Multi-marker Strategy of Natriuretic Peptide for ACS
Background Compared to troponin alone, a dual-marker strategy with natriuretic peptides may improve acute coronary syndrome (ACS) diagnosis with a single blood draw and provide physiologic information regarding underlying heart disease. We evaluate the value of adding natriuretic peptides (myocyte stress markers) to troponins (myocardial injury markers) for diagnosing ACS in emergency department patients with chest pain.
Methods In 328 patients (53 ± 12 years, 63% men) with an initially negative conventional troponin and nonischemic electrocardiogram who underwent 64-slice cardiac computed tomography (CT), we measured conventional troponin-T (cTnT), high-sensitivity troponin-T (hsTnT), N-terminal pro-B type natriuretic peptide, and mid-regional pro-atrial natriuretic peptide. ACS was defined as myocardial infarction or unstable angina. CT was evaluated for coronary plaque, stenosis, and regional wall motion abnormality.
Results Patients with ACS (n = 29, 9%) had higher concentrations of each biomarker compared to those without (all P < .01). Adding natriuretic peptides, especially N-terminal pro-B type natriuretic peptide, to both cTnT or hsTnT improved the C-statistics and net reclassification index for ACS, largely driven by correctly reclassifying events. Dual-negative marker results improved sensitivity (cTnT 38% to 83%-86%, hsTnT 59% to 86%-90%; all P < .01) and negative predictive value (cTnT 94% to 97%-98%, hsTnT 96% to 97%-98%) for ACS. Patients with dual-negative markers had the lowest percentage of CT coronary plaque, stenosis, and regional wall motion abnormality (all P-trend <.001).
Conclusion Among emergency department patients with low-intermediate likelihood of ACS, combining natriuretic peptides with either conventional or highly-sensitive troponin improved discriminatory capacity and allowed for better reclassification of ACS, findings supported by structural and functional CT results.
The current standard for the diagnosis of acute myocardial infarction (MI) includes the measurement of conventional troponin (cTn) levels due to the high specificity of this biomarker for detecting myocardial injury and necrosis, but these assays are limited by their low first-draw sensitivity, and the need for serial blood draws. Moreover, unstable angina (UAP) is part of the spectrum and represents a significant number of acute coronary syndrome (ACS) diagnoses that does not involve an elevation or the typical "rise and fall" pattern of cTn. Newer and more precise assays of myocardial injury and necrosis, high-sensitivity troponin (hsTn) assays, could replace cTn in the future because of their ability to detect minute quantities of myocardial injury, thus improving sensitivity for the diagnosis of acute MI. As we and others have shown, high-sensitivity troponin-T (hsTnT) has greater sensitivity than cTnT for ACS diagnosis in acute chest pain patients presenting to the emergency department (ED); however, its sensitivity remains moderate, particularly for the diagnosis of UAP.
The natriuretic peptides, including N-terminal pro-B type natriuretic peptide (NT-proBNP) and the newer mid-regional pro-atrial natriuretic peptide (MR-proANP), are cardiac biomarkers secreted into the circulation via atrial and ventricular myocytes, and used for diagnosis or exclusion of heart failure; both correlating well with cardiac structure and function. While natriuretic peptides are cardiac-specific, their role for diagnostic evaluation of patients with suspected ACS remains less well-understood, and results in this regard are mixed. Given the reduced first-draw sensitivity of troponin for ACS diagnosis, in theory, a clinical approach utilizing biomarkers with complementary physiologies (e.g., myocardial stress and necrosis) might be superior to a single biomarker strategy alone.
There are few data comparing the effectiveness of a multimarker strategy for ACS diagnosis in a single blood draw,and data are lacking regarding the value of this approach using newer assays such as hsTnT and MR-proANP. Thus, we aim to determine the diagnostic value of a dual marker strategy, particularly dual-negative marker results, for ACS and UAP diagnosis by combining markers of myocardial injury (cTnT or hsTnT) with markers of myocyte stress (NT-proBNP or MR-proANP) in acute chest pain patients presenting to the ED. In addition, we examine the dual marker results with imaging by evaluating its relationship with prevalence of cardiac computed tomography (CT) features of coronary plaque, stenosis, and regional wall motion abnormalities (RWMA).
Abstract and Introduction
Abstract
Background Compared to troponin alone, a dual-marker strategy with natriuretic peptides may improve acute coronary syndrome (ACS) diagnosis with a single blood draw and provide physiologic information regarding underlying heart disease. We evaluate the value of adding natriuretic peptides (myocyte stress markers) to troponins (myocardial injury markers) for diagnosing ACS in emergency department patients with chest pain.
Methods In 328 patients (53 ± 12 years, 63% men) with an initially negative conventional troponin and nonischemic electrocardiogram who underwent 64-slice cardiac computed tomography (CT), we measured conventional troponin-T (cTnT), high-sensitivity troponin-T (hsTnT), N-terminal pro-B type natriuretic peptide, and mid-regional pro-atrial natriuretic peptide. ACS was defined as myocardial infarction or unstable angina. CT was evaluated for coronary plaque, stenosis, and regional wall motion abnormality.
Results Patients with ACS (n = 29, 9%) had higher concentrations of each biomarker compared to those without (all P < .01). Adding natriuretic peptides, especially N-terminal pro-B type natriuretic peptide, to both cTnT or hsTnT improved the C-statistics and net reclassification index for ACS, largely driven by correctly reclassifying events. Dual-negative marker results improved sensitivity (cTnT 38% to 83%-86%, hsTnT 59% to 86%-90%; all P < .01) and negative predictive value (cTnT 94% to 97%-98%, hsTnT 96% to 97%-98%) for ACS. Patients with dual-negative markers had the lowest percentage of CT coronary plaque, stenosis, and regional wall motion abnormality (all P-trend <.001).
Conclusion Among emergency department patients with low-intermediate likelihood of ACS, combining natriuretic peptides with either conventional or highly-sensitive troponin improved discriminatory capacity and allowed for better reclassification of ACS, findings supported by structural and functional CT results.
Introduction
The current standard for the diagnosis of acute myocardial infarction (MI) includes the measurement of conventional troponin (cTn) levels due to the high specificity of this biomarker for detecting myocardial injury and necrosis, but these assays are limited by their low first-draw sensitivity, and the need for serial blood draws. Moreover, unstable angina (UAP) is part of the spectrum and represents a significant number of acute coronary syndrome (ACS) diagnoses that does not involve an elevation or the typical "rise and fall" pattern of cTn. Newer and more precise assays of myocardial injury and necrosis, high-sensitivity troponin (hsTn) assays, could replace cTn in the future because of their ability to detect minute quantities of myocardial injury, thus improving sensitivity for the diagnosis of acute MI. As we and others have shown, high-sensitivity troponin-T (hsTnT) has greater sensitivity than cTnT for ACS diagnosis in acute chest pain patients presenting to the emergency department (ED); however, its sensitivity remains moderate, particularly for the diagnosis of UAP.
The natriuretic peptides, including N-terminal pro-B type natriuretic peptide (NT-proBNP) and the newer mid-regional pro-atrial natriuretic peptide (MR-proANP), are cardiac biomarkers secreted into the circulation via atrial and ventricular myocytes, and used for diagnosis or exclusion of heart failure; both correlating well with cardiac structure and function. While natriuretic peptides are cardiac-specific, their role for diagnostic evaluation of patients with suspected ACS remains less well-understood, and results in this regard are mixed. Given the reduced first-draw sensitivity of troponin for ACS diagnosis, in theory, a clinical approach utilizing biomarkers with complementary physiologies (e.g., myocardial stress and necrosis) might be superior to a single biomarker strategy alone.
There are few data comparing the effectiveness of a multimarker strategy for ACS diagnosis in a single blood draw,and data are lacking regarding the value of this approach using newer assays such as hsTnT and MR-proANP. Thus, we aim to determine the diagnostic value of a dual marker strategy, particularly dual-negative marker results, for ACS and UAP diagnosis by combining markers of myocardial injury (cTnT or hsTnT) with markers of myocyte stress (NT-proBNP or MR-proANP) in acute chest pain patients presenting to the ED. In addition, we examine the dual marker results with imaging by evaluating its relationship with prevalence of cardiac computed tomography (CT) features of coronary plaque, stenosis, and regional wall motion abnormalities (RWMA).
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