Research Funding

ABSTRACT: Approximately 5-10% of older adults have aortic stenosis (AS) with anticipated doubling by 2050; with no available medical therapy to slow progression, treatment is limited to aortic valve replacement (AVR). While AVR has historically been reserved for symptomatic severe AS, cardiac remodeling and irreversible injury occur before the onset of symptoms and before AS is "severe" and contribute to death and persistent heart failure (HF) symptoms/rehospitalization in up to 40% of patients 1 year after AVR, suggesting that AVR before onset of irreversible changes to the heart is likely to improve post-AVR outcomes. Fortunately, randomized strategy trials are underway to test the benefit of earlier less invasive transcatheter AVR (TAVR) before symptoms and severe AS. However, earlier TAVR isn't a panacea; beyond inherent procedural risks, this will also lead to more repeat procedures (with risks/costs) when prosthetic valves degenerate. Echocardiography and standard biomarkers (e.g

Aortic stenosis (AS) is a valve condition that affects over 12.6 million adults and causes an estimated 102,700 deaths each year. Many patients with AS do not know about the diagnosis because it is difficult to diagnose with a stethoscope. It is estimated that there are over 560,000 undiagnosed cases of AS in the United States alone. When patients with symptomatic AS are not treated, 50% will die in 2 years. We have developed a method to automate the diagnosis of AS from cardiac ultrasound imaging using machine learning. This represents a new way to diagnose AS. In this proposal we will improve these networks to reliably identify severe AS patients that should be referred for evaluation. Additionally, we will train the networks to work with portable handheld ultrasound devices and we will study how to implement this tool in primary care offices to screen high risk patients. By developing and validating innovative machine learning (ML) methods for diagnosing AS we will establish tools t

The prevalence of calcific aortic valve disease (CAVD) is highest among adults ≥75 years old and aortic valve calcium (AVC) is the primary underlying cause leading to aortic stenosis (AS). As the US life expectancy continues to increase, the number of adults with severe AS is expected to double between 2025 and 2050 to 1.4 million. However, the true burden of AVC extends beyond AS, as AVC is also associated with an increased risk for dementia and stroke. Unfortunately, most research in this area has excluded adults ≥75 years old and as a result, there is no established algorithm to identify high-risk persons. Furthermore, there is no treatment to slow or prevent AS, making it both understudied and one of the very few cardiovascular diseases without a proven preventive therapy. Elevated levels of LDL-C and lipoprotein(a) [Lp(a)] lead to infiltration of the aortic valve leaflets, which is worsened by higher levels of inflammation (e.g. hsCRP). However, prior trials investigating lipid l

ABSTRACT Supravalvular aortic stenosis (SVAS) is characterized by focal narrowing of the aorta that increases the risk for sudden cardiac death. SVAS is caused by mutations in the elastin gene that lead to decreased elastin amounts and there are currently no pharmaceutical treatments. The mechanisms by which elastin insufficiency cause SVAS are not well understood. Elastin is a critical mechanical component of the aorta and contributes to the passive stiffness (or modulus) that determines how much the aorta will deform (or strain) under applied hemodynamic stresses. Strain on smooth muscle cells (SMCs) within the aortic wall affects differentiation, proliferation, and migration. Cellular transmembrane channels, including Piezo1/2, are mechanosensitive molecules that transduce mechanical changes (such as strain) into biological effects (such as differentiation). Activation of Piezo channels leads to increases in intracellular calcium that can stimulate nuclear translocation of YAP/TAZ,

ABSTRACT: Approximately 5-10% of older adults have aortic stenosis (AS) with anticipated doubling by 2050; with no available medical therapy to slow progression, treatment is limited to aortic valve replacement (AVR). While AVR has historically been reserved for symptomatic severe AS, cardiac remodeling and irreversible injury occur before the onset of symptoms and before AS is "severe" and contribute to death and persistent heart failure (HF) symptoms/rehospitalization in up to 40% of patients 1 year after AVR, suggesting that AVR before onset of irreversible changes to the heart is likely to improve post-AVR outcomes. Fortunately, randomized strategy trials are underway to test the benefit of earlier less invasive transcatheter AVR (TAVR) before symptoms and severe AS. However, earlier TAVR isn't a panacea; beyond inherent procedural risks, this will also lead to more repeat procedures (with risks/costs) when prosthetic valves degenerate. Echocardiography and standard biomarkers (e.g