Heart failure & cardiomyopathies
Prognostic Significance of Somatic Mutations in Myeloid Cells of Men with Chronic Heart Failure – Interaction Between Loss of Y Chromosome and Clonal Haematopoiesis
Authors' conclusion
Somatic mutations in blood cells-particularly LOY-are associated with increased mortality in male CHF patients, with LOY emerging as an independent prognostic marker.
Study context
- Population
- Men with chronic HF across the full spectrum of LVEF
- Participants
- 781 men
- Exposure
- LOY and/or DNMT3A/TET2 clonal haematopoiesis of indeterminate potential (CHIP) mutations vs none
- Outcome
- All-cause mortality
Methodological detailsvalidation cohort, single-cell RNA sequencing
- Validation cohort
- Single-cell RNA sequencing
Main finding
As reported in the abstract
- LOY independently predicted all-cause mortality in heart failure with reduced ejection fraction (HFrEF)
- Co-occurrence of LOY and DNMT3A/TET2 mutations further increased mortality among CHIP carriers
- Detrimental prognostic effect of LOY confirmed in a validation cohort of HFrEF patients
Observational data: associations, not effects.
Further findings
Co-occurrence of LOY and CHIP mutations, men >70 years
- LOY and CHIP mutations increased with age and co-occurred
- 27.1%
Single-cell RNA sequencing of PBMCs (HFrEF, ischaemic HF)
- LOY monocytes: elevated pro-fibrotic signalling (↑ S100A8, TLR2, CLEC4D; ↓ SMAD7, TGIF2)
- LOY + DNMT3A: enhanced pro-inflammatory gene expression (S100A8, HMGB2, IFNGR1, TRIM56, CD84)
Original publication
Prognostic Significance of Somatic Mutations in Myeloid Cells of Men with Chronic Heart Failure – Interaction Between Loss of Y Chromosome and Clonal Haematopoiesis. Eur J Heart Fail. Published 24 July 2025. doi:10.
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