Human epididymis protein 4 is a useful predictor of post-operative prognosis in patients with severe aortic stenosis

The human epididymis protein 4 (HE4), a novel fibrosis marker, is expressed only in activated fibroblasts and is thought to reflect ongoing left ventricular (LV) fibrosis. LV fibrosis is a feature of severe aortic stenosis (AS) and is related to the post-operative outcome of patients with AS. We investigated the relationship between serum levels of HE4 and the post-operative prognosis of patients with severe AS.

We measured the serum HE4 levels of 55 participants (80.8 ± 8.0 years old, male n = 26, 46%) with severe AS prior to surgical aortic valve replacement (n = 31, 56%) or transcatheter aortic valve implantation (n = 24, 44%) at Kumamoto University Hospital in 2018. We followed them for cardiovascular (CV) death or hospitalization for heart failure (HF) for 3 years. Serum HE4 levels were positively correlated with computed tomography-extracellular volume (CT-ECV) values (r = 0.53, P = 0.004). Kaplan-Meier curves demonstrated a significantly higher probability of hospitalization for HF or CV-related death in the patients with high HE4 (greater than the median HE4 value) compared with the patients with low HE4 (lower than the median HE4 value) (log-rank P = 0.003). Multivariate analysis showed HE4 (log(HE4)) to be an independent prognostic factor [hazard ratio (HR): 7.50; 95% confidence interval (CI): 1.81-31.1; P = 0.005]. Receiver operating characteristic (ROC) curve analysis suggested that HE4 is a marker of increased risk of CV-related death or hospitalization for HF at 3 years after surgery, with an area under the curve (AUC) of 0.76 (95% CI: 0.62-0.90; P = 0.003).

We found that HE4 is a potentially useful biomarker for predicting future CV events in patients scheduled for AS surgery. Measuring serum HE4 values could help consider AS surgery.