Sacubitril/valsartan treatment: effect on left ventricular remodelling and fibrosis assessed by novel heart failure biomarkers
Authors: Robles Mezcua A , Diaz Exposito A , Robles Mezcua M , Cruzado Alvarez C , Jimenez Navarro M , Garcia Pinilla J M 
Published: October 2022

Abstract

Background
In patients with heart failure and reduced ejection fraction (HFrEF), treatment with sacubitril-valsartan (SAC/VAL) reduces N-terminal B-type natriuretic peptide (NT-proBNP) levels and appears to have a beneficial effect on ventricular remodelling (VR), although the mechanism of this effect has yet to be established. ST2 is a novel biomarker reflecting inflammation and haemodynamic stress, closely related to the pathophysiology of heart failure (HF), fibrosis and VR. Several studies have shown that elevated levels of ST2 are associated with increased risk of developing HF and worse prognosis, being an independent predictor of adverse clinical outcomes, and even establishing a correlation with clinical changes and NT-proBNP levels.

Purpose
To evaluate the effect of SAC/VAL treatment on left ventricular remodelling and fibrosis in patients with HFrEF by monitoring ST2 and NTproBNP levels during follow-up.

Methods
Prospective single-centre, open-label, single-group, prospective study including patients with HFrEF and NYHA functional class II–IV, under follow-up in our HF Unit from April 2018 to July 2020 with a 12-month follow-up for each patient. Biomarker measurements and echocardiography were performed at baseline, 6 and 12 months after initiation of SAC/VAL treatment. In addition, cardiac magnetic resonance imaging (CMRI) was performed at baseline and after 12 months of treatment.

Results
68 patients were included (mean age 65.63±11.78 years; 29.4% female). Baseline characteristics are shown in table 1. The mean baseline NT-proBNP and ST2s concentration was 2238.24±2148.65 pg/mL and 42.31±28.38 ng/mL respectively, with a statistically significant reduction after 12 months with SAC/VAL (NTproBNP 701.65±778.13 pg/mL and ST2 30.22±9.70 ng/mL; p&lt;0.01 in both cases). In addition, there was an improvement in left ventricular ejection fraction (LVEF) on echocardiography from 31.01±5.65% at baseline to 45.03±9.45% at 12 months (p&lt;0.01). We also observed a statistically significant reduction in left ventricular end-diastolic and end-systolic diameter at 12 months from baseline (60.86±4.99 mm and 57.35±5.36 mm, p&lt;0.01; 40.70±3.76 mm and 37.23±4.37 mm, p&lt;0.01). These data suggesting reverse remodelling were also confirmed with CMRI, finding improved LVEF (32.90±6.65% vs 46.22±11.1%, p&lt;0.01) and reduced end-diastolic (192.06±60.63 and 160.73±49.68, p&lt;0.01) and end-systolic (125.28±52.07 and 90.74±41.79, p&lt;0.01) volumes. During follow-up there were no alterations in renal function (creatinine 0.98±0.28 mg/dL at baseline, 1.03±0.32 mg/dL at 12 months, p=0.04) or potassium levels (4.50±0.40 mEq/L at baseline, 4.76±0.38 mEq/L at 12 months, p=0.22).

Conclusion
SAC/VAL treatment is associated with a reduction in NT-proBNP and ST2 concentrations which seems to support its beneficial effect on ventricular remodelling, allowing its monitoring to assess the evolution and prognosis of HF patients.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): Novartis