A baseline six-minute walk distance under 350 meters was associated with higher all-cause mortality among patients with transthyretin amyloid cardiomyopathy, according to a retrospective analysis of a prospective, single-center registry. The association remained after adjustment for United Kingdom National Amyloidosis Centre stage.
In the analysis, the six-minute walk test (6MWT) and six-minute walk distance (6MWD) were used to assess functional capacity in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). A distance less than 350 meters at approximately 1-year follow-up again identified patients at higher risk of death. Across both time points, patients walking less than 350 meters had materially higher risk of death: at baseline the crude hazard ratio was 3.29 and 2.30 after adjustment for stage; at approximately one year the crude hazard ratio was 5.52 and 2.91 after adjustment. By disease stage, the less-than-350-meter cutoff separated survival in stages 1 and 2 but not in stage 3.
The study included 252 patients who completed a 6MWT at baseline; 190 underwent repeat testing at approximately 1 year. Over a median follow-up of nearly 22 months, 61 patients (24%) died.
Changes in 6MWD were not consistently prognostic after adjustment for disease stage. When models additionally accounted for changes in amyloid-specific treatment status, thresholds of a 35-meter decline or a 5% decline were associated with higher mortality—supporting the use of Δ6MWD primarily in patients on stable therapy.
The registry was conducted at the Medical University of Vienna from 2012 to 2024. Patients met diagnostic criteria for ATTR‑CM according to European Society of Cardiology guidance or—prior to adoption of the noninvasive diagnostic algorithm—by biopsy. The 6MWT followed American Thoracic Society standards. The primary endpoint was all‑cause mortality, with follow‑up up to 4 years using national registry data, clinic visits, and telephone interviews. The analysis was led by Michael Poledniczek, MD, of the Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, and colleagues.
Participants had a median age near 80 years and were predominantly male. The mean baseline 6MWD was about 360 meters; roughly 39% of patients walked less than 350 meters at their first test. Tafamidis use increased from 5% at baseline to 85% at 1 year. In linear models, baseline age, troponin T, and eGFR were associated with subsequent change in 6MWD; in multivariable analysis, no baseline characteristic remained significant. At follow-up, change in troponin T—but neither change in NT-proBNP nor change in eGFR—tracked with change in 6MWD. Patients with the largest declines in walking distance had the highest mortality rates in crude analyses, but Δ6MWD thresholds were not prognostic after stage adjustment unless accounting for treatment changes.
Limitations included the single-center design with potential selection bias, loss to follow-up (with reasons not always documented), and the possibility that non-cardiac factors (e.g., musculoskeletal and neurologic conditions) influenced 6MWT performance in this elderly cohort.
The researchers concluded that the six-minute walk test provides practical prognostic information in ATTR-CM. A baseline distance under 350 meters identifies patients at higher risk of death—independent of stage and in a treated, real-world cohort—whereas changes in walking distance are less reliable for prognosis when treatment is being initiated or adjusted.
Disclosures can be found in the study.
Source: Frontiers in Medicine
