Cholesterol crystal induced inflammation and mechanical cardiac valve injury: Implications for transcatheter aortic-valve replacement

Author(s): Manel Boumegouas, Abdullah Al-Abcha, Layan Elkhatib, Oliver G. Abela, Zulfiqar O. Baloch, Levi Fry, George S. Abela

The process of cardiac valve sclerosis and stenosis in non-rheumatic disease is related to inflammation via the innate immune system similar to atherosclerosis. Cardiac valve composition shares many features with arterial tissue. Cholesterol infiltration in the valve matrix results in cholesterol crystal formation and deposition that causes mechanical injury and triggers inflammation. Sclerotic human valve specimens as well as valves from atherosclerotic rabbit models reveal presence of cholesterol crystals and macrophage infiltration as seen in atherosclerosis. Lipid lowering by combination of simvastatin and ezetimibe demonstrates cholesterol reduction in valves only if used in a preventive manner. However, once the valve is infiltrated by cholesterol and crystals form in the tissue matrix, these become very difficult to extract and lipid lowering is no longer very effective. Furthermore, cholesterol crystals serve as a nidus for calcium phosphate deposition that distorts and stiffens the valve tissue leading to valve dysfunction. During Transcatheter Aortic Valve Replacement (TAVR) procedures, crystals can complicate the procedure by release of crystalline particles causing ischemic cerebral events and rupturing balloons.