Clonal hematopoiesis of indeterminate potential and heart disease: What every internist needs to know

How clonal hematopoiesis of indeterminate potential leads to heart disease. A somatic mutation in a hematopoietic stem cell may lead to clonal expansion and the emergence of mutant myeloid cell populations with altered inflammatory signaling, promoting activation of the inflammasome, a cellular protein complex that senses danger signals and triggers innate immune inflammation, with increased downstream interleukin (IL) 1 beta and IL-6 signaling. These proinflammatory pathways contribute to the development of cardiovascular disease. Clonal hematopoiesis is associated with various cardiovascular phenotypes, including atherosclerotic cardiovascular disease, arrhythmias, aortic stenosis, pericarditis and myocarditis, heart failure, and venous thromboembolism, with differing risk patterns by driver mutation (eg, in TET2, DNMT3A, ASXL1, JAK2, TP53, and PPM1D).