Natriuretic Peptide Response and Outcomes in Chronic Heart Failure With Reduced Ejection Fraction

James L. Januzzi, Tariq Ahmad, Hillary Mulder, Adrian Coles, Kevin J. Anstrom, Kirkwood F. Adams, Justin A. Ezekowitz, Mona Fiuzat, Nancy Houston-Miller, Daniel B. Mark, Ileana L. Piña, Gayle Passmore, David J. Whellan, Lawton S. Cooper, Eric S. Leifer, Patrice Desvigne-Nickens, G. Michael Felker, Christopher M. O'Connor

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial demonstrated that a strategy to “guide” application of guideline-directed medical therapy (GDMT) by reducing amino-terminal pro–B-type natriuretic peptide (NT-proBNP) was not superior to GDMT alone. Objectives: The purpose of this study was to examine the prognostic meaning of NT-proBNP changes following heart failure (HF) therapy intensification relative to the goal NT-proBNP value of 1,000 pg/ml explored in the GUIDE-IT trial. Methods: A total of 638 study participants were included who were alive and had available NT-proBNP results 90 days after randomization. Rates of subsequent cardiovascular (CV) death/HF hospitalization or all-cause mortality during follow-up and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall scores were analyzed. Results: A total of 198 (31.0%) subjects had an NT-proBNP ≤1,000 pg/ml at 90 days with no difference in achievement of NT-proBNP goal between the biomarker-guided and usual care arms. NT-proBNP ≤1,000 pg/ml by 90 days was associated with longer freedom from CV/HF hospitalization or all-cause mortality (p < 0.001 for both) and lower adjusted hazard of subsequent HF hospitalization/CV death (hazard ratio: 0.26; 95% confidence interval: 0.15 to 0.46; p < 0.001) and all-cause mortality (hazard ratio: 0.34; 95% confidence interval: 0.15 to 0.77; p = 0.009). Regardless of elevated baseline concentration, an NT-proBNP ≤1,000 pg/ml at 90 days was associated with better outcomes and significantly better KCCQ overall scores (p = 0.02). Conclusions: Patients with heart failure with reduced ejection fraction whose NT-proBNP levels decreased to ≤1,000 pg/ml during GDMT had better outcomes. These findings may help to understand the results of the GUIDE-IT trial.

Original languageEnglish (US)
Pages (from-to)1205-1217
Number of pages13
JournalJournal of the American College of Cardiology
Issue number9
StatePublished - Sep 3 2019


  • heart failure
  • natriuretic peptides
  • outcomes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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