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Received on August 31, 2004
Accepted on December 13, 2004
Proteomics and Protein Markers |
1 Division of Cardiovascular Diseases and Internal Medicine and Department of Clinical Biochemistry and Immunology, Mayo Clinic Rochester, MN
* To whom correspondence should be addressed. E-mail: miller.wayne{at}mayo.edu.
Background: Objective methods to assess the adequacy of medication therapy for patients with advanced heart failure are lacking. Serial measurements of biomarkers might be beneficial. Therapy guided by N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be helpful because NT-proBNP should be lowered by therapies that decrease endogenous BNP secretion.
Methods: NT-proBNP and BNP were measured in a nonconsecutive patient cohort receiving clinically indicated intravenous nesiritide. Blood samples were drawn before, at 6 and 24 h during, and at 6 h after infusion. A decrease in NT-proBNP was defined as a decrease from baseline during infusion (infusion responders) of >3 SD of the variability of the assay measurement (
20%). Patients with decreases >20% in both NT-pro BNP and BNP at 6 h postinfusion were designated "biochemical responders".
Results: Forty patients [27 males; mean (SE) age, 68 (2) years; mean (SE) left ventricular ejection fraction, 25 (1.4)%] were studied. All patients improved clinically. Overall, the changes in NT-proBNP were a 18 (4.6)% [mean (SE)] and 19.8% (median) decrease from baseline at 24 h of infusion and a 22 (6.0)% and 17.8% decrease at 6 h postinfusion (P <0.001 compared with baseline). In a large number of patients, decreases in NT-proBNP were, however, within the variability of the assay. Subgroup analysis showed that 22 of 40 patients were "infusion responders" with a >20% decrease from baseline in NT-proBNP during nesiritide infusion, whereas only 12 patients were biochemical responders with >20% decreases from baseline postinfusion for both NT-proBNP and BNP.
Conclusions: In this study, many patients had decreased NT-proBNP and BNP values after therapy with nesiritide, but the majority of patients did not demonstrate biochemically significant decreases in analytes despite a clinical response. Until we know more about the responses of natriuretic peptides to therapies such as nesiritide, a strategy of monitoring NT-proBNP and BNP to guide therapy cannot be universally advocated.
The following articles in journals at HighWire Press have cited this article:
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  K. B. Shah, W. J. Kop, R. H. Christenson, D. B. Diercks, D. Kuo, S. Henderson, K. Hanson, S.-Y. Li, and C. R. deFilippi Natriuretic peptides and echocardiography in acute dyspnoea: implication of elevated levels with normal systolic function Eur J Heart Fail, July 1, 2009; 11(7): 659 - 667. [Abstract] [Full Text] [PDF]
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 W. L. Miller, K. A. Hartman, D. E. Grill, J. C. Burnett Jr, and A. S. Jaffe Only Large Reductions in Concentrations of Natriuretic Peptides (BNP and NT-proBNP) Are Associated with Improved Outcome in Ambulatory Patients with Chronic Heart Failure Clin. Chem., January 1, 2009; 55(1): 78 - 84. [Abstract] [Full Text] [PDF]
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M. Metra, S. Nodari, G. Parrinello, C. Specchia, L. Brentana, P. Rocca, F. Fracassi, T. Bordonali, P. Milani, R. Danesi, et al. The role of plasma biomarkers in acute heart failure. Serial changes and independent prognostic value of NT-proBNP and cardiac troponin-T Eur J Heart Fail, August 1, 2007; 9(8): 776 - 786. [Abstract] [Full Text] [PDF]
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 F. S. Apple, A. H.B. Wu, A. S. Jaffe, M. Panteghini, R. H. Christenson, NACB COMMITTEE MEMBERS, R. H. Christenson, F. S. Apple, C. P. Cannon, G. Francis, et al. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical Issues for Biomarkers of Heart Failure Circulation, July 31, 2007; 116(5): e95 - e98. [Full Text] [PDF]
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W. L. Miller, K. A. Hartman, M. F. Burritt, D. E. Grill, R. J. Rodeheffer, J. C. Burnett Jr, and A. S. Jaffe Serial Biomarker Measurements in Ambulatory Patients With Chronic Heart Failure: The Importance of Change Over Time Circulation, July 17, 2007; 116(3): 249 - 257. [Abstract] [Full Text] [PDF]
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 P. R. Forfia, M. Lee, R. S. Tunin, M. Mahmud, H. C. Champion, and D. A. Kass Acute Phosphodiesterase 5 Inhibition Mimics Hemodynamic Effects of B-Type Natriuretic Peptide and Potentiates B-Type Natriuretic Peptide Effects in Failing But Not Normal Canine Heart J. Am. Coll. Cardiol., March 13, 2007; 49(10): 1079 - 1088. [Abstract] [Full Text] [PDF]
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A. S. Jaffe, L. Babuin, and F. S. Apple Biomarkers in Acute Cardiac Disease: The Present and the Future J. Am. Coll. Cardiol., July 4, 2006; 48(1): 1 - 11. [Abstract] [Full Text] [PDF]
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