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ORIGINAL RESEARCH article

Front. Med.

Sec. Precision Medicine

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1639586

The six-minute walk test in transthyretin cardiac amyloidosisprognostic utility put to the real-world test

Provisionally accepted
Michael PoledniczekMichael Poledniczek*Anna GrubmüllerAnna GrubmüllerChristina KronbergerChristina KronbergerRobin WillixhoferRobin WillixhoferNikita ErmolaevNikita ErmolaevRené RettlRené RettlChristina BinderChristina BinderLuciana Camuz LigiosLuciana Camuz LigiosBernhard GregshammerBernhard GregshammerLuca ListLuca ListChristian NitscheChristian NitscheAndreas Anselm KammerlanderAndreas Anselm KammerlanderChristian HengstenbergChristian HengstenbergJohannes KastnerJohannes KastnerJutta Bergler-KleinJutta Bergler-KleinRoza Badr EslamRoza Badr EslamFranz DucaFranz Duca*
  • Medical University of Vienna, Vienna, Austria

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The six-minute 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.Patients from a prospective ATTR-CM registry were analysed and included if a 6MWT was completed at baseline.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 deceased. A 6MWD <350 meters was associated with worse survival [hazard ratio (HR): 3.29, 95%-confidence interval (CI): 1.94-5.55, p<0.001], even after adjustment 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 adjustment for change in treatment status.The 6MWD is independently associated with mortality in ATTR-CM irrespective of treatment status. A baseline 6MWD of <350 meters 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 estimation of prognosis.

Keywords: Six-minute walk test, Transthyretin amyloid cardiomyopathy, exercise testing, physical performance, Outcome

Received: 02 Jun 2025; Accepted: 29 Jul 2025.

Copyright: © 2025 Poledniczek, Grubmüller, Kronberger, Willixhofer, Ermolaev, Rettl, Binder, Ligios, Gregshammer, List, Nitsche, Kammerlander, Hengstenberg, Kastner, Bergler-Klein, Eslam and Duca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Michael Poledniczek, Medical University of Vienna, Vienna, Austria
Franz Duca, Medical University of Vienna, Vienna, Austria

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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