Assessing Cardiac Amyloidosis Subtypes by Unsupervised Phenotype Clustering Analysis.


Journal

Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365

Informations de publication

Date de publication:
30 11 2021
Historique:
received: 17 06 2021
revised: 30 08 2021
accepted: 01 09 2021
entrez: 26 11 2021
pubmed: 27 11 2021
medline: 5 1 2022
Statut: ppublish

Résumé

Cardiac amyloidosis (CA) is a set of amyloid diseases with usually predominant cardiac symptoms, including light-chain amyloidosis (AL), hereditary variant transthyretin amyloidosis (ATTRv), and wild-type transthyretin amyloidosis (ATTRwt). CA are characterized by high heterogeneity in phenotypes leading to diagnosis delay and worsened outcomes. The authors used clustering analysis to identify typical clinical profiles in a large population of patients with suspected CA. Data were collected from the French Referral Center for Cardiac Amyloidosis database (Hôpital Henri Mondor, Créteil), including 1,394 patients with suspected CA between 2010 and 2018: 345 (25%) had a diagnosis of AL, 263 (19%) ATTRv, 402 (29%) ATTRwt, and 384 (28%) no amyloidosis. Based on comprehensive clinicobiological phenotyping, unsupervised clustering analyses were performed by artificial neural network-based self-organizing maps to identify patient profiles (clusters) with similar characteristics, independent of the final diagnosis and prognosis. Mean age and left ventricular ejection fraction were 72 ± 13 years and 52% ± 13%, respectively. The authors identified 7 clusters of patients with contrasting profiles and prognosis. AL patients were distinctively located within a typical cluster; ATTRv patients were distributed across 4 clusters with varying clinical presentations, 1 of which overlapped with patients without amyloidosis; interestingly, ATTRwt patients spread across 3 distinct clusters with contrasting risk factors, biological profiles, and prognosis. Clustering analysis identified 7 clinical profiles with varying characteristics, prognosis, and associations with diagnosis. Especially in patients with ATTRwt, these results suggest key areas to improve amyloidosis diagnosis and stratify prognosis depending on associated risk factors.

Sections du résumé

BACKGROUND
Cardiac amyloidosis (CA) is a set of amyloid diseases with usually predominant cardiac symptoms, including light-chain amyloidosis (AL), hereditary variant transthyretin amyloidosis (ATTRv), and wild-type transthyretin amyloidosis (ATTRwt). CA are characterized by high heterogeneity in phenotypes leading to diagnosis delay and worsened outcomes.
OBJECTIVES
The authors used clustering analysis to identify typical clinical profiles in a large population of patients with suspected CA.
METHODS
Data were collected from the French Referral Center for Cardiac Amyloidosis database (Hôpital Henri Mondor, Créteil), including 1,394 patients with suspected CA between 2010 and 2018: 345 (25%) had a diagnosis of AL, 263 (19%) ATTRv, 402 (29%) ATTRwt, and 384 (28%) no amyloidosis. Based on comprehensive clinicobiological phenotyping, unsupervised clustering analyses were performed by artificial neural network-based self-organizing maps to identify patient profiles (clusters) with similar characteristics, independent of the final diagnosis and prognosis.
RESULTS
Mean age and left ventricular ejection fraction were 72 ± 13 years and 52% ± 13%, respectively. The authors identified 7 clusters of patients with contrasting profiles and prognosis. AL patients were distinctively located within a typical cluster; ATTRv patients were distributed across 4 clusters with varying clinical presentations, 1 of which overlapped with patients without amyloidosis; interestingly, ATTRwt patients spread across 3 distinct clusters with contrasting risk factors, biological profiles, and prognosis.
CONCLUSIONS
Clustering analysis identified 7 clinical profiles with varying characteristics, prognosis, and associations with diagnosis. Especially in patients with ATTRwt, these results suggest key areas to improve amyloidosis diagnosis and stratify prognosis depending on associated risk factors.

Identifiants

pubmed: 34823661
pii: S0735-1097(21)07172-2
doi: 10.1016/j.jacc.2021.09.858
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2177-2192

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures Dr Bonnefous is supported by a PhD grant from GlaxoSmithKline. Dr Oghina has received honoraria from Pfizer. Dr Damy has received research and/or consultant fees from GlaxoSmithKline, Alnylam, Pfizer, Prothena, Ionis, Akcea, and Janssen. Dr Audureau has received consultant fees from GBT and Hemanext. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Auteurs

Louis Bonnefous (L)

AP-HP (Assistance Publique-Hôpitaux de Paris), Public Health Department, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France.

Mounira Kharoubi (M)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Cardiology Department, Henri Mondor University Hospital, Créteil, France.

Mélanie Bézard (M)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Cardiology Department, Henri Mondor University Hospital, Créteil, France.

Silvia Oghina (S)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Cardiology Department, Henri Mondor University Hospital, Créteil, France.

Fabien Le Bras (F)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Hematology Department, Henri Mondor University Hospital, Créteil, France.

Elsa Poullot (E)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Biology-Pathology Department, Henri Mondor University Hospital, Créteil, France.

Valérie Molinier-Frenkel (V)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Biology-Pathology Department, Henri Mondor University Hospital, Créteil, France.

Pascale Fanen (P)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Genetics Department, Henri Mondor University Hospital, Créteil, France.

Jean-François Deux (JF)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Radiology Department, Henri Mondor University Hospital, Créteil, France.

Vincent Audard (V)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Nephrology Department, Henri Mondor University Hospital, Créteil, France.

Emmanuel Itti (E)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Nuclear Medicine Department, Henri Mondor University Hospital, Créteil, France.

Thibaud Damy (T)

AP-HP (Assistance Publique-Hôpitaux de Paris), French Referral Centre for Cardiac Amyloidosis, Cardiogen Network, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), GRC Amyloid Research Institute, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Cardiology Department, Henri Mondor University Hospital, Créteil, France; AP-HP (Assistance Publique-Hôpitaux de Paris), Clinical Investigation Center 1430, Henri Mondor University Hospital, Créteil, France.

Etienne Audureau (E)

AP-HP (Assistance Publique-Hôpitaux de Paris), Public Health Department, Henri Mondor University Hospital, Créteil, France; Univ Paris Est Creteil, INSERM, IMRB, Créteil, France. Electronic address: etienne.audureau@aphp.fr.

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