CPX Variables and Mortality in Systolic Heart Failure

Study Questions:

What is the relative prognostic strength of multiple cardiopulmonary exercise (CPX) testing variables of mortality in systolic heart failure?


The study cohort was comprised of 2,100 systolic heart failure patients (including 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial. The investigators evaluated 10 CPX test variables measured at baseline including, peak oxygen uptake [VO2], exercise duration, percent predicted peak VO2 [%ppVO2], ventilatory efficiency, VE-VCO2 slope, respiratory exchange ratio (RER) (VCO2/VO2), heart rate reserve, VO2 at peak anaerobic threshold, peak oxygen pulse, and VO2 efficiency slope. They used the Cox proportions hazards model to plot 1- and 3-year survival probabilities by gender as a function of peak VO2. Kaplan-Meier curves were plotted and stratified based on peak VO2 category (<12, 12 to 18, >18 ml·kg–1·min–1) and peak RER (<1.05, ≥1.05).


During the median follow-up period of 32 months, there were 357 deaths. The investigators found that CPX testing variables, each adjusted for age and gender, except RER, were related to all-cause mortality (all p < 0.0001). Both exercise duration and %ppVO2 were equally able to predict (Wald chi-square: ∼141) and discriminate (c-index: 0.69) mortality. In men, peak VO2 (ml·kg–1·min–1) was the strongest predictor of mortality (Wald chi-square: 129), whereas in women, it was exercise duration (Wald chi-square: 41). Multivariable analyses showed that %ppVO2, exercise duration, and peak VO2 (ml·kg–1·min–1) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak VO2 of 10.9 ml·kg–1·min–1 versus 5.3 ml·kg–1·min–1 in women. For every 1 ml·kg–1·min–1 lower peak VO2, there was ~16% greater risk. Similarly, for every 5 percentage points lower %ppVO2, there was a corresponding ~19% higher risk.


The authors concluded that peak VO2, exercise duration, and %ppVO2 carried the strongest ability to predict and discriminate the likelihood of death in patients with systolic heart failure. The prognosis associated with a given peak VO2 differed by gender.


This post-hoc analysis validates the utilization of CPX in the assessment of patients with systolic heart failure. An important take-away is the gender differences in the peak VO2 cutoffs for predicting mortality. This is probably due to the fact that women may have more of the less aerobically active body fat.

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