# Serum ACE2 activity as a novel biomarker of assessment of severe aortic stenosis

## TL;DR

This study explores serum ACE2 as a new blood marker for assessing severe aortic stenosis, showing it outperforms traditional markers in detecting early heart dysfunction.

## Contribution

The study introduces serum ACE2 activity as a novel and more effective biomarker for evaluating severe aortic stenosis compared to NT-proBNP.

## Key findings

- Serum ACE2 activity increases with the severity of aortic stenosis and correlates with left ventricular dysfunction.
- ACE2 provides higher specificity than NT-proBNP in detecting subclinical left ventricular dysfunction.
- ACE2 activity can help improve clinical decision-making and timing for aortic valve replacement.

## Abstract

Aortic stenosis (AS) is the most prevalent valve disease in developed countries, with its incidence rising in the aging population. The current criteria for aortic valve replacement (AVR) are based on subjective symptoms and left ventricular ejection fraction (LVEF), which may not adequately reflect left ventricular (LV) dysfunction. This highlights the necessity for objective biomarkers to evaluate subclinical LV dysfunction. Serum angiotensin-converting enzyme 2 (sACE2) has emerged as a promising novel biomarker for cardiovascular diseases. To investigate the association between sACE2 activity and different flow-grade categories of severe AS, compare it with the traditional biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP), and assess the utility of sACE2 as a biomarker for AS. sACE2 and NT-proBNP were measured in 175 patients (97 male, 78 female, mean age 75 ± 8 years) diagnosed with severe AS (aortic valve area, AVA ≤ 1 cm2). Patients were classified into 5 groups depending on LV flow state and pressure gradient levels: normal flow-low gradient (NF-LG), normal flow-high gradient (NF-HG), low flow-high gradient (LF-HG), low flow-low gradient (LF-LG), and paradoxical low flow-low gradient (PLF-LG) AS. Both biomarkers showed a general increase with advanced stages of severe AS (NF-LG: 65.0 ± 3.5 U/ml; LF-LG: 148.1 ± 16.8 U/ml; P < 0.05 for sACE2 and NF-LG: 687 ± 193 pg/ml; LF-LG: 5966 ± 1076 pg/ml; P < 0.05 for NT-proBNP). Notably, PLF-LG patients exhibited NT-proBNP levels similar to NF groups (PLF-LG: 1010 ± 218 pg/ml). Both biomarkers negatively correlated with LVEF and AVA. Receiver operating characteristic (ROC) analysis revealed that sACE2 provides incremental value over NT-proBNP in detecting subclinical LV dysfunction, with a 44% specificity for sACE2 compared to 6% for NT-proBNP at 98,67% sensitivity. The assessment of sACE2 activity in patients with AS provides valuable insights into disease stage and progression, supporting clinical decision-making and optimizing the timing of AVR. Furthermore, sACE2 activity serves as a moderately sensitive blood biomarker for identifying patients at risk of AS.