Definition and EfficacyCardiac 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 American College of Cardiology (ACC) and the European Society of Cardiology (ESC).[1, 2, 3]

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 nonST-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]

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.[5, 6, 7, 8, 9] 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.[10]

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

Cardiac TroponinsThe 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 the ACC/ESC guidelines, any elevated measure of troponin above the 10% CV or 99th percentile upper reference limit in the appropriate clinical setting is defined as an MI.

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.[11]

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.[12, 13]

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.[14] 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.[13] 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 assays 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 assaysNACB recommendations specify that cardiac markers be available on an immediate basis 24 h/d, 7 d/wk, with a turnaround time of 1 hour.[15] 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).[16]

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.[17, 18] 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 troponinIn addition to its use in the diagnosis of MI, an elevated troponin level can identify patients at high risk for adverse cardiac events.[19, 20] 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.[21] 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.[19]

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.[22, 23]

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.[19, 22, 24, 25, 26]

Creatine KinaseMBPrior 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.[27]

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.[28] Thus, an isolated CK-MB elevation has limited prognostic value in patients with a non-ST elevation ACS.

CK-MB/CK relative indexThe 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.[29]

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 isoformsThe 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.[30, 31] The major disadvantage of this assay is that it is relatively labor intensive for the laboratory.

MyoglobinMyoglobin 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.[6, 8]

Testing StrategyIn 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[32] . 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.[33] 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%.

ACEPs 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, ACEPs 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 ACEPs 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)

Baseline3-4 h6-9 h12-24 h>24 hCK-MB isoforms, myoglobinXXXCK-MB, TnI, TnTXXXX

(only if very high risk)

Late presenters

(TnI, TnT)

XThe 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 ManagementClinical 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.[34, 35]

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.[36]

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.[37]

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.[38, 39] 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.[40]

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 CRFPatients 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,[41] and 2 other prospective studies reported that an elevated TnTbut not TnIincreased the risk of long-term mortality.[42, 43] 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.[44, 45]

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 DiseaseA 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.[46]

Isolated studies have shown evidence of MI and elevated TnI levels in patients with subarachnoid hemorrhage.[47] 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 MarkersInvestigations into emerging cardiac markers are focusing on increasing diagnostic sensitivity and specificity and on improving prognostic capability.

B-type natriuretic peptideB-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.[38] 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.[48] The PROMPT-TIMI 35 trial demonstrated that transient myocardial ischemia during exercise testing was associated with an immediate rise in BNP levels.[49] 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 proteinC-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.

MyeloperoxidaseMyeloperoxidase (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[50] ; 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.[51] 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.[52, 53]

Ischemia modified albuminIschemia 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 IMAs inability to bind to cobalt.[54] 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.[55]

A multimarker approach in one study, using a combination of ECG findings, TnT levels, and IMA levels, achieved a sensitivity of 95% for ACS,[56] while a second study calculated that the combination of IMA, myoglobin, CK-MB, and TnI increased the sensitivity to 97% for detecting myocardial ischemia.[57]

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 IMAs use in the ED diagnosis of ACS when the ECG and cardiac troponins levels are nondiagnostic.Definiie i eficacitateMarkeri cardiace sunt utilizate n diagnosticul i stratificarea riscului de pacienti cu dureri in piept si sindrom coronarian acut suspectat ( ACS ) . A troponinei cardiace , n special , au devenit markerii cardiace de alegere pentru pacientii cu ACS . ntr-adevr , troponinei este esenial pentru definirea infarctului miocardic acut ( MI) , n liniile directoare consens de la Colegiul American de Cardiologie ( ACC ) si a Societatii Europene de Cardiologie ( ESC ) [ 1 , 2 , 3 ] .

De exemplu , pacientii cu niveluri crescute ale troponinei dar creatinkinazei - MB ( CK - MB ) valori negative , care au fost anterior diagnosticat cu angin instabil sau leziuni miocardice minore sunt acum reclasificate ca - segmentului non - supradenivelare MI ST ( NSTEMI ) , chiar i n absena a electrocardiogramei (ECG ) schimbari de diagnosticare .

Similar , numai 1 nivel troponinei mai suscutoff stabilit este necesar pentru a stabili diagnosticul de infarct miocardic acut , n conformitate cu liniile directoare ACC pentru NSTEMI . [ 4 ]

Aceste modificri au fost instituite ca urmare a introducerii de teste ce n ce mai sensibile i precise troponinei . Pn la 80 % din pacientii cu infarct miocardic acut va avea un nivel troponinei n termen de 2-3 ore de la departamentul de urgenta ( ED ) sosire , comparativ cu 6-9 ore sau mai mult , cu CK - MB si a altor markeri cardiace .

n consecin , unii au susinut bazndu-se doar pe troponina i ntrerupereautilizrii CK - MB i ali markeri . [ 5 , 6 , 7 , 8 , 9 ] Cu toate acestea , CK - MB i alte markeri continu s fie folosite n unele spitale pentru a exclude MI i s monitorizeze pentru un prejudiciu suplimentar miocardului lungul timpului .

Reinei c markeri cardiace nu sunt necesare pentru diagnosticul pacienilor care prezint cu dureri in piept ischemic i EKG de diagnosticare cu supradenivelare de segment ST . Acesti pacienti pot fi candidati pentru terapia trombolitic sau prin angioplastie primar . Tratamentul nu ar trebui s fie amnat s atepte pentru rezultate marcator cardiace , mai ales deoarece sensibilitatea este sczut n primele 6 ore de la debutul simptomelor . ACC / American Heart Association ( AHA ) liniile directoare recomanda terapia de reperfuzie imediat pentru pacientii cu - segment ST ( IMA ST ) de calificare , fr a mai atepta rezultatele marcator cardiace . [ 10 ]

Du-te la infarct miocardic si a complicatiilor de infarct miocardic pentru informaii mai complete cu privire la aceste subiecte .

Troponinele cardiaceCele troponinele sunt proteine de reglementare gasite in muschii scheletici si cardiac . Au fost identificate trei subuniti : troponina I ( TNI ) , troponina T ( TNT) , i troponina C ( CTN) . Genele care codific pentru izoforme scheletice i cardiace ale TnC sunt identice , astfel , nu exist diferene structurale ntre ele . Cu toate acestea, subformularele scheletice i cardiace pentru TNI si troponina TNT sunt distincte , i imunotestele au fost concepute pentru a diferenia ntre ele .

Dou intervale de referin diferite sunt utilizate n teste troponin . Limita superioar de referin procentual dlimita superioar a ceea ce poate fi de ateptat ntr -o populaie normal , sntoas , pentru aduli , n timp cecoeficientul de variaie ( CV ) estevariaia n procente rezultatele testului , care poate fi de ateptat atunci cndaceeai prob este analizat n mod repetat .

n conformitate cu liniile directoare ACC / ESC , orice msur ridicat a troponinei sus a CV-ului de 10 % sau limita a 99- percentila de referin superioare n mediu clinic corespunztor, este definit ca un MI .

Sensibilitatea , specificitatea , i precizia diferitelor teste troponin disponibile comercial variaz considerabil . Aceste diferene sunt legate de o lips de standardizare ,utilizarea diferitelor anticorpi monoclonali , prezena modificat TnI i TnT nser , i variaiile anticorp reactivitate ncruciat la diverse forme detectabile de TnI care rezulta din degradarea acesteia .

Doar un singur productor produce testul TNT, i ei cutoffs percentila 99 i CV-ul de 10 %, sunt bine stabilite . Cu toate acestea , pn la variaia de 20 de ori a avut loc n rezultatele obinute cu multitudinea de teste comerciale TNI disponibile n prezent , fiecare cu propriile lor limite 99-a percentila de referin superioare i 10 % Nivelul de CV .

In cadrul studiului GUSTO IV , un relativ insensibil punct - de - ingrijire TNI testul a fost folosit pentru a ecran pacientii pentru eligibilitate de studiu . ntr -un studiu ulterior , probele de snge au fost reanalizata utilizndcutoff percentila 99 a unei mult mai sensibil central TnT test de laborator . Mai sensibil cutoff percentila 99- a acestui test TnT a identificat o sum suplimentar de 96 ( 28 % ) din 337 de pacienti cu un rezultat pozitiv, dar TNT negativ punct - de - ingrijire TNI ; . Acesti pacienti au avut rate mai mari de deces sau IM la 30 zile [ 11 ]

ntr- o reanalizarea similar a tacticile - TIMI 18 proces , 3 cutoffs TNI diferite au fost comparate pe 1821 de pacienti pentru a evalua riscul de 30 de zile de decesul sau IM : percentila 99 , CV 10 % , iar Organizaia Mondial a Sntii ( OMS ) acut cutoffs MI . (OMS Cutoffs defini infarct miocardic acut cu CK - MB i s raporteze nivelurile troponinei fie ca un mare " nivel de IM acut " sau un " nivel intermediar " inferior , care este corelat cu " scurgere " sau " prejudiciu miocardic minore . " )

Folosind10 % CV cutoff identificat , o suplimentare de 12 % mai multe cazuri au fost identificate n raportOMS acut MI tiere . 99 cutoff procentual a identificat un supliment de 10 % din cazurile raportate la10 % CV tiere , precum i o cretere de 22 % a numrului de cazuri pesteOMS acut MI tiere . Cu toate acestea , raporturile cote pentru adverse rate de eveniment cardiace de deces sau IM la 30 zile au fost similare pentru toate cele 3 cutoffs , sugerand ca cutoffs inferior detectat mai multi pacienti cu risc cardiovascular , fr a sacrifica specificitate [ 12 , 13 ] .

Academiei Nationale de Biochimie clinic ( NACB ) de lucru cu liniile directoare ACC / ESC a recomandat adoptarea de limita de 99 percentila de referin superioar ca cutoff recomandat pentru un rezultat pozitiv troponinei . n mod ideal ,de precizie a testului la acest nivel oprire trebuie msurat printr-un CV care este mai mic de 10 % .

Cu toate acestea , majoritatea analizelor TNI sunt imprecise la limita de referin percentila 99 . [ 14 ] , prin urmare, Unii au recomandat canivelul cutoff fi ridicat lanivelul uor mai mare CV 10 % n loc delimita de 99 de referin procentual a asigura precizie test adecvat .

n plus , studiile au artat c populaiile din limitele de referin pentru percentila 99 include pacienti cu niveluri scazute troponinei care au totui un risc cardiac crescut , i c adevratul cutoff percentila 99 pentru o populaie sntoas pacientul este de fapt un factor de 10-50 mai mic . n consecin , aceste anchete sugereaz c sensibilitatea mai mare sau testele troponinei ultrasensitive sunt necesare [ 13 ] Avantajul troponinelor ultrasensitive se bazeaz pe premisa c nivelurile de limita minim atinge o sensibilitate mai mare , care va permite diagnosticul mai devreme , de multe ori n termen de 90 de minute de prezentare . .

Pentru a optimiza utilizarea testului n ED , este important s fie familiarizai cu deosebit troponinei disponibil n laborator i de a ti dac cutoff este stabilit la nivelul CV 10 % sau limita de 99 percentila de referin superioar .

Teste punct - de - ingrijireRecomandrile NACB precizeaz c markeri cardiaci fi disponibile pe o baz imediat 24 de ore / zi , 7 zile / sptmn , cu un timp de rspuns de 1 or . [ 15 ] la punctul de ingrijire ( POC ) dispozitive care ofer rezultate rapide ar trebui s fie luate n considerare n spitale, laboratoare ale caror nu pot rspunde acestor linii directoare .

Teste POC pentru CK - MB , mioglobinei , iar cardiace troponinei TNI i TNT sunt disponibile . Doar teste calitative TnT sunt disponibile ca teste POC , dar att cantitative, ct i calitative POC testele TNI sunt n prezent comercializate .

ntr -un studiu multicentric ,timp pentru pozitivitate a fost semnificativ mai rapid pentruaparatul POC dect pentrulaborator local ( 2,5 ore vs 3,4 h ) . [ 16 ]

ntr-un alt studiu multicentric , care a evaluat POC TNI testul i-STAT n comparaie cu laboratorul central de la 2000 de pacienti cu SCA suspectate , testare POC a redus durata de edere de aproximativ 25 de minute pentru pacientii care au fost evacuate din ED . [ 17 , 18 ] sensibilitatea testelor de POC actuale cuplate cu beneficiul de timp de rspuns rapid a face teste POC instrumente clinice atractive n ED .

Valoarea de prognostic a troponineiIn plus fata de utilizarea sa n diagnosticul de MI , un nivel troponinei pot identifica pacientii cu risc crescut de evenimente adverse cardiace . [ 19 , 20 ] Mai exact , datele de la o meta- analiz a artat c un nivel troponinei la pacieni fr ST - supradenivelare de segment este asociat cu o crestere de aproape 4 ori a ratei mortalitii cardiace . [ 21 ] la pacieni fr supradenivelare de segment ST care au fost luate n considerare pentru tratament trombolitic , nivelurile iniiale TNI la admitere, corelate cu mortalitatea la 6 sptmni , dar CK - nivelurile de MB nu au fost de predictie de evenimente adverse cardiace i a avut nici o valoare de prognostic . [ 19 ]

Alte studii au evideniat c un nivel troponinei la momentul initial a fost un predictor independent de mortalitate , chiar si la pacientii cu dureri in piept si infarct miocardic acut cu supradenivelare de segment ST care au fost eligibili pentru terapia de reperfuzie . [ 22 , 23 ]

n cele din urm ,IIIB , GUSTO IIa , GUSTO IV ACS , i FRISC studiu TIMI demonstrat tot o corelaie direct ntre nivelul de TNI sau TNT i rata mortalitii i rata evenimentelor adverse cardiace n ACS . [ 19 , 22 , 24 , 25 , 26 ]

Creatinkinazei - MBnainte de introducerea a troponinelor cardiace , marker biochimic de alegere pentru diagnosticul de IM acut a fost izoenzimei CK - MB . Criteriul cel mai frecvent utilizate pentru diagnosticul de IM acut a fost de 2 cote de serie peste nivelul cutoff diagnostic sau un singur rezultat mai mult dect de dou ori limita superioar a normalului . Dei CK - MB este mai concentrat n miocard , este , de asemenea, exista in muschii scheletici si cresteri fals - pozitive apar ntr-o serie de setari clinice , inclusiv traume , efort greu , i miopatie .

CK - MB apare pentru prima dat de 4-6 ore de la debutul simptomelor , vrfuri La 24 ore , i revine la normal n 48-72 de ore . Valoarea n diagnosticul precoce i tardiv ( > 72 h ) de infarct miocardic acut este limitat . Cu toate acestea , cinetica sale de eliberare poate ajuta la diagnosticarea reinfarctizarea dac nivelul crete dup ce a refuzat iniial urmtoarele infarct miocardic acut .

n registru cruciada , o revizuire a aproape 30.000 de pacienti a aratat ca discordanta troponina i rezultatele CK - MB a avut loc in 28 % dintre pacienti . Cu toate acestea , pacientii care au fost troponina negativa , dar CK - MB pozitiv au avut rate de mortalitate in spital , care nu au crescut semnificativ de la pacientii care au fost negative pentru ambele biomarkeri . [ 27 ]

De asemenea, ntr-un raport de mai mult de 10.000 de pacienti cu SCA din registrul GRACE multicentric , mortalitatea intraspitaliceasc a fost mai mare atunci cnd att troponina i CK - MB au fost pozitive , intermediar la pacientii troponin-positive/CK-MB-negative , i cea mai mic n pacientii la care ambele markeri au fost negative i n cei care au fost troponin-negative/CK-MB-positive . [ 28 ] Astfel , un izolat CK - MB elevaie a limitat valoarea de prognostic la pacientii cu un non - ST ACS altitudine .

Index relativ CK-MB/CKIndicele relativ, calculat prin raportul dintre CK - MB ( masa ) total a CK pot ajuta la diferenierea cresteri fals - pozitive ale CK - MB decurg din muschii scheletici . Un raport mai mic de 3 este n concordan cu o surs de muchi scheletici , n timp ce raporturi mai mari de 5 indic o surs cardiace . Indicatori ntre 3 i 5 reprezint o zon gri . Nici un diagnostic definitiv poate fi stabilit fr determinri de serie pentru a detecta o cretere .

Indicele relativ CK-MB/CK fost introdus pentru a mbuntispecificitatea CK - MB elevaie pentru infarct miocardic . Cu toate acestea , sensibilitatea de infarct miocardic acut scade atunci cnd prejudiciului cardiace concomitent i leziuni musculare scheletice este prezent . ntr-un studiu de ED pe baz pentru a evaluaindicele relativ CK - MB comparativ cuabsolut CK - MB , specificitate a fost crescut , dar cu o pierdere de sensibilitate . [ 29 ]

Indicele relativ CK-MB/CK este util n cazul n care pacienii au doar un MI sau leziuni musculare numai scheletici , dar nu n cazul n care ambele au . Prin urmare , n stabilirea combinat de infarct miocardic acut i leziuni musculare scheletice ( rabdomioliz , exerciiu greu , polimiozita ) , scderea sensibilitii este semnificativ .

Reinei c diagnosticul de infarct miocardic acut nu trebuie s se bazeze pe un index relativ ridicat singur , deoarece indicele relativ pot fi crescute in setarile clinice, atunci cand, fie total CK sau CK - MB este n limite normale . Indicele relativ este util numai atunci cnd att clinicCK totale si nivelurile CK - MB sunt crescute.

Izoforme CK - MBCK - MB izoenzima exist ca 2 izoforme : CK - MB1 i CK - MB2 . Determinarea n laborator a CK - MB reprezinta , de fapt, simpla suma izoforme CK - MB1 i CK - MB2 . CK - MB2 este forma tesuturi si iniial este eliberat de la nivelul miocardului dup MI . Acesta este convertit periferic n ser la CK - MB1 izoenzimei rapid dup debutul simptomelor .

In mod normal , predominesutul CK - MB1 izoform , astfel ,raportul CK-MB2/CK-MB1 este de obicei mai puin de 1 . Un rezultat este pozitiv dacCK - MB2 este nlat iraportul este mai mare dect 1,7 .

CK - MB2 poate fi detectat n ser n decurs de 2-4 ore de la debut i vrfuri la 6-9 ore , ceea ce face un marker precoce de infarct miocardic acut . Dou studii clinice mari evaluare utilizarea sa relevat o sensibilitate de 92 % dup 6 ore de la apariia simptomelor , n comparaie cu 66 % pentru CK - MB i 79 % pentru mioglobin . [ 30 , 31 ]dezavantaj major al acestui test este faptul c este relativ muncii intensiv pentrulaborator .

mioglobinaMioglobina este o proteina heme gasit in muschii scheletici si cardiace , care a atras un interes considerabil ca un marker precoce de MI . Conturilor sale cu greutate molecular mic pentru profilul de eliberare timpurie : mioglobina se ridic de obicei 2-4 ore de la debutul infarctului , vrfuri la 6-12 ore , i revine la normal in urmatoarele 24-36 de ore .

Testele mioglobina rapide sunt disponibile , dar n general , au o lips de cardiospecificity . De prelevare a probelor de serie la fiecare 1-2 ore poate crete sensibilitatea i specificitatea , o cretere de 25-40 % de 1-2 ore este puternic sugestiv de infarct miocardic acut . Cu toate acestea , n cele mai multe studii , mioglobina realizat doar sensibilitate 90 % pentru IM acut , astfel nct valoarea predictiv negativ a mioglobinei nu este suficient de mare pentru a excludediagnosticul de infarct miocardic acut .

Studiile originale pe care mioglobina evaluat folosit definiia OMS IM acut , care a fost bazat pe un standard de CK - MB . Odat cu adoptarea unui standard troponinei pentru infarct miocardic acut n definiia ACC / ESC , sensibilitatea de mioglobina pentru IM acut este redus substanial . Acest lucru reduce semnificativ utilitatea sa , i o serie de studii au artat c testele contemporane troponinei cardiace face utilizarea de msurtori mioglobina [ 6 , 8 ] inutile .

testarea StrategiaLa pacientii cu SCA definite sau posibil , evaluarea serie de markeri cardiace este esenial pentru diagnosticarea infarct miocardic acut .

Colegiul American al Medicilor de urgenta ( ACEP ) recomanda trei strategii diferite de testare pentru a exclude NSTEMI n ED [ 32 ] . O strategie este de a folosi un singur negativ CK - MB , TNI , sau TNT msurat 8-12 ore de la debutul simptomelor .

O alt strategie este de a folosi mioglobina negativ n combinaie cu un negativ CK - MB sau TNI negativ, efectuate la nceputul i la 90 minute la pacienii care prezint mai mult de 8 ore de la debutul simptomelor .

O a treia abordare este de a utiliza un negativ de 2 ore delta CK - MB , n combinaie cu un negativ de 2 ore delta TNI la pacienii care prezint mai mult de 8 ore de la debutul simptomelor .

Reinei c ACEP nu se specific dac s utilizeze cutoff 99 percentila ,10 % CV oprire , sau cutoffs OMS acute MI pentru troponina .

90 de minute de regula , cu mioglobina recomandat de ACEP sa bazat pe un studiu care a folosit mioglobina n combinaie fie cu CK - MB sau TNI . [ 33 ]CK-MB/myoglobin protocol a dat o sensibilitate de 92 % , la 90 de minute, icombinaia mioglobinei / TnI dat o sensibilitate de 97 % , la 90 de minute.

ACEP recunoate lipsa relativ de specificitate pentru mioglobina i c multe dintre studiile de mioglobina nu a definit MI pe liniile directoare ACC / ESC . Cu toate acestea , este dificil de neles politica de clinica ACEP c accept o rat MI ratat de 3-8 % .

Recomandrile ACEPs cu privire la utilizarea de delta CK - MB i Delta TNI se bazeaz pe determinarea schimbrii nivelului de TNI sau CK - MB , pe eantioane prelevate dou or n afar . Cu toate acestea , evaluarea delta TNI se bazeaz parial pe utilizarea de teste n vrst TNI i depite OMS cutoffs IM acut intr-un studiu retrospectiv . De aceea , recomandarea ACEPs a utiliza o delta TnI coroborat cu un delta CK - MB nu pot fi generalizate la alte teste troponin disponibile comercial . Precauie trebuie s fie utilizate atunci cnd se utilizeaz recomandrile ACEPs la pacienii ED cu dureri in piept si ACS suspectate .

Tabelul de mai jos prezint frecvena recomandat de prelevare a probelor dup admitere ED pentru diferite markeri cardiaci .

Tabelul 1 . Frecvena de eantionare a markerilor cardiace ( Deschidere mas ntr-o fereastr nou )

De baz 3-4 ore 6-9 ore 12-24 de ore > 24 oreCK - MB izoforme , mioglobina X X XCK - MB , TNI , TNT X X X X

( numai n cazul n risc foarte ridicat )

prezentatori trziu

( TNI , TNT)

XTimpul de prob la 3-4 ore este util n durere unitatea de observare ED sau piept unde triaj rapida si diagnostic precoce sunt esentiale . La ali pacieni internai pentru ACS , biomarkeri trase la 3 - la interval de 4 ore nu sunt la fel de importante ca sunt la 6 - de a marca 9 - or . Liniile directoare ACC / AHA pentru tratamentul pacientilor cu angina pectorala instabila si NSTEMI recomanda o proba de referin la ED sosire i o prob, se repet de 6-9 ore de la prezentare .

Au fost efectuate cteva studii pe " timp de pozitivitate " , dar mostre de serie care devin pozitive in 12 - la fereastra de 24 de ore sunt considerate puin probabil , cu excepia cazului n care pacientul are simptome in curs de desfasurare de ischemie dup admitere . Prin urmare acut MI poate fi exclus n cazul pacienilor cu rezultate negative indicatoare de serie prin 6 - la perioada de 9 ore dup prezentarea .

Markeri cardiace n managementul terapeuticStudiile clinice au demonstrat beneficiile de a utiliza markeri cardiaci ca un indicator pentru interventii terapeutice specifice n ACS . Cu toate acestea , aceast utilizare rmne experimentale ; n prezent , nu algoritmi terapeutice validate se bazeaz pe un izolat rezultat pozitiv marker nabsena altor constatri clinice sau ECG .

Analiza de subgrup de studii cu heparina cu greutate moleculara mica ( HGMM ) au aratat o rata a scazut eveniment cardiace la pacientii cu un rezultat pozitiv pentru TNT i care au fost tratati cu o HGMM . [ 34 , 35 ]

De asemenea, n procesul PRISM , pacientii cu un TNI crescute , care au fost tratati cu glicoproteina ( GP ) IIb / IIIa tirofiban ( Aggrastat ) a demonstrat o scdere semnificativ a evenimentelor cardiace comparativ cu pacienii fr un nivel ridicat TNI . Nici o diferenta semnificativa a rezultatelor a fost observata la pacientii fara TNI creteri care au fost tratati cu tirofiban comparativ cu placebo . [ 36 ]

n studiul PURSUIT , pacientii care au fost tratati cu GP IIb / IIIa eptifibatid ( Integrilin ) n termen de 6 ore de la debutul simptomelor a obinut cel mai mare beneficiu , i analiza de subgrup a aratat ca pacientii cu un nivel troponinei au avut , de asemenea, rspunsuri mai bune la tratament a facut decat cei al cror rezultat troponina a fost negativ [ 37 ] .

n cele din urm , n tactica - TIMI 18 studiu , pacientii cu cresteri ale TNI sau TNT o reducere semnificativ n moarte , IM , sau rehospitalization pentru ACS termen de 6 luni dup ce a fost tratati cu terapie invazive precoce format din aspirina , heparina , tirofiban , i cateterism / revascularizare n termen de 4-48 ore [ 38 , 39 ] analiza de subgrup observat . c o altitudine de CK - MB nu au beneficiat grupul invazive precoce n comparaie cu grupul de management conservator . Cu toate acestea , terapia invaziv precoce a beneficia subgrupul de pacieni cu valori troponinei dar niveluri normale ale CK - MB . [ 40 ]

Aceste studii sugereaza ca un rezultat pozitiv troponinei singur este un predictor independent de risc crescut de evenimente adverse cardiace , i c tratamentul cu HGMM i / sau GP IIb / IIIa pare s conferemai multe beneficii la pacientii cu niveluri crescute ale troponinelor cardiace .

Troponinelor n CRFPacienii cu insuficien renal cronic (IRC ), care sunt n program de hemodializ sunt la risc crescut de boli coronariene si ACS acute , i conturi de boli cardiovasculare pentru aproximativ 50 % din decesele la acesti pacienti . Primele studii a artat o prevalen ridicat de niveluri crescute ale troponinelor cardiace la pacientii cu CRF , i mai ales de TNT . Cu toate acestea , semnificatia clinica a unui nivel ridicat TNT este neclar .

Studiile biochimice au demonstrat ccota troponina provine demiocard i nu este legat demiopatie asociat cu insuficien renal . Cu toate acestea , pacientii cu CRF au frecvent insuficienta cronica cardiaca congestiva ( ICC ) i hipertensiune arterial , care poate crete n mod independent nivelul troponinei . n plus , datele sugereaza ca nivelurile troponinei crescute la pacientii asimptomatici pot reflecta microinfarctions subclinice , care sunt distincte clinic de la ACS .

Mari studii prospective au confirmat asocierea dintre TnT altitudine si a mortalitatii cardiace la pacientii cu IRC . GUSTO studiu ACSIV a artat c pacienii cu insuficien renal i un TnT crescute au avut cel mai mare risc global de obiectivul compozit de deces sau IM acut , [ 41 ] i 2 alte studii prospective au raportat ca un crescute TNT , dar nu TNI- a crescut riscul de mortalitate pe termen lung . [ 42 , 43 ] fie ridicat TnT creste riscul cardiac pe termen scurt ( de exemplu , 30 d ) este neclar , dar pacienii fr risc pe termen scurt nu pot necesita spitalizare si potential ar putea fi gestionate pe o ambulatoriu baz .

Acesta a fost sugerat c nivelurile cronic crescute ale troponinelor reprezint bolile cardiovasculare structurale cronice , cum ar fi MI nainte , cronice CHF , sau hipertensiune arteriala in stabilirea de CRF . Dac este adevrat , acesti pacienti sunt la risc cardiac mai mare n comparaie cu , populatia normala pacient sntos i troponina rmne un marker util n stabilirea de CRF [ 44 , 45 ] .

Reinei c dializa nu afecteaz nivelurile de TNT TNI , nivelurile de predializai i postdialysis sunt n esen, neschimbate . CK - MB , cu toate acestea , este dializabil , iar nivelurile sunt sczute postdialysis . Prin urmare , un singur nivel ridicat TnT la pacientii cu CRF i posibile ACS este nondiagnostic pentru infarct miocardic acut n absena altor constatri . Determinri de serie sunt de obicei necesare , cu un accent pe o cretere a nivelului troponinei .

Verifica dac un troponinei la pacieni cu IRC reprezint adevrate IM acut sau un rezultat fals - pozitiv poate fi dificil . La pacienii cu factori de risc cardiac , care sunt considerate clinic pentru a fi la risc moderat - mare pentru ACS , abordarea prudent ar fi de a observa i de a efectua markeri cardiaci seriale de peste 6-9 ore . La pacientii asimptomatici cu risc sczut i n absena oricror alte constatri indic ACS , rezultatul crescute ale troponinelor este mult mai probabil s fie fals pozitive pentru infarct miocardic acut .

Troponinele in bolile de inima nonischemicUn numr de studii au demonstrat c TnT pot fi folosite pentru stratificarea riscului la pacienii cu ICC fr ischemie . Concret , troponinele cardiace crescute sunt asociate cu scderea fraciei de ejecie a ventriculului stng i prognostic saraci la pacientii cu ICC i sunt legate de severitatea de insuficienta cardiaca . [ 46 ]

Studii izolate au artat dovezi de MI i niveluri ridicate TNI la pacientii cu hemoragie subarahnoidiana . [ 47 ] vasoactive peptide eliberate n timpul hemoragie subarahnoidian acut induce profunde rsturnri undei T pe ECG care indic leziuni miocardice . Similar , TNT sa dovedit a fi un predictor independent de rezultatul la pacientii cu embolism pulmonar ; tulpina ventriculului drept sau infarct de hipertensiune pulmonara acuta cauzeaza nivelul troponinei .

Nivelurile de troponinei au fost , de asemenea, documentate n alte state nonischemic boli cardiace , cum ar fi tahiaritmii , hipertensiune , miocardita , i contuzie miocardic .

Markere n curs de dezvoltareInvestigaiile n markeri cardiaci n curs de dezvoltare se concentreaz pe creterea sensibilitii i specificitate de diagnostic i la mbuntirea capacitii de prognostic .

B - peptidic natriuretic de tipB - peptidic natriuretic de tip ( BNP ) este secretat in principal de catre miocardul ventricular , ca raspuns la stres perete , inclusiv expansiunea volumului i supraincarcare de presiune . Multiple studii au demonstrat c BNP poate fi , de asemenea, un indicator de prognostic util n ACS . TIMI Grupul de studiu efectuat mai multe investigaii arat c nivelul BNP prezis mortalitii cardiace i a altor evenimente adverse cardiace in intregul spectru de ACS . Rata de mortalitate aproape sa dublat de cnd au fost ridicate att la nivel TNI i BNP .

n tactica - TIMI 18 proces , un nivel ridicat BNP a fost asociata cu stenoza vinovat strict , mai mare corectat TIMI numrul de cadru , i a plecat implicarea anterioar artera descendent . [ 38 ] Aceste date sugereaz c o cretere a nivelului BNP pot fi corelate cu severitate mai mare de ischemie miocardica i ar putea explica parial asocierea dintre nivelele crescute de BNP si a rezultatelor negative .

Datele de la OPUS - TIMI 16 i tactici de - TIMI 18 au demonstrat ca cresteri de baz ale TNI , proteinei C - reactive ( CRP ) , i nivelurile de BNP la pacienii cu NSTEMI au fost predictori independente de obiectivul compozit de deces , MI , sau CHF . [ 48 ]PROMPT - TIMI 35 studiu a demonstrat ca ischemie miocardica tranzitorie n timpul testului de efort a fost asociata cu o crestere imediata a nivelului de BNP [ 49 ] n plus , severitatea de ischemie a fost direct proporional cu cota din BNP . .

Prezena CHF acuta la pacientii cu SCA este un predictor cunoscut de evenimente adverse cardiace si risc mai mare . De aceea , nu este surprinztor faptul c un nivel ridicat BNP , ca un marker al CHF , este , de asemenea, predictiv al evenimentelor adverse cardiace la pacienii cu SCA . Dei BNP a fost validat ca un marker de diagnostic pentru CHF , sunt disponibile pentru a evaluautilizarea BNP ca un marker cardiac de diagnostic pentru ACS nED date insuficiente .

Proteina C - reactivaProteinei C - reactive ( CRP ) , un marker nespecific al inflamatiei , este considerat a fi implicat direct n aterogenez placa coronariene . Studii extensive nceput la nceputul anilor 1990 au aratat ca un nivel ridicat CRP independent a prezis evenimente adverse cardiace la nivel prevenirea primar i secundar .

Datele indic faptul c CRP este un indicator de prognostic util la pacientii cu SCA , ca nivelurile crescute de CRP sunt predictori independente de deces cardiac , infarct miocardic acut , si CHF . n combinaie cu TNI i BNP , CRP poate fi un adjuvant util , dar natura sa nespecifice limiteaz utilizarea sa ca un marker cardiac de diagnostic pentru ACS in ED .

myeloperoxidaseMyeloperoxidase ( MPO ) este o enzim de leucocite care genereaz specii oxidant reactantilor si a fost legata de prothrombotic produciei de lipide oxidate , instabilitatea placa , crearea placa moale lipide - Laden , i vasoconstricia la epuizare oxid de azot . Primele studii au aratat a crescut semnificativ nivelurile de MPO la pacientii cu boala arterelor coronare documentate angiografic [ 50 ] ; aceste constatari stimulat investigatii suplimentare in MPO ca un marker cardiac roman .

La 604 pacieni secveniale care prezinta la ED cu dureri in piept , nivelurile de MPO crescute independent a prezis un risc crescut de evenimente cardiace majore adverse , inclusiv MI , reinfarct , au nevoie de revascularizare , sau deces la 30 de zile si la 6 luni. [ 51 ] Dintre pacientii care a prezentat la ED cu dureri in piept , dar care au fost n cele din urm exclus pentru MI , un nivel MPO ridicat la prezentare a prezis reactiile adverse cardiovasculare majore ulterioare . ntr-un subgrup de pacienti cu negativ iniial TNT, nivelurile de MPO au fost semnificativ crescute , chiar i n termen de 2 ore de la debutul simptomelor .

MPO poate fi un marker precoce util nED bazat pe capacitatea sa de a detecta vulnerabilitate placa care precede ACS . Cu toate acestea , sunt necesare studii suplimentare de validare pe MPO , ngeneral, ED populaiei dureri in piept pentru a determina sensibilitatea i specificitatea acestuia , precum i valorile sale pozitive i negative predictive [ 52 , 53 ] .

Ischemia modificat albuminaIschemie modificat albumin ( IMA ) este un marker roman de ischemie care este produs atunci cnd circul albumin seric contacte esuturile cardiace ischemice . IMA poate fi msurat prinanaliza cu liant cobalt albumin , care se bazeaz pe incapacitatea IMA de a lega de cobalt . [ 54 ] Un test rapid cu un timp de 30 de minute cu schimbare de direcie de laborator a fost dezvoltat i comercializat caprimul disponibil comercial US Food and Drug Administration ( FDA ) a aprobat - marker de ischemie miocardica .

Pe baza investigaiilor de ischemie miocardic indus de inflaie balon n timpul interventie coronariana percutanata , nivelurile de IMA ridica la cteva minute de ischemie tranzitorie , vrf de 6 ore , i pot rmne crescute pentru atta timp ct 12 ore.

Studii cu privire la utilizarea de IMA la pacientii cu durere in piept in ED a constatat sensibilitile care a variat de 71-98 % i specificul 45-65 % , cu o valoare predictiv negativ de 90-97 % pentru ACS . [ 55 ]

O abordare multimarker ntr-un studiu , folosind o combinaie de constatri ECG , nivelurile de TNT, i nivelurile de IMA , realizat o sensibilitate de 95 % pentru ACS , [ 56 ] n timp ce un al doilea studiu a calculat c o combinaie de IMA , mioglobinei , CK - MB , i TnI crescutsensibilitatea la 97 % pentru detectarea ischemiei miocardice . [ 57 ]

Cu toate acestea , nivelurile de IMA sunt , de asemenea, crescut la pacienii cu ciroz , anumite infectii , si cancer avansat , ceea ce reduce specificitatea testului . Validarea in continuare si rezultatele studiilor sunt necesare pentru a evalua utilizarea IMA n diagnosticul ED a ACS atunci cnd ECG i nivelul cardiace troponinelor sunt nondiagnostic .