Clonal Hematopoiesis Linked to Increased Myocarditis Risk: JAMA

A recent biobank cohort analysis published in the Journal of the American Medical Association revealed that clonal hematopoiesis of indeterminate potential (CHIP) was identified as a risk factor for myocarditis. The findings of research suggests a potential role of age-related clonal mutations in inflammatory cardiac conditions.

This research analyzed health and genetic data from more than 360,000 participants from the National Institutes of Health’s All of Us Research Program and Vanderbilt University Medical Center’s BioVU. Their findings confirmed earlier results from a UK-based study, by reinforcing the idea that CHIP is not just a benign marker of aging, but a clinically relevant risk factor for cardiovascular inflammation.

CHIP occurs when blood stem cells acquire mutations commonly associated with leukemia, which leads to the expansion of altered blood cell populations. While often asymptomatic, CHIP has increasingly been linked to inflammatory processes in the body, those involving the NLRP3 inflammasome and interleukin-1 beta (IL-1β).

In this analysis, individuals with CHIP were found to have a 65% higher risk of developing pericarditis when compared to those without the condition. The risk was even more pronounced in individuals with larger mutated cell populations. Also, mutations in the DNMT3A gene appeared to be the primary contributor to this increased risk, while mutations in another gene, TET2, showed weaker and less consistent associations.

These findings replicate and strengthen prior evidence that CHIP contributes to pericardial inflammation, which highlights the consistency of results across different populations and study designs. This study did not find a statistically significant association between CHIP and myocarditis, another inflammatory heart condition affecting the heart muscle itself.

The biological link between CHIP and pericarditis is supported by previous research showing that inflammatory pathways activated by CHIP mutations are also central to the development of pericarditis. Therapies targeting IL-1β have already proven effective in treating recurrent cases of the condition, which suggests potential clinical applications of these findings.

The limitation of this study include reliance on diagnostic codes rather than direct clinical assessments, possible residual confounding factors, and less precise genetic sequencing methods. Further research is imperative to better understand the role of CHIP in myocarditis and to explore targeted anti-inflammatory treatments. Overall, the study adds to mounting evidence that CHIP may play a direct role in cardiovascular disease than being just a genetic curiosity. 

Source:

Pershad, Y., Zhao, K., Heimlich, J. B., & Bick, A. G. (2026). Clonal hematopoiesis and risk of incident pericarditis and myocarditis in 2 US biobank cohorts. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2026.0258