardiac events, and that therapy with LMWHs and/or GP IIb/IIIa inhibitors appears to confer the most benefit on patients with elevated cardiac troponins levels.


Troponins in CRF

Patients with chronic renal failure (CRF) who are on hemodialysis are at increased risk of coronary artery disease and acute ACS, and cardiovascular disease accounts for about 50% of deaths in these patients. Early studies revealed a high prevalence of elevated cardiac troponin levels in patients with CRF, and especially of TnT. However, the clinical significance of an elevated TnT level is unclear.

Biochemical studies have demonstrated that the troponin elevation originates from the myocardium and is not related to the myopathy associated with renal failure. Yet, patients with CRF frequently have chronic congestive heart failure (CHF) and hypertension, which may independently elevate the troponin level. In addition, data suggest that elevated troponin levels in asymptomatic patients may reflect subclinical microinfarctions that are clinically distinct from ACS.

Large prospective studies have confirmed the association between TnT elevation and cardiac mortality in patients with CRF. The GUSTO IV ACS trial showed that patients with renal insufficiency and an elevated TnT had the highest overall risk of the composite endpoint of death or acute MI,[44] and 2 other prospective studies reported that an elevated TnT—but not TnI—increased the risk of long-term mortality.[45, 46] Whether elevated TnT increases cardiac risk in the short term (ie, 30 d) is unclear, but patients without short-term risk may not require hospitalization and potentially could be managed on an outpatient basis.

It has been suggested that chronically elevated troponin levels represent chronic structural cardiovascular disease, such as prior MI, chronic CHF, or hypertension in the setting of CRF. If true, these patients are at higher cardiac risk compared with the normal, healthy patient population and troponin remains a useful marker in the setting of CRF.[47, 48]

Note that dialysis does not affect TnT or TnI levels; predialysis and postdialysis levels are essentially unchanged. CK-MB, however, is dialyzable, and levels are decreased postdialysis. Therefore, a single elevated TnT level in patients with CRF and possible ACS is nondiagnostic for acute MI in the absence of other findings. Serial determinations are usually required, with a focus on a rise in the troponin level.

Ascertaining whether an elevated troponin in patients with CRF represents true acute MI or a false-positive result can be difficult. In patients with cardiac risk factors who are deemed clinically to be at moderate-high risk for ACS, the prudent approach would be to observe and perform serial cardiac markers over 6-9 hours. In low-risk asymptomatic patients and in the absence of any other findings indicative of ACS, the elevated troponin result is more likely to be false positive for acute MI.


Troponins in Nonischemic Heart Disease

A number of studies have demonstrated that TnT can be used for risk stratification of patients with CHF without ischemia. Specifically, elevated cardiac troponins are associated with decreased left ventricular ejection fraction and poor prognosis in patients with CHF and are related to the severity of heart failure.[49]

Isolated studies have shown evidence of MI and elevated TnI levels in patients with subarachnoid hemorrhage.[50] Vasoactive peptides released during acute subarachnoid hemorrhage induce deep T-wave inversions on ECG that indicate myocardial injury. Similarly, TnT has been shown to be an independent predictor of outcome in patients with pulmonary embolism; right ventricular strain or infarction from acute pulmonary hypertension causes the elevated troponin level.

Elevated troponin levels have also been documented in other nonischemic cardiac disease states, such as tachyarrhythmias, hypertension, myocarditis, and myocardial contusion.


Emerging Markers

Investigations into emerging cardiac markers are focusing on increasing diagnostic sensitivity and specificity and on improving prognostic capability.

B-type natriuretic peptide

B-type natriuretic peptide (BNP) is secreted primarily by the ventricular myocardium in response to wall stress, including volume expansion and pressure overload. Multiple studies have demonstrated that BNP may also be a useful prognostic indicator in ACS. The TIMI study group performed several investigations showing that the BNP level predicted cardiac mortality and other adverse cardiac events across the entire spectrum of ACS. The mortality rate nearly doubled when both TnI and BNP levels were elevated.

In the TACTICS-TIMI 18 trial, an elevated BNP level was associated with tighter culprit stenosis, higher corrected TIMI frame count, and left anterior descending artery involvement.[41] These data suggest that increased BNP levels may correlate with greater severity of myocardial ischemia and could partially explain the association between increased BNP levels and adverse outcomes.

Data from OPUS-TIMI 16 and TACTICS-TIMI 18 demonstrated that baseline elevations of TnI, C-reactive protein (CRP), and BNP levels in patients with NSTEMI were independent predictors of the composite endpoint of death, MI, or CHF.[51] The PROMPT-TIMI 35 trial demonstrated that transient myocardial ischemia during exercise testing was associated with an immediate rise in BNP levels.[52] In addition, the severity of ischemia was directly proportional to the elevation in BNP.

The presence of acute CHF in patients with ACS is a well-known predictor of adverse cardiac events and higher risk. Therefore, it is not surprising that an elevated BNP level, as a marker of CHF, is also predictive of adverse cardiac events in patients with ACS. Although BNP has been validated as a diagnostic marker for CHF, insufficient data are available to evaluate the use of BNP as a diagnostic cardiac marker for ACS in the ED.

C-reactive protein

C-reactive protein (CRP), a nonspecific marker of inflammation, is considered to be directly involved in coronary plaque atherogenesis. Extensive studies beginning in the early 1990s showed that an elevated CRP level independently predicted adverse cardiac events at the primary and secondary prevention levels.

Data indicate that CRP is a useful prognostic indicator in patients with ACS, as elevated CRP levels are independent predictors of cardiac death, acute MI, and CHF. In combination with TnI and BNP, CRP may be a useful adjunct, but its nonspecific nature limits its use as a diagnostic cardiac marker for ACS in the ED.


Myeloperoxidase (MPO) is a leukocyte enzyme that generates reactant oxidant species and has been linked to prothrombotic oxidized lipid production, plaque instability, lipid-laden soft plaque creation, and vasoconstriction from nitrous oxide depletion. Early studies showed significantly increased MPO levels in patients with angiographically documented coronary artery disease[53] ; these findings spurred further investigation into MPO as a novel cardiac marker.

In 604 sequential patients presenting to the ED with chest pain, elevated MPO levels independently predicted increased risk for major adverse cardiac events, including MI, reinfarction, need for revascularization, or death at 30 days and at 6 months.[54] Among the patients who presented to the ED with chest pain but who were ultimately ruled out for MI, an elevated MPO level at presentation predicted subsequent major adverse cardiovascular outcomes. In a subgroup of patients with negative baseline TnT, MPO levels were significantly elevated at baseline, even within 2 hours after symptom onset.

MPO may be a useful early marker in the ED based on its ability to detect plaque vulnerability that precedes ACS. However, further validation studies on MPO in the general ED chest pain population are needed to determine its sensitivity and specificity, as well as its negative and positive predictive values.[55, 56]

Ischemia modified albumin

Ischemia modified albumin (IMA) is a novel marker of ischemia that is produced when circulating serum albumin contacts ischemic heart tissues. IMA can be measured by the albumin cobalt binding assay that is based on IMA’s inability to bind to cobalt.[57] A rapid assay with a 30-minute laboratory turnaround time has been developed and marketed as the first commercially available US Food and Drug Administration (FDA)–approved marker of myocardial ischemia.

Based on investigations of myocardial ischemia induced by balloon inflation during percutaneous coronary intervention, IMA levels rise within minutes of transient ischemia, peak within 6 hours, and can remain elevated for as long as 12 hours.

Studies on the use of IMA in patients with chest pain in the ED found sensitivities that ranged from 71-98% and specificities of 45-65%, with a negative predictive value of 90-97% for ACS.[58]

A multimarker approach in one study, using a combination of ECG findings, TnT levels, and IMA levels, achieved a sensitivity of 95% for ACS,[59] while a second study calculated that the combination of IMA, myoglobin, CK-MB, and TnI increased the sensitivity to 97% for detecting myocardial ischemia.[60]

However, IMA levels are also elevated in patients with cirrhosis, certain infections, and advanced cancer, which reduces the specificity of the assay. Further validation and outcome studies are required to evaluate IMA’s use in the ED diagnosis of ACS when the ECG and cardiac troponins levels are nondiagnostic.

Contributor Information and Disclosures

Donald Schreiber, MD, CM Associate Professor of Surgery (Emergency Medicine), Stanford University School of Medicine

Donald Schreiber, MD, CM is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.


Suzanne M Miller, MD Clinical Instructor, Emergency Medicine, George Washington University School of Medicine and Health Sciences; Attending Physician, Department of Emergency Medicine, INOVA Fairfax Hospital; Chief Executive Officer, MDadmit

Suzanne M Miller, MD is a member of the following medical societies: American Academy of Emergency Medicine, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, Society for Academic Emergency Medicine, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians

Disclosure: Nothing to disclose.


Edward Bessman, MD, MBA Chairman and Clinical Director, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University School of Medicine

Edward Bessman, MD, MBA is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School

Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management position; Royalty Other

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

  1. [Guideline] Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct. 33(20):2551-67. [Medline].

  2. Collinson P, Gaze D, Thokala P, Goodacre S. Randomised Assessment of Treatment using Panel Assay of Cardiac markers - Contemporary Biomarker Evaluation (RATPAC CBE). Health Technol Assess. 2013 Apr. 17(15):1-122. [Medline].

  3. Diercks DB, Mumma BE, Frank Peacock W, et al. Incremental value of objective cardiac testing in addition to physician impression and serial contemporary troponin measurements in women. Acad Emerg Med. 2013 Mar. 20(3):265-70. [Medline].

  4. [Guideline] American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions, O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Jan 29. 61(4):e78-140:78-140. [Medline].

  5. [Guideline] Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interve... J Am Coll Cardiol. 2007 Aug 14. 50(7):e1-e157. [Medline].

  6. [Guideline] Anderson JL, Adams CD, Antman EM, et al. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013 Jun 11. 61(23):e179-347. [Medline].

  7. Apple FS, Parvin CA, Buechler KF, Christenson RH, Wu AH, Jaffe AS. Validation of the 99th percentile cutoff independent of assay imprecision (CV) for cardiac troponin monitoring for ruling out myocardial infarction. Clin Chem. 2005 Nov. 51(11):2198-200. [Medline].

  8. Eggers KM, Oldgren J, Nordenskjold A, Lindahl B. Diagnostic value of serial measurement of cardiac markers in patients with chest pain: limited value of adding myoglobin to troponin I for exclusion of myocardial infarction. Am Heart J. 2004 Oct. 148(4):574-81. [Medline].

  9. Macrae AR, Kavsak PA, Lustig V, Bhargava R, Vandersluis R, Palomaki GE, et al. Assessing the requirement for the 6-hour interval between specimens in the American Heart Association Classification of Myocardial Infarction in Epidemiology and Clinical Research Studies. Clin Chem. 2006 May. 52(5):812-8. [Medline].

  10. Kavsak PA, MacRae AR, Newman AM, et al. Effects of contemporary troponin assay sensitivity on the utility of the early markers myoglobin and CKMB isoforms in evaluating patients with possible acute myocardial infarction. Clin Chim Acta. 2007 May 1. 380(1-2):213-6. [Medline].

  11. Saenger AK, Jaffe AS. Requiem for a heavyweight: the demise of creatine kinase-MB. Circulation. 2008 Nov 18. 118(21):2200-6. [Medline].

  12. [Guideline] Antman EM, Hand M, Armstrong PW, et al. 2007 Focused Update of the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial I... Circulation. 2008 Jan 15. 117(2):296-329. [Medline].

  13. [Guideline] Kushner FG, Hand M, Smith SC Jr, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009 Dec 1. 54(23):2205-41. [Medline].

  14. James SK, Lindahl B, Armstrong P, et al. A rapid troponin I assay is not optimal for determination of troponin status and prediction of subsequent cardiac events at suspicion of unstable coronary syndromes. Int J Cardiol. 2004 Feb. 93(2-3):113-20. [Medline].

  15. Morrow DA, Cannon CP, Rifai N, et al. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. JAMA. 2001 Nov 21. 286(19):2405-12. [Medline].

  16. Wu AH, Jaffe AS. The clinical need for high-sensitivity cardiac troponin assays for acute coronary syndromes and the role for serial testing. Am Heart J. 2008 Feb. 155(2):208-14. [Medline].

  17. Panteghini M, Pagani F, Yeo KT, et al; Committee on Standardization of Markers of Cardiac Damage of the IFCC. Evaluation of imprecision for cardiac troponin assays at low-range concentrations. Clin Chem. 2004 Feb. 50 (2):327-32. [Medline].

  18. [Guideline] Nichols JH, Christenson RH, Clarke W, et al. Executive summary. The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guideline: evidence-based practice for point-of-care testing. Clin Chim Acta. 2007 Apr. 379(1-2):14-28; discussion 29-30. [Medline].

  19. Newby LK, Storrow AB, Gibler WB, et al. Bedside multimarker testing for risk stratification in chest pain units: The chest pain evaluation by creatine kinase-MB, myoglobin, and troponin I (CHECKMATE) study. Circulation. 2001 Apr 10. 103(14):1832-7. [Medline].

  20. Apple FS, Murakami MM, Christenson RH, et al. Analytical performance of the i-STAT cardiac troponin I assay. Clin Chim Acta. 2004 Jul. 345(1-2):123-7. [Medline].

  21. Ryan RJ, Lindsell CJ, Hollander JE, et al. A multicenter randomized controlled trial comparing central laboratory and point-of-care cardiac marker testing strategies: the Disposition Impacted by Serial Point of Care Markers in Acute Coronary Syndromes (DISPO-ACS) trial. Ann Emerg Med. 2009 Mar. 53(3):321-8. [Medline].

  22. Antman EM, Tanasijevic MJ, Thompson B, et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 1996 Oct 31. 335(18):1342-9. [Medline].

  23. Heidenreich PA, Alloggiamento T, Melsop K, McDonald KM, Go AS, Hlatky MA. The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis. J Am Coll Cardiol. 2001 Aug. 38(2):478-85. [Medline].

  24. Iliou MC, Fumeron C, Benoit MO, et al. Prognostic value of cardiac markers in ESRD: Chronic Hemodialysis and New Cardiac Markers Evaluation (CHANCE) study. Am J Kidney Dis. 2003 Sep. 42(3):513-23. [Medline].

  25. Ohman EM, Armstrong PW, Christenson RH, et al. Cardiac troponin T levels for risk stratification in acute myocardial ischemia. GUSTO IIA Investigators. N Engl J Med. 1996 Oct 31. 335(18):1333-41. [Medline].

  26. Stubbs P, Collinson P, Moseley D, Greenwood T, Noble M. Prognostic significance of admission troponin T concentrations in patients with myocardial infarction. Circulation. 1996 Sep 15. 94(6):1291-7. [Medline].

  27. Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. N Engl J Med. 2000 Oct 19. 343(16):1139-47. [Medline].

  28. Newby LK, Christenson RH, Ohman EM, et al. Value of serial troponin T measures for early and late risk stratification in patients with acute coronary syndromes. The GUSTO-IIa Investigators. Circulation. 1998 Nov 3. 98(18):1853-9. [Medline].

  29. Lindahl B, Venge P, Wallentin L. Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease. The FRISC study group. Circulation. 1996 May 1. 93(9):1651-7. [Medline].

  30. Newby LK, Roe MT, Chen AY, et al. Frequency and clinical implications of discordant creatine kinase-MB and troponin measurements in acute coronary syndromes. J Am Coll Cardiol. 2006 Jan 17. 47(2):312-8. [Medline].

  31. Goodman SG, Steg PG, Eagle KA, et al. The diagnostic and prognostic impact of the redefinition of acute myocardial infarction: lessons from the Global Registry of Acute Coronary Events (GRACE). Am Heart J. 2006 Mar. 151(3):654-60. [Medline].

  32. Adams JE 3rd, Bodor GS, Davila-Roman VG, et al. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation. 1993 Jul. 88(1):101-6. [Medline].

  33. Zimmerman J, Fromm R, Meyer D, et al. Diagnostic marker cooperative study for the diagnosis of myocardial infarction. Circulation. 1999 Apr 6. 99(13):1671-7. [Medline].

  34. Puleo PR, Meyer D, Wathen C, et al. Use of a rapid assay of subforms of creatine kinase-MB to diagnose or rule out acute myocardial infarction. N Engl J Med. 1994 Sep 1. 331(9):561-6. [Medline].

  35. Fesmire FM, Decker WW, Diercks DB, et al. Clinical policy: critical issues in the evaluation and management of adult patients with non-ST-segment elevation acute coronary syndromes. Ann Emerg Med. 2006 Sep. 48(3):270-301. [Medline].

  36. McCord J, Nowak RM, McCullough PA, et al. Ninety-minute exclusion of acute myocardial infarction by use of quantitative point-of-care testing of myoglobin and troponin I. Circulation. 2001 Sep 25. 104(13):1483-8. [Medline].

  37. Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997 Aug 14. 337(7):447-52. [Medline].

  38. Fragmin during Instability in Coronary Artery Disease (FRISC) study group. Low-molecular-weight heparin during instability in coronary artery disease, Fragmin during Instability in Coronary Artery Disease (FRISC) study group. Lancet. 1996 Mar 2. 347(9001):561-8. [Medline].

  39. PRISM-PLUS Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med. 1998 May 21. 338(21):1488-97. [Medline].

  40. Bhatt DL, Topol EJ. Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. JAMA. 2000 Sep 27. 284(12):1549-58. [Medline].

  41. Morrow DA, de Lemos JA, Sabatine MS, et al. Evaluation of B-type natriuretic peptide for risk assessment in unstable angina/non-ST-elevation myocardial infarction: B-type natriuretic peptide and prognosis in TACTICS-TIMI 18. J Am Coll Cardiol. 2003 Apr 16. 41(8):1264-72. [Medline].

  42. Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001 Jun 21. 344(25):1879-87. [Medline].

  43. Kleiman NS, Lakkis N, Cannon CP, et al. Prospective analysis of creatine kinase muscle-brain fraction and comparison with troponin T to predict cardiac risk and benefit of an invasive strategy in patients with non-ST-elevation acute coronary syndromes. J Am Coll Cardiol. 2002 Sep 18. 40(6):1044-50. [Medline].

  44. Aviles RJ, Askari AT, Lindahl B, et al. Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. N Engl J Med. 2002 Jun 27. 346(26):2047-52. [Medline].

  45. deFillippi C, Yoon A, Bounds C. Early detection of myocardial ischemia by a novel blood-based biomarker: the kinetics of ischemia modified albumin. JACC. 2003;41(6):Supplement 2:340A-341A.

  46. Stolear JC, Georges B, Shita A, Verbeelen D. The predictive value of cardiac troponin T measurements in subjects on regular haemodialysis. Nephrol Dial Transplant. 1999 Aug. 14(8):1961-7. [Medline].

  47. Ooi DS, Zimmerman D, Graham J, Wells GA. Cardiac troponin T predicts long-term outcomes in hemodialysis patients. Clin Chem. 2001 Mar. 47(3):412-7. [Medline].

  48. Freda BJ, Tang WH, Van Lente F, Peacock WF, Francis GS. Cardiac troponins in renal insufficiency: review and clinical implications. J Am Coll Cardiol. 2002 Dec 18. 40(12):2065-71. [Medline].

  49. Potluri S, Ventura HO, Mulumudi M, Mehra MR. Cardiac troponin levels in heart failure. Cardiol Rev. 2004 Jan-Feb. 12(1):21-5. [Medline].

  50. Sandhu R, Aronow WS, Rajdev A, et al. Relation of cardiac troponin I levels with in-hospital mortality in patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Am J Cardiol. 2008 Sep 1. 102(5):632-4. [Medline].

  51. Sabatine MS, Morrow DA, de Lemos JA, et al. Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation. 2002 Apr 16. 105(15):1760-3. [Medline].

  52. Sabatine MS, Morrow DA, de Lemos JA, et al. Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia. J Am Coll Cardiol. 2004 Nov 16. 44(10):1988-95. [Medline].

  53. Zhang R, Brennan ML, Fu X, et al. Association between myeloperoxidase levels and risk of coronary artery disease. JAMA. 2001 Nov 7. 286(17):2136-42. [Medline].

  54. Brennan ML, Penn MS, Van Lente F, et al. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med. 2003 Oct 23. 349(17):1595-604. [Medline].

  55. Apple FS, Wu AH, Mair J, et al. Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome. Clin Chem. 2005 May. 51(5):810-24. [Medline].

  56. Apple FS, Smith SW, Pearce LA, Murakami MM. Assessment of the multiple-biomarker approach for diagnosis of myocardial infarction in patients presenting with symptoms suggestive of acute coronary syndrome. Clin Chem. 2009 Jan. 55(1):93-100. [Medline].

  57. Abadie JM, Blassingame CL, Bankson DD. Albumin cobalt binding assay to rule out acute coronary syndrome. Ann Clin Lab Sci. 2005 Winter. 35(1):66-72. [Medline].

  58. Peacock F, Morris DL, Anwaruddin S, et al. Meta-analysis of ischemia-modified albumin to rule out acute coronary syndromes in the emergency department. Am Heart J. 2006 Aug. 152(2):253-62. [Medline].

  59. Sinha MK, Roy D, Gaze DC, Collinson PO, Kaski JC. Role of "Ischemia modified albumin", a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes. Emerg Med J. 2004 Jan. 21(1):29-34. [Medline]. [Full Text].

  60. Anwaruddin S, Januzzi JL Jr, Baggish AL, Lewandrowski EL, Lewandrowski KB. Ischemia-modified albumin improves the usefulness of standard cardiac biomarkers for the diagnosis of myocardial ischemia in the emergency department setting. Am J Clin Pathol. 2005 Jan. 123(1):140-5. [Medline].

Use of cardiac markers in the ED. Studies on troponins in acute coronary syndrome.
Use of cardiac markers in the ED. Troponin I levels and cardiac mortality in acute coronary syndrome.
Use of cardiac markers in the ED. Cardiac event rates in the platelet receptor inhibition for ischemic syndrome (PRISM) study based on troponin I results.
Use of cardiac markers in the ED. Effect of time to treatment in patients with acute coronary syndrome (ACS) who are treated with the GIIb/IIIa inhibitor eptifibatide.
Table 1. Sampling Frequency of Cardiac Markers
  Baseline 3-4 h 6-9 h 12-24 h >24 h
CK-MB isoforms, myoglobin X X X    

(only if very high risk)

Late presenters

(TnI, TnT)

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