The Effect of Ramipril in Suppressing ST2 Expression in Rheumatic Mitral Stenosis Patients

Objective propose: to investigate the effect of Ramipril in suppressing ST2 (suppression of tumorigenicity 2) in the cardiac mitral valve in patients with Rheumatic Heart Disease. We hypothesized that we hypothesized that ramipril will improve rheumatic mitral valve fibrosis through the downregulation of ST2.

The efficacy of secondary prevention is limited in the prevention of RHD progression. For this reason, new strategies and therapies are needed to prevent the progression of RHD. Neutralizing inflammatory cytokines or antagonizing their receptor function has been considered as a useful therapeutic strategy to treat autoimmune diseases. In this respect, new therapies targeting ST 2 and their receptors as studied in some autoimmune diseases may promise a new approach for patients with RHD. Angiotensin II induces the upregulation of Transforming growth factor β (TGF-β) and latter the binding of IL-33 to sST2 and not to the natural ligand (ST2L). The binding of IL-33 to sST2 will cause fibrogenesis even more. Thus, ACEI is hypothesized to attenuate this vicious cycle through the inhibition of Angiotensin II and consequently increase Bradykinin that furtherly inhibits fibrosis through the negative regulation of angiotensin II activity in Mitogen Activator Protein Kinase (MAPK) pathways through the suppression of the Ca2+ response and the Na+ transportACE inhibitor were agents with anti-fibrosis effects. The investigators keen to investigate the effect of Ramipril in suppressing ST2 expression as biomarkers of fibrosis in cardiac mitral valve in patients with Rheumatic Heart Disease in the National Cardiac Center Harapan Kita hospital Jakarta Indonesia. This study was designed as a randomized clinical trial. Patients with mitral stenosis valvular dysfunction due to rheumatic process planned for cardiac valve replacement surgery were given Ramipril or placebo for a minimum of 12 weeks (3 months). ST2 expression will be analyzed as the fibrosis biomarker in the mitral valve. This study will be conducted in the Department of Cardiology and Vascular Medicine, University Indonesia, National Cardiac Center Harapan Kita Hospital, Jakarta, Indonesia from June 2019

Eligibility Criteria:
Inclusion Criteria:

* Patients with mitral valve stenosis or a combination
* aged more than 18 years
* undergo cardiac valve replacement operation with or without a tricuspid valve repair,
* patients with systolic blood pressure (SBP) ≥ 100 mmHg and diastolic blood pressure (DBP) ≥ 60 mmHg
* passed in medication phase without side effect minimum 4 weeks until operation schedule

Exclusion Criteria:

1. Patients with congenital heart disease
2. patients with non-mitral valve surgery
3. patients with coronary artery bypass surgery
4. patients who refuse to join this study.
5. adults aged over 65 years or older
6. pregnant women
7. patients with autoimmune disease.
8. Patients with persistent hypotension (systolic blood pressure (BP) \< 100 mm Hg)
9. severe aortic stenosis (aortic valve orifice \< 0.75 cm2 )
10. chronic renal dysfunction with serum creatinine \> 2.5 mg/ dL,
11. known ACEI intolerance.