Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size.
clonal hematopoiesis
dilated cardiomyopathy
heart failure
Journal
JACC. Heart failure
ISSN: 2213-1787
Titre abrégé: JACC Heart Fail
Pays: United States
ID NLM: 101598241
Informations de publication
Date de publication:
25 Aug 2023
25 Aug 2023
Historique:
received:
24
03
2023
revised:
12
06
2023
accepted:
28
06
2023
pubmed:
28
8
2023
medline:
28
8
2023
entrez:
28
8
2023
Statut:
aheadofprint
Résumé
Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones that induce cardiovascular inflammation and thereby impact the disease course in atherosclerosis and ischemic heart failure. CH of indeterminate potential refers to a variant allele frequency (VAF; a marker for clone size) in blood of ≥2%. The impact of CH clones-including small clone sizes (VAF <0.5%)-in nonischemic dilated cardiomyopathy (DCM) remains largely undetermined. The authors sought to establish the prognostic impact of CH in DCM including small clones. CH is determined using an ultrasensitive single-molecule molecular inversion probe technique that allows detection of clones down to a VAF of 0.01%. Cardiac death and all-cause mortality were analyzed using receiver-operating characteristic curve-optimized VAF cutoff values. A total of 520 DCM patients have been included. One hundred and nine patients (21%) had CH driver mutations, of which 45 had a VAF of ≥2% and 31 <0.5%. The median follow-up duration was 6.5 years [IQR: 4.7-9.7 years]. DCM patients with CH have a higher risk of cardiac death (HR: 2.33 using a VAF cutoff of 0.36%, 95% CI: 1.24-4.40) and all-cause mortality (HR: 1.72 using a VAF cutoff of 0.06%, 95% CI: 1.10-2.69), independent of age, sex, left ventricular ejection fraction, and New York Heart Association classification. CH predicts cardiac death and all-cause mortality in DCM patients with optimal thresholds for clone size of 0.36% and 0.06%, respectively. Therefore, CH is prognostically relevant, independent of clone size in patients with DCM.
Sections du résumé
BACKGROUND
BACKGROUND
Clonal hematopoiesis (CH) gives rise to mutated leukocyte clones that induce cardiovascular inflammation and thereby impact the disease course in atherosclerosis and ischemic heart failure. CH of indeterminate potential refers to a variant allele frequency (VAF; a marker for clone size) in blood of ≥2%. The impact of CH clones-including small clone sizes (VAF <0.5%)-in nonischemic dilated cardiomyopathy (DCM) remains largely undetermined.
OBJECTIVES
OBJECTIVE
The authors sought to establish the prognostic impact of CH in DCM including small clones.
METHODS
METHODS
CH is determined using an ultrasensitive single-molecule molecular inversion probe technique that allows detection of clones down to a VAF of 0.01%. Cardiac death and all-cause mortality were analyzed using receiver-operating characteristic curve-optimized VAF cutoff values.
RESULTS
RESULTS
A total of 520 DCM patients have been included. One hundred and nine patients (21%) had CH driver mutations, of which 45 had a VAF of ≥2% and 31 <0.5%. The median follow-up duration was 6.5 years [IQR: 4.7-9.7 years]. DCM patients with CH have a higher risk of cardiac death (HR: 2.33 using a VAF cutoff of 0.36%, 95% CI: 1.24-4.40) and all-cause mortality (HR: 1.72 using a VAF cutoff of 0.06%, 95% CI: 1.10-2.69), independent of age, sex, left ventricular ejection fraction, and New York Heart Association classification.
CONCLUSIONS
CONCLUSIONS
CH predicts cardiac death and all-cause mortality in DCM patients with optimal thresholds for clone size of 0.36% and 0.06%, respectively. Therefore, CH is prognostically relevant, independent of clone size in patients with DCM.
Identifiants
pubmed: 37638520
pii: S2213-1779(23)00509-7
doi: 10.1016/j.jchf.2023.06.037
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Funding Support and Author Disclosures This work was supported by the Dutch Cardiovascular Alliance, an initiative with support of the Dutch Heart Foundation, and Stichting Hartedroom for financing the Double Dose program 2020-B005, and CVON Arena-PRIME, 2017-18. The methodology developed for patient classification has been possible thanks to the support of IMI2-CARDIATEAM (N° 821508). Dr Verdonschot is supported by a grant from the Dutch Heart Foundation–Dekker Clinical Scientist. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.