Stratifying Disease Progression in Patients With Cardiac ATTR Amyloidosis

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

doi:10.1016/j.jacc.2023.12.036

Stratifying Disease Progression in Patients With Cardiac ATTR Amyloidosis

J Am Coll Cardiol. 2024 Mar 1;83(14):1276-1291. doi: 10.1016/j.jacc.2023.12.036. Online ahead of print.

Authors

Adam Ioannou¹, Francesco Cappelli², Michele Emdin³, Christian Nitsche⁴, Simone Longhi⁵, Ahmad Masri⁶, Alberto Cipriani⁷, Mattia Zampieri², Federica Colio², Michael Poledniczek⁴, Aldostefano Porcari⁸, Yousuf Razvi¹, Alberto Aimo³, Giuseppe Vergaro³, Laura De Michieli⁹, Muhammad U Rauf¹, Rishi K Patel¹, Eugenia Villanueva¹, Yael Lustig¹, Lucia Venneri¹, Ana Martinez-Naharro¹, Helen Lachmann¹, Ashutosh Wechalekar¹, Carol Whelan¹, Aviva Petrie¹⁰, Philip N Hawkins¹, Scott Solomon¹¹, Julian D Gillmore¹, Marianna Fontana¹²

Affiliations

¹ National Amyloidosis Centre, University College London, London, United Kingdom.
² Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy.
³ Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, Pisa, Italy; Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
⁴ Division of Cardiology, Department of Internal Medicine, Medical University of Vienna, Vienna, Austria.
⁵ Cardiology Unit, Cardiac Thoracic and Vascular Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁶ OHSU Center for Hypertrophic Cardiomyopathy and Amyloidosis, Portland, Oregon, USA.
⁷ Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy; Cardiology Unit, University Hospital Padua, Padua, Italy.
⁸ National Amyloidosis Centre, University College London, London, United Kingdom; Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Trieste, Italy.
⁹ Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy.
¹⁰ University College London, Biostatistics Unit, UCL Eastman Dental Institute, London, United Kingdom.
¹¹ Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹² National Amyloidosis Centre, University College London, London, United Kingdom. Electronic address: m.fontana@ucl.ac.uk.

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.