Heart failure & cardiomyopathiesDiagnostic or prognostic study
Clonal Hematopoiesis of Indeterminate Potential Proteomic Risk Score for Predicting Clinical Outcome in Patients With Heart Failure With Preserved Ejection Fraction
- development and external validation of a clonal hematopoiesis of indeterminate potential (CHIP)-proteomic risk score
- derivation in TOPCAT participants
- external validation in a composite of 3 independent heart failure with preserved ejection fraction (HFpEF) cohorts
- SomaScan proteomic profiling
- nested cross-validated least absolute shrinkage and selection operator
Authors' conclusion
CHIP is associated with alterations in plasma concentrations of immune/inflammatory proteins. A CHIP-ProtRS is independently associated with adverse outcomes in HFpEF, supporting its potential role as a biomarker of risk and underlying pathobiology.
Study context
- Population
- Patients with heart failure with preserved ejection fraction (HFpEF)derivation cohort (TOPCAT) 118 · validation cohorts 654
- Comparison
- CHIP-ProtRS and the primary end point, derivation and validation cohorts
- Outcome
- Composite of:
- Death
- HF hospitalization
Performance
As reported in the abstract
CHIP-ProtRSAdjusted hazard ratio (95% CI)
derivation cohort
1.42(1.01–2.00)
validation cohorts
1.16(1.01–1.32)
Further findings
CHIP mutation prevalence
- TOPCAT participants carrying ≥1 CHIP mutation
- 30.5%
Protein associations with CHIP mutations
- TET2 proteins
- 7
- DNMT3A proteins
- 10
- PPM1D proteins
- 5
- all enriched in immune and inflammatory pathways
Discrimination of gene-specific least absolute shrinkage and selection operator models for CHIP mutation
- area under the curves
- 0.752-0.898
CHIP-ProtRS composition
- only the TET2 -derived proteomic signature retained a nonzero coefficient
Original publication
Clonal Hematopoiesis of Indeterminate Potential Proteomic Risk Score for Predicting Clinical Outcome in Patients With Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. Published 21 September 2026. doi:10.1161/circheartfailure.126.014345
Summarised from the published abstract; every number is checked against it