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The role of cardiac biomarkers in the diagnosis and management of patients presenting with suspected acute coronary syndrome.

Christenson E, Christenson RH - Ann Lab Med (2013)

Bottom Line: As assays for cTn have been evolved that are capable of reliably detecting smaller and smaller quantities in the blood, a dilemma has emerged as to how to use this new information.Several studies have attempted to answer this question and have shown that these lower concentrations of cTn have important prognostic significance and, more importantly, that intervention in these patients leads to improved clinical outcomes.New algorithms incorporating BNP, NT-proBNP, and more sensitive cTn assays hold promise for more rapid diagnosis or rule-out of MI, allowing for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Johns Hopkins Hospital, Baltimore, USA.

ABSTRACT
Myocardial infarction (MI) is the leading cause of death in the developed world. Biomarkers have an essential role in diagnosis, risk stratification, guiding management and clinical decision making in the setting of patients presenting with signs and symptoms of MI. Cardiac troponin (cTn) rose to prominence during the 1990s and has evolved to be the cornerstone for diagnosis of MI. The current criteria for MI diagnosis include a rise and/or fall in cTn with at least one value above the 99th percentile of the upper reference limit. Along with cTn, the natriuretic peptides B-type natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) have an important role in determining prognosis and guiding management. As assays for cTn have been evolved that are capable of reliably detecting smaller and smaller quantities in the blood, a dilemma has emerged as to how to use this new information. Several studies have attempted to answer this question and have shown that these lower concentrations of cTn have important prognostic significance and, more importantly, that intervention in these patients leads to improved clinical outcomes. New algorithms incorporating BNP, NT-proBNP, and more sensitive cTn assays hold promise for more rapid diagnosis or rule-out of MI, allowing for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.

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Implementation of a sensitive cardiac troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. Adapted with permission from JAMA 2011;305:1210-6.
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Figure 3: Implementation of a sensitive cardiac troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. Adapted with permission from JAMA 2011;305:1210-6.

Mentions: Are more sensitive assays picking up clinically insignificant Tn release, or does detection contribute to improved patient outcomes? Stated differently: Do patients with signs and symptoms of MI have better outcomes if the 99th percentile is utilized as the MI cutoff, versus use of a higher Tn cutoff like that necessary with earlier cTn assays? Mills et al. [24] examined this question by evaluating the clinical impact of replacing a conventional cTnI assay with a cutoff of 0.20 ng/mL with a new more sensitive cTnI assay having a cutoff of 0.05 ng/mL. In this study suspected MI patients were analyzed in three strata based on their cTnI results: 1) <0.05 ng/mL, below the 99th percentile of the new sensitive assay, 2) between 0.05 and 0.19 ng/mL, and 3) ≥0.20 ng/mL, the cutoff for earlier conventional assay's decision limit. The study design included two phases: the first was the validation phase, in which patients (n=1,038) had the sensitive cTnI measurement, but the previous conventional assay's MI cutoff of 0.2 ng/mL was used for decision making. The second phase was implementation; in which the 99th percentile value of <0.05 ng/mL was used as the MI cutoff for these patients (n=1,054). Event-free survival at 1 yr (i.e. patients absent recurrent MI and mortality) was the measured outcome. Fig. 3 shows that outcomes in the validation phase for the patients with levels <0.05 ng/mL were low at <7% and event-free survival of patients with results >0.20 ng/mL was about 24% at 1 yr. However, patients who had cTnI values between 0.05 and 0.19 ng/mL were at highest risk with 1 yr events at -40%, about 2-fold higher compared to the >0.20 ng/mL strata. This is possibly secondary to lower rates of intervention and risk modification. In the implementation phase when the sensitive assay's cutoff of <0.05 ng/mL was used for decision making, Fig. 3 shows that the 1-yr outcomes for both the <0.05 and >0.20 ng/mL strata were virtually identical to the validation phase. However, the 0.05 to 0.20 ng/mL strata had outcomes that were ~50% (39% down to 21%) improved from in the implementation phase. Therefore, implementation of the lower 99th percentile diagnostic cTnI threshold was associated with major reductions in 1-yr mortality and recurrent MI [24]. Patients with signs and symptoms of MI have better outcomes if a sensitive assay's 99th percentile is utilized as the MI cutoff, versus use of a higher Tn cutoff such as that necessary with earlier cTn assays.


The role of cardiac biomarkers in the diagnosis and management of patients presenting with suspected acute coronary syndrome.

Christenson E, Christenson RH - Ann Lab Med (2013)

Implementation of a sensitive cardiac troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. Adapted with permission from JAMA 2011;305:1210-6.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756234&req=5

Figure 3: Implementation of a sensitive cardiac troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. Adapted with permission from JAMA 2011;305:1210-6.
Mentions: Are more sensitive assays picking up clinically insignificant Tn release, or does detection contribute to improved patient outcomes? Stated differently: Do patients with signs and symptoms of MI have better outcomes if the 99th percentile is utilized as the MI cutoff, versus use of a higher Tn cutoff like that necessary with earlier cTn assays? Mills et al. [24] examined this question by evaluating the clinical impact of replacing a conventional cTnI assay with a cutoff of 0.20 ng/mL with a new more sensitive cTnI assay having a cutoff of 0.05 ng/mL. In this study suspected MI patients were analyzed in three strata based on their cTnI results: 1) <0.05 ng/mL, below the 99th percentile of the new sensitive assay, 2) between 0.05 and 0.19 ng/mL, and 3) ≥0.20 ng/mL, the cutoff for earlier conventional assay's decision limit. The study design included two phases: the first was the validation phase, in which patients (n=1,038) had the sensitive cTnI measurement, but the previous conventional assay's MI cutoff of 0.2 ng/mL was used for decision making. The second phase was implementation; in which the 99th percentile value of <0.05 ng/mL was used as the MI cutoff for these patients (n=1,054). Event-free survival at 1 yr (i.e. patients absent recurrent MI and mortality) was the measured outcome. Fig. 3 shows that outcomes in the validation phase for the patients with levels <0.05 ng/mL were low at <7% and event-free survival of patients with results >0.20 ng/mL was about 24% at 1 yr. However, patients who had cTnI values between 0.05 and 0.19 ng/mL were at highest risk with 1 yr events at -40%, about 2-fold higher compared to the >0.20 ng/mL strata. This is possibly secondary to lower rates of intervention and risk modification. In the implementation phase when the sensitive assay's cutoff of <0.05 ng/mL was used for decision making, Fig. 3 shows that the 1-yr outcomes for both the <0.05 and >0.20 ng/mL strata were virtually identical to the validation phase. However, the 0.05 to 0.20 ng/mL strata had outcomes that were ~50% (39% down to 21%) improved from in the implementation phase. Therefore, implementation of the lower 99th percentile diagnostic cTnI threshold was associated with major reductions in 1-yr mortality and recurrent MI [24]. Patients with signs and symptoms of MI have better outcomes if a sensitive assay's 99th percentile is utilized as the MI cutoff, versus use of a higher Tn cutoff such as that necessary with earlier cTn assays.

Bottom Line: As assays for cTn have been evolved that are capable of reliably detecting smaller and smaller quantities in the blood, a dilemma has emerged as to how to use this new information.Several studies have attempted to answer this question and have shown that these lower concentrations of cTn have important prognostic significance and, more importantly, that intervention in these patients leads to improved clinical outcomes.New algorithms incorporating BNP, NT-proBNP, and more sensitive cTn assays hold promise for more rapid diagnosis or rule-out of MI, allowing for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Johns Hopkins Hospital, Baltimore, USA.

ABSTRACT
Myocardial infarction (MI) is the leading cause of death in the developed world. Biomarkers have an essential role in diagnosis, risk stratification, guiding management and clinical decision making in the setting of patients presenting with signs and symptoms of MI. Cardiac troponin (cTn) rose to prominence during the 1990s and has evolved to be the cornerstone for diagnosis of MI. The current criteria for MI diagnosis include a rise and/or fall in cTn with at least one value above the 99th percentile of the upper reference limit. Along with cTn, the natriuretic peptides B-type natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) have an important role in determining prognosis and guiding management. As assays for cTn have been evolved that are capable of reliably detecting smaller and smaller quantities in the blood, a dilemma has emerged as to how to use this new information. Several studies have attempted to answer this question and have shown that these lower concentrations of cTn have important prognostic significance and, more importantly, that intervention in these patients leads to improved clinical outcomes. New algorithms incorporating BNP, NT-proBNP, and more sensitive cTn assays hold promise for more rapid diagnosis or rule-out of MI, allowing for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.

Show MeSH
Related in: MedlinePlus