Background and aims:
Blood cell clones carrying cancer-related mutations are frequently present in the elder, often without determining symptomatic hematological disease. This condition is defined clonal hematopoiesis of inderminate potential (CHIP). In recent years, epidemiological investigations have clearly shown that CHIP increases not only the risk of blood cancer but also the risk of atherosclerosis and cardiovascular mortality. The present study aims to evaluate the possible association between CHIP and aortic valve stenosis and to explore the pathological mechanism of calcified aortic valve disease (CAVD) in CHIP carriers.
We enrolled 105 CAVD patients undergoing surgical aortic valve replacement in which we assessed the presence of CHIP by next generation sequencing (NGS) of DNA extracted from blood cells. Moreover, we investigated the effect of CHIP on 1-year all-cause mortality. Finally, to reveal possible mechanisms linking CHIP to CAVD, we extracted the RNA from a subset of explanted aortic valves and compared the whole transcriptome of patients with or without CHIP.
We found that CHIP is present in patients with CAVD, with a frequency of around 30%. Analysis of the transcriptome of aortic valves revealed that high immune infiltration and immunoglobulins presence frequently occur in CHIP patients. Importantly, we observed that the presence of CHIP is associated with increased mortality within 12 months after surgery.
Our findings indicate that the broad cellular and humoral immune response in the aortic valves of the CHIP patients reflects alterations in the immune cells that may be linked to the poor prognosis after valve replacement.