AUTHOR=Poledniczek Michael , Grubmüller Anna , Kronberger Christina , Willixhofer Robin , Ermolaev Nikita , Rettl René , Binder Christina , Camuz Ligios Luciana , Eslami Mahshid , Gregshammer Bernhard , List Luca , Nitsche Christian , Kammerlander Andreas Anselm , Hengstenberg Christian , Kastner Johannes , Bergler-Klein Jutta , Badr Eslam Roza , Duca Franz 

TITLE=The 6-min walk test in transthyretin cardiac amyloidosis: prognostic utility put to the real-world test

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1639586

DOI=10.3389/fmed.2025.1639586

ISSN=2296-858X

ABSTRACT=BackgroundThe 6-min walk test distance (6MWD) was identified as a predictor of mortality in transthyretin amyloid cardiomyopathy (ATTR-CM). However, its real-world applicability remains uncertain, as only therapy-naïve patients were included in the primary analysis.MethodsPatients from a prospective ATTR-CM registry were analyzed and included if a 6MWT was completed at baseline.ResultsA total of 252 patients [79.8 years, interquartile range (IQR): 75.4–83.7] were included. After a median of 21.7 (IQR: 12.7–34.1) months, 61 (24.2%) patients died. A 6MWD of <350 m was associated with worse survival [hazard ratio (HR): 3.29, 95% confidence interval (CI): 1.94–5.55, p < 0.001], even after adjusting for National Amyloidosis Centre stage (HR: 2.30, 95% CI: 1.29–4.10, p = 0.005). The Δ6MWD thresholds of <−35 meters/−5% were only associated with mortality after adjusting for change in treatment status.ConclusionThe 6MWD is independently associated with mortality in ATTR-CM irrespective of treatment status. A baseline 6MWD of <350 m is associated with a ~3-fold risk for all-cause mortality. However, our results suggest that the Δ6MWD should only be used in patients on stable background therapy for the estimation of prognosis.