Active clinical trials for "Aortic Valve Stenosis"

The VIVALL-2 study is a randomized trial to compare the self-expandable supra-annular Allegra and the balloon-expandable intra-annular Edwards transcatheter valve systems in patients with degenerated biological aortic surgical valve.

Calcific aortic stenosis (AS) has become the most common cardiac disease after coronary artery disease and hypertension. Unfortunately no medical therapies have been proven to decrease either the progression of valve stenosis or the resulting adverse effects on myocardial remodeling and function. In light of the studies performed in PROGRESSA, it becomes obvious that: i) AS is a complex and actively regulated process that involves the interaction of several pathways including lipid infiltration and retention, chronic inflammation, osteogenic activation, and active mineralization within the valvular tissues; ii) AS is not a disease strictly limited to the aortic valve but rather a systemic disease that often involves calcification and stiffening of the aorta and impairment of LV function as a consequence of pressure overload. Our findings suggest that the dysmetabolic milieu linked to visceral obesity may accelerate the deterioration of the structure and function not only of the aortic valve but also of the aorta and of the left ventricle. These findings open new avenues of research and provide strong impetus for the elaboration of prospective studies focusing on the "valvulo-metabolic risk" in AS. The general hypotheses are: The metabolic abnormalities linked to visceral obesity accelerate (1) the progression of valvular calcification and stenosis, aortic calcification and stiffness; (2) the progression of myocardial fibrosis and dysfunction. The general objectives of the study are to elucidate the mechanisms implicated in the pathogenesis of AS and to identify the metabolic factors that determine the progression of: i) aortic valve calcification and stenosis; ii) myocardial fibrosis and dysfunction; and iii) clinical outcomes. This study will contribute to identifying the key metabolic determinants of AS progression and will pave the way for the future development of non surgical therapies for this disease. The results of this study would provide strong support to the realization of randomized trial to test the efficacy of lifestyle modification program or new pharmacological treatment aiming at the reduction of visceral fat and associated metabolic abnormalities in the AS population. Furthermore, this study will contribute to the identification of novel blood and imaging biomarkers of faster disease progression, which will help to optimize risk stratification and timing of AVR in the AS population.

The primary aim of the present study was to examine the haemodynamic changes in primary hypertension and secondary hypertension (renal diseases, endocrine diseases, obesity-associated hypertension) with a non-invasive haemodynamic measurement protocol utilizing radial pulse wave analysis and whole-body impedance cardiography in both supine position and during head-up tilt. For comparison, haemodynamics of subjects with chronic fatigue syndrome will also be recorded.

Traditional and transcatheter surgical treatments of severe aortic valve stenosis (SAVS) are increasing in parallel with the improved life-expectancy. Recent randomized trials (RCTs) reported comparable or non-inferior mortality with transcatheter treatments compared to traditional surgery. However, RCTs have the limitation of being a mirror of the predefined inclusion/exclusion criteria, without reflecting the "real clinical world". Technological improvements have recently allowed the development of minimally invasive surgical accesses and the use of sutureless valves, but their impact on the clinical scenario is difficult to assess because of the monocentric design of published studies and limited sample-size. A prospective multicentre registry including all patients referred for a surgical treatment of SAVS (traditional, through full-sternotomy; minimally-invasive; or transcatheter; with both "sutured" and "sutureless" valves) will provide a "real-world" picture of available results of current surgical options, and will help to clarify the "grey zones" of current guidelines. E-AVR is a prospective observational open registry designed to collect all data from patients admitted for SAVS, with or without coronary artery disease, in 16 cardiac surgery Centres located in six countries (France, Germany, Italy, Spain, Switzerland, and United Kingdom). Patients will be enrolled over a 2-year period and followed-up for a minimum of 5 years to a maximum of 10 years after enrolment. Outcome definitions are concordant with VARC-2 criteria and established guidelines. Primary outcome is 5-year all-cause mortality. Secondary outcomes aim at establishing "early" 30-day all-cause and cardiovascular mortality, as well as major morbidity, and "late" cardio-vascular mortality, major morbidity, structural and non-structural valve complications, quality of life and echocardiographic results. The study protocol is approved by Local Ethics Committees. Any formal presentation or publication of data will be considered as a joint publication by the participating physician(s) and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE) for authorship.

Background: People with Williams Syndrome (WS) and supravalvular aortic stenosis (SVAS) have less elasticity in their blood vessels. This is called blood vessel stiffness. Blood vessels may have focal narrowings called stenoses or may just be globally more narrow. Objectives: Researchers want to see how blood vessel differences in people with Williams Syndrome and supravalvular aortic stenosis affect organs in the body including the heart, gut, kidneys, and brain. Eligibility: People ages 3-85 who have WS or SVAS Healthy volunteers ages 3-85 Design: Participants will have yearly visits for up to 10 years. All participants will be offered the same tests. Participants will give consent for the study team to review their medical records. If the participant is a child or an adult with WS, a parent or guardian will give the consent. Participants will visit the NIH where they will have a physical exam and medical history. Based on their health history, participants will undergo a series of imaging tests and measures of blood vessel function over the course of 2-4 days. Tests of cognitive abilites will also be performed. Blood will be drawn and an IV may be placed for specific tests.

Background: DNA tells the body how to grow and function. Williams-Beuren syndrome (WS) and Supravalvular Aortic Stenosis (SVAS) are rare diseases caused by changes in a part of a person s DNA. Symptoms of both conditions include vascular problems including narrow blood vessels and supravalvular aortic stenosis (SVAS) or supravalvular pulmonary stenosis. Individuals with WS may also have developmental challenges and personality differences. Researchers at the NIH want to find out why only some people with WS and SVAS have severe symptoms. They want to collect samples and data to see what DNA or environmental changes affect the severity of the disease. Objective: To identify the DNA differences or environmental changes that change the severity of WS and SVAS from person to person. Eligibility: People ages 0-85 with either WS, SVAS, and/or an SVAS-like condition Children and people with WS must have a parent or legal guardian to consent or help answer questions. Design: Participants will be screened with questions and medical history. Participants will have a 60-minute visit. They will provide blood or saliva samples. They or their parent/guardian will: Answer questions about how WS and SVAS affect them. Sign a form releasing their medical records for the study. If participant s regular doctor recommends surgery, researchers will ask the surgeon for skin or tissue samples that they might otherwise discard. These will be used to create stem cells to study in a lab. For up to 20 years, participants will have annual questionnaires by phone, email, or mail about their WS or SVAS. Participants may also be contacted if: They need to provide a new blood or saliva sample. Researchers need any other data. There is a follow-up study.

Transcatheter aortic valve replacement (TAVR) represents an effective treatment to improve symptoms and prognosis in patients with symptomatic severe aortic stenosis (AS) (1-2). Giving an established uniform approach towards anticoagulation and antithrombotic therapy after TAVR in the post POPULAR-TAVI era, recent data coming from the analysis of different trials, highlight the relevance of the patient's background on the occurrence of ischemic and bleeding events. Despite this a targeted antithrombotic strategy remains unexplored and all patients undergoing TAVR without other indication to DAPT or OAC, were currently treated according with the concept of "less is more" (only SAPT or only OAC) regardless the risk level (5-6). The keys points of the project will be 1) the assessment of ischemic and bleeding risk after TAVR stratified according with antithrombotic therapy and surgical risk; 2) the evaluation of the impact of prostheses type and the complete blood count variables (hemoglobine and platelets) on the daily average ischemic and bleeding risk and 3) the evaluation of the dynamic therapeutic changes after TAVR during the follow up.

The objective of ENVISION is to evaluate the safety and effectiveness of the Navitor Transcatheter Aortic Valve Implantation (TAVI) System for treating patients with symptomatic, severe native aortic stenosis who are considered intermediate or low risk for surgical mortality.

Rationale: Transcatheter aortic valve implantation (TAVI) has become the standard therapy for elderly patients with high surgical risks. Paravalvular leakage after TAVI is relatively common and there is conflicting evidence regarding the clinical impact of mild paravalvular leakage in self-expanding devices. Prospective data for self-expanding devices are required to compare the extent of paravalvular leakage as a result of device design. Grading paravalvular leakage after TAVI is difficult. Echocardiography and angiography systematically underestimate paravalvular leakage (PVL) as compared to cardiac MRI. Hemodynamic measurements are used to aid decision making directly after TAVI implantation. Prospective data comparing hemodynamic measurements with cardiac MRI are needed to design an optimal strategy to grade paravalvular leakage peri-operatively in order to optimize TAVI outcomes. Objective: To assess procedural hemodynamic measurements in patients with paravalvular regurgitation quantified by means of cardiac MRI (CMR) and to analyse its association with impaired clinical outcome during 5-year follow-up. Study design: This is a prospective, single center clinical trial. Patients will receive a TAVI. After implantation different hemodynamic indices of paravalvular leakage will be assessed. At 1 month a cardiac MRI will be performed to quantify the amount of paravalvular leakage. Standardized clinical follow-up will take place at discharge, 30 days, 3 months and yearly up to 5 years. Study population: Approximately 80 patients with severe symptomatic aortic valve stenosis with an indication for TAVI will be included. Intervention: Patients will undergo cardiac MRI on top of standard clinical care within 30 days after TAVI. Main study parameters/endpoints: The primary endpoint is defined as paravalvular leakage regurgitation fraction as measured by cardiac MRI. The secondary endpoint will comprise a composite of device success, early safety and clinical efficacy as defined by the Valve Academic Research Consortium-2 (VARC-2)(1) and will comprise death, vascular complications, stroke/ Transient Ischemic Attack (TIA), life threatening bleeding requiring transfusion, and acute kidney injury requiring dialysis.

Aortic stenosis (AS) is caused by narrowing of one of the main heart valves. Replacing the valve is the only treatment to prevent the heart from failing or death. The timing of replacement is currently often too late - half of patients are left with permanent scarring and a quarter die within 3.5 years. Studies are underway to see if earlier replacement makes a difference. But for those with scarring of the heart, there is currently no tailored treatment. I want to change this by understanding why and how patients with scar are dying and what the investigators can do to prevent this. In this study, the investigators will use a heart scan (MRI) to detect scarring before valve replacement. After replacement, patients will receive a tiny monitor (paper clip size), which the investigators inject underneath the skin. This monitor continuously checks the heartbeat and can detect increased body fluid due to heart failure. The investigators will monitor patients for an average of 3 years to see if scarring is linked to abnormal heart rhythms and heart failure. Once the investigators know how and why, the investigators can target patients with available medications and design studies using specialised treatments, eg defibrillator implantation, to protect patients with scar from dying.