Sex Profile and Risk Assessment With Cardiopulmonary Exercise Testing in Heart Failure: Propensity Score Matching for Sex Selection Bias

Abstract Background In heart failure (HF), women show better survival despite a comparatively low peak oxygen consumption ( V ˙ o 2 ): this raises doubt about the accuracy of risk assessment by cardiopulmonary exercise testing (CPET) in women. Accordingly, we aimed to check (1) whether the predictive role of well-known CPET risk indexes, ie, peak V ˙ o 2 and ventilatory response ( V ˙ e/ V ˙ co 2 slope), is sex independent and (2) if sex-related characteristics that impact outcome in HF should be considered as associations that may confound the effect of sex on survival. Methods The study population consisted of 2985 patients with HF, 498 (17%) of whom were women, from the multicentre Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI): the end point was cardiovascular death within a 3-year period. Results During the follow-up, 305 (12%) men and 39 (8%) women ( P  = 0.005) died, and female sex was linked to better survival on univariate analysis ( P  = 0.008) and independent of peak V ˙ o 2 and V ˙ e/ V ˙ co 2 slope on multivariate analysis. According to propensity score matching for female sex to exclude a sex selection bias and sample discrepancy, 498 men were selected: the standardized percentage bias ranged from 20.8 ( P P  = 0.667). After clinical profile harmonizing, female sex was predictive of HF at univariate analysis. Conclusions The low peak V ˙ o 2 and female association with better outcome in HF might be counterfeit: the female prognostic advantage is lost when sex-specific differences are correctly taken into account with propensity score matching, suggesting that for an effective and efficient HF model, adjustment must be made for sex-related characteristics.