Page 245 - Haematologica May 2020

Plasma Cell Disorders
Cardiac biomarkers are prognostic in systemic light chain amyloidosis with no cardiac involvement by standard criteria
Ferrata Storti Foundation
Haematologica 2020 Volume 105(5):1405-1413
Faye A. Sharpley, Marianna Fontana, Ana Martinez-Naharro, Richa Manwani, Shameem Mahmood, Sajitha Sachchithanantham, Helen J. Lachmann, Julian D. Gillmore, Carol J. Whelan, Philip N. Hawkins
and Ashutosh D. Wechalekar
National Amyloidosis Centre, University College London, London, UK
ABSTRACT
Patients with systemic immunoglobulin light chain amyloidosis (AL) with no evidence of cardiac involvement by consensus criteria have excellent survival, but 20% will die within 5 years of diagnosis and prognostic factors remain poorly characterised. We report the outcomes of 378 prospectively followed Mayo stage I patients (N-terminal pro b-type natriuretic peptide <332 ng/L, high sensitivity cardiac troponin <55 ng/L). The median presenting N-terminal pro b-type natriuretic peptide was 161 ng/L, high sensitivity cardiac troponin 10 ng/L, creatinine 76 mmol/L and mean left ventricular septal wall thickness, 10 mm. Median follow up was 42 (1-117 months), with 71 deaths; median overall survival was not reached (78% survival at 5 years). Although no patients had cardiac involvement by echocardiogram, a proportion (n=25/90, 28%) had cardiac involvement by cardiac magnetic resonance imaging. Age, autonomic nervous system involvement, N-terminal pro b-type natriuretic peptide >152 ng/L, high sen- sitivity cardiac troponin >10 ng/L and cardiac involvement by magnetic res- onance imaging were predictive for survival; on multivariate analysis only N-terminal pro b-type natriuretic peptide >152 ng/L (P<0.008, hazard ratio [HR] 3.180, confidence interval [CI]: 1.349-7.495) and cardiac involvement on magnetic resonance imaging (P=0.026, HR=5.360, CI: 1.219-23.574) were prognostic. At 5 years, 70% of patients with N-terminal pro b-type natriuretic peptide >152 ng/L were alive. In conclusion, N-terminal pro b- type natriuretic peptide is prognostic for survival in patients with no cardiac involvement by consensus criteria and cardiac involvement is detected by magnetic resonance imaging in such cases. This suggests that N-terminal pro b-type natriuretic peptide thresholds for cardiac involvement in AL may need to be redefined.
Introduction
Systemic immunoglobulin light chain amyloidosis (AL) is characterised by the extracellular deposition of misfolded immunoglobulin light chains resulting in pro- gressive organ dysfunction. Patient outcomes are largely dependent upon the sever- ity and pattern of organ involvement.1 Accurate stratification of patients is needed to assess prognosis and to facilitate treatment decisions. Cardiac involvement is the critical determinant of survival. NT-proBNP (N-terminal pro b-type natriuretic pep- tide) is a remarkably sensitive marker of cardiac involvement and is one of the cor- nerstones of the international amyloidosis consensus group diagnostic criteria for cardiac involvement.2 Change in NT-proBNP is crucial in monitoring the effect of therapy in patients with cardiac amyloidosis.3 These findings have followed from the seminal work by the Mayo clinic group discovering NT-proBNP and troponin T (TNT) as sensitive biomarkers for prognosis in AL4 and the development of the 2004 Mayo prognostic scoring system, which has been further refined in 2012.5 The widely used 2004 staging system uses thresholds of NT-proBNP <332 ng/L and a TNT <0.035 μg/L to classify patients into stage I, II or
Correspondence:
FAYE A. SHARPLEY
f.sharpley@gmail.com
Received: February 7, 2019. Accepted: August 7, 2019. Pre-published: August 8, 2019.
doi:10.3324/haematol.2019.217695
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/5/1405
©2020 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2020; 105(5)
1405
ARTICLE