Prognostic value of six-minute walk distance in patients with heart failure: A meta-analysis

Cardiopulmonary exercise testing for evaluation of peak oxygen consumption is a gold standard method to evaluate exercise capacity. However, this test is expensive and time-consuming, and patients with substantial heart failure cannot conduct maximal symptom-limited exercises. The six-minute walk distance (6MWD), a simple submaximal exercise test, has been recommended as an alternative to cardiopulmonary exercise testing. This test has been increasingly incorporated and accepted into contemporary heart failure practice. Several studies have investigated the prognostic value of 6MWD in predicting mortality or hospital readmission in heart failure patients. However, the prognostic value of 6MWD remains controversial. This meta-analysis aimed to evaluate the prognostic significance of baseline 6MWD for prediction of death or readmission in patients with heart failure. Two authors independently searched Pubmed, Embase and Web of Science to identify relevant studies up to November 2017 by using the following keywords: ‘6-min walk’ OR ‘six-min walk’ OR ‘walk test’ AND ‘heart failure’ OR ‘cardiac failure’ AND ‘death’ OR ‘mortality’ OR ‘hospital readmission’ or ‘rehospitalization’ AND ‘follow-up’. The inclusion criteria were as follows: (a) observational studies enrolling patients with heart failure; (b) baseline 6MWD as exposure; (c) reported multivariable-adjusted risk estimates of all-cause mortality, readmission or combined endpoint. Studies not providing the quantitative risk estimate for the endpoint or enrolling acute decompensated patients with heart failure were excluded. The Newcastle– Ottawa scale (NOS) was used to assess the methodological quality of the included studies. Data analyses were performed using RevMan (version 5.2, Oxford, UK). For categorical analysis, we pooled risk estimates for the shortest versus longest 6MWD category. For analysing prognostic values as continuous values, we recalculated the risk ratio (RR) to each 50m 6MWD reduction by the following formula: RR501⁄4 exp (ln (RR1) 50). Among the 486 relevant records identified from the electronic medical database search, 13 studies comprising 6076 patients with heart failure were finally included in the meta-analysis (Table 1). For methodological quality assessment, the NOS scores ranged from 5 to 8. The meta-analysis showed that the shortest 6MWD was associated with an increased risk of allcause mortality (RR 1.96; 95% confidence interval (CI) 1.10–3.50; I1⁄4 77.0%; p1⁄4 0.005; Supplementary Material Figure S1-A online) in a random effect model. In addition, each 50m decrease in 6MWD significantly increased by 18%, indicating a high risk of all-cause mortality (RR 1.18; 95% CI 1.07–1.29; I1⁄4 51.0%; p1⁄4 0.11; Supplementary Figure S1-B) in a random effect model. Each 50m decrease in 6MWD was associated with 43% risk of readmission (RR 1.43; 95% CI 1.10–1.86; I1⁄4 88.0%; p< 0.001; Supplementary Figure S2) in a random effect model meta-analysis. For the combined endpoint, the shortest 6MWD was associated with high risk of the combined endpoint of death or readmission (RR 1.86; 95% CI 1.40–2.46; I1⁄4 0.0%; p1⁄4 0.76; Supplementary Figure S3-A) in a fixed-effect model meta-analysis. A random effect model meta-analysis suggested that each 50m decrease in 6MWD was associated with a 20% risk of the combined endpoint of death or readmission (RR 1.20; 95% CI 1.09–1.32; I1⁄4 52.0%; p1⁄4 0.15; Supplementary Figure S3-B). We opted not to perform the publication bias test as the number of studies analysed was less than the recommended arbitrary minimum number of studies. This meta-analysis demonstrates that short 6MWD is independently associated with high risk of all-cause mortality, readmission and the combined endpoint of