Ioannou, AdamFumagalli, CarloRazvi, YousufPorcari, AldostefanoRauf, Muhammad UMartinez-Naharro, AnaVenneri, LuciaMoody, WilliamSteeds, Richard PPetrie, AvivaWhelan, CarolWechalekar, AshutoshLachmann, HelenHawkins, Philip NSolomon, Scott DGillmore, Julian DFontana, Marianna2024-07-082024-07-082024-05-13Ioannou A, Fumagalli C, Razvi Y, Porcari A, Rauf MU, Martinez-Naharro A, Venneri L, Moody W, Steeds RP, Petrie A, Whelan C, Wechalekar A, Lachmann H, Hawkins PN, Solomon SD, Gillmore JD, Fontana M. Prognostic Value of a 6-Minute Walk Test in Patients With Transthyretin Cardiac Amyloidosis. J Am Coll Cardiol. 2024 Jul 2;84(1):43-58. doi: 10.1016/j.jacc.2024.04.011. Epub 2024 May 13.1558-359710.1016/j.jacc.2024.04.01138739065http://hdl.handle.net/20.500.14200/5068Background: The 6-minute walk test (6MWT) represents a comprehensive functional assessment that is commonly used in patients with heart failure; however, data are lacking in patients with transthyretin cardiac amyloidosis (ATTR-CA). Objectives: This study aimed to assess the prognostic importance of the 6MWT in patients with ATTR-CA. Methods: A retrospective analysis of patients diagnosed with ATTR-CA at the National Amyloidosis Centre who underwent a baseline 6MWT between 2011 and 2023 identified 2,141 patients, of whom 1,118 had follow-up at 1 year. Results: The median baseline 6MWT distance was 347 m (Q1-Q3: 250-428 m) and analysis by quartiles demonstrated an increased death rate with each distance reduction (deaths per 100 person-years: 6.3 vs 9.2 vs 13.6 vs 19.0; log-rank P < 0.001). 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), with a similar increased risk across National Amyloidosis Centre disease stages (P for interaction = 0.761) and genotypes (P for interaction = 0.172). An absolute (reduction of >35 m) and relative worsening (reduction of >5%) of 6MWT at 1 year was 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), which was similar across the aforementioned subgroups. When combined with established measures 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). Conclusions: The baseline 6MWT distance can refine risk stratification beyond traditional prognosticators. A worsening 6MWT distance can stratify disease progression and, when combined with established markers, identifies patients at the highest risk of mortality.enCopyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.CardiologyArticleJournal of the American College of Cardiology