Development of a cardiopulmonary exercise prognostic score for optimizing risk stratification in heart failure: The (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE) study

Marco Guazzi, Patrizia Boracchi, Ross Arena, Jonathan Myers, Marco Vicenzi, Mary Ann Peberdy, Daniel Bensimhon, Paul Chase, Giuseppe Reina

Research output: Contribution to journalArticlepeer-review


Background: Cardiopulmonary exercise testing (CPET) provides powerful information on risk of death in heart failure (HF). We sought to define the relative and additive contribution of the 3 landmark (CPET) prognostic markers - peak oxygen consumption (VO2), minute ventilation/carbon dioxide production (VE/VCO2) slope, and exercise periodic breathing (EPB) - to the overall risk of cardiac death and to develop a prognostic score for optimizing risk stratification in HF patients. Methods and Results: A total of 695 stable HF patients (average LVEF: 25 ± 8%) underwent a symptom-limited CPET maximum test after familiarization and were prospectively tracked for cardiac mortality. At multivariable Cox analysis EPB emerged as the strongest prognosticator. Using a statistical bootstrap technique (5000 data resamplings), point estimates, and 95% confidence intervals were obtained. Thirty-two configurations were adopted to classify patients into a given cell, according to EPB presence or absence and values of the 2 other covariates. Configurations without EPB and with VE/VCO2 slope ≤30 were not significantly different from 0 (reference value). Statistical power of configurations increased with higher VE/VCO2 slope and lower peak VO2. This prompted us to formulate a score including EPB as a discriminating variable, the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE), which ranges between -1 and 1, with zero as reference configuration, that would help to optimize the prognostic accuracy of CPET-derived variables. The greatest PROBE score impact was provided by EPB, followed by VE/VCO 2 slope, whereas peak VO2 added minimal prognostic power. Conclusions: EPB with an elevated VE/VCO2 slope leads to the highest and most precise PROBE score, whereas no additional risk information emerges when EPB is present with a peak VO2 ≤10 mL O2· kg-1·min-1. PROBE score appears to provide a step forward for optimizing CPET use in HF prognostic definition.

Original languageEnglish
Pages (from-to)799-805
Number of pages7
JournalJournal of Cardiac Failure
Issue number10
Publication statusPublished - Oct 2010


  • Cardiopulmonary testing
  • heart failure
  • prognosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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