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VALVULAR DISEASE

Clonal haematopoiesis, aortic stenosis and reduced survival after TAVI

Clonal haematopoiesis of indeterminate potential (CHIP) is defined as the presence of an expanded somatic blood cell clone without other haematological abnormalities and has been associated with an increased incidence of coronary artery disease and calcification. A new study now shows that CHIP-driver mutations in DNMT3A or TET2 are associated with increased medium-term mortality in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI).

The investigators studied 279 patients with severe aortic stenosis and found that 93 (33%) had a CHIP-driver mutation with a variant allele frequency ≥ 2% in DNMT3A (n = 53) or TET2 (n = 40). The incidence of these mutations increased with age from 25% in those aged 55–69 years to 53% in those aged 90–100 years.

After a successful TAVI procedure, patients with a DNMT3A or TET2 CHIP-driver mutation had a significantly increased risk of death in the first 8 months. This increased risk of death remained even after accounting for the potential effects of age and sex (HR 3.1, 95% CI 1.17–8.08, P = 0.022).

With the use of fluorescence-activated cell sorting analysis, patients with a TET2 CHIP-driver mutation were found to have increased levels of circulating non-classical monocytes (CD14dimCD16++), which are known to secrete high levels of inflammatory cytokines. By contrast, patients with a DNMT3A CHIP-driver mutation had a significantly increased TH17:Treg ratio, indicating pro-inflammatory T-cell polarization. The researchers speculate that the presence of DNMT3A or TET2 CHIP-driver mutations might have contributed to the development of the aortic stenosis.

References

Original article

  1. Mas-Peiro, S. et al. Clonal haematopoiesis in patients with degenerative aortic valve stenosis undergoing transcatheter aortic valve implantation. Eur. Heart J. https://doi.org/10.1093/eurheartj/ehz591 (2019)

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Related articles

  1. Jaiswal, S. & Libby, P. Clonal haematopoiesis: connecting ageing and inflammation in cardiovascular disease. Nat. Rev. Cardiol. https://doi.org/10.1038/s41569-019-0247-5 (2019)

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Correspondence to Gregory B. Lim.

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Lim, G.B. Clonal haematopoiesis, aortic stenosis and reduced survival after TAVI. Nat Rev Cardiol 16, 650 (2019). https://doi.org/10.1038/s41569-019-0275-1

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