1. Clonal Hematopoiesis Has Prognostic Value in Dilated Cardiomyopathy Independent of Age and Clone Size.
- Author
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Sikking MA, Stroeks SLVM, Henkens MTHM, Raafs AG, Cossins B, van Deuren RC, Steehouwer M, Riksen NP, van den Wijngaard A, Brunner HG, Hoischen A, Verdonschot JAJ, and Heymans SRB
- Subjects
- Humans, Female, Male, Middle Aged, Prognosis, Aged, Mutation, Gene Frequency, Adult, Age Factors, Cardiomyopathy, Dilated genetics, Cardiomyopathy, Dilated physiopathology, Clonal Hematopoiesis genetics
- Abstract
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: The authors sought to establish the prognostic impact of CH in DCM including small clones., 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: A total of 520 DCM patients have been included. A total of 109 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 NYHA functional classification., 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., Competing Interests: 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., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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