| Autor: |
Sikking MA; Department of Cardiology Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC) Maastricht the Netherlands., Stroeks SLVM; Department of Cardiology Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC) Maastricht the Netherlands., Waring OJ; Department of Pathology Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC) Maastricht the Netherlands., Henkens MTHM; Department of Pathology Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC) Maastricht the Netherlands.; Netherlands Heart Institute (NLHI) Utrecht the Netherlands., Riksen NP; Department of Internal Medicine Radboud University Medical Center Nijmegen the Netherlands., Hoischen A; Department of Human Genetics Radboud University Medical Center Nijmegen the Netherlands., Heymans SRB; Department of Cardiology Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC) Maastricht the Netherlands.; Department of Cardiovascular Research University of Leuven Belgium., Verdonschot JAJ; Department of Cardiology Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center (MUMC) Maastricht the Netherlands.; Department of Clinical Genetics Maastricht University Medical Center (MUMC) Maastricht the Netherlands. |
| Abstrakt: |
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. |
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