Deceptive meaning of oxygen uptake measured at the anaerobic threshold in patients with systolic heart failure and atrial fibrillation

Background: Oxygen uptake at the anaerobic threshold (VO 2 AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO 2 AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. Design: We tested the prognostic role of VO 2 AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Methods: Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). Results: The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p=0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO 2 ) showed a prognostic capacity (C-index) similar to that obtained including VO 2 AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO 2 AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. Conclusions: VO 2 AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO 2 AT cut-off values between SR and AF HF patients should be adopted.