Aortic Valve Stenosis Clinical Trials

Aortic stenosis (AS) is a serious and common condition that affects 2-3% of the population >65 years of age in Western countries. It is also responsible for extraordinarily high healthcare expenditures, estimated to be over $6 billion annually,2 in part because the primary treatment for severe AS is aortic valve replacement (AVR) which is resource-intensive. Valve abnormalities are frequently recognized before AS becomes severe, or before there is need for guideline-directed procedural intervention, thereby providing an opportunity for pharmacologic intervention to slow disease progression. Yet, all attempts to prevent AS progression in those with degenerative non-congenital forms of disease have failed. The only non-procedural intervention that benefits patients with moderate or greater AS is the aggressive treatment of hypertension, which reduces net left ventricular (LV) afterload (valvulo-arterial impedance [Zva]) and can slow secondary LV remodeling. The overall goal of this proposal is to integrate advanced imaging and vascular biology to study how von Willebrand factor (VWF) and platelet adhesion promote AS progression through many parallel pathways, thereby representing a potential therapeutic target. We are hypothesizing that blood markers of abnormal VWF proteolysis and platelet-derived factors, and abnormal valve shear patterns which can be detected by advanced analysis of spectral Doppler on echocardiography are predictors for progressive AS. Read Less

The TVT Registry™ is a benchmarking tool developed to track patient safety and real-world outcomes related to the transcatheter aortic valve replacement (TAVR) procedure. Created by The Society of Thoracic Surgeons (STS) and the American College of Cardiology (ACC), the TVT Registry is designed to monitor the safety and efficacy of this new procedure for the treatment of aortic stenosis. Read Less

Common barriers to receiving appropriate guideline-driven care for patients with severe aortic stenosis include referral biases by primary care providers (lack of provider education), patient comorbidities (degree of fragility), as well as psychosocial issues and cultural barriers. Additionally, race, ethnicity, socioeconomic status (SES) and education level are shown to be persistent barriers to accessing healthcare services and healthcare systems, creating a significant practice gap between various patient populations. The most recent transcatheter valve therapies (TVT) registry data show that >94% of TAVR recipients are Caucasian, followed by less than 4% of African-Americans and Hispanics, respectively. There is a critical need to understand the barriers to treatment and care among severe aortic valve disease patients of disparate groups. This study is a multi-center, retrospective and prospective cohort study of patients diagnosed with severe aortic stenosis. Additionally, we will be surveying referring primary care providers, cardiologists and cardiovascular surgeons to assess their current referral practices for patients with severe aortic stenosis. Read Less

The overall goal of this PET-MR imaging trial is to evaluate 11C-Martinostat, a histone deacetylase targeted radioligand, in patients with aortic stenosis, individuals with diabetes, and healthy volunteers. Read Less

In this study, the investigators evaluate whether routine double inflation of the valve could have a lasting impact. The investigators hypothesize that a routine second reinflation of the balloon, or "double tap", will improve flow across the valve when compared to a single inflation. The investigators hypothesize that "double tap" (1) will decrease mean gradient between first and second inflation during the procedure, (2) will decrease mean gradient on immediate post procedure and 30 day postprocedure echocardiograms when compared to mean gradient gradient after single inflation. Less obstruction indicated by lower mean gradient early after deployment may translate to improved 5 and 10 year outcomes. Furthermore, the investigators hypothesize that this small change in technique will have no effect on procedure time or complications and the change will not result in any increase in perioperative vascular complications, or new permanent pacemaker insertion. The primary objective of this study is to determine if double valve inflation during a TAVR procedure improves valve area and mean gradients as measured by echocardiogram immediately following the procedure and at 30 days follow up. Read Less

Low-flow, low-gradient (LF-LG) aortic stenosis (AS) may occur with depressed (i.e. Classical LF; CLF) or preserved (i.e. Paradoxical LF; PLF) LV ejection fraction (LVEF) and both situations are amongst the most challenging encountered in patients with valvular heart disease. Although, CLF-LG AS is recognized has an important clinical entity, current ACC/AHA-ESC guidelines however do not provide precise recommendations for clinical management of these patients . PLF-LG AS is a new entity recently described by our group, which is characterized by more pronounced LV concentric remodeling with smaller LV cavity size and a restrictive physiology leading to impaired LV filling, altered myocardial function, and a low-flow state. Up to recently, this entity was often misdiagnosed, leading to underestimation of AS severity and inappropriate delays for aortic valve replacement surgery (SAVR). The two main challenges in patients with CLF- or PLF- LG AS are to distinguish between a true-severe (TS) versus a pseudo-severe (PS) stenosis and to accurately quantify the extent of myocardial impairment. Unfortunately, the traditional resting and stress echocardiographic parameters currently used to assess the severity of valvular and myocardial dysfunction in patients with LF-LG AS are far from being optimal, and as a consequence, quantification of disease severity and therapeutic management may not be appropriate in a substantial proportion of these patients. THE GENERAL OBJECTIVES of the TOPAS study are to develop and validate new parameters and biomarkers to improve the assessment of stenosis severity and myocardial impairment, the risk-stratification, and the clinical decision making in patients with LF-LG AS and to assess the impact of the different therapeutic strategies on patient outcomes. Read Less