After modifying for variations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and New York Heart Association (NYHA) functional class, the study’s primary objective was to ascertain the prognostic significance of changes in 6MWT to predict mortality in stable patients with HFrEF. The secondary objective was to detect predictors of changes in 6MWT.
The authors wrote, “Functional capacity provides important clinical information in patients with heart failure (HF) and reduced ejection fraction (HFrEF). The 6-minute 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.”
The researchers examined data from chronic heart failure (HF) outpatients in the National Norwegian Heart Failure Registry between 2013 and 2020. Participants performed a 6MWT at their initial and follow-up visits after stabilizing on maximum tolerated doses of guideline-directed medical therapy (GDMT). Researchers employed Cox proportional hazard models to evaluate the correlation between changes in 6MWT distance and all-cause mortality.
Among 3,636 patients diagnosed with chronic HFrEF, the average age was 67.3 ± 11.6 years, 23.0% were women, the average BMI was 27.2 ± 5.6, and the average left ventricular ejection fraction was 30 ± 7%. Their average baseline 6MWT was 438 ± 125 meters, the median NT-proBNP level was 1574 ng/L, and 26.6% were NYHA class III or IV.
The results revealed that after optimizing GDMT (median 147 days), the 6MWT distance increased by an average of 40 ± 74 meters and, the NT-proBNP levels diminished by median 425 ng/L, and 38% of patients improved in the NYHA class. Younger patients with greater 6MWT improvements also exhibited better NYHA class and NT-proBNP reductions.
Moreover, over an average follow-up of 845 ± 595 days, 419 (11.5%) patients died. A 50-meter increase in 6MWT was associated with a 17% lower mortality risk (hazard ratio, 0.84; 95% CI, 0.77-0.90; P <.001) in the fully adjusted model, including changes in NYHA class, NT-proBNP concentrations, and other established risk factors, and these correlations were more robust in patients with lower baseline 6MWT and older age.
The authors wrote, “This study demonstrates that changes in 6MWT in HFrEF patients strongly predict mortality, independent of changes in NT-proBNP, alterations in NYHA class, and other risk factors. These findings document the important contribution of alterations in 6MWT as an independent marker of mortality in chronic HFrEF patients.”
The authors concluded that improvement in 6MWT for HFrEF patients is linked with augmented survival, independent of changes in NT-proBNP and NYHA class, supporting its use as a surrogate outcome in HF trials.
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