Heart failure & cardiomyopathies

Novel biomarkers distinguish heart failure with preserved vs reduced ejection fraction

ESC Heart FailPublished Exploratory biomarker study

Authors' conclusion

Among seven novel biomarker assays, higher MYBPC3 (reflecting muscle injury and myopathy) and FGF23 (endothelial dysfunction, oxidative stress) distinguished HFrEF from HFpEF. Higher MYBPC3 was most prognostic in HFrEF while higher ANGPT2 and IGFBP7 (endothelial dysfunction and oxidative stress) in HFpEF. These hypothesis-generating findings support primary cardiomyocyte injury as a driver of HFrEF and systemic inflammation and oxidative stress as a driver of HFpEF.

Study context

Population
Patients with heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction
Participants
36 vs 76
Comparison
HFrEF vs HFpEF
  • HFrEFn = 36
  • HFpEFn = 76
Outcome
Age and sex
Methodological details19 plasma biomarkers including seven novel research assays, hypothesis-generating
  • 19 plasma biomarkers including seven novel research assays
  • Hypothesis-generating

Main finding

As reported in the abstract

Female

Years

OutcomeHFpEFHFrEF
Age7363

Further findings

Outcome (HFpEF: all-cause death, heart failure (HF) hospitalization; HFrEF: all-cause death, LVAD or heart transplantation)

HR (95% CI)
ANGPT2More strongly in HFpEF1.45 (1.00–2.13)
IGFBP7More strongly in HFrEF2.51 (0.95–6.64)
MYBPC31.62 (0.99–2.64)

Novel biomarker levels

All seven novel biomarkers except FABP3 tended to be higher in HFrEF vs HFpEF and associated with worse NYHA class and lower eGFR in both LVEF categories

Discrimination between LVEF categories

MYBPC3 AUC
85.8
FGF23 AUC
80.0
  • MYBPC3 and FGF23 higher in HFrEF

Associations with cardiac function in HFpEF

ANGPT2 and TAPSE β
−1.03
ANGPT2 and LV-GLS β
1.29
ANGPT2 and LA-GLS β
5.03
IGFBP7 and E/eʹ β
4.09
MYBPC3 and E/eʹ β
1.36
  • TAPSE P = .04
  • LV-GLS P = .03
  • LA-GLS P < .001
  • IGFBP7 E/eʹ P = .02
  • MYBPC3 E/eʹ P = .01

Outcome (HFpEF: all-cause death, HF hospitalization; HFrEF: all-cause death, LVAD or heart transplantation)

All biomarkers except DKK3 were positively associated with the outcome

Original publication

Novel biomarkers distinguish heart failure with preserved vs reduced ejection fraction. ESC Heart Fail. Published 8 January 2026. doi:10.1093/eschf/xvaf011

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