Correlation between circulating fibrosis biomarkers with left atrial function and left atrial volume index in rheumatic mitral stenosis.

Mitral stenosis is the most common rheumatic heart disease (RHD) disorder worldwide, including in Indonesia. This pathological condition causes left atrial pressure, leading to left atrial fibrosis that affects the structure and function of the left atrial as well as the clinical condition. The aim of this study was to assess the correlation between circulating fibrosis biomarkers with net atrioventricular compliance (Cn) as a parameter of left atrial function, and left atrial volume index (LAVI) as a parameter left atrium structure of changes. A cross-sectional study was conducted at Panti Rahayu Hospital and Permata Bunda Hospital, Purwodadi, Central Java, with a total of 40 RHD patients with severe mitral stenosis. The ELISA was used to measure the levels of carboxy-terminal propeptide of type I procollagen (PICP), matrix metalloproteinase I (MMP-1), tissue inhibitor matrix metalloproteinase 1 (TIMP-1), and transforming growth factor-ß1 (TGF-ß1). The left atrial function was assessed by measuring Cn, and the LAVI parameters were measured to assess left atrium structure/size. The mean levels of circulating fibrosis biomarkers were as follows: PICP 153.96±89.12 ng/mL; MMP-1 1.44±2.12 ng/mL; MMP-1/TIMP-1 ratio 0.38±0.54 and TGF-ß1 2.66±1.96 pg/mL. From the echocardiographic evaluation, the mean Cn was 5.24±1.93 mL/mmHg and the mean LAVI was 152.55±79.36 mL/m2. There were significant correlation between MMP-1 and MMP-1/TIMP-1 ratio with Cn (r=0.345 and r=0.333, respectively; both had p<0.05). PICP and TGF-ß1 biomarkers did not significantly correlate with Cn (p>0.05). Meanwhile, none of the biomarkers had a significant correlation with LAVI (p>0.05). This study highlights that MMP-1 and MMP-1/TIMP-1 ratio are potentially to be used as markers to determine the Cn in RHD patients with severe mitral stenosis. However, further studies with a higher sample size are needed to confirm this finding.

Effect of Dapagliflozin on Patients with Rheumatic Heart Disease Mitral Stenosis.

(1) Background: Mitral stenosis is the most common rheumatic heart disease (RHD). Inflammation and fibrosis are the primary pathophysiology, resulting in left atrial stress and dysfunction. Dapagliflozin is a new heart failure treatment with anti-inflammation and anti-fibrosis effects from previous studies. However, the specific role of dapagliflozin in RHD mitral stenosis is unknown. This study aims to investigate (i) the effect of dapagliflozin on biomarkers of fibrosis, NT-pro BNP levels and left atrial function; (ii) the relationship between the changes in fibrosis biomarkers with left atrial function and NT-pro BNP levels. (2) Methods: An open-label randomized study was conducted on 33 RHD mitral stenosis patients divided into a dapagliflozin group which received 10 mg dapagliflozin and standard therapy, and a control group which only received standard therapy. All patients were examined for levels of PICP, MMP-1/TIMP-1 ratio, TGF-ß1, NT-proBNP, mitral valve mean pressure gradient (MPG), and net atrioventricular compliance (Cn) pre- and post-intervention. (3) Results: This study found a significant increase in PICP and TGF-ß1 and a reduction in the MMP-1/TIMP-1 ratio in the dapagliflozin group and the control group (p < 0.05). In the dapagliflozin group, the levels of NT-pro BNP decreased significantly (p = 0.000), with a delta of decreased NT-pro BNP levels also significantly greater in the dapagliflozin group compared to the control (p = 0.034). There was a significant increase in Cn values in the dapagliflozin group (p = 0.017), whereas there was a decrease in the control group (p = 0.379). Delta of changes in Cn values between the dapagliflozin and control groups also showed a significant value (p = 0.049). The decreased MPG values of the mitral valve were found in both the dapagliflozin and control groups, with the decrease in MPG significantly greater in the dapagliflozin group (p = 0.031). There was no significant correlation between changes in the value of fibrosis biomarkers with Cn and NT-pro BNP (p > 0.05). (4) Conclusions: This study implies that the addition of dapagliflozin to standard therapy for RHD mitral stenosis patients provides benefits, as evidenced by an increase in net atrioventricular compliance and decreases in the MPG value of the mitral valve and NT-pro BNP levels (p < 0.05). This improvement was not directly related to changes in fibrosis biomarkers, as these biomarkers showed ongoing fibrosis even with dapagliflozin administration.