Novel biomarkers distinguish heart failure with preserved vs reduced ejection fraction

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.

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. Heart failure with preserved ejection fraction 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 = .04) and left ventricular function (LV-GLS; β = 1.29;P = .03) and left atrial strain (LA-GLS: β = 5.03;P < .001) whereas higher IGFBP7 and MYBPC3 with diastolic dysfunction (E/e': β = 4.09;P = .02 and β = 1.36;P = .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 1.45(95% CI 1.00-2.13)] more strongly in HFpEF and IGFBP7 [2.51(0.95-6.64)] more strongly in HFrEFand MYBPC3 [1.62(0.99-2.64)].

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.

ClinicalTrials.gov NCT00774709.