Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 1;83(14):1276-1291.
doi: 10.1016/j.jacc.2023.12.036. Online ahead of print.

Stratifying Disease Progression in Patients With Cardiac ATTR Amyloidosis

Adam Ioannou  1 , Francesco Cappelli  2 , Michele Emdin  3 , Christian Nitsche  4 , Simone Longhi  5 , Ahmad Masri  6 , Alberto Cipriani  7 , Mattia Zampieri  2 , Federica Colio  2 , Michael Poledniczek  4 , Aldostefano Porcari  8 , Yousuf Razvi  1 , Alberto Aimo  3 , Giuseppe Vergaro  3 , Laura De Michieli  9 , Muhammad U Rauf  1 , Rishi K Patel  1 , Eugenia Villanueva  1 , Yael Lustig  1 , Lucia Venneri  1 , Ana Martinez-Naharro  1 , Helen Lachmann  1 , Ashutosh Wechalekar  1 , Carol Whelan  1 , Aviva Petrie  10 , Philip N Hawkins  1 , Scott Solomon  11 , Julian D Gillmore  1 , Marianna Fontana  12
Affiliations

Stratifying Disease Progression in Patients With Cardiac ATTR Amyloidosis

Adam Ioannou et al. J Am Coll Cardiol. .

Abstract

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.

Keywords: NT-proBNP; cardiac ATTR amyloidosis; disease progression; outpatient diuretic intensification.

PubMed Disclaimer

Conflict of interest statement

Funding Support and Author Disclosures Dr Fontana is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/18/21/33447); and has received consulting income from Intellia, Novo Nordisk, Pfizer, Eidos, Prothena, Akcea, Alnylam, Caleum, Alexion, Janssen, Ionis, and AstraZeneca. Dr Gilmore has received consulting income from Ionis, Eidos, Intellia, Alnylam, and Pfizer. Dr Wechalekar has received consulting income from Alexia, AstraZeneca, Janssen, Attralus, and Prothena. Dr Cappelli has received consulting income from Alnylam, Pfizer, AstraZeneca, Bridgebio, and Novo Nordisk. Dr Cipriani has received consulting income from AstraZeneca. Dr Solomon has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and has served as a consultant for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
NT-proBNP Progression and Survival Landmark Kaplan-Meier curves demonstrating the association between N-terminal pro–B-type natriuretic peptide (NT-proBNP) progression at 1 year and subsequent survival. (A) Overall National Amyloidosis Centre (NAC) cohort, (B) wild-type transthyretin cardiac amyloidosis (wtATTR-CA) subgroup, (C) p.(V142I) hereditary transthyretin cardiac amyloidosis (hATTR-CA), (D) non-p.(V142I) hATTR-CA, and (E) external validation cohort.
Figure 2
Figure 2
Disease Progression in Clinical Trials and Disease-Modifying Therapy Landmark Kaplan-Meier curves demonstrating the association between (A) N-terminal pro–B-type natriuretic peptide (NT-proBNP) progression and (B) outpatient diuretic intensification (ODI) at 1 year, and subsequent survival in patients enrolled into clinical trials or prescribed disease-modifying therapy.
Figure 3
Figure 3
Degree of ODI and Survival Landmark Kaplan-Meier curves demonstrating the association between the degree of ODI at 1 year and subsequent survival. (A) Overall NAC cohort. (B) External validation cohort. Abbreviations as in Figures 1 and 2.
Figure 4
Figure 4
ODI and Survival Landmark Kaplan-Meier curves demonstrating the association between ODI at 1 year and subsequent survival. (A) Overall NAC cohort, (B) wtATTR-CA subgroup, (C) p.(V142I) hATTR-CA, (D) non-p.(V142I) hATTR-CA, and (E) external validation cohort. Abbreviations as in Figures 1 and 2.
Figure 5
Figure 5
Combination NT-proBNP Progression and ODI Landmark Kaplan-Meier curves demonstrating the association between the NT-proBNP progression and ODI at 1 year and subsequent survival. (A) Overall NAC cohort, (B) wtATTR-CA subgroup, (C) p.(V142I) hATTR-CA, (D) non-p.(V142I) hATTR-CA, and (E) external validation cohort. Abbreviations as in Figures 1 and 2.
Central Illustration
Central Illustration
N-Terminal Pro–B-Type Natriuretic Peptide Progression and Outpatient Diuretic Intensification Detect Disease Progression N-terminal pro-B-type natriuretic peptide (NT-proBNP) progression and outpatient diuretic intensification (ODI) are associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in the National Amyloidosis Centre (NAC) and external validation cohorts.
See this image and copyright information in PMC

References

    1. Ioannou A., Patel R.K., Razvi Y., et al. Multi-imaging characterization of cardiac phenotype in different types of amyloidosis. J Am Coll Cardiol Img. 2022;14:464–477.
    1. Ruberg F.L., Grogan M., Hanna M., et al. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73:2872. - PMC - PubMed
    1. Porcari A., Razvi Y., Masi A., et al. Prevalence, characteristics and outcomes of older patients with hereditary versus wild-type transthyretin amyloid cardiomyopathy. Eur J Heart Fail. 2023;25:515–524. - PubMed
    1. Patel R.K., Ioannou A., Razvi Y., et al. Sex differences among patients with transthyretin amyloid cardiomyopathy – from diagnosis to prognosis. Eur J Heart Fail. 2022;24:2355–2363. - PMC - PubMed
    1. Maurer M.S., Schwartz J.H., Gundapaneni B., et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007–1016. - PubMed