Changes in 6-min walk test is an independent predictor of death in chronic heart failure with reduced ejection fraction

Peder L Myhre; Øyunn Kleiven; Kristian Berge; Morten Grundtvig; Lars Gullestad; Stein Ørn

doi:10.1002/ejhf.3391

Changes in 6-min walk test is an independent predictor of death in chronic heart failure with reduced ejection fraction

Eur J Heart Fail. 2024 Jul 26. doi: 10.1002/ejhf.3391. Online ahead of print.

Authors

Peder L Myhre^{1

2}, Øyunn Kleiven³, Kristian Berge^{1

2}, Morten Grundtvig⁴, Lars Gullestad^{5

6}, Stein Ørn^{3

7}

Affiliations

¹ Division of Medicine, Department of Cardiology, Akershus University Hospital, Lørenskog, Norway.
² K.G. Jebsen Center for Cardiac Biomarkers, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
⁴ Medical Department, Innlandet Hospital Trust Division Lillehammer, Lillehammer, Norway.
⁵ Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁶ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁷ Department of Electrical Engineering and Computer Science, University of Stavanger, Stavanger, Norway.

PMID: 39058228
DOI: 10.1002/ejhf.3391

Abstract

Aims: Functional capacity provides important clinical information in patients with heart failure (HF) and reduced ejection fraction (HFrEF). The 6-min walk test (6MWT) is a simple and inexpensive tool for assessing functional capacity and risk. Although change in 6MWT is frequently used as a surrogate outcome in HF trials, the association with mortality is unclear. We aimed to assess the prognostic importance of changes in 6MWT.

Methods and results: Patients with chronic HFrEF referred to HF outpatient clinics in Norway completed a 6MWT at the first visit (baseline) and at a stable follow-up visit after treatment optimization (follow-up). Absolute and relative changes in 6MWT were analysed in association with mortality risk using Cox regression models and flexible cubic splines. The study included 3636 HFrEF patients aged 67.3 ± 11.6 years, 23% women, with left ventricular ejection fraction 30 ± 7%. At baseline, mean 6MWT was 438 ± 125 m, median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1574 (732-3093) ng/L, and 27% had New York Heart Association (NYHA) class III/IV. After optimization of guideline-directed medical therapy (median 147 [86-240] days), 6MWT increased by mean 40 ± 74 m, NT-proBNP decreased by median 425 (14-1322) ng/L, and NYHA class improved in 38% of patients. Patients with greater improvements in 6MWT were younger, with greater improvements in NYHA class (r = 0.27, p < 0.001) and larger reductions in NT-proBNP concentrations (r = 0.19, p < 0.001). After mean 845 ± 595 days, 419 (11.5%) patients were dead. Both absolute and relative changes in 6MWT were non-linearly associated with survival, attenuating as 6MWT increased. A 50 m increase in 6MWT was associated with a 17% lower mortality risk (hazard ratio 0.84, 95% confidence interval 0.77-0.90, p < 0.001) in the fully adjusted model, including changes in NYHA class, NT-proBNP concentrations, and other established risk factors. The associations were more pronounced in patients with lower baseline 6MWT and higher age.

Conclusion: Improvement in 6MWT in patients with HFrEF is associated with increased survival, independent of changes in NT-proBNP and NYHA class. These findings support 6MWT change as a surrogate outcome in HF trials.

Keywords: 6‐min walk test; Guideline‐directed medical therapy; Heart failure; Heart failure with reduced ejection fraction; Prognosis.