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

BackgroundCardiopulmonary 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 ResultsA 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/VCO2 slope, whereas peak VO2 added minimal prognostic power.ConclusionsEPB 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.