Novel Applications of Cardiac Biomarkers in Heart Failure

Shanmugam Uthamalingam, James L Januzzi
US Cardiology, 2009;6(1):41-45
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Abstract

Cardiac biomarkers, both established and emerging ones, have various novel applications in heart failure. The role of established biomarkers such as natriuretic peptides—both B-type natriuretic peptide (BNP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP)—in acute heart failure has been well studied. The role of natriuretic peptides in the primary care setting and utilization of natriuretic peptides along with clinical evaluation in the treatment of patients with chronic heart failure are promising. In addition, other markers such as cardiac-specific troponins or C-reactive protein (CRP), as well as more emerging markers of matrix remodeling such as matrix metalloproteinases, tissue inhibitors of metalloproteinases, galectin-3, and ST2, may have a role not only for prognostication of patients with heart failure but also in the optimal management of these patients.
Keywords
Biomarkers, natriuretic peptides, BNP, NT-proBNP, novel cardiac biomarkers, galectin-3, ST2
Disclosure James J Januzzi, Jr, MD, FACC, receives grant support, speaking fees, and/or consulting income from Roche Diagnostics, Siemens Diagnostics, Critical Diagnostics, BG Medicine, and Inverness Diagnostics. Shanmugam Uthamalingam, MD, has no conflicts of interest to declare.
Received: January 31, 2009 Accepted February 26, 2009
Correspondence: James L Januzzi, Jr, MD, FACC, Massachusetts General Hospital, 32 Fruit Street, Yawkey 5984, Boston, MA 02114. E: jjanuzzi@partners.org

Several cardiac biomarkers may aid in the diagnostic and prognostic evaluation of acute and chronic heart failure. In this article we discuss more novel and emerging applications of such established cardiac biomarkers in heart failure and review emerging data for several other promising markers.

Novel Applications of Established Cardiac Biomarkers—Natriuretic Peptides

B-type natriuretic peptide (BNP) and its amino-terminal cleavage equivalent N-terminal prohormone brain natriuretic peptide (NT-proBNP) originate from a pre-proBNP hormone of 134 residues that is cleaved to yield a 108 amino acid intracellular pro-hormone, proBNP108; from proBNP108, BNP and NT-proBNP are liberated in varying amounts.1 The utility of BNP and NT-proBNP for the diagnostic evaluation of suspected acute heart failure in patients presenting with acute dyspnea has been well studied and previously reviewed.2–5 Emerging applications of BNP and NT-proBNP include their application in primary care, as well as their use in better managing patients with heart disease besides acute heart failure.

Natriuretic Peptides and Evaluation of Dyspnea in the Primary Care Setting

The emerging utilities of BNP and NT-proBNP levels in the primary care setting include evaluation of patients with dyspnea as well as screening for asymptomatic left ventricular (LV) dysfunction. As both BNP and NT-proBNP are greatly affected by hemodynamic stress, it is well accepted that the optimal cut-off values for both BNP and NT-proBNP levels are lower in primary care patients than seen in patients with acute dyspnea presenting to the emergency room. Tang et al.6 demonstrated that the use of a BNP cut-point of 100ng/l was associated with a disastrously low sensitivity among symptomatic heart failure patients in a heart failure clinic. Given this fact, lower BNP cut-points than those applied for acute heart failure screening are clearly necessary; in this context, the primary care application for BNP and NT-proBNP is best considered as a ‘rule-out’ rather than ‘rule-in’ tool. In other words, the choice of cut-off for these markers should be made based on the ability of the marker to exclude heart failure in a symptomatic patient rather than to identify it. This requires good understanding of the negative predictive value (NPV) for BNP and NT-proBNP in primary care and the factors that affect the peptides. Important physiological variables to consider when interpreting natriuretic peptides are detailed in Table 1.

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