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

Date Published: 2025-09-08

Abstract:
The 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. Patients from a prospective ATTR-CM registry were analyzed and included if a 6MWT was completed at baseline. A 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 ?6MWD thresholds of <?35?meters/?5% were only associated with mortality after adjusting for change in treatment status. The 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 ?6MWD should only be used in patients on stable background therapy for the estimation of prognosis.

Introduction:
The 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.

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