Pick Your Threshold: A Comparison Among Different Methods of Anaerobic Threshold Evaluation in Heart Failure Prognostic Assessment

Abstract

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). AT of oxygen uptake (V.O₂; V.O₂AT) has been reported as an absolute value (V.O₂ATabs), as a percentage of predicted peak V.O₂ (V.O₂AT%peak_pred), or as a percentage of observed peak V.O₂ (V.O₂AT%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: In this observational cohort study, we screened data of 7,746 patients with HF with a history of reduced ejection fraction (< 40%) recruited between 1998 and 2020 and enrolled in the Metabolic Exercise Combined With Cardiac and Kidney Indexes register. All patients underwent a maximum cardiopulmonary exercise test, executed using a ramp protocol on an electronically braked cycle ergometer.

Results: This study considered 6,157 patients with HF with identified AT. Follow-up was median, 4.2 years (25th-75th percentiles, 1.9-5.0 years). Both V.O₂ATabs (mean ± SD, 823 ± 305 mL/min) and V.O₂AT%peak_pred (mean ± SD, 39.6 ± 13.9%), but not V.O₂AT%peak_obs (mean ± SD, 69.2 ± 17.7%), well stratified the population regarding prognosis (composite end point: cardiovascular death, urgent heart transplant, or left ventricular assist device). Comparing area under the receiver operating characteristic curve (AUC) values, V.O₂ATabs (0.680) and V.O₂AT%peak_pred (0.688) performed similarly, whereas V.O₂AT%peak_obs (0.538) was significantly weaker (P < .001). Moreover, the V.O₂AT%peak_pred AUC value was the only one performing as well as the AUC based on peak V.O₂ (0.710), with an even a higher AUC (0.637 vs 0.618, respectively) in the group with severe HF (peak V.O₂ < 12 mL/min/kg). Finally, the combination of V.O₂AT%peak_pred with peak V.O₂ and V. per CO₂ production shows the highest prognostic power.

Interpretation: In HF, V.O₂AT%peak_pred is the best way to report V.O₂ at AT in relationship to prognosis, with a prognostic power comparable to that of peak V.O₂ and, remarkably, in patients with severe HF.

Keywords: anaerobic threshold; cardiopulmonary exercise test; heart failure; prognosis.