Higher MYBPC3 and FGF23 levels distinguished HFrEF from HFpEF, with MYBPC3 being most prognostic in HFrEF (HR 1.62) and ANGPT2 in HFpEF (HR 1.45).
Do novel plasma biomarkers distinguish between HFpEF and HFrEF and predict clinical outcomes?
Novel biomarkers MYBPC3 and FGF23 can distinguish HFrEF from HFpEF, supporting the hypothesis that primary cardiomyocyte injury drives HFrEF while systemic inflammation and oxidative stress drive HFpEF.
Abstract Aims Heart failure (HF) with preserved (HFpEF) and reduced (HFrEF) ejection fraction may be driven by different pathophysiologies. We explored novel biomarkers, associations with clinical characteristics, discrimination between LVEF categories and associations with outcomes. Methods and Results In HFpEF(n=76) and HFrEF(n=36), 19 plasma biomarkers were measured including seven novel research assays for ANGPT2, BMP10, DKK3, FABP3, FGF23, IGFBP7 and MYBPC3. HFpEF patients were older (73 vs 63 years), more often female (50% vs 14%). 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. MYBPC3 and FGF23 (higher in HFrEF) discriminated best between LVEF categories (AUC 85.8 and 80.0 respectively). In HFpEF, higher ANGPT2 was associated with worse right (TAPSE:β=-1.03;p=0.04) and left ventricular function (LV-GLS; β=1.29;p=0.03) and left atrial strain (LA-GLS:β=5.03;p0.001) whereas higher IGFBP7 and MYBPC3 with diastolic dysfunction (E/e´:β=4.09;p=0.02 and β=1.36;p=0.01 respectively). All biomarkers except DKK3 were positively associated with the outcome (HFpEF:all-cause death, HF-hospitalization;HFrEF: all-cause death, LVAD or heart transplantation). Specifically (ANGPT2 (HR 1.4595% CI 1.00-2.13) more strongly in HFpEF and IGFBP7 (2.510.95-6.64) more strongly in HFrEF (MYBPC3 (1.620.99-2.64). 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. Clinical Trial Registration ClinicalTrials.gov NCT00774709
Hage et al. (2026) studied this question. Higher MYBPC3 and FGF23 levels distinguished HFrEF from HFpEF, with MYBPC3 being most prognostic in HFrEF (HR 1.62) and ANGPT2 in HFpEF (HR 1.45).