Januzzi_subbed.qxp 20/4/09 3:45 pm Page 41
Heart Failure
Novel Applications of Cardiac Biomarkers in Heart Failure
Shanmugam Uthamalingam, MD
1
and James L Januzzi, Jr, MD, FACC
2
1. Department of Internal Medicine, Dartmouth Hitchcock Clinic;
2. Director, Cardiology Intensive Care Unit, Massachusetts General Hospital, and Associate Professor, Harvard Medical School
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 that the optimal cut-off values for both BNP and NT-proBNP levels are
evaluation of acute and chronic heart failure. In this article we discuss lower in primary care patients than seen in patients with acute dyspnea
more novel and emerging applications of such established cardiac presenting to the emergency room. Tang et al.
6
demonstrated that the use
biomarkers in heart failure and review emerging data for several other of a BNP cut-point of 100ng/l was associated with a disastrously low
promising markers. sensitivity among symptomatic heart failure patients in a heart failure
clinic. Given this fact, lower BNP cut-points than those applied for acute
Novel Applications of Established Cardiac heart failure screening are clearly necessary; in this context, the primary
Biomarkers—Natriuretic Peptides care application for BNP and NT-proBNP is best considered as a ‘rule-out’
B-type natriuretic peptide (BNP) and its amino-terminal cleavage rather than ‘rule-in’ tool. In other words, the choice of cut-off for these
equivalent N-terminal prohormone brain natriuretic peptide (NT-proBNP) markers should be made based on the ability of the marker to exclude
originate from a pre-proBNP hormone of 134 residues that is cleaved to heart failure in a symptomatic patient rather than to identify it. This
yield a 108 amino acid intracellular pro-hormone, proBNP108; from requires good understanding of the negative predictive value (NPV) for BNP
proBNP108, BNP and NT-proBNP are liberated in varying amounts.
1
The and NT-proBNP in primary care and the factors that affect the peptides.
utility of BNP and NT-proBNP for the diagnostic evaluation of suspected Important physiological variables to consider when interpreting natriuretic
acute heart failure in patients presenting with acute dyspnea has been peptides are detailed in Table 1.
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 In the primary care setting, it has been suggested that the NPV optimal
better managing patients with heart disease besides acute heart failure. cut-off for BNP would be 20–30ng/l, although there are relatively few data
prospectively supporting this cut-point. NT-proBNP has been studied and
Natriuretic Peptides and Evaluation of Dyspnea in the validated in the primary care setting; for this use, an optimal NPV value of
Primary Care Setting 125ng/l for ruling out heart failure among patients <75 years of age is useful;
7
The emerging utilities of BNP and NT-proBNP levels in the primary care as the median value of NT-proBNP among those ≥75 years of age has been
setting include evaluation of patients with dyspnea as well as screening for shown to be 150ng/l, a higher cut-point is necessary for the elderly. While
asymptomatic left ventricular (LV) dysfunction. As both BNP and 450ng/l has been advocated, a lower value of 300ng/l may have slightly better
NT-proBNP are greatly affected by hemodynamic stress, it is well accepted NPV for those >75 years of age.
8–12
© TOUCH BRIEFINGS 2009 41
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100