HUMAN EPIDIDYMIS PROTEIN 4 (HE4) IS ASSOCIATED WITH OUTCOME IN LOW-FLOW, LOW-GRADIENT AORTIC STENOSIS

Abstract

Plasma level of Human Epididymis protein 4 (HE4) has been shown to be associated with increased risk of mortality in patients with heart failure. The objective of this study was to examine the prognostic value of HE4 in patients with low-flow, low-gradient aortic stenosis (LF-LG AS) with either preserved or reduced LVEF. Eighty patients (mean age: 73±10 year; 75% men) with LF-LG AS (LVEF < 50% and/or stroke volume index [SVi] < 35 ml/m2, mean gradient < 40 mmHg, and indexed aortic valve area < 0.6 cm/m2) prospectively enrolled in the True or Pseudo-severe Aortic Stenosis (TOPAS) study were included in this analysis. Forty-seven patients (58%) underwent aortic valve replacement (AVR) within 3 months following inclusion. The cohort was divided into two groups according to the median value of HE4 plasma levels (90 pmol/l). The primary endpoint was all-cause mortality. Patients with higher HE4 plasma level were older and had lower LVEF (all p < 0.05). Twenty-seven patients died during a median follow-up of 2.8 years [IQR=1.2-4.0]. The 3-year survival rate was significantly lower in patients with higher HE4 plasma level (65±8% vs. 93±7%; p=0.0002). In Cox proportional hazard regression model adjusted for EuroSCORE and LVEF, HE4 ≥90 pmol/l was associated with increased risk of all-cause mortality (Model #1: HR=5.46; p=0.003). Further adjustment for type of treatment (AVR vs. conservative) provided similar results (Model #2: HR=4.78; p=0.007). HE4 remained associated with an increased mortality rate when adjusted for NTpro-BNP instead of LVEF in Model #2 (HR=4.04; p=0.01). In patients with LF-LG AS, elevated HE4 plasma level was associated with higher risk of mortality even after adjustment for clinical risk, type of treatment, LV function, and natriuretic peptide level. This new biomarker may be useful to enhance risk stratification in LF-LG AS patients.