cardiovascular-agents and Bicuspid-Aortic-Valve-Disease

Valvular heart diseases (VHDs) place a hemodynamic load on the left and/or right ventricle that, if severe, prolonged, and untreated, damages the myocardium, leading to heart failure and death. Because all VHDs are mechanical problems, definitive therapy usually requires valve repair or replacement. In most valve disease the onset of symptoms marks a change in disease prognosis and is usually an indication for prompt surgical correction. Echocardiography is an indispensable modality for assessing lesion severity, its effect on cardiac function, and the proper timing for lesion correction. Intervention enhanced with percutaneous options now allows patients to benefit from mechanical correction.

Topics: Aortic Valve; Bicuspid Aortic Valve Disease; Cardiovascular Agents; Echocardiography; Heart Defects, Congenital; Heart Valve Diseases; Hemodynamics; Humans; Physical Examination; Prognosis

Bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm (TAA). There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis. Insufficiency of NOTCH1 expression is highly related to BAV-TAA, but the underlying mechanism remains to be clarified.. A comparative proteomics analysis was used to explore the biological differences between non-diseased and BAV-TAA aortic tissues. A microfluidics-based aorta smooth muscle-on-a-chip model was constructed to evaluate the effect of NOTCH1 deficiency on contractile phenotype and mitochondrial dynamics of human aortic smooth muscle cells (HAoSMCs).. Protein analyses of human aortic tissues showed the insufficient expression of NOTCH1 and impaired mitochondrial dynamics in BAV-TAA. HAoSMCs with NOTCH1-knockdown exhibited reduced contractile phenotype and were accompanied by attenuated mitochondrial fusion. Furthermore, we identified that mitochondrial fusion activators (leflunomide and teriflunomide) or mitochondrial fission inhibitor (Mdivi-1) partially rescued the disorders of mitochondrial dynamics in HAoSMCs derived from BAV-TAA patients.. The aorta smooth muscle-on-a-chip model simulates the human pathophysiological parameters of aorta biomechanics and provides a platform for molecular mechanism studies of aortic disease and related drug screening. This aorta smooth muscle-on-a-chip model and human tissue proteomic analysis revealed that impaired mitochondrial dynamics could be a potential therapeutic target for BAV-TAA.. National Key R and D Program of China, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Major Project, Shanghai Science and Technology Commission, and Shanghai Municipal Education Commission.. To function properly, the heart must remain a one-way system, pumping out oxygenated blood into the aorta – the largest artery in the body – so it can be distributed across the organism. The aortic valve, which sits at the entrance of the aorta, is a key component of this system. Its three flaps (or ‘cusps’) are pushed open when the blood exits the heart, and they shut tightly so it does not flow back in the incorrect direction. Nearly 1.4% of people around the world are born with ‘bicuspid’ aortic valves that only have two flaps. These valves may harden or become leaky, forcing the heart to work harder. This defect is also associated with bulges on the aorta which progressively weaken the artery, sometimes causing it to rupture. Open-heart surgery is currently the only way to treat these bulges (or ‘aneurysms’), as no drug exists that could slow down disease progression. This is partly because the biological processes involved in the aneurysms worsening and bursting open is unclear. Recent studies have highlighted that many individuals with bicuspid aortic valves also have lower levels of a protein known as NOTCH1, which plays a key signalling role for cells. Problems in the mitochondria – the structures that power up a cell – are also observed. However, it is not known how these findings are connected or linked with the aneurysms developing. To answer this question, Abudupataer et al. analyzed the proteins present in diseased and healthy aortic muscle cells, confirming a lower production of NOTCH1 and impaired mitochondria in diseased tissues. They also created an ‘aorta-on-a-chip’ model where aortic muscle cells were grown in the laboratory under conditions resembling those found in the body – including the rhythmic strain that the aorta is under because of the heart beating. Abudupataer et al. then reduced NOTCH1 levels in healthy samples, which made the muscle tissue less able to contract and reduced the activity of the mitochondria. Applying drugs that tweak mitochondrial activity helped tissues from patients with bicuspid aortic valves to work better. These compounds could potentially benefit individuals with deficient aortic valves, but experiments in animals and clinical trials would be needed first to confirm the results and assess safety. The aorta-on-a-chip model developed by Abudupataer et al. also provides a platform to screen for drugs and examine the molecular mechanisms at play in aortic diseases.

Topics: Adult; Aged; Aorta; Aortic Aneurysm; Bicuspid Aortic Valve Disease; Cardiovascular Agents; Cell Line; Female; Humans; Lab-On-A-Chip Devices; Male; Middle Aged; Mitochondrial Dynamics; Myocytes, Smooth Muscle; Tissue Array Analysis

Topics: Aortic Valve; Atherectomy, Coronary; Bicuspid Aortic Valve Disease; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessel Anomalies; Heart Defects, Congenital; Heart Failure; Heart Valve Diseases; Humans; Stroke Volume; Treatment Outcome; Vascular Calcification; Ventricular Function, Left

In 2012, the European Society of Cardiology (ESC) published an updated version of its guidelines on the management of valvular heart disease. Novelties include the use of advanced techniques for risk stratification and prognostic evaluation, such as stress and 3D echocardiography as well as measurement of left ventricular strain by speckle tracking. Equally important is the inclusion of percutaneous valve replacement or repair procedures, reflecting their ever-increasing use in clinical practice. Finally, the importance of a multidisciplinary approach to valvular heart disease, with collaboration of multiple specialities in a heart team has been put forward. We discuss practical aspects of the diagnostic and therapeutic approach to aortic valvular disease, including an outline of the surgical indications according to the ESC guidelines.

Topics: Aortic Valve; Bicuspid Aortic Valve Disease; Cardiac Surgical Procedures; Cardiovascular Agents; Choice Behavior; Diagnostic Techniques, Cardiovascular; Heart Defects, Congenital; Heart Valve Diseases; Humans

Topics: Acute Disease; Age Factors; Aneurysm, False; Aorta, Abdominal; Aorta, Thoracic; Aortic Diseases; Aortic Dissection; Aortic Valve; Atherosclerosis; Bicuspid Aortic Valve Disease; Cardiovascular Agents; Clinical Laboratory Techniques; Diagnostic Imaging; Early Diagnosis; Endovascular Procedures; Female; Genetic Diseases, Inborn; Heart Defects, Congenital; Heart Valve Diseases; Hematoma; Humans; Long-Term Care; Male; Neoplasms, Vascular Tissue; Physical Examination; Risk Factors; Vascular Calcification; Vascular Stiffness; Vascular Surgical Procedures