TY - JOUR
T1 - Clonal Hematopoiesis has Prognostic Value in Dilated Cardiomyopathy independent of Age and Clone Size
AU - Sikking, Maurits A
AU - Stroeks, Sophie L V M
AU - Henkens, Michiel T H M
AU - Raafs, Anne G
AU - Cossins, Benjamin
AU - van Deuren, Rosanne C
AU - Steehouwer, Marlies
AU - Riksen, Niels P
AU - van den Wijngaard, Arthur
AU - Brunner, Han G
AU - Hoischen, Alexander
AU - Verdonschot, Job A J
AU - Heymans, Stephane R B
PY - 2024/5
Y1 - 2024/5
N2 - 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.
AB - 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.
KW - clonal hematopoiesis
KW - dilated cardiomyopathy
KW - heart failure
U2 - 10.1016/j.jchf.2023.06.037
DO - 10.1016/j.jchf.2023.06.037
M3 - Article
SN - 2213-1787
VL - 12
SP - 905
EP - 914
JO - JACC: Heart Failure
JF - JACC: Heart Failure
IS - 5
ER -