Abstract
AIMS: This study aimed to investigate the impact of baseline 6 min walk test distance (6MWTD) on time to major cardiovascular (CV) events in heart failure with reduced ejection fraction (HFrEF) and its impact in clinically relevant subgroups. METHODS AND RESULTS: In the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial, 6MWTD at baseline was available in 2102 HFrEF patients. Median follow-up was 3.4 years. All-cause death and heart failure hospitalization (HFH) exhibited a significant non-linear relationship with 6MWTD (P = 0.023 and 0.032, respectively), whereas a significant association between 6MWTD and CV death was shown in a linear model [hazard ratio (HR) per 10 m increase, 0.989; P = 0.011]. In linear splines with the best cut-off point at 200 m, the positive effect of a longer 6MWTD on all-cause death and HFH was only observed for 6MWTD > 200 m (HR per 10 m increase, 0.987; P = 0.0036 and 0.986; P = 0.0022, respectively). The associations between 6MWTD and CV outcomes were consistent across clinical subgroups; for age, a significant relationship between 6MWTD and HFH was observed in patients ≥60 years (HR per 10 m increase, 0.98; P < 0.001), but not in patients <60 years (HR per 10 m increase, 1.00; P = 0.98; P = 0.02 for the interaction). CONCLUSIONS: In HFrEF, 6MWTD is independently associated with all-cause death, CV death, and HFH. 6MWTD of 200 m is the best cut-off point for predicting these adverse events. The prognostic impact of 6MWTD for HFH was only observed in older patients.