Abstract

Objective: Angiotensin-converting enzyme 2 (ACE2) is present on endothelial cells with a role to degrade angiotensin II. In this study, we investigate plasma ACE2 levels in patients admitted with acute decompensated heart failure (ADHF) and determine if levels differ according to ejection fraction (EF). Design and Method: We prospectively recruited 9 controls and 117 ADHF inpatients, determined EF using echocardiography, measured plasma ACE2 activity using an in-house assay and NT-proBNP levels using a commercially available assay. Patients were classified according to 2021 European Guidelines as HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) or preserved EF (HFpEF). Results: In addition to NT-proBNP level, median plasma ACE2 activity was increased in ADHF patients (n = 117) compared to controls (1.33 [0.02, 4.02] vs 15.36 [9.02, 27.9] pmol/mL/min, p < 0.0001). In ADHF, plasma ACE2 activity was negatively associated with EF (r = -0.43, p < 0.0001). Overall, 58% of patients had HFrEF, 10% had HFmrEF and 32% had HFpEF. Patients with HFrEF had a higher median plasma ACE2 activity compared to those with HFpEF (18.3 [12.3, 30.0] vs 11.4 [4.8, 17.9] pmol/mL/min, p = 0.001) and higher NT-proBNP levels (p = 0.001). There was no difference in plasma ACE2 activity between patients with HFmrEF and HFpEF or HFmrEF and HFrEF. Conclusions: Plasma ACE2 activity is elevated in patients hospitalised with ADHF and is significantly higher in HFrEF compared to other types of HF. Further studies are needed to determine if measurement of plasma ACE2 can assist in better definition /classification of the patient phenotype to facilitate improved treatment.

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