Published Online
on June 25, 2007

A more recent version of this article appeared on July 17, 2007

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Submitted on July 13, 2006
Accepted on April 18, 2007

Serial Biomarker Measurements in Ambulatory Patients With Chronic Heart Failure. The Importance of Change Over Time

Wayne L. Miller MD, PhD^*, Karen A. Hartman BSN, CCRC, Mary F. Burritt PhD, Diane E. Grill MSc, Richard J. Rodeheffer MD, John C. Burnett Jr MD, and Allan S. Jaffe MD

From the Division of Cardiovascular Diseases, Department of Medicine (W.L.M., K.A.H., R.J.R., J.C.B., A.S.J.), Department of Laboratory Medicine and Pathology (M.F.B., A.S.J.), and Division of Biostatistics (D.E.G.), Mayo Clinic, Rochester, Minn.

^* To whom correspondence should be addressed. E-mail: miller.wayne{at}mayo.edu.

Background--Cardiac troponin T (cTnT) and B-type natriuretic peptide (BNP) have been used to estimate prognosis in heart failure; however, most studies have evaluated decompensated patients with single measurements. To determine if there are advantages to serial measurements, we evaluated stable chronic heart failure patients every 3 months for 2 years.

Methods and Results--A cohort of 190 New York Heart Association class III-IV heart failure patients was prospectively enrolled from June 2001 to January 2004. Primary end points were death, cardiac transplantation, or hospitalization. At study enrollment cTnT was <0.01 ng/mL in 87 (45.8%) patients, 0.01 to 0.03 ng/mL in 50 (26.3%) patients, and >0.03 ng/mL in 53 (27.9%) patients. An increase in cTnT above normal (<0.01 ng/mL) carried a 3.4-fold increased risk (P=0.019). Further increases (20%) from an elevated level worsened the overall risk (hazard ratio, 5.09; P<0.001). BNP was elevated (>95th percentile for age and gender normal population) in 122 (64.2%) patients. An elevation of BNP from normal at any time during the study was associated with a poor outcome, but, once elevated, further changes in BNP (increases or decreases) remained associated with the same risk (hazard ratio, 5.09; P<0.001). Combined elevations of cTnT (>0.03 ng/mL) and BNP defined the highest risk group (hazard ratio, 8.58; P<0.001).

Conclusions--Elevations of cTnT or BNP from normal detected at any time during clinical follow-up in ambulatory patients with chronic heart failure are highly associated with an increased risk of events. Further increases in cTnT contribute to additional risk. Combined elevations of cTnT and BNP contribute the highest risk. The ability to monitor changes by serial measurements adds substantially to the assessment of risk in this patient population.

Key words: heart failure • natriuretic peptides • prognosis • troponin

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