Incremental prognostic value of functional impairment assessed by six minute walking test for the prediction of mortality in heart failure

Natriuretic peptides (NP) are recognized as the most powerful predictors of adverse outcomes in heart failure (HF). We hypothesized that a measure of functional limitation, as assessed by six-minute walking test (6MWT), would improve the accuracy of a prognostic model incorporating a NP. We studied the prognostic value of severe functional impairment (SFI), defined as the inability to perform a 6MWT or a distance walked during a 6MWT <300 m, in 1696 patients with HF admitted to cardiac rehabilitation. The primary outcome was 1-year all-cause mortality. After adjusting for the baseline multivariable risk model -including age, sex, systolic blood pressure, moderate-to-severe anemia, renal dysfunction, sodium level, and NT-proBNP- or for the MAGGIC score, SFI had an odds ratio of 2.58 (95% CI 1.72-3.88; p <.001) and 3.12 (95% CI 2.16-4.52; p<.001), respectively. Adding SFI to the baseline risk model or the MAGGIC score yielded a significant improvement in discrimination and risk classification, with the majority of the patients with events being reclassified upwards. Our data suggest that a simple, 6MWT-derived measure of SFI is a strong predictor of death and provide incremental prognostic information over well-established risk markers in HF, including a NP, and over the MAGGIC score.