The six-minute walk test (6MWT) is a reliable and accurate prognosticator of outcomes in patients with transthyretin cardiac amyloidosis (ATTR-CA), according to a retrospective analysis by Adam Ioannou, MBBS, BSc, et al., presented at ESC Heart Failure 2024 and simultaneously published in JACC.

The analysis, using data from the National Amyloidosis Centre in the UK, identified 2,141 patients diagnosed with ATTR-CA between 2011 and 2023 (average age, 76.5; 88% men; 82.2% White, 16.5% Afro-Caribbean). Of these patients, 1,118 had a repeat 6MWT at one year. The median absolute
reduction in 6MWT distance was 17 m and the mean relative percent reduction was 4.5%.

Analysis by quartiles found that each distance reduction from the median baseline of 347 m was associated with an increased death rate (deaths per 100 person-years: 6.3 vs. 9.2 vs. 13.6 vs. 19.0; log-rank p<0.001). Participants with a shorter 6MWT tended to be older, were more often female and Afro-Caribbean, and more commonly had the p.(V142I) genotype.

A 6MWT distance of <350 m was associated with a 2.2-fold higher risk of mortality (HR, 2.15; 95% CI, 1.85-2.50; p<0.001). These risks were similar across National Amyloidosis Centre disease stages (p for interaction = 0.761) and genotypes (p for interaction = 0.172).

Both an absolute reduction of >35 m and relative worsening (reduction of >5%) of 6MWT at one year were also associated with an increased risk of mortality (HR, 1.80; 95% CI, 1.51-2.15; p<0.001 and HR, 1.89; 95% CI, 1.59-2.24; p<0.001, respectively). Researchers found that when combined with established measure of disease progression (N-terminal pro–B-type natriuretic peptide progression and outpatient diuretic intensification), each incremental increase in progression markers was associated with an increased death rate (deaths per 100 person-years: 7.6 vs. 13.9 vs. 22.4 vs. 32.9; log-rank p<0.001).

Baseline 6MWT can refine risk stratification, write the authors.

In an accompanying editorial comment, Ahmad Masri, MD, FACC, wrote that, "The current investigation represents the largest and most extensive evaluation into the useful prognostic role of 6MWT in patients with ATTR-CA."

However, Masri added, "The prognostic value of 6MWT does not necessarily translate to its ability to reliably detect treatment effect." He wrote that in these trials, training effect may be inadvertently introduced, competing death events muddy the analysis, and there is still a need to establish the change in a blinded, randomized clinical trial. Nevertheless, he called the study, "a major step in the search for surrogate endpoints in patients with ATTR-CA, facilitating easier conduct of clinical trials and earlier access to therapies in an elderly population that is growing rapidly."

This was just one of the studies simultaneously published in JACC and presented at ESC Heart Failure 2024. Read here for more.