Heart failure & cardiomyopathies

A Pilot Study on DNA Methylation Changes for Non-Invasive Molecular Diagnostics in Heart Failure

ESC Heart FailPublished Post hoc analysis of the PRESMET clinical trial

Authors' conclusion

We demonstrate that circulating CD4+ T cell-specific methylation levels of network-oriented CKAP4, CPT1A, EIF2S2, SPTB, SYT6 and RAB11FIP1 genes can distinguish between IsHF and NIsHF. In particular, hypomethylation of EIF2S2, SPTB and RAB11FIP1 genes is significantly correlated with key clinical features in isHF patients

Study context

Population
Patients with HF with reduced ejection fraction (HFrEF); DNA methylation in circulating CD4+ T lymphocytes (reduced representation bisulfite sequencing (RRBS))
Participants
8 vs 4
Comparison
IsHF vs NIsHF
  • IsHFn = 8
  • NIsHFn = 4reference
Primary endpoint
Differentially methylated CpG positions distinguishing IsHF from NIsHF
Methodological detailspilot study, network-oriented analysis
  • Pilot study
  • Network-oriented analysis

Primary result

As reported in the abstract

Network-oriented DMPs distinguishing IsHF vs NIsHF
6 DMPs distinguished IsHF vs NIsHF
AUC > 0.8
DMPs significantly hypomethylated in IsHF vs NIsHF, annotated to CKAP4, CPT1A, EIF2S2, spectrin beta (SPTB), SYT6 and RAB11FIP1
P < 0.05

Further findings

Correlation of CD4+ T cell methylation with clinical features (IsHF)

EIF2S2 hypomethylation vs VO2 max
ρ = 0.73, P = 0.04
RAB11FIP1 hypomethylation vs MECKI score
ρ = −0.85, P = 0.001
SPTB vs VO2 max
ρ = 0.73, P = 0.04
SPTB vs LV mass index
ρ = −0.91, P = 0.005
SPTB vs LVEF
ρ = 0.83, P = 0.01

Original publication

A Pilot Study on DNA Methylation Changes for Non-Invasive Molecular Diagnostics in Heart Failure. ESC Heart Fail. Published 2 September 2025. doi:10.1002/ehf2.15402

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