Vericiguat to slow calcific aortic valve narrowing

Inclusion Criteria:

1. The participant agrees to enter this clinical trial and consents to long-term follow-up;
2. 35 ≤ age \< 80 years;
3. Echocardiographically confirmed mild-to-moderate (peak aortic jet velocity ≥ 2.5 m/s and \< 4.0 m/s, aortic valve area \> 1.0 cm², and mean aortic valve pressure gradient \< 40 mmHg) non-rheumatic aortic valve stenosis;
4. Baseline aortic valve calcium score (Agatston score) ≥ 200 AU as measured by cardiac CT;
5. Male participants, or female participants who are not of childbearing potential, or female participants who commit to avoiding pregnancy through 4 weeks after the end of the trial.

Exclusion Criteria:

1. Severe aortic stenosis (AS peak velocity ≥ 4.0 m/s, or mean transvalvular aortic pressure gradient ≥ 40 mmHg, or aortic valve area ≤ 1.0 cm², or indexed effective aortic valve area \< 0.6 cm²/m²), or very mild stenosis (AS peak velocity \< 2.5 m/s), or a planned aortic valvuloplasty/replacement procedure;
2. Concomitant severe mitral or tricuspid valve disease (moderate or greater mitral or tricuspid regurgitation, or prior mitral or tricuspid valve repair/valvuloplasty/replacement);
3. Concomitant moderate or greater aortic regurgitation;
4. Use, within 1 month prior to the screening visit, of medications affecting the NO-sGC-cGMP pathway (e.g., sildenafil, nitrates, etc.), or known hypersensitivity to vericiguat or its components;
5. Left ventricular ejection fraction (LVEF) \< 50%, or NYHA class III-IV (see Appendix 4 for NYHA classification criteria);
6. Presence of a malignancy (except those with an expected cure) or other serious non-cardiac disease with a life expectancy of less than 3 years;
7. Rheumatic valvular heart disease;
8. Systolic blood pressure (SBP) \< 120 mmHg, or a history of symptomatic hypotension, or a history of hemodynamic instability or hypovolemia within the 4 weeks prior to screening;
9. Presence of hypertrophic obstructive cardiomyopathy (outflow tract obstruction defined as a peak left ventricular outflow tract pressure gradient ≥ 30 mmHg at rest or after provocative testing);
10. Infective endocarditis or complex congenital heart disease;
11. Estimated glomerular filtration rate \< 15 mL/min/1.73 m², or on dialysis;
12. Severe pulmonary disease requiring continuous home oxygen therapy;
13. Interstitial lung disease;
14. Concomitant disorder of calcium-phosphate metabolism;
15. Current use of warfarin;
16. ALT and AST ≥ 3 times the upper limit of normal, or severe hepatic insufficiency (e.g., cirrhosis, chronic active liver disease);
17. Inability to undergo contrast-enhanced CT, or contrast media allergy;
18. Concomitant acute myocarditis, cardiac amyloidosis, cardiac sarcoidosis, or stress (takotsubo) cardiomyopathy;
19. Presence of acute coronary syndrome (including unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction) within 60 days prior to randomization, or an indication for coronary revascularization (percutaneous intervention/bypass surgery); or a need for coronary revascularization identified at the time of randomization;
20. History of cerebrovascular accident (including TIA or stroke) within 60 days prior to randomization;
21. Psychiatric disorder or legal incapacity precluding the ability to provide informed consent;
22. Any medical condition, circumstance, or history that, in the investigator's judgment, would compromise the participant's ability to participate in or complete the study.