Sex profile and risk assessment with cardiopulmonary exercise testing in heart failure: propensity score matching for sex selection bias

Background: In heart failure (HF), women show better survival despite a comparatively low peak oxygen consumption (V˙o2): 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˙o2 and ventilatory response (V˙e/V˙co2 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˙o2 and V˙e/V˙co2 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 < 0.0001) to 3.3 (P = 0.667). After clinical profile harmonizing, female sex was predictive of HF at univariate analysis. Conclusions: The low peak V˙o2 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.