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Aortic Valve Stenosis

Disease Details

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Description: Aortic valve stenosis is a condition where the aortic valve narrows, restricting blood flow from the heart into the aorta and onward to the rest of the body.
Type: Aortic valve stenosis is typically classified as a valvular heart disease. It can have different types of genetic transmission, including autosomal dominant and autosomal recessive inheritance patterns, though many cases are due to age-related calcification or other non-genetic factors.
Signs And Symptoms: Symptoms related to aortic stenosis depend on the degree of stenosis. Most people with mild to moderate aortic stenosis do not have symptoms. Symptoms usually present in individuals with severe aortic stenosis, though they may also occur in those with mild to moderate aortic stenosis. The three main symptoms of aortic stenosis are loss of consciousness, anginal chest pain and shortness of breath with activity or other symptoms of heart failure such as shortness of breath while lying flat, episodes of shortness of breath at night, or swollen legs and feet. It may also be accompanied by the characteristic "Dresden china" appearance of pallor with a light flush.
Prognosis: If untreated, severe symptomatic aortic stenosis carries a poor prognosis, with a 2-year mortality rate of 50-60% and a 3-year survival rate of less than 30%. Prognosis after aortic valve replacement for people younger than 65 is about five years less than that of the general population; for people older than 65 it is about the same.
Onset: Aortic valve stenosis can develop gradually over many years or even decades. It often emerges due to age-related calcification, but can also be present at birth (congenital) or result from rheumatic fever or other diseases. Initial symptoms may be subtle or nonexistent, progressing to more noticeable signs such as chest pain, breathlessness, and fainting spells as the condition advances.
Prevalence: Aortic valve stenosis is a relatively common condition, particularly among older adults. It affects about 2-7% of people over the age of 65. The prevalence increases with age, and it is more common in males than females.
Epidemiology: Approximately 2% of people over the age of 65, 3% of people over age 75, and 4% percent of people over age 85 have aortic valve stenosis. The prevalence is increasing with the aging population in North America and Europe.Risk factors known to influence disease progression of AS include factors similar to those of coronary artery disease such as hypertension, advanced age, being male, hyperlipidemia, diabetes mellitus, cigarette smoking, metabolic syndrome, and end-stage kidney disease.
Intractability: Aortic valve stenosis can be considered intractable in cases where it is severe and not manageable through medical treatments alone. In these instances, surgical intervention such as valve replacement or repair is often required to alleviate symptoms and prevent complications. The choice of treatment depends on the severity of the condition and the overall health of the patient.
Disease Severity: Aortic valve stenosis is characterized by the narrowing of the aortic valve opening, which can impede blood flow from the heart into the aorta and onward to the rest of the body. The severity of aortic valve stenosis is generally classified into mild, moderate, and severe categories based on clinical evaluations, including imaging studies like echocardiograms. Severe aortic valve stenosis can lead to significant symptoms and complications, such as chest pain, fainting, heart failure, or sudden cardiac death, necessitating prompt medical or surgical intervention.
Healthcare Professionals: Disease Ontology ID - DOID:1712
Pathophysiology: The human aortic valve normally consists of three cusps or leaflets and has an opening of 3.0-4.0 square centimeters. When the left ventricle contracts, it forces blood through the valve into the aorta and subsequently to the rest of the body. When the left ventricle expands again, the aortic valve closes and prevents the blood in the aorta from flowing backward (regurgitation) into the left ventricle. In aortic stenosis, the opening of the aortic valve becomes narrowed or constricted (stenotic) (e.g., due to calcification). Degenerative (the most common variety), and bicuspid aortic stenosis both begin with damage to endothelial cells from increased mechanical stress. Inflammation is thought to be involved in the earlier stages of the pathogenesis of AS and its associated risk factors are known to promote the deposition of LDL cholesterol and lipoprotein(a), a highly damaging substance, into the aortic valve, causing significant damage and stenosis over time. Infiltration of inflammatory cells (macrophages, T lymphocytes), followed by the release of inflammatory mediators such as interleukin-1-beta and transforming growth factor beta-1 occurs.
Subsequently, fibroblasts differentiate into osteoblast-like cells, which results in abnormal bone matrix deposition leading to progressive valvular calcification and stenosis.As a consequence of this stenosis, the left ventricle must generate a higher pressure with each contraction to effectively move blood forward into the aorta. Initially, the LV generates this increased pressure by thickening its muscular walls (myocardial hypertrophy). The type of hypertrophy most commonly seen in AS is known as concentric hypertrophy, in which the walls of the LV are (approximately) equally thickened.
In the later stages, the left ventricle dilates, the wall thins, and the systolic function deteriorates (resulting in impaired ability to pump blood forward). Morris and Innasimuthu et al. showed that different coronary anatomy is associated with different valve diseases. Research was in progress in 2010 to see if different coronary anatomy might lead to turbulent flow at the level of valves leading to inflammation and degeneration.
Carrier Status: Aortic valve stenosis is a condition characterized by narrowing of the aortic valve, impeding blood flow from the heart to the aorta and onward to the rest of the body. Carrier status is not applicable (nan) to aortic valve stenosis, as it is not a condition passed down by genetic carriers. It can be caused by congenital defects, age-related calcification, or rheumatic fever.
Mechanism: Aortic valve stenosis (AVS) is a condition characterized by the narrowing of the aortic valve opening, which restricts blood flow from the left ventricle to the aorta.

### Mechanism:
1. **Valve Calcification**: The primary mechanism involves the progressive calcification of the aortic valve leaflets. Over time, calcium deposits accumulate on the valve, causing it to stiffen and narrow.
2. **Pressure Overload**: Due to the narrowed valve, the left ventricle has to work harder to pump blood through the restricted opening, leading to pressure overload.
3. **Left Ventricular Hypertrophy (LVH)**: The increased workload causes the left ventricular muscle to thicken (hypertrophy) in an attempt to maintain adequate cardiac output.
4. **Reduced Cardiac Output**: As the stenosis progresses, the ability of the left ventricle to pump blood effectively diminishes, potentially leading to heart failure.

### Molecular Mechanisms:
1. **Oxidative Stress and Inflammation**: These processes play crucial roles in the initiation and progression of valve calcification. Inflammatory cytokines and oxidative stress markers promote the transformation of valvular interstitial cells into osteoblast-like cells which contribute to calcification.
2. **Lipoprotein Deposition**: Elevated levels of LDL cholesterol and lipoprotein(a) in the blood can deposit on the aortic valve, triggering atherosclerotic-like changes and contributing to calcification.
3. **Bone Morphogenetic Proteins (BMPs)**: These proteins are involved in bone formation and are upregulated in calcified aortic valves, promoting the differentiation of interstitial cells into bone-forming cells.
4. **Transforming Growth Factor-Beta (TGF-β)**: This signaling molecule is known to promote fibrosis and calcification within the valve by influencing cellular differentiation and collagen production.
5. **Matrix Metalloproteinases (MMPs)** and **Tissue Inhibitors of Metalloproteinases (TIMPs)**: These enzymes regulate extracellular matrix remodeling. An imbalance between MMPs and TIMPs can lead to pathological changes in the valve structure.

Understanding these mechanisms helps in identifying potential therapeutic targets for treating or preventing aortic valve stenosis.
Treatment: Treatment for aortic valve stenosis depends on the severity of the condition and symptoms. Options include:

1. **Monitoring**: Regular check-ups if the stenosis is mild and asymptomatic.
2. **Medications**: To manage symptoms and prevent complications, such as diuretics, beta-blockers, or statins.
3. **Aortic Valve Replacement (AVR)**: The primary treatment for severe stenosis, involving either surgical valve replacement or transcatheter aortic valve replacement (TAVR).
4. **Balloon Valvuloplasty**: A less common, temporary measure to widen the valve in certain patients.

It is essential to consult a healthcare provider to determine the most appropriate treatment based on individual patient factors.
Compassionate Use Treatment: Compassionate use, also known as expanded access, refers to the use of investigational drugs or therapies for patients with serious or life-threatening conditions who have no other treatment options available. For aortic valve stenosis, compassionate use treatments may include investigational drugs or procedures not yet approved by regulatory agencies but showing promise in clinical trials.

Several off-label or experimental treatments for aortic valve stenosis might include:

1. **Transcatheter Aortic Valve Implantation (TAVI)**
- Originally approved for patients at high or intermediate surgical risk, TAVI is sometimes used off-label for patients at lower risk or for those with specific anatomical challenges.

2. **Balloon Aortic Valvuloplasty (BAV)**
- This procedure can be used as a palliative measure or as a bridge to more definitive interventions like TAVI or surgical valve replacement, especially in patients who are not candidates for these procedures.

3. **Experimental Medications**
- Certain medications that are still in the experimental stages may help to manage symptoms or slow disease progression. These could be accessible via clinical trials or compassionate use programs.

4. **Gene and Stem Cell Therapies**
- Ongoing research and early-phase clinical trials are investigating the potential of gene and stem cell therapies to treat underlying causes or symptoms of aortic valve stenosis.

Patients considering these options should consult with their healthcare providers to understand potential risks, benefits, and the eligibility criteria for compassionate use or participation in clinical trials.
Lifestyle Recommendations: For aortic valve stenosis, some lifestyle recommendations include:

1. **Regular Monitoring**: Keep regular appointments with your cardiologist to monitor the progression of the disease.
2. **Healthy Diet**: Follow a heart-healthy diet low in saturated fats, cholesterol, and sodium. Focus on fruits, vegetables, whole grains, and lean proteins.
3. **Weight Management**: Maintain a healthy weight to reduce the strain on your heart.
4. **Exercise**: Engage in moderate exercise as recommended by your doctor. Avoid high-intensity activities if you have significant symptoms.
5. **Avoid Smoking and Limit Alcohol**: Smoking and excessive alcohol consumption can worsen heart problems.
6. **Control Blood Pressure and Diabetes**: Keep these conditions well-managed if you have them.
7. **Medication Adherence**: Take any prescribed medications as directed.
8. **Stay Hydrated**: Proper hydration is important, but follow any fluid restrictions advised by your healthcare provider.
9. **Stress Management**: Practice stress-reducing techniques such as meditation, yoga, or deep breathing exercises.

Always consult with your healthcare provider for personalized advice.
Medication: Observational studies demonstrated an association between lowered cholesterol with statins and decreased progression, but a randomized clinical trial published in 2005 failed to find any effect on calcific aortic stenosis. The effect of statins on the progression of AS is unclear. A 2007 study found a slowing of aortic stenosis with rosuvastatin. In 2013 it was reported that trials did not show any benefit in slowing AS progression, but did demonstrate a decrease in ischemic cardiovascular events.In general, medical therapy has relatively poor efficacy in treating aortic stenosis. However, it may be useful to manage commonly coexisting conditions that correlate with aortic stenosis:
Any angina is generally treated with beta-blockers and/or calcium blockers. Nitrates are contraindicated due to their potential to cause profound hypotension in aortic stenosis.
Any hypertension is treated aggressively, but caution must be taken in administering beta-blockers. The optimal blood pressure in patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus was found to be a systolic blood pressure of 130-139 mmHg and a diastolic blood pressure of 70-90 mmHg.
Any heart failure is generally treated with digoxin and diuretics, and, if not contraindicated, cautious administration of ACE inhibitors.
Repurposable Drugs: Repurposable drugs for aortic valve stenosis are limited, as the current primary treatments often involve surgical procedures such as valve repair or replacement. However, some medications originally intended for other conditions may have potential benefits in managing symptoms or slowing disease progression:

1. **Statins (e.g., Atorvastatin)**: Initially used for lowering cholesterol, statins may have a role in slowing the progression of aortic valve calcification.

2. **ACE Inhibitors (e.g., Ramipril)** and **ARBs (e.g., Losartan)**: These antihypertensive drugs are used to manage blood pressure and could potentially help in managing the hemodynamic burden on the heart.

3. **Beta-blockers (e.g., Metoprolol)**: Commonly prescribed for heart failure and hypertension, beta-blockers can help manage some of the symptoms associated with aortic valve stenosis.

Clinical efficacy and safety of these drugs specifically for aortic valve stenosis are still under investigation, and they should be used under the guidance of a healthcare professional.
Metabolites: Aortic valve stenosis does not have specific metabolites uniquely associated with it. It is primarily a structural heart disease characterized by the narrowing of the aortic valve opening. As for the term "nan," without additional context, it is unclear what is being referred to. If you meant "not applicable" (N/A) in relation to metabolites, that would be correct in this context.
Nutraceuticals: Nutraceuticals are not a primary treatment for aortic valve stenosis. This condition typically requires medical or surgical intervention. However, maintaining overall cardiovascular health through diet and supplements may support general heart health. Omega-3 fatty acids, antioxidants, coenzyme Q10, and certain vitamins and minerals can be beneficial for cardiovascular function. Always consult with a healthcare provider before starting any nutraceutical regimen, especially if you have aortic valve stenosis.
Peptides: Aortic valve stenosis is a condition where the aortic valve narrows, leading to reduced blood flow from the heart into the aorta. In terms of peptides, certain peptides like B-type Natriuretic Peptide (BNP) and N-terminal-pro B-type Natriuretic Peptide (NT-proBNP) are often elevated in patients with this condition, indicating heart stress and aiding in diagnosis. For the involvement of nanoparticles in treatment or diagnosis, recent research has explored using nanoparticles for targeted drug delivery and imaging to improve management and outcomes, though these are not yet standard clinical practice.