Pick your threshold. a comparison among different methods of anaerobic threshold evaluation in heart failure prognostic assessment

Background: In clinical practice, anaerobic threshold (AT), is used to guide training and rehabilitation programs, to define risk of major thoracic or abdominal surgery, and to assess prognosis in heart failure (HF). VO2AT has been reported as absolute value (VO2ATabs), as percentage of predicted peak VO2 (VO2AT%peak_pred) or as percentage of observed peak VO2 value (VO2AT%peak_obs). A direct comparison of the prognostic power among these different ways to report AT is missing. Research question: What is the prognostic power of these different ways to report AT? Study design and methods: Observational cohort study. We screened data of 7746 HF patients with history of reduced ejection fraction (<40%), recruited between 1998 and 2020 and enrolled in the MECKI register. All patients underwent a maximal cardiopulmonary exercise test (CPET), executed using a ramp protocol on an electronically braked cycle ergometer. Results: In this study we considered 6157HF patients with identified AT. Follow up was 4.2 years (1.9-5.0). Both VO2ATabs (823(305 mL/min)) and VO2AT%peak_pred (39.6(13.9%)) but not VO2AT%peak_obs (69.2(17.7%)) well stratified the population as regards prognosis (composite endpoint: cardiovascular death, urgent heart transplant or left ventricular assist device). Comparing AUC values, VO2ATabs (0.680) and VO2AT%peak_pred (0.688) performed similarly, while VO2AT%peak_obs (0.538) was significantly weaker (P<0.001). Moreover, VO2AT%peak_pred AUC value was the only performing as well as AUC based on peakVO2 (0.710), with even a higher AUC (0.637 vs. 0.618 respectively) in the group with severe HF (peakVO2<12mL/min/kg). Finally, the combination of VO2AT%peak_pred with Peak VO2 and VE/VCO2 shows the highest prognostic power. Interpretation: In HF, VO2AT%peak_pred is the best way to report VO2 at AT in relation to prognosis, with a prognostic power comparable to that of peak VO2 and, remarkably, in severe HF patients.