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Clinical Chemistry 53: 2086-2096, 2007. First published October 22, 2007; 10.1373/clinchem.2007.095679
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(Clinical Chemistry. 2007;53:2086-2096.)
© 2007 American Association for Clinical Chemistry, Inc.

Evidence-Based Laboratory Medicine and Test Utilization

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Use of Cardiac Troponin and B-Type Natriuretic Peptide or N-Terminal proB-Type Natriuretic Peptide for Etiologies Other than Acute Coronary Syndromes and Heart Failure

NACB WRITING GROUP MEMBERS, Alan H.B. Wu1, Allan S. Jaffe2, Fred S. Apple3, Robert L. Jesse4, Gary L. Francis5, David A. Morrow6, L. Kristin Newby7, Jan Ravkilde8, W.H. Wilson Tang5, Robert H. Christenson9,a NACB COMMITTEE MEMBERS, Robert H. Christenson, Chair, Fred S. Apple, Christopher P. Cannon6, Gary L. Francis, Robert L. Jesse, David A. Morrow, L. Kristin Newby, Jan Ravkilde, Alan B. Storrow, W.H. Wilson Tang, Alan H.B. Wu, Section Leader

1 University of California at San Francisco, San Francisco, CA.
2 Mayo Clinic, Rochester, MN.
3 Hennepin County Medical Center, Minneapolis, MN.
4 Medical College of Virginia, Richmond, VA.
5 Cleveland Clinic, Cleveland, OH.
6 Harvard University, Boston, MA.
7 Duke University Medical Center, Durham, NC.
8 Aarhus University Hospital (Aalborg), Aalborg, Denmark.
9 University of Maryland School of Medicine, Baltimore, MD.

aAddress correspondence to this author at: University of Maryland School of Medicine, Laboratories of Pathology, University of Maryland Medical Center, 22 South Greene St., Baltimore, MD 21201. Fax 410-328-5880; e-mail rchristenson{at}umm.edu.


   Abstract
Top
 Abstract
Introduction
 Preamble
 I. Overview of Other...
 II. Use of Cardiac...
 III. Use of Biomarkers...
 IV. Use of Biomarkers...
 V. Biomarker Use after...
 VI. Use of Biomarkers...
 References
 


   Introduction
Top
 Abstract
 Introduction
Preamble
 I. Overview of Other...
 II. Use of Cardiac...
 III. Use of Biomarkers...
 IV. Use of Biomarkers...
 V. Biomarker Use after...
 VI. Use of Biomarkers...
 References
 


   Preamble
Top
 Abstract
 Introduction
 Preamble
I. Overview of Other...
 II. Use of Cardiac...
 III. Use of Biomarkers...
 IV. Use of Biomarkers...
 V. Biomarker Use after...
 VI. Use of Biomarkers...
 References
 
Over the past decade, cardiac troponin (cTn)1 has become the cornerstone laboratory medicine measurement for assessment of myocardial infarction (MI) in suspected acute coronary syndrome (ACS) patients. In the past 5–7 years, methods for measuring the natriuretic peptide B-type natriuretic peptide (BNP) and its inert cometabolite N-terminal proBNP (NT-proBNP) have become available, and much knowledge has accumulated regarding their clinical use in the context of heart failure and hemodynamic stress. In addition to ACS and heart failure, there are common and clinically important patient cohorts in whom these measurements can aid in diagnosis and management. For this reason, the National Academy of Clinical Biochemistry (NACB) formed a Laboratory Medicine Practice Guidelines (LMPG) committee to extend cardiac biochemical marker recommendations and establish modern guidelines for utilization in etiologies other than ACS and heart failure. During development, updated draft revisions of the guidelines were prepared and placed for comment on the NACB World Wide Web site (http://www.aacc.org/AACC/members/nacb/LMPG/OnlineGuide/DraftGuidelines/BioHearFailure/) beginning in August 2004. The draft LMPG and suggested revisions were presented for public and stakeholder comment at the October 2004 Arnold O. Beckman Conference titled Cardiac Markers: Establishing Guidelines and Improving Results. The resulting draft guidelines can be viewed in their entirety at on the NACB World Wide Web site (http://www.aacc.org/AACC/members/nacb/LMPG/OnlineGuide/PublishedGuidelines/ACSHeart/heartpdf.htm).

The scope of the guidelines presented here represent the writing group’s recommendations for cTn, BNP, and NT-proBNP in the rapidly evolving area of etiologies other than ACS and heart failure in adult patients. Other sections of the biochemical cardiac marker guidelines involving clinical and analytical issues of ACS and heart failure and issues of logistics and point-of-care testing are available at http://www.aacc.org/AACC/members/nacb/LMPG/OnlineGuide/PublishedGuidelines. More explicit detail on guideline development and the groups providing stakeholder input is available in the Preamble to the overall guideline, which is available at http://www.aacc.org/AACC/members/nacb/LMPG/OnlineGuide/PublishedGuidelines/ACSHeart/heartpdf.htm.

The writing group of this document represents a multidisciplinary subcommittee consisting of laboratorians and specialist clinicians from the NACB guidelines committee with the addition of 1 ad hoc member (A.S.J.). The process for developing the recommendations was collaborative and iterative with input from all members of the writing group; the effort and process was chaired by R.H.C.; write-up of the document was spearheaded by the section leader A.H.B.W.

The strength of scientific data supporting each recommendation is characterized using the scoring criteria adopted from the American Heart Association/American College of Cardiology, as summarized in Table 1 . For each recommendation, the designations I, IIa, IIb, and III describe the indications, and the uppercase letters A through C describe the weight of evidence.


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  		Table 1. American College of Cardiology/American Heart Association classifications.

The target groups for this guideline are both laboratory professionals and clinicians. These guidelines were developed with best available evidence and incorporated substantial input from acknowledged experts and professional organizations. As such, they represent the current best practice for utilization of biochemical cardiac markers in etiologies other than ACS and heart failure.


   I. Overview of Other Etiologies
Top
 Abstract
 Introduction
 Preamble
 I. Overview of Other...
II. Use of Cardiac...
 III. Use of Biomarkers...
 IV. Use of Biomarkers...
 V. Biomarker Use after...
 VI. Use of Biomarkers...
 References
 
a. background and scope
Currently available cardiac biomarkers can define cell death, damage, or dysfunction to particular organ systems but cannot define the mechanisms of the effects seen. Cardiologists, emergency medicine physicians, and clinical laboratorians have often acted as if cardiac biomarkers such as cardiac troponins T (cTnT) and I (cTnI), BNP, and NT-proBNP are specific only to the presence of ACS and heart failure, and imply diagnosis of ACS and heart failure, and their etiology. Although it is true that release of cTn into blood is the result of myocardial damage, it is not necessarily damage related to a coronary artery abnormality, or even the result of acute myocardial ischemia. Therefore the diagnosis of acute MI (AMI) must always be framed in the correct clinical context; this includes the caveat that the combination of ischemia plus necrosis does not in and of itself imply a coronary etiology. This is particularly more important when lower cutoff values are used, such as the 99th percentile limit of a healthy population, which detect a variety of more subtle abnormalities(1). Table 2 shows a list of conditions that can cause an increase in cTn in the absence of overt ischemic heart disease(2).


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  		Table 2. Elevations of cardiac troponins without overt ischemic heart disease.1

In a similar manner, increases in BNP and NT-proBNP concentrations are not specific for heart failure alone. Table 3 lists conditions other than heart failure than can cause an increase in BNP and NT-proBNP(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Renal dysfunction is a confounder for cTnT and cTnI as well as BNP and NT-proBNP. Cardiac surgery will release cardiac biomarkers into blood because of the damage to the heart during the procedure itself. Although increased concentrations of cTn and natriuretic peptides are not specific to ischemic damage or heart failure, a detectable increase in these cardiac biomarkers has been associated with worse prognosis regardless of the etiology of the increase.


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  		Table 3. Increased concentrations of BNP/NT-proBNP without overt heart failure (references).

Finally, it must also be clinically recognized that false-positive increases in cTn, BNP, and NT-proBNP can occur, although very infrequently, as a result of analysis errors. Although the incidence of assay interferences caused by atypical antibodies has been reduced, all immunoassays have the potential for both false-positive and false-negative interference(23)(24).

The recommendations in this section will focus on other etiologies that can affect the interpretation of cTn and the natriuretic peptides. Recommendations will be provided where there is sufficient scientific and medical evidence. Note that an overview of ACS and heart failure containing definitions, pathogenesis, and management from the perspective of biochemical markers is presented in Chapters 1 and 3. Chapters 1 and 3 also include specific recommendations for the use of biochemical markers for the diagnosis and risk stratification of patients and clinical decisions in the context of ACS and heart failure. Recommendations addressing analytical issues for cardiac biomarkers of ACS and heart failure are presented in Chapters 2 and 4, respectively.


   II. Use of Cardiac Biomarkers in the Evaluation of Patients with Chronic Renal Failure
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 Abstract
 Introduction
 Preamble
 I. Overview of Other...
 II. Use of Cardiac...
III. Use of Biomarkers...
 IV. Use of Biomarkers...
 V. Biomarker Use after...
 VI. Use of Biomarkers...
 References
 
a. utilization of cardiac biochemical marker in the setting of chronic renal failure
Recommendations for use of biochemical markers in the setting of chronic renal failure

class i

  1. In renal failure patients with symptoms (e.g., acute chest pain) or electrocardiograph or other clinical evidence suggesting myocardial ischemia, measurement of cTn is warranted for evaluation of MI (Level of evidence A).
  2. For end-stage renal disease (ESRD) patients, as for all patients who may have baseline elevations of cTn, who present with possible ACS, relying on dynamic changes in the cTn values of 20% or more should be used to define those with AMI (Level of evidence B).

class iib

  1. cTnT and cTnI can be used as aids for defining the risk of mortality in ESRD patients and provide baseline values for comparison when measured in the setting of an acute clinical change (Level of evidence B).
  2. In renal failure patients, BNP or NT-proBNP testing can be used in the acute setting to rule out or to confirm the diagnosis of heart failure among patients presenting with ambiguous signs and symptoms. However, different decision point (cutoff) values must be used than in patients with estimated glomerular filtration rate >60 mL · min–1 · (1.73 m2)–1 (Level of evidence B).

class iii

  1. Routine BNP/NT-proBNP measurement is not warranted in asymptomatic ESRD patients (Level of evidence B).

1. biomarkers in chronic renal failure
Increases in the concentration of cTnT and cTnI in the setting of ESRD indicate cardiac damage. In patients with suspected ACS, a dynamic change in the cTnI indicates a diagnosis of AMI(25)(26) and warrants further investigation/treatment. A recommended cutoff cTn value of ≥20% in the 6–9 h after presentation represents a significant (3 SD) change in cTn on the basis of a 5%–7% analytical CV typical for most assays in the concentration range indicating AMI. Patients with ESRD who have increased cTn concentrations have a higher (long-term) risk of death than corresponding patients without increases in cTn in this setting. Using a cut point of 0.03 µg/L for cTnT (10% CV), Aviles et al.(27) reported a 2.7-fold higher (95% CI 1.9–3.8) risk of MI or death at 30 days among patients with suspected ACS in the lowest quartile for creatinine clearance. Recent data suggest that even if there is an increased baseline concentration, further increase above that baseline occurs in acute ischemic damage. Thus acute increases can be differentiated from more chronic elevations when a rising pattern of results is observed(28)(29)(30). Given the prognostic importance of the acute increases, which is similar to that seen in the absence of ESRD, some have suggested that the benefits of acute pharmacologic or invasive interventions in patients with evidence of ischemia and increased cTn outweigh the risks of bleeding and increased renal dysfunction(31).

Acute changes in cTn are an important consideration in those ESRD patients with chronic increases that are not in and of themselves benign. These abnormal concentrations have been significant predictors of an adverse short- and/or long-term prognosis in nearly every available study. In a study of 224 individuals, increased concentrations of cTnT were strongly associated with diffuse coronary artery disease and an independent predictor of death(32). Virtually identical results were obtained for the outcome of death by cTnT concentrations at 1, 2, and 3 years of follow-up for cTnT among 733 patients; odds ratios (ORs) ranged from 2.2 to 2.5 and there was a gradation of risk related to the magnitude of the increases(33). The incidence of abnormal values in this cohort was considerably higher for cTnT than for cTnI; 82% of ESRD patients had an increase in cTnT compared with only 6% for cTnI when the 99th percentile cutoff limit was used(33). Furthermore, the prevalence of increased cTn concentrations varied by which assay was used for measurement. A substantially greater number of patients had an increased cTnT (85%) compared with cTnI by either cTnI method (19% Beckman, 5% Dade). Percentage of agreement between the Beckman and Dade assays for increased cTnI was 85% ({kappa} 0.32). Two-year mortality rates based on an increased cTnI regardless of cTnT status was 61% for the Dade assay and 47% for the Beckman assay(34). Therefore, both markers are predictive of risk in ESRD.

cTnI appears to be less useful on a routine basis, however, because the frequency of increased values associated with increased risk of adverse events is markedly lower. Although the exact reason for this difference is unknown, it is likely related to the mechanism by which cTns are differentially released into the circulation, degraded, and/or cleared from the circulation. There is some suggestion that the dialysis process itself may affect cTn values, although changes in cTn concentrations due to the procedure are not large(35). Recently, the Food and Drug Administration has cleared cTnT as a biomarker for risk stratification in ESRD patients for all-cause death, and the use of cTnT for this indication is suggested by the Kidney Disease Outcomes Quality Initiative(29). In the absence of myocardial ischemia, there are no specific therapeutic interventions known to reduce cardiovascular risk that can be recommended based solely on the results of cTn testing in patients with ESRD. However, the availability of such baseline values would simplify the care of patients with ESRD who present with a variety of problems for emergency department (ED) and/or hospital evaluation and care. Increases in the concentration of BNP and NT-proBNP have also been observed to have prognostic significance in patients with ESRD; however, recommended reference intervals for BNP and NT-proBNP have not been validated for patients with chronic renal failure.

Zoccali et al.(36) reported a relative OR of 6.7 (95% CI 2.4–18.5) for cardiovascular death among patients on dialysis with an increased concentration of BNP. Several investigators have combined the results of biomarkers to determine whether they provide additive risk stratification information. In an analysis of cTnT, cTnI, and atrial and BNPs in chronic dialysis patients, only cTnT was an independent predictor of death(37). However, Apple et al.(34) found that cTnT, cTnI, and high-sensitivity C-reactive protein were each independent predictors of death in ESRD patients. In his study, NT-proBNP had prognostic value, but it was not independent of cTn. Comparing BNP results directly against NT-proBNP in patients with chronic kidney disease, Vickery et al.(38) suggested that NT-proBNP concentrations were more affected by declining kidney function. NT-proBNP does not have receptors and is not degraded by neutral endopeptidases but is excreted in the urine(39).


   III. Use of Biomarkers in the Evaluation of Other Nonischemic Etiologies
Top
 Abstract
 Introduction
 Preamble
 I. Overview of Other...
 II. Use of Cardiac...
 III. Use of Biomarkers...
IV. Use of Biomarkers...
 V. Biomarker Use after...
 VI. Use of Biomarkers...
 References
 
a. use of cardiac biomarkers in the setting of nonischemic etiologies
Recommendations for use of biochemical markers in other nonischemic etiologies

class iib

  1. Increased cardiac telemetry may be warranted for patients who have increased cTn values after blunt chest trauma (Level of evidence B).
  2. The measurement of cTn can be used to define risk among patients who are critically ill (Level of evidence A).
  3. Increased cTn values identify individuals at increased risk for the development of congestive heart failure when treated with adriamycin therapy for cancer (Level of evidence B).
  4. Increased cTn values identify individuals at increased risk of acute pulmonary embolism (Level of evidence B).
  5. Routine BNP/NT-proBNP measurements may be warranted among patients with nonischemic etiologies such as sepsis, myocarditis, or pulmonary embolism (Level of evidence C).

class iii

  1. Release of cTn from patients with cancer undergoing cardiotoxic chemotherapies represents myocardial damage, which may be associated with a worse prognosis (Level of evidence B). However, routine cTnT or cTnI measurements are not warranted among cancer patients undergoing chemotherapies that are toxic to the heart (except those receiving adriamycin) (Level of evidence C).

1. ctn and bnp/ntprobnp in other nonischemic etiologies
Years after the release of the first commercial cTn assays, there have been no basic or clinical studies that have shown that cTn can be released from any tissues except the heart. Therefore, cTn found in concentrations exceeding the 99th percentile of a reference population reflects recent myocardial damage. However, increases in cTnT or cTnI neither imply an ischemic etiology for the damage nor are necessarily associated with an acute coronary event. cTn can be observed in nonischemic injuries to the heart, among patients with critical illnesses(40)(41)(42)(43)(44)(45)(46)(47), chemotherapy(48)(49)(50)(51)(52)(53), myocarditis(54), blunt chest trauma(55)(56), stroke(57), pulmonary embolism (PE)(58)(59)(60)(61)(62), sepsis(63)(64)(65), and other conditions(66)(67). These findings are believed to represent ongoing myocardial damage. Regardless, there are several situations in which detection of increased cTn values may be clinically helpful. In a metaanalysis conducted on 6 studies of blunt chest trauma in which myocardial contusion was suspected(56), it was concluded that cTn was a sensitive indicator of myocardial damage. Because myocardial contusion is known to cause QTc prolongation, which can be associated with malignant life-threatening arrhythmias, monitoring such individuals for arrhythmias is a rational but as yet unproven adjunct to care. Troponin can also be released in patients undergoing chemotherapy, such as with the anthracyclines, who can develop heart failure. Recent studies suggest that for patients with increased cTn, treatment with angiotensin-converting enzyme inhibitors dramatically reduces the frequency of heart failure(49).

2. ctn and bnp/ntprobnp in pe
Among patients with PE, data substantiate the association of cTn increases with worse prognosis. La Vecchia et al.(59) demonstrated that when cTnI was ≤0.6 µg/L, the mortality was 4.8% vs 36% for cTnI >0.6 µg/L. In a study of 56 consecutive patients with confirmed PE, in-hospital mortality was 44% among patients who were cTnT positive (>0.1 µg/L) vs 3% among those in whom cTnT was ≤0.1 µg/L(59). In addition to mortality, the use of inotropic drugs, need for resuscitation, and mechanical ventilation were all significantly higher among the cTnT-positive patients. This result is likely because increases in cTn correlate with the degree of right ventricular dysfunction, a factor known to be associated with prognosis among patients with PE(60). Although the therapeutic implications of such increases are not clear, it is important to assign the correct diagnosis in these patients, because mortality among cTn-positive PE patients is substantially higher than that among AMI patients, with the exception of those with cardiogenic shock. In both of the studies cited above, the rate of cTn-positive PE patients was approximately 30%, whereas only approximately 5% of AMI patients developed cardiogenic shock in the National Registry of Myocardial Infarction (NRMI)-2 and NRMI-3 registries (1994–2000). It is unlikely that AMI risk adjustment models would reflect the high PE mortality rates; although mortality for cardiogenic shock is high, the incidence of shock is low. Thus assigning the diagnosis of AMI to patients with PE would most probably produce a skewed observed:expected AMI mortality ratio that could contribute to a mortality outlier status for the facility.

It is unclear at present what to do therapeutically in response to such increases and whether cTn and/or BNP or NT-proBNP increases provide more information. Some experts have recommended consideration of fibrinolytic therapy or invasive thrombectomy for those identified as high risk on the basis of increased cTn and/or BNP or NT-proBNP among patients with submassive PE(62).

3. ctn in critical care patients
Increases of cTn are common among critically ill patients, e.g., those with sepsis. Although closely related to the extent of left ventricular dysfunction and the need for inotropic support and prognosis(63)(64), the therapeutic implications of such increases have not yet been fully defined. These principles may hold for many other situations in which there are increases of cTn. However, until systematic studies are conducted addressing the utility of the cTn for diagnosis, prognosis, and treatment in these nonischemic etiologies, the relationship will remain unclear. BNP and NT-proBNP have also been used in many of these same clinical conditions(65)(66)(67), but these studies are less extensive at present than those with cTn.


   IV. Use of Biomarkers after Noncardiac Surgery
Top
 Abstract
 Introduction
 Preamble
 I. Overview of Other...
 II. Use of Cardiac...
 III. Use of Biomarkers...
 IV. Use of Biomarkers...
V. Biomarker Use after...
 VI. Use of Biomarkers...
 References
 
a. use of cardiac biochemical markers after noncardiac surgery
Recommendations for use of cardiac markers after noncardiac surgery

class iib

  1. cTnT and cTnI are recommended for patients undergoing noncardiac surgery if there is a question of cardiac ischemia. Cutoff concentrations that are used for diagnosis of MI are appropriate (Level of evidence C).
  2. cTnT and cTnI may be considered for postsurgical assessment of patients undergoing vascular surgery given the high frequency of underlying coronary artery disease and associated perioperative events. Such increases appear to be due to ischemia and are highly prognostic for both short- and long-term mortality. Cutoff concentrations that are used for diagnosis of MI are appropriate (Level of evidence B).
  3. Increases of cTn postoperatively are associated with adverse prognosis and should prompt clinical follow-up (Level of evidence B).

class iii

  1. Routine BNP/NT-proBNP measurements are not warranted among patients undergoing noncardiac surgery (Level of evidence C).

1. biomarkers after noncardiac surgery
Ischemic myocardial damage can occur in patients undergoing surgery that does not involve the myocardium. Creatine kinase (CK) and CK-MB are less reliable biomarkers than cTn for assessing ischemic myocardial complications because these enzymes are released from skeletal muscle damage as the result of the surgery(68). cTn is specific to heart damage and is not normally released in noncardiac surgery(69). Therefore, increased cTn concentrations after noncardiac surgery are a marker of myocardial damage and are predictive of an adverse outcome at 6 and 12 months(70)(71)(72). Increases in cTnT above 0.03 µg/L (10% CV cut point) were indicative of occult myocardial necrosis and an independent marker of mortality (OR 14.9, 95% CI 3.7–60.3)(73). Similar results have been shown for cTnI (OR 9.8, 95% CI 3.0–32)(72). Although it appears that increases of cTn provide prognostic information in many surgical settings, the etiology of increases, the absolute value of the increases, and whether there is short- or long-term prognostic significance may vary. For example, in vascular surgery patients, increases of cTn are closely associated with severity and duration of ST-segment changes in a group of patients known to have a high incidence of underlying coronary artery disease, and these increases are highly prognostic(74). Furthermore, increases are associated with both early and late clinical consequences, suggesting the need for intervention acutely when increases occur in the hospital(68). It is only for vascular surgery patients that present evidence suggests a role for the routine monitoring of cardiac markers. Though less well studied, increases in orthopedic patients (depending on age and other characteristics) might not be related to ischemic heart disease but might more likely be associated with pulmonary emboli, which are frequent postoperative complications(75). Thus, each surgical group should be evaluated individually. It is only for vascular surgery patients that the present evidence suggests a role for monitoring of cTn. Currently, there is no evidence for the potential role of BNP/NT-proBNP in noncardiac surgery.


   V. Biomarker Use after Percutaneous Coronary Intervention
Top
 Abstract
 Introduction
 Preamble
 I. Overview of Other...
 II. Use of Cardiac...
 III. Use of Biomarkers...
 IV. Use of Biomarkers...
 V. Biomarker Use after...
VI. Use of Biomarkers...
 References
 
a. use of cardiac biochemical markers after Percutaneous Coronary Intervention
Recommendations for use of biomarkers after percutaneous coronary intervention

class iib

  1. It is appropriate to measure cTnT or cTnI before and after percutaneous coronary intervention (PCI) to determine the presence of ischemic cardiac damage if the baseline preprocedural value is less than the 99th percentile for the reference control population. Any increase is indicative of cardiac damage. There is currently insufficient evidence to recommend the specific cTn cutoff concentration (Level of evidence C).

class iii

  1. Routine BNP/NT-proBNP measurements are not warranted among patients undergoing PCI (Level of evidence C).
  2. If the preprocedural baseline cTn is increased above the 99th percentile of a reference control population, then biochemical markers should not be used to estimate whether increases are related to the procedure or to progression of the underlying disease state that caused the need for the procedure (Level of evidence C). If serial preprocedural cTn values are available, a falling trend followed by a postprocedural increase of 20% or more may be indicative of new myocardial injury, even if any or all of the preprocedural results are above the 99th percentile.

1. biomarkers after pci
Periprocedural myocardial damage has been the subject of debate since the inception of the technique 30 years ago(76). cTn release after PCI ranges in incidence from 14% to 48%(77)(78)(79)(80)(81)(82). This wide variation is caused by the assay and corresponding cutoff concentrations used, as well as the underlying indication for the revascularization procedure (e.g., acute vs elective) and the type of procedure performed. In the majority of these studies, cTnT or cTnI cutoff concentrations were higher than either the 99th percentile or the 10% CV value. These and other studies have consistently shown that postprocedural increases in cTn and/or CK-MB are associated with major adverse clinical events. Indeed, minor increases in CK-MB are associated with an increase in 6-month mortality, a risk similar to that observed with spontaneous AMI at any given CK-MB concentration(82). In a study of elective PCI, increased cTnI (13.6% of patients) was associated with the presence of procedural side branch occlusions and thrombus formation(79). In the 481 patients with ACS and PCI enrolled in the SYMPHONY trial, 48% had increased cTnI, which was associated with 90-day events of MI, severe recurrent ischemia, and the combination of death or MI(78). Similar results have been reported for cTnT, in which abnormal concentrations resulted in an OR for death or MI of 2.6 (95% CI 1.4–5.1)(77). Postprocedural increases in cTnI were also associated with decreased tissue-level perfusion as measured by angiography using TIMI (thrombolysis in MI) myocardial perfusion grade and intracoronary myocardial contrast echocardiography(80). Although the mechanism is unknown, decreased tissue perfusion in patients with high cTn may be responsible for the increased incidence of adverse cardiac events.

Recent data have challenged the concept that postprocedure biomarker elevations carry prognostic significance. When one uses baseline cTn in the analysis, the prognostic significance of postprocedure values is totally obviated, suggesting that it is the preprocedure value that defines risk. If the baseline cTn value is increased, attempting to distinguish PCI-induced injury from the injury leading to the admission is probably not something that can be accomplished unless there is substantial time (2 samples at least 6 h apart) before the PCI. Similar principles should be applied for CK-MB, whose rise may not be detected due to its substantial lack of sensitivity compared with troponin. In this situation, the baseline value predicts subsequent risk(83). If the cTn values are stable over time, using criteria for reinfarction is suggested. When the baseline cTn value is normal, increases in both cTn and CK-MB are modest and unassociated with long-term events(83) but at least in this situation, the mechanism can be more clearly ascertained. The European Society of Cardiology Task Force on Invasive Cardiology recommended a CK-MB cutoff concentration of 5 times the upper limit of normal(84). The previous convention has been the use of a 3-fold increase(85).


   VI. Use of Biomarkers after Cardiac Surgery
Top
 Abstract
 Introduction
 Preamble
 I. Overview of Other...
 II. Use of Cardiac...
 III. Use of Biomarkers...
 IV. Use of Biomarkers...
 V. Biomarker Use after...
 VI. Use of Biomarkers...
References
 
a. use of cardiac biochemical markers after cardiac surgery
Recommendations for use of biomarkers after cardiac surgery

class iia

  1. In addition to >5-fold increase in cTn after the procedure, clinical and other (nonlaboratory medicine) diagnostic testing criteria should be used to distinguish components related to the operative procedure and cardioprotection from vascular events (Level of evidence C).
  2. Preprocedural baseline cTn increases help to define risk among patients undergoing cardiac surgery (Level of evidence C).

class iii

  1. At this time, there is insufficient evidence to recommend routine measurement of BNP/NT-proBNP before or after cardiac surgery (Level of evidence C).

1. biomarkers after cardiac surgery
It has been recognized for many years that patients undergoing cardiac surgery release some amount of cardiac proteins such as CK and cTn. There is a relationship between increases of biomarkers and the details of the procedure itself, such as the duration of the cross clamp and cardiopulmonary bypass times, the nature of the cardioplegic solution, cold vs warm solutions, and so on(86)(87)(88)(89)(90)(91)(92)(93)(94). Recent MRI data suggest that most of the damage observed after bypass surgery is subendocardial and apical and likely is a result of issues related to cardiac preservation(90). Transmural damage is observed only with very marked increases of cTn that and are potentially related to a primary vascular event(88)(90). Therefore, if the diagnosis of MI must reflect a primary vascular event, an appropriate cutoff value is difficult to define. Several clinical studies have demonstrated that cTnT and cTnI concentrations that are much greater than the AMI cutoffs are associated with in-hospital and long-term morbidity and mortality(95)(96)(97)(98)(99)(100); in general, the higher the value, the worse the prognosis(89). In addition, the higher the value, the greater the likelihood of transmural involvement, which some might equate to a vascular event as opposed to cardiac damage related to the procedure itself(88). However, studies using angiography to define graft and/or native vessel occlusion have found that there remains substantial overlap between the values in those with graft occlusion and those without(101). In a recent series that used a marked increase of cTn to define possible graft occlusion(102), only 67 of 118 patients had a primary vascular event. Thus, additional criteria over and above markers are needed to define a vascular event after bypass surgery. Given that fact and the need to evaluate patients with a variety of surgical types (off pump, for example), using a low cutoff value (for example a 5-fold increase) together with other criteria might be advised. Nonetheless, regardless of the mechanism, the higher the value, the greater the likelihood of subsequent adverse clinical events.

At present, there are few data on the use of BNP and NT-proBNP for risk stratification for adverse events after cardiac surgery. In contrast to cTn, most studies on BNP have focused on the predictive value of preoperative concentrations. One study suggested that preoperative values of BNP predicted the need for intraaortic balloon pumps, prolonged hospital length of stay, and 1-year mortality(103). In another study, increase preoperative BNP predicted postoperative atrial fibrillation(104). Such studies address the suitability of patients undergoing cardiac surgery and not perioperative complications or events.


   Acknowledgments
 
Grant/funding support: None declared.

Financial disclosures: All financial disclosures and relationships with industry for the writing group members are reported online at:http://www.aacc.org/AACC/members/nacb/LMPG/OnlineGuide/PublishedGuidelines/ACSHeart/.


   Footnotes
 
The materials in this publication represent the opinions of the authors and committee members, and do not represent the official position of the NACB. The NACB is the academy of the American Association for Clinical Chemistry.

1 Nonstandard abbreviations: cTn, cardiac troponin; MI, myocardial infarction; ACS, acute coronary syndrome; BNP, B-type natriuretic peptide; NT-proBNP, N-terminal proBNP; NACB, National Academy of Clinical Biochemistry; LMPG, Laboratory Medicine Practice Guidelines; cTnT, cardiac troponin T; cTnI, cardiac troponin I; AMI, acute MI; ESRD, end-stage renal disease; ED, emergency department; PE, pulmonary embolism; NRMI, National Registry of Myocardial Infarction; CK, creatine kinase; OR, odds ratio; PCI, percutaneous coronary intervention.


   References
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 Abstract
 Introduction
 Preamble
 I. Overview of Other...
 II. Use of Cardiac...
 III. Use of Biomarkers...
 IV. Use of Biomarkers...
 V. Biomarker Use after...
 VI. Use of Biomarkers...
 References
 

  1. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: a consensus document of the joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-969.[Free Full Text]
  2. Babuin L, Jaffe AS. Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ 2005;173:1191-1202.[Abstract/Free Full Text]
  3. Mocelin AO, Issa VS, Bacal F, Guimaraes GV, Cunha E, Bocchi EA. The influence of aetiology on inflammatory and neurohumoral activation in patients with severe heart failure: a prospective study comparing Chagas’ heart disease and idiopathic dilated cardiomyopathy. Eur J Heart Fail 2005;7:869-873.[Abstract/Free Full Text]
  4. Finkelstein A, Michowitz Y, Abashidze A, Miller H, Keren G, George J. Temporal association between circulating proteolytic, inflammatory and neurohormonal markers in patients with coronary ectasia. Atherosclerosis 2005;179:353-359.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  5. Karadag O, Calguneri M, Yavuz B, Atalar E, Akdogan A, Kalyoncu U, et al. B-type natriuretic peptide (BNP) levels in female systemic lupus erythematosus patients: what is the clinical significance?. Clin Rheumatol 2007;26:1701-1704.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  6. Park MH, Uber PA, Scott RL, Mehra MR. B-type natriuretic peptide in heart transplantation: an important marker of allograft performance. Heart Fail Rev 2003;8:359-363.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  7. Pruszczyk P. N-terminal pro-brain natriuretic peptide as an indicator of right ventricular dysfunction. J Card Fail 2005;11(Suppl 5):S65-S69.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  8. Persu A, De Plaen JF. Recent insights in the development of organ damage caused by hypertension. Acta Cardiol 2004;59:369-381.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  9. Burke MA, Cotts WG. Interpretation of B-type natriuretic peptide in cardiac disease and other comorbid conditions. Heart Fail Rev 2007;12:23-36.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  10. Yap LB. B-type natriuretic peptide and the right heart. Heart Fail Rev 2004;9:99-105.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  11. Yap LB, Ashrafian H, Mukerjee D, Coghlan JG, Timms PM. The natriuretic peptides and their role in disorders of right heart dysfunction and pulmonary hypertension. Clin Biochem 2004;37:847-856.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  12. Safley DM, Awad A, Sullivan RA, Sandberg KR, Mourad I, Boulware M, et al. Changes in B-type natriuretic peptide levels in hemodialysis and the effect of depressed left ventricular function. Adv Chronic Kidney Dis 2005;12:117-124.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  13. Horl WH. Natriuretic peptides in acute and chronic kidney disease and during renal replacement therapy. J Invest Med 2005;53:366-370.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  14. Yap LB, Mukerjee D, Timms PM, Ashrafian H, Coghlan JG. Natriuretic peptides, respiratory disease, and the right heart. Chest 2004;126:1330-1336.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  15. Yildiz R, Yildirim B, Karincaoglu M, Harputluoglu M, Hilmioglu F. Brain natriuretic peptide and severity of disease in non-alcoholic cirrhotic patients. J Gastroenterol Hepatol 2005;20:1115-1120.[Web of Science][Medline] [Order article via Infotrieve]
  16. Henriksen JH, Gotze JP, Fuglsang S, Christensen E, Bendtsen F, Moller S. Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease. Gut 2003;52:1511-1517.[Abstract/Free Full Text]
  17. Kato J, Etoh T, Kitamura K, Eto T. Atrial and brain natriuretic peptides as markers of cardiac load and volume retention in primary aldosteronism. Am J Hypertens 2005;18:354-357.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  18. Lee YJ, Lin SR, Shin SJ, Lai YH, Lin YT, Tsai JH. Brain natriuretic peptide is synthesized in the human adrenal medulla and its messenger ribonucleic acid expression along with that of atrial natriuretic peptide are enhanced in patients with primary aldosteronism. J Clin Endocrinol Metab 1994;79:1476-1482.[Abstract]
  19. Totsune K, Takahashi K, Murakami O, Satoh F, Sone M, Ohneda M, et al. Immunoreactive brain natriuretic peptide in human adrenal glands and adrenal tumors. Eur J Endocrinol 1996;135:352-356.[Abstract/Free Full Text]
  20. Wei T, Zeng C, Tian Y, Chen Q, Wang L. B-type natriuretic peptide in patients with clinical hyperthyroidism. J Endocrinol Invest 2005;28:8-11.[Web of Science][Medline] [Order article via Infotrieve]
  21. Schultz M, Faber J, Kistorp C, Jarlov A, Pedersen F, Wiinberg N, et al. N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) in different thyroid function states. Clin Endocrinol 2004;60:54-59.[CrossRef][Medline] [Order article via Infotrieve]
  22. Kohno M, Horio T, Yasunari K, Yokokawa K, Ikeda M, Kurihara N, et al. Stimulation of brain natriuretic peptide release from the heart by thyroid hormone. Metabolism 1993;42:1059-1064.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  23. Kricka LJ. Interferences in immunoassay: still a threat. Clin Chem 2000;46:1037-1038.[Free Full Text]
  24. Eriksson S, Halenius H, Pilkki K, Hellman J, Pettersson K. Negative interference in cardiac troponin I immunoassays by circulating cardiac troponin autoantibodies. Clin Chem 2005;51:839-847.[Abstract/Free Full Text]
  25. McLaurin MD, Apple FS, Falahati A, Murakami MA, Miller EA, Sharkey SW. Cardiac troponin I and creatine kinase MB mass to rule out myocardial injury in hospitalized patients with renal insufficiency. Am J Cardiol 1998;82:973-975.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  26. McCullough PA, Nowack RM, Foreback C, Tokarski G, Tomianovich MC, Khoury KR, et al. Performance of multiple cardiac biomarkers measured in the emergency department in patients with chronic kidney disease and chest pain. Acad Emerg Med 2002;9:1389-1396.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  27. Aviles RJ, Askari AT, Lindahl B, Wallentin L, Jia G, Ohman EM, et al. Troponin T levels in patients with acute coronary syndromes, with and without renal dysfunction. N Engl J Med 2002;346:2047-2052.[Abstract/Free Full Text]
  28. Le EHY, Klootwijk PJ, Weimar W, Zietse R. Significance of acute versus chronic troponin T elevation in dialysis patients. Nephron Clin Prac 2004;98:c87-c92.[CrossRef]
  29. . Kidney Disease Outcomes Quality Initiative. Clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005;45(Suppl 3):S1-S154.[Medline] [Order article via Infotrieve]
  30. Jaffe AS. Chasing troponin: how low can you go if you can see the rise?. J Am Coll Cardiol 2006;48:1763-1764.[Free Full Text]
  31. Scirica BM, Morrow DA. Troponins in acute coronary syndromes. Prog Cardiovasc Dis 2004;47:177-188.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  32. deFilippi C, Wasserman S, Rosanio S, Tiblier E, Sperger H, Tocchi M, et al. Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. JAMA 2003;290:353-359.[Abstract/Free Full Text]
  33. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation 2002;106:2941-2945.[Abstract/Free Full Text]
  34. Apple FS, Murakami MM, Pearce LA, Herzog CA. Multi-biomarker risk stratification of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and cardiac troponin T and I in end-stage renal disease for all cause death. Clin Chem 2004;50:2279-2285.[Abstract/Free Full Text]
  35. Wayand D, Baum H, Schatzle G, Scharf J, Neumeier D. Cardiac troponin T and I in end-stage renal failure. Clin Chem 2000;46:1345-1350.[Abstract/Free Full Text]
  36. Zoccali C, Mallamaci F, Benedetto FA, Tripepi G, Parlongo S, Cataliotti A, et al. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients. J Am Soc Nephrol 2001;12:1508-1515.[Abstract/Free Full Text]
  37. Ishii J, Nomura M, Okuma T, Minagawa T, Naruse H, Mori Y, et al. Risk stratification using serum concentrations of cardiac troponin T in patients with end-stage renal disease on chronic maintenance dialysis. Clin Chim Acta 2001;312:69-79.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  38. Vickery S, Price CP, John RI, Abbas NA, Webb MC, Kempson ME, et al. B-type natriuretic peptide and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy. Am J Kidney Dis 2005;46:610-620.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  39. Ng LL, Geeranavar S, Jennings SC, Loke I, O’Brien RJ. Diagnosis of heart failure using urinary natriuretic peptides. Clin Sci 2004;106:129-133.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  40. Guest TM, Ramanathan AV, Tuteur PG, Schechtman KB, Ladenson JH, Jaffe AS. Myocardial injury in critically ill patients: a frequently unrecognized complication. JAMA 1995;273:1945-1949.[Abstract/Free Full Text]
  41. Wright RS, Williams BA, Lewis L, Ladenson JH, Cramner H, Gallahue F, et al. Elevations of cardiac troponin I are associated with increased short-term mortality in non-cardiac critically ill emergency department patients. Am J Cardiol 2002;90:634-636.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  42. Wu TT, Yuan A, Chen CY, Chen WJ, Luh KT, Kuo SH, et al. Cardiac troponin I levels are a risk factor for mortality and multiple organ failure in noncardiac critically ill patients and have an additive effect to the APACHE II score in outcome prediction. Shock 2004;22:95-101.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  43. Landesberg G, Vesselov Y, Einav S, Goodman S, Sprung CL, Weissman C. Myocardial ischemia, cardiac troponin, and long-term survival of high-cardiac risk critically ill intensive care unit patients. Crit Care Med 2005;33:1281-1287.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  44. King DA, Codish S, Novack V, Barski L, Almog Y. The role of cardiac troponin I as a prognosticator in critically ill medical patients: a prospective observational cohort study. Crit Care 2005;9:R390-R395.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  45. Relos RP, Hasinoff IK, Beilman GJ. Moderately increased serum troponin concentrations are associated with increased morbidity and mortality rates in surgical intensive care unit patients. Crit Care Med 2003;31:2598-2603.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  46. Quenot JP, Le Teuff G, Quantin C, Doise JM, Abrahamowicz M, Masson D, et al. Myocardial injury in critically ill patients: relation to increased cardiac troponin I and hospital mortality. Chest 2005;128:2758-2764.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  47. Minkin R, Cotiga D, Noack S, Dobrescu A, Homel P, Shapiro JM. Use of admission troponin in critically ill medical patients. J Intensive Care Med 2005;20:334-338.[Medline] [Order article via Infotrieve]
  48. Cardinale D, Sandri MGT, Martinoni A, Tricca A, Civelli M, Lamantgia G, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol 2000;36:517-522.[Abstract/Free Full Text]
  49. Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civilli M, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 2006;114:2474-2481.[Abstract/Free Full Text]
  50. Kilickap S, Barista I, Akgul E, Aytemir K, Aksoyek S, Aksoy S, et al. cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Ann Oncology 2005;16:798-804.[Abstract/Free Full Text]
  51. Specchia G, Buquicchio C, Pansini N, Di Serio F, Liso V, Pastore D, et al. Monitoring of cardiac function on the basis of serum troponin I levels in patients with acute leukemia treated with anthracyclines. J Lab Clin Med 2005;145:212-220.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  52. Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 2004;351:145-153.[Abstract/Free Full Text]
  53. Lipshultz SE, Rifai N, Sallan SE, Lipsitz SR, Dalton V, Sacks DB, et al. Predictive value of cardiac troponin T in pediatric patients at risk for myocardial injury. Circulation 1997;96:2641-2648.[Abstract/Free Full Text]
  54. Greaves K, Oxford JS, Price CP, Clarke GH, Crake T. The prevalence of myocarditis and skeletal muscle injury during acute viral infection in adults: measurement of cardiac troponins I and T in 152 patients with acute influenza infection. Arch Intern Med 2003;163:165-168.[Abstract/Free Full Text]
  55. Bertinchant JP, Polge A, Mohty D, Nguyen-Ngoc-Lam R, Estorc J, Cohendy R, et al. Evaluation of incidence, clinical significance, and prognostic value of circulating cardiac troponin I and T elevation in hemodynamically stable patients with suspected myocardial contusion after blunt chest trauma. J Traum Injury Infect Crit Care 2000;48:924-931.[CrossRef]
  56. Jackson L, Stewart A. Use of cardiac troponin for the diagnosis of myocardial contusion after blunt chest trauma. Emerg Med J 2005;22:193-195.[Abstract/Free Full Text]
  57. di Angelantonio E, Fiorelli M, Toni D, Sacchetti ML, Lorenzano S, Falcou A, et al. Prognostic significance of admission levels of cardiac troponin I in patients with acute ischaemic stroke. J Neurol Neurosurg Psych 2005;76:76-81.[Abstract/Free Full Text]
  58. Giannitis E, Muller-Bardorff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M, et al. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary emboli. Circulation 2000;102:211-217.[Abstract/Free Full Text]
  59. La Vecchia L, Ottani F, Favero L, Spadaro GL, Rubboli A, Boanno C, et al. Increased cardiac troponin I on admission predicts in-hospital mortality in acute pulmonary embolism. Heart 2004;90:633-637.[Abstract/Free Full Text]
  60. Scridon T, Scridon C, Skali H, Alverez A, Goldhaber SZ, Solomon SD. Prognostic significance of troponin elevation and right ventricular enlargement in acute pulmonary embolism. Am J Cardiol 2005;96:303-305.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  61. Kucher N, Printzen G, Doernhoefer T, Windecker S, Meier B, Hess OM, et al. Low pro-brain natriuretic peptide levels predict benign clinical outcome in acute pulmonary embolism. Circulation 2003;107:1576-1578.[Abstract/Free Full Text]
  62. Piazza G, Goldhaber SZ. Acute pulmonary embolism: part II: treatment and prophylaxis. Circulation 2006;114:e42-e47.[Free Full Text]
  63. Maeder M, Fehr T, Rickli H, Ammann P. Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides. Chest 2006;129:1349-1366.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  64. Spies C, Haude V, Fitzner R, Schroder K, Overbeck M, Runkel N, et al. Serum cardiac troponin T as a prognostic marker in early sepsis. Chest 1998;113:1055-1063.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  65. Ammann P, Fehr T, Minder EI, Gunter C, Bertel O. Elevation of troponin I in sepsis and septic shock. Int Care Med 2001;27:965-969.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  66. Castillo JR, Zagler A, Carrillo-Jimenez R, Hennekens CH. Brain natriuretic peptide: a potential marker for mortality in septic shock. Int J Infect Dis 2004;8:271-274.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  67. Maron BJ, Link MS, Wang PJ, Estes NA, III. Clinical profile of commotion cordis: an under appreciated cause of sudden death in the young during sports and other activities. J Cardiovasc Electrophysiol 1999;10:114-120.[Web of Science][Medline] [Order article via Infotrieve]
  68. Landesberg G, Shatz V, Akopnik I, Wolf YG, Mayer M, Berlatzky Y, et al. Association of cardiac troponin, CK-MB, and postoperative myocardial ischemia with long-term survival after major vascular surgery. J Am Coll Cardiol 2003;42:1547-1554.[Abstract/Free Full Text]
  69. Akhtar S, Silverman DG. Assessment and management of patients with ischemic heart disease. Crit Care Med 2004;32(Suppl):S126-S136.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  70. Bursi F, Babuin L, Barbieri A, Politi L, Zennaro M, Grimaldi T, et al. Vascular surgery patients: perioperative and long-term risk according to the ACC/AHA guidelines, the additive role of post-operative cardiac troponin elevation. 2005;26:2448-2456.
  71. Lopez-Jimenez F, Goldman L, Sacks DB, Thomas EJ, Johnson PA, Cook EF, et al. Prognostic value of cardiac troponin T after noncardiac surgery: 6-month follow-up data. J Am Coll Cardiol 1997;29:1241-1245.[Abstract]
  72. Filipovic M, Jeger R, Probst C, Girard T, Pfisterer M, Gurke L, et al. Heart rate variability and cardiac troponin I are incremental and independent predictors of one-year all-cause mortality after major noncardiac surgery in patients at risk of coronary artery disease. J Am Coll Cardiol 2003;42:1767-1776.[Abstract/Free Full Text]
  73. Oscarsson A, Eintrei C, Anskar S, Engdahl O, Fagerstrom L, Blomqvist P, et al. Troponin T-values provide long-term prognosis in elderly patients undergoing non-cardiac surgery. Acta Anaesthesiol Scand 2004;48:1071-1079.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  74. Landesberg G, Jaffe AS. A small step for man, a leap for postoperative management. J Am Coll Cardiol 2003;42:1555-1557.[Free Full Text]
  75. Ol ED, Caprini JA, Colwell CW, Frostick SP, Haas S, Hull RD, et al. Fatal vascular outcomes following major orthopedic surgery. Thromb Haemost 2005;93:860-866.[Web of Science][Medline] [Order article via Infotrieve]
  76. Herrmann J. Peri-procedural myocardial injury: 2005 update. Eur Heart J 2005;26:2493-2519.[Abstract/Free Full Text]
  77. Nageh T, Sherwood RA, Harris BM, Thomas MR. Prognostic role of cardiac troponin I after percutaneous coronary intervention in stable coronary disease. Heart 2005;91:1181-1185.[Abstract/Free Full Text]
  78. Cantor WJ, Newby LK, Christenson RH, Tuttle RH, Hasselblad V, Armstrong PW, et al. SYMPHONY and 2nd SYMPHONY Cardiac Markers Substudy Investigators. Prognostic significance of increased cardiac troponin I after percutaneous coronary intervention. J Am Coll Cardiol 2002;39:1738-1744.[Abstract/Free Full Text]
  79. Ricciardi MJ, Davidson CJ, Gubernikoff G, Beohar N, Eckman LJ, Parker MA, et al. Troponin I elevation and cardiac events after percutaneous coronary intervention. Am Heart J 2003;145:522-528.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  80. Bolognese L, Ducci K, Angioli P, Falsini G, Liistro F, Baldassarre S, et al. Elevations in cardiac troponin I after percutaneous coronary interventions are associated with abnormal tissue-level perfusion in high-risk patients with non-ST segment elevation acute coronary syndromes. Circulation 2004;110:1592-1597.[Abstract/Free Full Text]
  81. Kizer JR, Muttrej MR, Matthai WH, McConnell J, Nardone H, Sonel AF, et al. Role of cardiac troponin T in the long-term risk stratification of patients undergoing percutaneous coronary intervention. Eur Heart J 2003;24:1314-1322.[Abstract/Free Full Text]
  82. Akkerhuis KM, Alexander JH, Tardiff BE, Boersma E, Harrington RA, Lincoll AM, et al. Minor myocardial damage and prognosis: Are spontaneous and percutaneous coronary intervention-related events different?. Circulation 2002;105:554-556.[Abstract/Free Full Text]
  83. Miller WL, Garratt KN, Burrit MF, Lennon RJ, Reeder GS, Jaffe AS. Baseline troponin level: key to understanding the importance of post-PCI cardiac troponin elevations. Eur Heart J 2006;27:1061-1069.[Abstract/Free Full Text]
  84. Silber S, Albertsson P, Aviles FF, Camici P, Colombo A, Hamm C, et al. , for the Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Guidelines for percutaneous coronary interventions. Eur Heart J 2005;226:804-847.
  85. Califf RM, Abdelmeguid AE, Kuntz RE, Popma JJ, Davidson CJ, Cohen EA, et al. Myonecrosis after revascularization procedures. J Am Coll Cardiol 1998;31:241-251.[Abstract/Free Full Text]
  86. Thielmann M, Massoudy P, Schmermund A, Neuhauser M, Marggraf G, Kamler M, et al. Diagnostic discrimination between graft-related and non-graft-related perioperative myocardial infarction with cardiac troponin I after coronary artery bypass surgery. Eur Heart J 2005;26:2440-2447.[Abstract/Free Full Text]
  87. Onorati F, De Feo M, Mastroroberto P, Cristodoro L, Pezzo F, Renzulli A, et al. Determinants and prognosis of myocardial damage after coronary artery bypass grafting. Ann Thorac Surg 2005;79:837-845.[Abstract/Free Full Text]
  88. Selvanayagam JB, Pigott D, Balacumaraswami L, Petersen SE, Neubauer S, Taggart DP. Relationship of irreversible myocardial injury to troponin I and creatine kinase-MB elevation after coronary artery bypass surgery: insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 2005;45:629-631.[Free Full Text]
  89. Croal BL, Hillis GS, Gibson PH, Fazal MT, El-Shafei H, Gibson G, et al. Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery. Circulation 2006;114:1468-1475.[Abstract/Free Full Text]
  90. Steuer J, Bjerner T, Duvernoy O, Jideus L, Johansson L, Ahlstrom H, et al. Visualization and quantification of peri-operative myocardial infarction after coronary artery bypass surgery with contrast-enhanced magnetic resonance imaging. Eur Heart J 2004;25:1293-1299.[Abstract/Free Full Text]
  91. Thielmann M, Massoudy P, Neuhauser M, Tsagakis K, Marggraf G, Kamler M, et al. Prognostic value of preoperative cardiac troponin I in patients undergoing emergency coronary artery bypass surgery with non-ST-elevation or ST-elevation acute coronary syndromes. Circulation 2006;114(Suppl 1):I448-1453.[Web of Science][Medline] [Order article via Infotrieve]
  92. Greaves SC, Rutherford JD, Aranki SF, Cohn LH, Couper GS, Adams DH, et al. Current incidence and determinants of perioperative myocardial infarction in coronary artery surgery. Am Heart J 1996;132:572-578.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  93. Harff GA, Jeurissen RWM, Dijkstra JB, Reitjens TJM, Schonberger JPAM. Differentiation between transmural perioperative myocardial infarction and subendocardial injury after coronary artery bypass grafting using biochemical tests, elaborated by cluster and discriminant analysis. Clin Chim Acta 1998;274:29-41.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  94. Murphy CO, Pan-Chih , Gott JP, Guyton RA. Microvascular reactivity after crystalloid, cold blood, and warm blood cardioplegic arrest. Ann Thoracic Surg 1005;60:1021-1027.[CrossRef]
  95. Januzzi JL, Lewandrowski K, MacGillivray TE, Newell JB, Kathiresan S, Servoss SJ, et al. A comparison of cardiac troponin T and creatine kinase-MB for patient evaluation after cardiac surgery. J Am Coll Cardiol 2002;39:1518-1523.[Abstract/Free Full Text]
  96. Greenson N, Macoviak J, Krishnaswamy P, Morrisey R, James C, Clopton P, et al. Usefulness of cardiac troponin I in patients undergoing open heart surgery. Am Heart J 2001;141:447-455.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  97. Lehrke S, Steen H, Sievers HH, Peters H, Opitz A, Muller-Bardorff M, et al. Cardiac troponin T for prediction of short- and long-term morbidity and mortality after elective open heart surgery. Clin Chem 2004;50:1560-1567.[Abstract/Free Full Text]
  98. Baggish AL, MacGillivray TE, Hoffman W, Newell JB, Lewandrowski KB, Lee-Lewandrowski E, et al. Postoperative troponin-T predicts prolonged intensive care unit length of stay following cardiac surgery. Crit Care Med 2004;32:1866-1871.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  99. Fellahi JL, Gue X, Richomme X, Monier E, Guillou L, Riou B. Short- and long-term prognostic value of postoperative cardiac troponin I concentrations in patients undergoing coronary artery bypass grafting. Anesthesiol 2003;99:270.4.
  100. Lasocki S, Provenchere S, Benessiano J, Vicaut E, Lecharny JB, Desmonts JM, et al. Cardiac troponin I is an independent predictor of in-hospital death after adult cardiac surgery. Anesthesiol 2002;97:405-411.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  101. Holmvang L, Jurlander B, Rasmussen C, Thiis JJ, Grande P, Clemmensen P. Use of biochemical markers of infarction for diagnosing perioperative myocardial infarction and early graft occlusion after coronary artery bypass surgery. Chest 2002;121:103-111.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  102. Thielmann M, Massoudy P, Jaeger BR, Neuhauser M, Marggraf G, Sack S, et al. Emergency re-revascularization with percutaneous coronary intervention, reoperation, or conservative treatment in patients with acute perioperative graft failure following coronary artery bypass surgery. Eur J Cardiothorac Surg 2006;30:117-124.[Abstract/Free Full Text]
  103. Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, et al. Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery. J Am Coll Cardiol 2004;43:1873-1879.[Abstract/Free Full Text]
  104. Wazni OM, Martin DO, Marrouche NF, Latif AA, Ziada K, Shaaraoui M, et al. Plasma B-type natriuretic peptide levels predict postoperative atrial fibrillation in patients undergoing cardiac surgery. Circulation 2004;110:124-127.[Abstract/Free Full Text]



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