Could Renin-angiotensin System Inhibitors Reduce Fibrosis in Rheumatic Heart Disease by Inhibiting Soluble Suppression of Tumorigenicity 2 (sST2)?: Systematic Review

Introduction: Fibrosis and valvular thickening are clinical signs of rheumatic heart disease (RHD), which can cause significant hemodynamic disturbances. Fibrogenesis is associated with immune processes, there is a sensitive biomarker of cardiac fibrosis called soluble suppression of tumorigenicity 2 (sST2). Soluble ST2 is affected by angiotensin II and cardiomyocyte stretch. It is hypothesised that inhibiting the angiotensin II pathway can reduce cardiac fibrosis through sST2 inhibition by renin-angiotensin system inhibitors, but clinical trials in the RHD population are limited. Thus, this study will systematically review other heart disease populations with a fibrogenesis process similar to RHD. Materials and methods: We conducted a data search on online databases: PubMed, ScienceDirect, and Google Scholar. Data screening and selection process using PRISMA flowchart. We assessed the quality of articles using the GRADE method. Results: 770 articles were obtained and 8 of them were relevant. The use of sacubitril/ valsartan compared to valsartan or enalapril was shown to significantly reduce sST2 levels at the end of the study (p< 0.05) and improved the risk of morbidity, mortality, hospitalisation, and echocardiographic outcomes. Objective parameters that showed sST2 reduction indirectly reduced cardiac fibrosis were decreased left ventricular end-diastolic volume index (p= 0.02), left ventricular end-systolic volume index (p= 0.045), left atrial volume index (p< 0.001), and mitral E/e′ ratio (p= 0.001). Conclusion: Although this study did not directly utilize the RHD patient population, therapy using renin-angiotensin system inhibitors may reduce the incidence of cardiac fibrosis through the sST2 inhibition pathway in conditions with similar pathogenesis.