Top Things to Know: Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets
Published: June 17, 2024
Prepared by Katherine A. Sheehan, PhD
- VHD includes diseases such as stenosis or regurgitation of the aortic, mitral, tricuspid, or pulmonary valves, contributing significantly to global morbidity and mortality.
- In contrast to atherosclerotic CVD, there are no medical therapies available to prevent or slow the progression of VHD and severe VHD is treated with valve replacement or repair procedures.
- Cardiac valves have a complex anatomy that enables forward blood flow through a range of pressures due to ventricular contraction. Valve leaflets are composed of tissue layers containing collagen, proteoglycans, and elastin, providing the structure and flexibility needed for proper valve function.
- Calcific aortic valve disease (CAVD) is a common pathology of the aortic valve disease process, resulting in aortic stenosis (AS), the most common valvular heart disease globally, and aortic regurgitation. Although there is ongoing research on the molecular mechanisms for valve calcification and several potential therapeutic targets identified, more studies are needed.
- Congenital bicuspid and unicuspid aortic valves are the most common valve malformations, where valves may be fused or absent. While a heritable condition, a genetic basis for the disease has not yet been identified.
- Mitral valve disease is also common and can lead to regurgitation into the left atrium or prolapse. Several potential contributing genes and enzymes have been identified that may evolve as potential therapeutic targets.
- More is known about the pathology of rheumatic heart disease (RHD), an auto-immune disease. About 80% of cases are in women. Studies suggest that binding of autoantibodies to the valve surface increases the expression of molecules that promote inflammation. Primary treatment of acute group A streptococcus infection is critical to RHD treatment.
- Right sided VHD in adults are generally secondary to left sided heart disease although a few occur as primary conditions.
- Although there are advances in identifying the mechanisms that underlie the development of VHD, the primary drivers of early development are still unknown, highlighting the need for additional research.
- To build on recent advances in the search for the molecular mechanisms underlying primary VHD with potential for early-stage therapeutics, future research will require translational study designs to bridge the gap between bench and bedside to evaluate the clinical efficacy of target drug candidates, as well as attention to factors such as cost and accessibility.
Citation
Small AM, Yutzey KE, Binstadt BA, Voigts Key K, Bouatia-Naji N, Milan D, Aikawa E, Otto CM, St. Hilaire C; on behalf of the American Heart Association Council on Genomic and Precision Medicine; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; and Council on Cardiovascular and Stroke Nursing. Unraveling the mechanisms of valvular heart disease to identify medical therapy targets: ascientific statement from the American Heart Association. Circulation. Published online June 17, 2024. doi: 10.1161/CIR.0000000000001254