Exercise oscillatory breathing and NT-proBNP levels in stable heart failure provide the strongest prediction of cardiac outcome when combining biomarkers with cardiopulmonary exercise testing

Marco Guazzi, Patrizia Boracchi, Valentina Labate, Ross Arena, Giuseppe Reina

Research output: Contribution to journalArticle


Background: N-Terminal pro-brain natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (CPET)-derived variables are gold standards for assessing prognosis in heart failure (HF) patients. We sought to refine cardiac events prediction by performing a combined analysis of NT-proBNP with markers of exercise ventilatory efficiency. Methods and Results: A total of 260 stable HF patients underwent measurements of plasma NT-proBNP levels before, at peak exercise, and at 1-minute CPET recovery phase along with peak oxygen uptake (VO 2), ventilation to CO 2 production (VE/VCO 2) slope, and exercise periodic breathing (EPB) determinations. After a median follow-up period of 20.6 months, there were 54 cardiac-related deaths. Univariate analysis including NT-proBNP at rest, at peak exercise, and at 1 minute recovery, peak VO 2, VE/VCO 2 slope, and EPB showed NT-proBNP to be the strongest independent predictor with equivalent performance for rest, peak, and recovery levels. Thus, only NT-proBNP at rest was considered (Harrel C 0.783, 95% confidence interval [CI] 0.722-0.844) with VE/VCO 2 slope (Harrel C 0.720, 95% CI 0.646-0.794), EPB (Harrel C 0.685, 95% CI 0.619-0.751), and peak VO 2 (Harrel C 0.618, 95% CI 0.533-0.704). With bivariate stepwise analyses, NT-proBNP along with EPB emerged as the strongest prognosticators (Harrel C 0.800, 95% CI 0.737-0.862). Conclusions: In the refinement for robust outcome predictors in HF patients, NT-proBNP levels together with EPB led to the most powerful definition. VE/VCO 2 slope and peak VO 2 did not provide any prognostic adjunct. A biomarker/CPET approach seems very promising to warrant the continuous implementation in the prognostic work-up of HF patients.

Original languageEnglish
Pages (from-to)313-320
Number of pages8
JournalJournal of Cardiac Failure
Issue number4
Publication statusPublished - Apr 2012



  • exercise periodic breathing
  • heart failure
  • Natriuretic peptide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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