Aortic valve stenosis (AS) is a disease of the heart valves in which the opening of the aortic valve is narrowed. The aortic valve is the valve located between the left ventricle of the heart and the aorta, the largest artery in the body, which carries the entire output of blood to the systemic circulation. Aortic stenosis is now the most common valvular heart disease in the Western World.
Signs and symptoms
Symptoms related to aortic stenosis depend on the degree of valve stenosis. Most people with mild to moderate aortic stenosis are asymptomatic. Symptoms usually present in individuals with severe aortic stenosis, though they may occur in those with mild to moderate aortic stenosis as well. The three cardinal 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, paroxysmal nocturnal dyspnea, or pedal edema.
Angina
Angina in setting of heart failure also increases the risk of death. In patients with angina, the 5 year mortality rate is 50% if the aortic valve is not replaced.
Angina in the setting of AS is secondary to the left ventricular hypertrophy (LVH) that is caused by the constant production of increased pressure required to overcome the pressure gradient caused by the AS. While the muscular layer of the left ventricle thickens, the arteries that supply the muscle do not get significantly longer or bigger, so the muscle may not receive enough blood supply to meet its requirement for oxygen. This ischemia may first be evident during exercise, when the heart muscle requires increased blood supply to compensate for the increased workload. The individual may complain of anginal chest pain with exertion. At this stage, a cardiac stress test with imaging may be suggestive of ischemia.
Eventually, however, the cardiac muscle will require more blood supply at rest than can be supplied by the coronary artery branches. At this point there may be signs of ventricular strain pattern (ST segment depression and T wave inversion) on the EKG, suggesting subendocardial ischemia. The subendocardium is the region that becomes ischemic because it is the most distant from the epicardial coronary arteries.
Syncope
Syncope (fainting spells) from aortic valve stenosis is usually exertional. In the setting of heart failure it increases the risk of death. In patients with syncope, the 3 year mortality rate is 50%, if the aortic valve is not replaced.
It is unclear why aortic stenosis causes syncope. One popular theory is that severe AS produces a nearly fixed cardiac output. When the patient exercises, their peripheral vascular resistance will decrease as the blood vessels of the skeletal muscles dilate to allow the muscles to receive more blood to allow them to do more work. This decrease in peripheral vascular resistance is normally compensated for by an increase in the cardiac output. Since patients with severe AS cannot increase their cardiac output, the blood pressure falls and the patient will syncopize due to decreased blood perfusion to the brain.
A second theory as to why syncope may occur in AS is that during exercise, the high pressures generated in the hypertrophied LV cause a vasodepressor response, which causes a secondary peripheral vasodilation that, in turn, causes decreased blood flow to the brain resulting in loss of consciousness. Indeed, in aortic stenosis, because of the fixed obstruction to bloodflow out from the heart, it may be impossible for the heart to increase its output to offset peripheral vasodilation.
A third mechanism may sometimes be operative. Due to the hypertrophy of the left ventricle in aortic stenosis, including the consequent inability of the coronary arteries to adequately supply blood to the myocardium (see "Angina" below), arrhythmias may develop. These can lead to syncope.
Finally, in calcific aortic stenosis at least, the calcification in and around the aortic valve can progress and extend to involve the electrical conduction system of the heart. If that occurs, the result may be heart block - a potentially lethal condition of which syncope may be a symptom.
Congestive heart failure
Congestive heart failure (CHF) carries a grave prognosis in patients with AS. Patients with CHF attributable to AS have a 2 year mortality rate of 50% if the aortic valve is not replaced. CHF in the setting of AS is due to a combination of left ventricular hypertrophy with fibrosis, systolic dysfunction (a decrease in the ejection fraction) and diastolic dysfunction (elevated filling pressure of the LV).
Associated symptoms
In Heyde's syndrome, aortic stenosis is associated with gastrointestinal bleeding due to angiodysplasia of the colon. Recent research has shown that the stenosis causes a form of von Willebrand disease by breaking down its associated coagulation factor (factor VIII-associated antigen, also called von Willebrand factor), due to increased turbulence around the stenosed valve.
Complications
Notwithstanding the foregoing, the American Heart Association has recently changed its recommendations regarding antibiotic prophylaxis for endocarditis. Specifically, as of 2007, it is recommended that such prophylaxis be limited only to those with prosthetic heart valves, those with previous episode(s) of endocarditis, and those with certain types of congenital heart disease.
Since the stenosed aortic valve may limit the heart's output, people with aortic stenosis are at risk of syncope and dangerously low blood pressure should they use any of a number of medications for cardiovascular diseases that often coexist with aortic stenosis. Examples include nitroglycerin, nitrates, ACE inhibitors, terazosin (Hytrin), and hydralazine. Note that all of these substances lead to peripheral vasodilation. Under normal circumstances, in the absence of aortic stenosis, the heart is able to increase its output and thereby offset the effect of the dilated blood vessels. In some cases of aortic stenosis, however, due to the obstruction of blood flow out of the heart caused by the stenosed aortic valve, cardiac output cannot be increased. Low blood pressure or syncope may ensue.
Causes
Aortic stenosis is most commonly caused by age-related progressive calcification of a normal (three-leafed) aortic valve (>50% of cases) with a mean age of 65 to 70 years old. Other causes of aortic stenosis include calcification of a congenital bicuspid aortic valve (30-40% of cases) and acute rheumatic fever post-inflammatory (less than 10% of cases). Rare causes of aortic stenosis include Fabry disease, systemic lupus erythematosus, Paget disease, hyperuricemia, and infection.
Normal aortic valves have three leaves (tricuspid), but some individuals are born with an aortic valve that has two leaves (bicuspid). Typically, aortic stenosis due to calcification of a bicuspid valve appears earlier, in the 40s or 50s, whereas aortic stenosis due to calcification of a normal tricuspid aortic valve appears later, usually in the 70s and 80s.
Pathophysiology
The human aortic valve normally consists of three leaflets (trileaflets) and has an orifice of 3.0-4.0 square centimeters. When the left ventricle (LV) contracts, it forces blood through the valve into the aorta and subsequently to the rest of the body. When the LV expands again, the aortic valve closes and prevents the blood in the aorta from flowing backward into the left ventricle. In aortic stenosis, the opening of the aortic valve becomes narrowed or constricted (stenotic) (i.e., due to calcification). Degenerative aortic stenosis, 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 a highly damaging substance known as Lipoprotein(a) into the aortic valve resulting in significant damage and stenosis over time.
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 is ongoing to see if different coronary anatomy might lead to turbulent flow at the level of valves leading to inflammation and degeneration.
Diagnosis
Aortic stenosis is most often diagnosed when it is asymptomatic and can sometimes be detected during routine examination of the heart and circulatory system. Good evidence exists to demonstrate that certain characteristics of the peripheral pulse can rule in the diagnosis. In particular, there may be a slow and/or sustained upstroke of the arterial pulse, and the pulse may be of low volume. This is sometimes referred to as pulsus parvus et tardus. There may also be a noticeable delay between the first heart sound (on auscultation) and the corresponding pulse in the carotid artery (so-called 'apical-carotid delay'). In similar manner, there may be a delay between the appearance of each pulse in the brachial artery (in the arm) and the radial artery (in the wrist).
The first heart sound may be followed by a sharp ejection sound ("ejection click") best heard at the lower left sternal border and the apex, and, thus, appear to be "split". The ejection sound, caused by the impact of left ventricular outflow against the partially fused aortic valve leaflets, is more commonly associated with a mobile bicuspid aortic valve than an immobile calcified aortic valve. The intensity of this sound does not vary with respiration, which helps distinguish it from the ejection click produced by a stenotic pulmonary valve, which will diminish slightly in intensity during inspiration.
An easily heard systolic, crescendo-decrescendo (i.e., 'ejection') murmur is heard loudest at the upper right sternal border, at the 2nd right intercostal space, and radiates to the carotid arteries bilaterally. The murmur increases with squatting and decreases with standing and isometric muscular contraction such as the Valsalva maneuver, which helps distinguish it from hypertrophic obstructive cardiomyopathy (HOCM). The murmur is louder during expiration, but is also easily heard during inspiration. The more severe the degree of the stenosis, the later the peak occurs in the crescendo-decrescendo of the murmur.
The second heart sound (A2) tends to become decreased and softer as the aortic stenosis becomes more severe. This is a result of the increasing calcification of the valve preventing it from "snapping" shut and producing a sharp, loud sound. Due to increases in left ventricular pressure from the stenotic aortic valve, over time the ventricle may hypertrophy, resulting in a diastolic dysfunction. As a result, one may hear a fourth heart sound due to the stiff ventricle. With continued increases in ventricular pressure, dilatation of the ventricle will occur, and a third heart sound may be manifest.
Finally, aortic stenosis often co-exists with some degree of aortic insufficiency (aortic regurgitation). Hence, the physical exam in aortic stenosis may also reveal signs of the latter, for example an early diastolic decrescendo murmur. Indeed, when both valve abnormalities are present, the expected findings of either may be modified or may not even be present. Rather, new signs that reflect the presence of simultaneous aortic stenosis and insufficiency, e.g., pulsus bisferiens, emerge.
According to a meta analysis, the most useful findings for ruling in aortic stenosis in the clinical setting were slow rate of rise of the carotid pulse (positive likelihood ratio ranged 2.8â€"130 across studies), mid to late peak intensity of the murmur (positive likelihood ratio, 8.0â€"101), and decreased intensity of the second heart sound (positive likelihood ratio, 3.1â€"50).
Other peripheral signs include:
- sustained, heaving apex beat, which is not displaced unless systolic dysfunction of the left ventricle has developed
- A precordial thrill
- narrowed pulse pressure
Electrocardiogram
Although aortic stenosis does not lead to any specific findings on the electrocardiogram (ECG), it still often leads to a number of electrocardiographic abnormalities. ECG manifestations of left ventricular hypertrophy (LVH) are common in aortic stenosis and arise as a result of the stenosis having placed a chronically high pressure load on the left ventricle (with LVH being the expected response to chronic pressure loads on the left ventricle no matter what the cause).
As noted above, the calcification process that occurs in aortic stenosis can progress to extend beyond the aortic valve and into the electrical conduction system of the heart. Evidence of this phenomenon may rarely include ECG patterns characteristic of certain types of heart block such as Left bundle branch block.
Heart catheterization
Cardiac chamber catheterization provides a definitive diagnosis, indicating severe stenosis in valve area of <1.0Â cm2 (normally about 3Â cm2). It can directly measure the pressure on both sides of the aortic valve. The pressure gradient may be used as a decision point for treatment. It is useful in symptomatic patients before surgery. However, cardiac catheterization is not recommended to assess the severity of aortic stenosis when noninvasive testing is sufficient to make the diagnosis.
Echocardiogram
Echocardiogram (heart ultrasound) is the best non-invasive tool / test to evaluate the aortic valve anatomy and function.
The aortic valve area can be calculated non-invasively using echocardiographic flow velocities. Using the velocity of the blood through the valve, the pressure gradient across the valve can be calculated by the continuity equation or using the modified Bernoulli's equation:
Gradient = 4(velocity)² mmHg
A normal aortic valve has a gradient of only a few mmHg. A decreased valvular area causes increased pressure gradient, and these parameters are used to classify and grade the aortic stenosis as mild, moderate or severe. The pressure gradient can be abnormally low in the presence of mitral stenosis, heart failure, co-existent aortic regurgitation and also ischaemic heart disease (disease related to decreased blood supply and oxygen causing ischaemia).
Echocardiogram may also show left ventricular hyperthrophy, thickened and immobile aortic valve and dilated aortic root. However, it may appear deceptively normal in acute cases.
Chest X-ray
Chest X-ray can also assist in the diagnosis, showing calcific aortic valve, and, in longstanding disease, enlarged left ventricle and atrium.
Management
Treatment is generally not necessary in people without symptoms. In moderate cases, echocardiography is performed every 1â€"2 years to monitor the progression, possibly complemented with a cardiac stress test. In severe cases, echocardiography is performed every 3â€"6 months. In both moderate and mild cases, the patient should immediately make a revisit or be admitted for inpatient care if any new related symptoms appear. There are no current therapeutic options currently available to treat patients with aortic valve stenosis; however, studies have indicated that the disease occurs as a result of active cellular processes, suggesting that targeting these processes may lead to viable therapeutic approaches.
Medical Management
The effect of statins on the progression of AS is still unclear. The latest trials do not show any benefit in slowing AS progression, but did demonstrate a decrease in ischemic cardiovascular events. Angiotensin-converting enzyme (ACE) and angiotensin II receptors have been found in stenotic aortic valves. This leads to the hypothesis that the renin-angiotensin system may play a role in the progression of the disease. To date, there is no randomized trial examining the impact of ACE inhibitors in AS. Innasimuthu et al. showed that patients on bisphosphonates have less progression of aortic stenosis and some regressed. This finding led to multiple trials which is ongoing. Subsequent research has failed to confirm the initial positive result.
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
- Any heart failure is generally treated with digoxin and diuretics, and, if not contraindicated, cautious inpatient administration of ACE inhibitors.
Since calcific aortic stenosis shares many pathological features and risk factors with atherosclerosis, and since atherosclerosis may be prevented and/or reversed by cholesterol lowering, there has been interest in attempting to modify the course of calcific aortic stenosis by lowering cholesterol levels with statin drugs. Although a number of small, observational studies demonstrated an association between lowered cholesterol and decreased progression, and even regression, of calcific aortic stenosis, a recent, large randomized clinical trial, published in 2005, failed to find any predictable effect of cholesterol lowering on calcific aortic stenosis. A 2007 study did demonstrate a slowing of aortic stenosis with the statin rosuvastatin. However, a large randomized controlled trial published in the New England Journal of Medicine in 2008 failed to find any beneficial effect of intensive cholesterol lowering on the course of aortic stenosis.
Aortic valve replacement
In adults, symptomatic severe aortic stenosis usually requires aortic valve replacement (AVR). While AVR has been the standard of care for aortic stenosis for several decades, currently aortic valve replacement approaches include open heart surgery, minimally invasive cardiac surgery (MICS) and minimally invasive catheter-based (percutaneous) aortic valve replacement.
Apicoaortic conduit
Apicoaortic Conduit (AAC), or Aortic Valve Bypass (AVB), has been shown to be an effective treatment for aortic stenosis. There is long-term stability of the left ventricular hemodynamics after AVB, with no further biologic progression of native aortic valve stenosis. Once the pressure gradient across the native valve is substantially reduced, the narrowing and calcification of the native valve halts.
Surgical Valve Replacement
A diseased aortic valve is most commonly replaced using a surgical procedure with either a mechanical or a tissue valve. The procedure is done either in an open-heart surgical procedure or, in a smaller but growing number of cases, a minimally invasive cardiac surgery (MICS) procedure.
Transcatheter Aortic Valve Replacement (TAVR)
Globally more than 40,000 patients have received transcatheter aortic valve replacement. For patients who are not candidates for surgical valve replacement, transcatheter valve replacement may be a suitable alternative. When selecting the optimal therapy for individual patients, the percutaneous (transcatheter) approach must be carefully weighed against the excellent results achieved with conventional surgery.
Balloon valvuloplasty
For infants and children, balloon valvuloplasty, where a balloon is inflated to stretch the valve and allow greater flow, may also be effective. In adults, however, it is generally ineffective, as the valve tends to return to a stenosed state. The surgeon will make a small incision at the top of the patient's leg and proceed to insert the balloon into the artery. The balloon is then advanced up to the valve and is inflated to stretch the valve open.
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%.
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 lifestyle habits similar to those of coronary artery disease such as hypertension, advanced age, being male, hyperlipidemia, diabetes mellitus, cigarette smoking, metabolic syndrome, and end-stage renal disease.
History
Aortic stenosis was first described by French physician Lazare Riviere in 1663.
References
External links
- Aortic valve stenosis at DMOZ
- Aortic Stenosis information for parents.
- Aortic Stenosis Infographic for patients, their family members and friends.
- Aortic Stenosis in infants and children.