TY - JOUR
T1 - Clonal Hematopoiesis of Indeterminate Potential From a Heart Failure Specialist’s Point of View
AU - Sikking, Maurits A.
AU - Stroeks, Sophie L.V.M.
AU - Waring, Olivia J.
AU - Henkens, Michiel T.H.M.
AU - Riksen, Niels P.
AU - Hoischen, Alexander
AU - Heymans, Stephane R.B.
AU - Verdonschot, Job A.J.
N1 - Funding Information:
This work was funded by the Dutch Cardiovascular Alliance, an initiative with support of the Dutch Heart Foundation, and Stichting Hartedroom for financing the Double Dose program 2020B005 (principal investigator: S.R.B.H.). J.A.J.V. is supported by a research grant from the Dutch Heart Foundation.
Publisher Copyright:
© 2023 The Authors.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Clonal hematopoiesis of indeterminate potential (CHIP) is a common bone marrow abnormality induced by age-related DNA mutations, which give rise to proinflammatory immune cells. These immune cells exacerbate atherosclerotic cardiovascular disease and may induce or accelerate heart failure. The mechanisms involved are complex but point toward a central role for proinflammatory macrophages and an inflammasome-dependent immune response (IL-1 [interleukin-1] and IL-6 [interleukin-6]) in the atherosclerotic plaque or directly in the myocardium. Intracardiac inflammation may decrease cardiac function and induce cardiac fibrosis, even in the absence of atherosclerotic cardiovascular disease. The pathophysiology and consequences of CHIP may differ among implicated genes as well as subgroups of patients with heart failure, based on cause (ischemic versus nonischemic) and ejection fraction (reduced ejection fraction versus preserved ejection fraction). Evidence is accumulating that CHIP is associated with cardiovascular mortality in ischemic and nonischemic heart failure with reduced ejection fraction and involved in the development of heart failure with preserved ejection fraction. CHIP and corresponding inflammatory pathways provide a highly potent therapeutic target. Randomized controlled trials in patients with well-phenotyped heart failure, where readily available anti-inflammatory therapies are used to intervene with clonal hematopoiesis, may pave the way for a new area of heart failure treatment. The first clinical trials that target CHIP are already registered.
AB - Clonal hematopoiesis of indeterminate potential (CHIP) is a common bone marrow abnormality induced by age-related DNA mutations, which give rise to proinflammatory immune cells. These immune cells exacerbate atherosclerotic cardiovascular disease and may induce or accelerate heart failure. The mechanisms involved are complex but point toward a central role for proinflammatory macrophages and an inflammasome-dependent immune response (IL-1 [interleukin-1] and IL-6 [interleukin-6]) in the atherosclerotic plaque or directly in the myocardium. Intracardiac inflammation may decrease cardiac function and induce cardiac fibrosis, even in the absence of atherosclerotic cardiovascular disease. The pathophysiology and consequences of CHIP may differ among implicated genes as well as subgroups of patients with heart failure, based on cause (ischemic versus nonischemic) and ejection fraction (reduced ejection fraction versus preserved ejection fraction). Evidence is accumulating that CHIP is associated with cardiovascular mortality in ischemic and nonischemic heart failure with reduced ejection fraction and involved in the development of heart failure with preserved ejection fraction. CHIP and corresponding inflammatory pathways provide a highly potent therapeutic target. Randomized controlled trials in patients with well-phenotyped heart failure, where readily available anti-inflammatory therapies are used to intervene with clonal hematopoiesis, may pave the way for a new area of heart failure treatment. The first clinical trials that target CHIP are already registered.
KW - atherosclerotic cardiovascular disease
KW - clonal hematopoiesis
KW - heart failure
KW - inflammation
U2 - 10.1161/JAHA.123.030603
DO - 10.1161/JAHA.123.030603
M3 - (Systematic) Review article
C2 - 37489738
SN - 2047-9980
VL - 12
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 15
M1 - e030603
ER -