TY - JOUR
T1 - Stratifying Disease Progression in Patients With Cardiac ATTR Amyloidosis
AU - Ioannou, Adam
AU - Cappelli, Francesco
AU - Emdin, Michele
AU - Nitsche, Christian
AU - Longhi, Simone
AU - Masri, Ahmad
AU - Cipriani, Alberto
AU - Zampieri, Mattia
AU - Colio, Federica
AU - Poledniczek, Michael
AU - Porcari, Aldostefano
AU - Razvi, Yousuf
AU - Aimo, Alberto
AU - Vergaro, Giuseppe
AU - De Michieli, Laura
AU - Rauf, Muhammad U.
AU - Patel, Rishi K.
AU - Villanueva, Eugenia
AU - Lustig, Yael
AU - Venneri, Lucia
AU - Martinez-Naharro, Ana
AU - Lachmann, Helen
AU - Wechalekar, Ashutosh
AU - Whelan, Carol
AU - Petrie, Aviva
AU - Hawkins, Philip N.
AU - Solomon, Scott
AU - Gillmore, Julian D.
AU - Fontana, Marianna
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/4/9
Y1 - 2024/4/9
N2 - Background: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy. The clinical course varies among individuals and there are no established measures to assess disease progression. Objectives: The goal of this study was to assess the prognostic importance of an increase in N-terminal pro–B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA. Methods: We evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n = 1,598) and validated in the external cohort from the remaining centers (n = 677). Results: Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase >700 ng/L and >30%), which was associated with mortality (NAC cohort: HR: 1.82; 95% CI: 1.57-2.10; P < 0.001; validation cohort: HR: 1.75; 95% CI: 1.32-2.33; P < 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95% CI: 1.62-2.18; P < 0.001; validation cohort: HR: 2.05; 95% CI: 1.53-2.74; P < 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95% CI: 1.65-2.27; P < 0.001; validation cohort: HR: 1.94; 95% CI: 1.36-2.77; P < 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95% CI: 2.42-3.67; P < 0.001; validation cohort: HR: 3.23; 95% CI: 2.17-4.79; P < 0.001). Conclusions: NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA.
AB - Background: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy. The clinical course varies among individuals and there are no established measures to assess disease progression. Objectives: The goal of this study was to assess the prognostic importance of an increase in N-terminal pro–B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA. Methods: We evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n = 1,598) and validated in the external cohort from the remaining centers (n = 677). Results: Between baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase >700 ng/L and >30%), which was associated with mortality (NAC cohort: HR: 1.82; 95% CI: 1.57-2.10; P < 0.001; validation cohort: HR: 1.75; 95% CI: 1.32-2.33; P < 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95% CI: 1.62-2.18; P < 0.001; validation cohort: HR: 2.05; 95% CI: 1.53-2.74; P < 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95% CI: 1.65-2.27; P < 0.001; validation cohort: HR: 1.94; 95% CI: 1.36-2.77; P < 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95% CI: 2.42-3.67; P < 0.001; validation cohort: HR: 3.23; 95% CI: 2.17-4.79; P < 0.001). Conclusions: NT-proBNP progression and ODI are frequent and consistently associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA.
KW - NT-proBNP
KW - cardiac ATTR amyloidosis
KW - disease progression
KW - outpatient diuretic intensification
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U2 - 10.1016/j.jacc.2023.12.036
DO - 10.1016/j.jacc.2023.12.036
M3 - Article
AN - SCOPUS:85188436206
SN - 0735-1097
VL - 83
SP - 1276
EP - 1291
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 14
ER -