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CLINICAL RESEARCH: HEART FAILURE

Prognostic Value of Changes in N-Terminal Pro-Brain Natriuretic Peptide in Val-HeFT (Valsartan Heart Failure Trial)

Serge Masson, PhD^_*,_*, Roberto Latini, MD^_*,, Inder S. Anand, MD, FACC, FRCP, DPhil (Oxon), Simona Barlera, MS^_*, Laura Angelici, MS^_*, Tarcisio Vago, BiolD, Gianni Tognoni, MD^||, Jay N. Cohn, MD, FACC^¶ for the Val-HeFT Investigators

^_* Department of Cardiovascular Reearch, Istituto Mario Negri, Milan, Italy
Department of Medicine, New York Medical College, Valhalla, New York
Cardiology Section, Veterans Affairs Medical Center, Minneapolis, Minnesota
Laboratorio di Endocrinologia, Ospedale Luigi Sacco, Milan, Italy
^|| Consorzio Mario Negri Sud, S. Maria Imbaro, Chieti, Italy
^¶ Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota

Manuscript received January 10, 2008; revised manuscript received March 18, 2008, accepted April 23, 2008.

^_* Reprint requests and correspondence: Dr. Serge Masson, Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20156 Milan, Italy (Email: masson{at}marionegri.it).

Objectives: This study sought to evaluate the association between changes over time of N-terminal pro-brain natriuretic peptide (NT-proBNP) expressed in different ways and outcome in patients with stable and chronic heart failure (HF).

Background: Although previous studies examined the prognostic value of repeated determinations of BNP in HF, there are only limited data on the clinical utility of serial measurements of the inactive peptide NT-proBNP in a large population of ambulatory patients with chronic HF with sufficient follow-up time.

Methods: The NT-proBNP was measured at randomization and after 4 months in 1,742 patients enrolled in the placebo arm of Val-HeFT (Valsartan Heart Failure Trial). Changes in NT-proBNP concentrations over 4 months were expressed as absolute change from baseline, percent relative changes, or categorical changes across a threshold value and related to subsequent mortality.

Results: A single determination of NT-proBNP (area under the curve at 4 months: 0.702, 95% confidence interval [CI]: 0.669 to 0.735) showed a higher prognostic discrimination than continuous changes of concentrations, expressed either as absolute (0.592, 95% CI: 0.549 to 0.634) or relative changes (0.602, 95% CI: 0.566 to 0.639). A Cox proportional hazards model showed that stratification of patients into 4 categories according to NT-proBNP levels at 2 time points 4 months apart with respect to a threshold concentration provided prognostic information in patients with chronic HF beyond that of a single determination.

Conclusions: Serial determinations of NT-proBNP concentration and classification into few categories of changes according to threshold levels may be a superior strategy for risk stratification of patients with chronic and stable HF.

Key Words: natriuretic peptide • heart failure • prognosis

Abbreviations and Acronyms   AUC = area under the receiver-operator characteristic curve   BNP = brain natriuretic peptide   CI = confidence interval   cTnT = cardiac troponin T   HF = heart failure   HR = hazard ratio   LV = left ventricular   LVEF = left ventricular ejection fraction   NT-proBNP = N-terminal pro-brain natriuretic peptide   NYHA = New York Heart Association   ROC = receiver-operator characteristic

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