Association of Clonal Hematopoiesis of Indeterminate Potential With Inflammatory Gene Expression in Patients With Severe Degenerative Aortic Valve Stenosis or Chronic Postischemic Heart Failure.

Importance Cytokine release syndrome is a complication of coronavirus disease 2019. Clinically, advanced age and cardiovascular comorbidities are the most important risk factors. Objective To determine whether clonal hematopoiesis of indeterminate potential (CHIP), an age-associated condition with excess cardiovascular risk defined as the presence of an expanded, mutated somatic blood cell clone in persons without other hematological abnormalities, may be associated with an inflammatory gene expression sensitizing monocytes to aggravated immune responses. Design, Setting, and Participants This hypothesis-generating diagnostic study examined a cohort of patients with severe degenerative aortic valve stenosis or chronic postinfarction heart failure, as well as age-matched healthy control participants. Single-cell RNA sequencing and analyses of circulating peripheral monocytes was done between 2017 and 2019 to assess the transcriptome of circulating monocytes. Exposures Severe degenerative aortic valve stenosis or chronic postinfarction heart failure. Main Outcomes and Measures CHIP-driver sequence variations in monocytes with a proinflammatory signature of genes involved in cytokine release syndrome. Results The study included 8 patients with severe degenerative aortic valve stenosis, 6 with chronic postinfarction heart failure, and 3 healthy control participants. Their mean age was 75.7 (range, 54-89) years, and 6 were women. Mean CHIP-driver gene variant allele frequency was 4.2% (range, 2.5%-6.9%) forDNMT3Aand 14.3% (range, 2.6%-37.4%) forTET2. Participants withDNMT3AorTET2CHIP-driver sequence variations displayed increased expression of interleukin 1β (no CHIP-driver sequence variations, 1.6217 normalized Unique Molecular Identifiers [nUMI];DNMT3A, 5.3956 nUMI;P  Conclusions and Relevance Monocytes of individuals who carry CHIP-driver sequence variations and have cardiovascular disease appear to be primed for excessive inflammatory responses. Further studies are warranted to address potential adverse outcomes of coronavirus disease 2019 in patients with CHIP-driver sequence variations.