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Editorial
January 2019

CHIPping Away at the Pathogenesis of Heart Failure

Author Affiliations
  • 1Division of Cardiovascular, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Department of Pathology and Program in Immunology, Stanford University, Stanford, California
  • 3Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts
  • 4Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
  • 5Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
JAMA Cardiol. 2019;4(1):5-6. doi:10.1001/jamacardio.2018.4039

A new window has just opened, illuminating a novel and unsuspected aspect of the pathogenesis of heart failure. As we age, we accumulate somatic mutations in bone marrow stem cells that confer a proliferative advantage, yielding clones in the peripheral blood of mutant leukocytes (Figure).1 Expectedly, those who harbor these clones have a greater liability of developing hematologic cancers, such as acute myeloid leukemia, after accumulating successive mutations that arise in the same clone. Unexpectedly, carriers of these clones of mutant leukocytes have a striking increase in risk of ischemic heart events.2 Because most individuals with these clones will never develop leukemia during their lifespan, this condition has been termed clonal hematopoiesis of indeterminate potential (CHIP). Clonal hematopoiesis of indeterminate potential mutations commonly arise in a surprisingly restricted set of genes. A consensus cut point of 2% of circulating leukocytes that bear such driver mutations defines CHIP.3

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