ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Medical management of asymptomatic aortic stenosis in adults

Medical management of asymptomatic aortic stenosis in adults
Author:
Catherine M Otto, MD
Section Editor:
Patricia A Pellikka, MD, FACC, FAHA, FASE
Deputy Editor:
Susan B Yeon, MD, JD
Literature review current through: Jan 2024.
This topic last updated: Sep 14, 2022.

INTRODUCTION — In individuals with normal aortic valves, the effective area of valve opening equals the cross-sectional area of the left ventricular (LV) outflow tract, which is approximately 3.0 to 4.0 cm2 in adults. As aortic stenosis (AS) develops, a minimal valve gradient is present until the orifice area becomes less than half of normal. The natural history of AS therefore begins with a prolonged period without hemodynamically significant outflow obstruction and without symptoms due to AS. However, even without valve obstruction, the early changes of calcific valve disease (aortic sclerosis) are associated with increased atherosclerotic cardiovascular risk, as discussed separately. (See "Aortic valve sclerosis and pathogenesis of calcific aortic stenosis", section on 'Clinical significance of aortic sclerosis'.)

Serial hemodynamic examinations in several studies show that progressive valve obstruction occurs in nearly all adults with calcific aortic valve disease once even mild valve obstruction is present, typically defined as an antegrade aortic velocity greater than 2.0 m/s (figure 1). Patients remain asymptomatic as aortic velocity increases and valve area decreases until the severity of obstruction results in an inadequate cardiac output with exercise leading to symptom onset. (See "Natural history, epidemiology, and prognosis of aortic stenosis", section on 'Risk factors for progression'.)

In general, symptoms in patients with AS and normal LV systolic function rarely occur until the stenosis is severe, as defined by an antegrade maximum aortic velocity over 4.0 m/s and/or mean transvalvular gradient exceeding 40 mmHg. Typically valve area is 1.0 cm2 or less but may be larger with mixed stenosis and regurgitation or with a large body size (table 1). However, many patients do not develop symptoms until even more severe valve obstruction is present, and some patients with less severe AS or with mixed stenosis and regurgitation are symptomatic. Some of these asymptomatic patients with hemodynamically severe AS benefit from aortic valve replacement (AVR) (see 'Risk stratification and indications for valve replacement' below), but most can be managed conservatively until symptoms supervene. (See "Clinical manifestations and diagnosis of aortic stenosis in adults", section on 'Complications'.)

The only effective treatment for symptomatic severe AS is valve replacement (surgical AVR [SAVR] or transcatheter aortic valve implantation [TAVI]). Choice of therapy in patients with symptomatic severe AS is discussed separately. (See "Choice of intervention for severe calcific aortic stenosis".)

Among asymptomatic patients, there are no medical therapies that have been proven to delay progression of the leaflet disease. Although retrospective studies of statin therapy were promising, a large randomized prospective study demonstrated that statin therapy does not prevent disease progression. However, many patients meet criteria for statin therapy based on standard risk factor evaluation and should be treated according to guidelines. In addition, most adults with AS have concurrent cardiac conditions that require therapy, including hypertension, coronary heart disease, atrial fibrillation (AF), and LV dysfunction.

The medical management of patients with asymptomatic AS will be reviewed here. The pathophysiology, natural history, and clinical features of AS, the timing of valve replacement for AS, and the treatment of patients with bicuspid aortic valve are discussed separately. (See "Clinical manifestations and diagnosis of aortic stenosis in adults" and "Natural history, epidemiology, and prognosis of aortic stenosis" and "Indications for valve replacement for high gradient aortic stenosis in adults" and "Valvular heart disease in older adults", section on 'Aortic stenosis' and "Bicuspid aortic valve: General management in adults".)

SERIAL EVALUATION — Serial echocardiography is useful for measurement of hemodynamic severity and monitoring disease progression. Echocardiography also provides information about LV function and associated lesions and is an important part of an integrated approach that includes a detailed history, a careful physical examination, and evaluation of exercise tolerance, in selected cases [1]. Invasive hemodynamic evaluation is not recommended in asymptomatic patients and is usually unnecessary unless noninvasive testing is inconclusive. Patients should receive education about the expected disease course and symptoms that should be reported such as dyspnea, reduced exercise tolerance, exertional chest pain, lightheadedness, and syncope. (See "Natural history, epidemiology, and prognosis of aortic stenosis".)

We agree with the 2020 American College of Cardiology/American Heart Association valve guideline recommendations for serial echocardiography in patients with AS (table 1 and table 2 and table 3) [1]. In patients with stage B mild AS (transvalvular velocity 2 to 2.9 m/s), echocardiography is recommended every three to five years. In patients with stage B moderate AS (transvalvular velocity 3 to 3.9 m/s), echocardiography is recommended every one to two years.

In patients with mild or greater AS, there is a progressive reduction in aortic valve area that averages 0.1 cm2/year and a progressive increase in aortic jet velocity that averages 0.3 m/s per year, with considerable variation between patients in the rate of progression. Risk factors for hemodynamics progression include a smaller valve area, LV hypertrophy, and moderate to severe valve calcification.

In patients with asymptomatic stage C1 severe AS (transvalvular velocity 4 m/s or higher), echocardiography is recommended every 6 to 12 months. Echocardiography is indicated earlier than the standard interval if there is a change in symptoms or signs suggestive of worsening cardiac status.

Symptom status can be assessed by a careful history in most patients, having the patient compare current exercise capacity to exercise capacity in the preceding year. Development of symptomatic severe AS (table 1) (with high gradient or low gradient) is an indication for aortic valve replacement, as discussed separately. (See "Indications for valve replacement for high gradient aortic stenosis in adults" and "Management and prognosis of low gradient aortic stenosis".)

Symptom status may be challenging to evaluate in patients with severe AS because symptom onset may be insidious or attributed to other conditions, such as aging. If symptom status is unclear, or if the clinical history cannot confirm that the patient has had no diminution in exercise capacity, exercise testing is appropriate. Exercise testing may identify findings such as provoked symptoms, impaired exercise capacity (compared with age and sex-matched standards), and blunted blood pressure response to exercise, which are indications for aortic valve replacement, as discussed separately. (See "Indications for valve replacement for high gradient aortic stenosis in adults", section on 'Indications for valve replacement'.)

Periodic measurement of serum B-type natriuretic peptide also is reasonable in asymptomatic patients with severe AS [2].

Asymptomatic patients with severe AS have a high rate of developing symptoms during follow-up (67 percent at five years) [3] and a low rate of survival free from valve replacement (56 to 63 percent at two years and 25 to 33 percent at four to five years in two studies) [3,4]. Adverse outcomes are more likely with more severe AS, and a markedly elevated peak aortic jet velocity (>5.0 or 5.5 m/s) is an independent predictor of cardiac mortality [5-7]. (See "Natural history, epidemiology, and prognosis of aortic stenosis", section on 'Risk factors for progression'.)

RISK STRATIFICATION AND INDICATIONS FOR VALVE REPLACEMENT — The initial steps in risk stratification of the patient with asymptomatic AS are to ensure AS severity is measured accurately and that the patient does not have early symptoms. AS severity should be assessed when the patient is normotensive because hypertension can mask the presence of severe AS. Patients with aortic velocity between 3 and 4 m/s should be evaluated for low-gradient severe AS, as discussed separately. (See "Clinical manifestations and diagnosis of low gradient severe aortic stenosis".)

Indications for aortic valve replacement in patients with asymptomatic severe AS are discussed separately. (See "Indications for valve replacement for high gradient aortic stenosis in adults" and "Management and prognosis of low gradient aortic stenosis".)

PREVENTION OF DISEASE PROGRESSION — There are no treatments to prevent AS progression [8-10], although preliminary data and ongoing clinical trials offer promise that medical therapy may be possible [11]. On a worldwide basis, primary prevention of rheumatic fever is important to prevent aortic and mitral valve disease initiation, however there is no evidence that secondary prevention of rheumatic fever will prevent disease progression once AS is present [12]. Rheumatic fever is now an uncommon disease in developed countries in which most cases of AS are due to calcific disease of a congenitally bicuspid or anatomically normal trileaflet aortic valve. (See "Acute rheumatic fever: Treatment and prevention", section on 'Secondary prevention (antibiotic prophylaxis)'.)

Hypercholesterolemia and statin therapy

Rationale — In patients with calcific AS of a trileaflet or bicuspid valve, it has been hypothesized that medical therapy might slow or prevent disease progression. In particular, there has been an association between AS progression and hypercholesterolemia [13,14], as well as an association between AS (usually supravalvular) and familial hypercholesterolemia [15]. (See "Valvar aortic stenosis in children".)

These observations suggest that the valve lesion in calcific AS or aortic valve sclerosis might be similar to atherosclerosis and that progression may be related to known atherosclerotic risk factors [16]. (See "Aortic valve sclerosis and pathogenesis of calcific aortic stenosis".)

Consistent with this hypothesis are the observations that aortic valve calcification and its progression are increased in patients with a serum low density lipoprotein (LDL) cholesterol >130 mg/dL (>3.36 mmol/L) [13] and initial reports suggesting that statin therapy may slow the rate of hemodynamic progression of aortic valve sclerosis [17] or AS [18-21].

Statin trials — A meta-analysis included four randomized-controlled trials of statin versus placebo therapy in a total of 2360 participants (1185 receiving statin therapy) [22]. No significant differences were found between the two treatment groups in mean pressure gradient, valve area, freedom from valve replacement, and death from cardiovascular cause.

The meta-analysis included the following randomized trials:

●The SALTIRE trial enrolled 155 adults (mean age 68) with calcific AS (an aortic jet velocity of at least 2.5 m/s, mean aortic valve area of 1.03 cm2) who were randomly assigned to atorvastatin (80 mg/day) or placebo [23]. The primary end points were the nonclinical end points of change in aortic jet velocity and aortic valve calcium score. At a median follow-up of 25 months, there was no difference in the rate of increase in aortic jet velocity (0.20 m/s per year) or of progression of aortic valve calcification (22 percent per year).

●The larger prospective SEAS study enrolled 1873 adults (mean age 68) with mild to moderate AS (mean aortic jet velocity 3.1 m/s) who were randomly assigned to treatment with simvastatin plus ezetimibe or placebo [24]. At median follow-up of 52 months, there was no difference between groups in the primary end point (35.3 versus 38.2 percent; hazard ratio [HR] 0.96, 95% CI 0.83-1.12). The primary end point included cardiovascular death, aortic valve replacement, non-fatal myocardial infarction, hospitalized unstable angina pectoris, heart failure (HF) as a result of progression of AS, coronary artery bypass grafting, percutaneous coronary interventions, and non-hemorrhagic stroke. There was also no difference in the rate of aortic valve replacement (28 versus 30 percent) or in the rate of hemodynamic progression of AS with an increase in aortic jet velocity of 0.62±0.61 m/s in the placebo group compared with 0.61±0.59 m/s in the treatment group. Although there were fewer ischemic events in the treatment group, this difference was only due to a lower rate of coronary bypass grafting at the time of aortic valve surgery, so the clinical relevance of this finding is unclear. Overall, the results of the SEAS study do not provide convincing evidence that statin therapy affects the disease process in the valve leaflets [25].

●The ASTRONOMER trial enrolled a younger cohort (mean age 58) of 269 adults with mild to moderate AS (mean aortic jet velocity 3.2 m/s) who were randomly assigned to rosuvastatin 40 mg daily or placebo [26]. Unlike earlier trials in which bicuspid aortic valve was rare (<5 percent), a bicuspid valve was present in nearly half of the subjects in this study. At a mean follow-up of 3.5 years, the annualized increase in peak AS gradient was similar in the rosuvastatin and placebo groups (6.3±6.9 versus 6.1±8.2 mmHg).

●In the PROCAS trial, 63 patients with congenital AS (most with bicuspid aortic valve) of varying severity (mean aortic jet velocity 3.5 m/s) were randomly assigned to receive either rosuvastatin 10 mg daily or placebo with median follow-up of 2.4 years [27]. There was no significant difference in the change in peak aortic valve velocity, ascending aorta diameter, or LV mass between treatment groups. Although there was a nominal difference in change in N-terminal pro-B-type natriuretic peptide levels in the two groups, this difference was not statistically significant.

Statin conclusion — The effect of statin therapy on progression of AS has been evaluated in prospective trials, which have not demonstrated an impact on the rate of progression of stenosis or clinical outcomes [22]. We agree with the 2020 American College of Cardiology/American Heart Association valve guideline that statin therapy is not indicated for prevention of hemodynamic progression in adults with mild to moderate calcific aortic valve disease [1]. However, statin therapy is recommended for most older adults with AS because it is indicated for primary or secondary prevention of atherosclerotic cardiovascular disease, as discussed separately (see "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease"). The potential effect of therapy on valve leaflet changes earlier in the disease process (eg, on aortic sclerosis) has not been evaluated.

Other potential preventive therapies — The value of other potential medical therapies to reduce progression, morbidity or mortality is unproven.

Elevated blood pressure is associated with an increased risk of aortic valve disease [28]. In a cohort analysis of 5.4 million UK adults with no known cardiovascular or valvular disease as baseline, a new diagnosis of AS was made in 0.38 percent over 9.2 years of follow up. Systolic blood pressure was continuously related to the risk of AS with each 20 mmHg increase in systolic blood pressure associated with a 41 percent higher risk of AS (HR 1.41, 95% CI 1.38-1.45). This is an association study so it does not establish a cause-effect relationship but suggests that further studies are needed to determine whether treatment of hypertension might reduce the risk of AS.

The potential value of blockade of the renin angiotensin aldosterone system to prevent further changes in the valve leaflets in patients with AS has been examined in a few studies with conflicting results [20,29-31].

●A retrospective study of 2117 adults with AS followed for a mean of 4.4 years found that those treated with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers had a significantly lower all-cause mortality with an adjusted HR of 0.76 (95% CI 0.62-0.92) and fewer cardiovascular events with an adjusted HR of 0.77 (95% CI 0.65-0.92) [30]. This observational study does not establish causation or provide information on the mechanism of potential benefit; potential mechanisms include prevention of progression in leaflet disease, effects on concurrent coronary atherosclerotic disease, lowering of systemic blood pressure, or beneficial effects on the LV myocardium [32]. Further studies will be needed to examine these possibilities.

●In a randomized prospective study of aldosterone blockade in 65 adults with asymptomatic moderate-severe AS, eplerenone did not slow onset of LV systolic or diastolic dysfunction, decrease LV mass, or reduce progression of valve stenosis [31].

Another potential target of therapy in AS includes treatment that affects tissue calcification. Only small studies suggesting a benefit of osteoporosis therapy are available to date [33,34].

ENDOCARDITIS PROPHYLAXIS — Patients with a murmur due to aortic valve stenosis (AS) are considered to be at moderate risk for infective endocarditis (IE) and underlying AS is the predisposing factor for endocarditis in 10 to 18 percent of cases in published series. (See "Native valve endocarditis: Epidemiology, risk factors, and microbiology".)

The risk is highest in those with a congenital bicuspid valve. The magnitude of risk was evaluated in a series of 2401 patients with congenital heart lesions who were followed prospectively; those with AS developed IE at a rate of 0.27 percent per year [35]. A higher peak gradient across the aortic valve was associated with a greater risk of IE. Although definitive data are lacking, clinical experience suggests that the risk of IE is lower in older patients with heavily calcified valves than in younger patients with less severe abnormalities [36]. (See "Clinical manifestations and diagnosis of bicuspid aortic valve in adults".)

The 2007 American Heart Association (AHA) guidelines on the prevention of bacterial endocarditis (and the similar recommendations in the 2020 American College of Cardiology/AHA valve guidelines) recommended that only patients with the highest risk of the development of endocarditis receive antimicrobial prophylaxis [37]. Most patients with valvular heart disease, including those with AS or a bicuspid valve, are not included in this group and therefore do not require antimicrobial prophylaxis. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Patients with AS should be educated about the importance of optimal dental hygiene, including regular dental cleanings, to decrease the likelihood of sustained bacteremia.

HYPERTENSION — Hypertension is common in patients with AS and can attenuate some of the physical findings in AS. As an example, the carotid impulse may be brisk due to decreased vascular compliance, even though valve stenosis is present. In addition, there are experimental data suggesting that hypertension can result in underestimation of stenosis severity using pressure gradients or Doppler velocities, with valve area providing a more accurate measure of disease severity [38].

In patients with asymptomatic AS and hypertension, the LV is exposed to the "double-load" of increased systemic blood pressure and valve stenosis [39]. AS severity should be reevaluated after control of blood pressure if initial measurements were made when the patient is hypertensive.

Hypertension in patients with asymptomatic AS should be treated according to standard guideline-based medical therapy [40]. Antihypertensive therapy should be started at low doses and titrated upward slowly with frequent monitoring and a greater degree of caution with more severe valve obstruction [41]. (See "Overview of hypertension in adults".)

●Angiotensin converting enzyme inhibitors may have beneficial effects on LV fibrosis in addition to control of hypertension [42].

●Beta blockers may be appropriate in patients with concurrent coronary artery disease. A post hoc analysis of the SEAS study did not show any increase in risk of all-cause mortality, sudden cardiac death, or cardiovascular disease in adults with mild-moderate AS treated with beta-blockers [43].

●Diuretics generally should be avoided, particularly if the LV chamber is small due to concentric hypertrophy. Any further reduction in LV volumes (eg, with a diuretic) in patients with a small, noncompliant, hypertrophied LV could lead to a fall in cardiac output.

●Historically, there was concern that a fixed obstruction at the valve level might blunt the expected rise in cardiac output as afterload is reduced (eg, with a vasodilator), possibly leading to hypotension and decreased coronary perfusion. However, in patients with asymptomatic AS, the valve leaflets are still flexible and the degree of leaflet opening can increase with increases in transvalvular flow rates even when valve obstruction is severe [44-47]. There is no evidence that antihypertensive treatment increases the risk of syncope in adults with asymptomatic AS. In a single observational study, syncope was more likely in older women with a low stroke volume index, but the prevalence of syncope appeared to be similar in treated hypertensive and nonhypertensive patients [48].

CORONARY ARTERY DISEASE — There is a high prevalence of coronary artery disease (CAD) in adults with AS, as approximately 40 percent of patients undergoing valve replacement require concurrent coronary bypass grafting [49]. The reasons for this high prevalence include the similar age and sex distribution and the shared risk factors of these two diseases.

Risk factor reduction — In patients with valvular heart disease, conventional coronary risk factors should be evaluated and treated based upon accepted guidelines for adults. Although there are no definitive data showing that risk factor reduction prevents disease progression in the valve leaflets, it is important to prevent concurrent coronary disease. (See 'Hypercholesterolemia and statin therapy' above and "Overview of primary prevention of cardiovascular disease" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Symptomatic CAD — Angina with effort occurs in approximately two-thirds of patients with severe AS. Approximately one-half of these patients have underlying coronary artery disease, while angina in the remaining patients is due to LV hypertrophy [50]. In addition, pre-existing valvular heart disease is present in approximately 5 percent of patients with an acute coronary syndrome, with approximately one-third having moderate to severe AS [51]. Patients with pre-existing valve disease are more likely to present with HF and have worse outcomes than patients without valvular heart disease.

It can be difficult to determine if the symptoms are due to the valve disease or to coexisting coronary disease. There is no absolute value of AS severity that correlates with the presence of symptoms. However, angina is unlikely to be due to valve obstruction when the valve area is greater than 1.2 cm2, jet velocity is less than 3.5 m/s, and mean transvalvular gradient is less than 30 mmHg (table 1).

Among adults with any degree of AS and symptoms of angina, assessment of coronary artery disease should be considered [52]. If there is concern that AS might be the cause of symptoms, exercise testing is contraindicated. In this situation, direct evaluation of coronary anatomy by computed tomography coronary angiography or cardiac catheterization is the preferred approach.

The therapeutic approach varies with the findings from this evaluation:

●Patients with angina due to coronary disease who have mild to moderate AS (table 1) can be treated like any other patient with coronary disease with medical therapy and revascularization as appropriate. (See "Chronic coronary syndrome: Overview of care" and "Chronic coronary syndrome: Indications for revascularization".)

●Patients with angina due to valve obstruction should undergo aortic valve replacement, since they are at high risk for mortality (figure 1). (See "Indications for valve replacement for high gradient aortic stenosis in adults".)

●Among patients with both severe AS and significant coronary disease, it is difficult to determine which condition contributes to the anginal symptoms. In this setting, surgical intervention for treatment of both conditions is appropriate [49]. Percutaneous coronary intervention with stenting may be considered if the patient is at high risk for surgery, but symptoms will persist if valve obstruction is the cause.

The issues of aortic valve replacement at the time of coronary artery bypass graft surgery in adults with asymptomatic AS is discussed separately. (See "Indications for valve replacement for high gradient aortic stenosis in adults".)

PHYSICAL ACTIVITY AND EXERCISE — The marked increase in cardiac output with exercise can, in patients with AS, lead to increases in the valve gradient and LV systolic pressure. The magnitude of this effect varies with the severity of the AS (table 1) and with the intensity and type of exercise.

Taking these factors into account, we suggest the following recommendations modified from the 2015 American Heart Association and American College of Cardiology scientific statement for competitive athletes [53]:

●Asymptomatic athletes with severe AS should avoid strenuous or prolonged physical activity and should not participate in competitive sports.

●Symptomatic patients with AS should undergo aortic valve replacement as discussed separately. Physical activity should be avoided during any interval of time between symptom onset and valve replacement. (See "Indications for valve replacement for high gradient aortic stenosis in adults".)

●Athletes with asymptomatic AS should be evaluated yearly to determine whether sports participation can continue.

•Athletes with mild to moderate AS should undergo yearly history, physical examination, and Doppler echocardiogram to evaluate disease severity. Exercise testing should be performed to ensure that effort tolerance is commensurate with the proposed athletic activity without exercise hypotension or electrocardiographic evidence of ischemia.

-Athletes with mild AS and normal maximal exercise response can participate in all sports.

-Athletes with moderate AS can participate in low and moderate static or low and moderate dynamic competitive sports (classes IA, IB, and IIA (figure 2)) if exercise tolerance testing to at least the level of activity achieved in competition and training demonstrates satisfactory exercise capacity without symptoms, ST-segment depression, or ventricular tachyarrhythmias, and with a normal blood pressure response.

Recommendations for exercise in patients with bicuspid aortic valves who have aortic root dilatation are presented separately. (See "Bicuspid aortic valve: General management in adults", section on 'Physical activity and exercise'.)

ATRIAL FIBRILLATION — AF can occur in patients with AS and, in a previously asymptomatic patient, may precipitate overt HF. Because of the noncompliant LV, there is a relative shift of LV filling to the later part of diastole with a greater dependence upon atrial contraction. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Atrial systole'.)

In patients with AS with AF, selection of candidates for anticoagulation and management of anticoagulation is the same as for patients without AS [1]. (See "Atrial fibrillation in adults: Selection of candidates for anticoagulation" and "Atrial fibrillation in adults: Use of oral anticoagulants".)

HEART FAILURE — Valve replacement is indicated in patients with severe AS who develop symptomatic HF or with asymptomatic LV systolic dysfunction, defined as an LV ejection fraction <50 percent (figure 1). (See "Indications for valve replacement for high gradient aortic stenosis in adults".)

Some patients with HF due to primary myocardial disease or coronary disease have or develop concurrent AS. If evaluation confirms that AS is only mild to moderate, standard medical treatment of HF is indicated rather than valve replacement. Such therapy includes optimization of volume status and evidence-based medical therapies with careful dose titration, frequent monitoring, and cardiac resynchronization therapy, if appropriate [39,54].

It has been hypothesized that relief of outflow obstruction might benefit patients with HF with reduced ejection fraction (HFrEF) with moderate AS based on the concept of afterload reduction. This hypothesis is being tested in a randomized controlled clinical trial. We recommend patients with moderate AS and HFrEF be treated according to current guidelines or enrolled in a clinical trial [55].

A potential diagnostic problem is that some patients with severe AS and LV systolic dysfunction have a low or moderate transvalvular pressure gradient. Distinguishing severe AS from pseudosevere AS in this situation is challenging. The pathophysiology and evaluation of patients with low-gradient AS are discussed separately. (See "Clinical manifestations and diagnosis of low gradient severe aortic stenosis".)

Management of symptomatic patients with severe AS, including critically ill patients, is discussed separately. (See "Medical management of symptomatic aortic stenosis".)

CONCURRENT DISEASE OF THE AORTA — Most adults with a bicuspid aortic valve eventually develop AS, with a smaller number developing severe regurgitation; a bicuspid valve accounts for approximately 50 percent of aortic valve replacements in the United States [56]. Some patients with a bicuspid valve also have an associated aortopathy with an increased risk of progressive dilatation of the aortic root and/or ascending aorta, and an increased risk of aortic dissection. As a result, monitoring of patients with bicuspid AS includes assessment for and monitoring of aortic dilation, if present (table 4). (See "Clinical manifestations and diagnosis of bicuspid aortic valve in adults", section on 'Diseases of the aorta' and "Bicuspid aortic valve: General management in adults", section on 'Surveillance' and "Clinical manifestations and diagnosis of bicuspid aortic valve in adults", section on 'Clinical manifestations'.)

The 2020 American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease did not find convincing evidence that medical therapy reduces the rate of aortic dilation in patients with AS or a bicuspid aortic valve [1]. Blood pressure should be controlled with any appropriate medication. Beta blockers and angiotensin receptor blockers have theoretical benefits but clinical studies supporting reduced progression rates are lacking.

NONCARDIAC SURGERY — Clinical deterioration can occur in patients with asymptomatic AS during the hemodynamic stress associated with noncardiac surgery (as well as other stresses such as infection, anemia, or pregnancy). HF was the most common perioperative complication among patients with severe AS undergoing intermediate- or high-risk surgery [57]. Most adverse events occur because the diagnosis of AS was not known to the surgical team. Preoperative echocardiographic evaluation of any murmur that is not clearly benign should avoid this problem. The risk of surgery and management of such patients are discussed separately. (See "Noncardiac surgery in adults with aortic stenosis".)

PREGNANCY — The management of pregnant women with congenital AS is discussed elsewhere. These women have a higher prevalence of unicuspid disease, since bicuspid valves are usually not stenotic until later in life [56]. (See "Bicuspid aortic valve: Management during pregnancy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Aortic stenosis (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Goals of therapy – The primary goals in treating patients with asymptomatic aortic stenosis (AS) is monitoring of disease, early detection of symptom onset, and treatment of cardiovascular risk factors and comorbidities. (See 'Introduction' above and 'Serial evaluation' above.)

●Risk stratification – Risk stratification allows identification of patients with asymptomatic severe AS who may benefit from valve replacement. Onset of symptoms caused by severe AS is an indication for aortic valve intervention (surgery or transcatheter aortic valve implantation). (See 'Risk stratification and indications for valve replacement' above and "Indications for valve replacement for high gradient aortic stenosis in adults" and "Management and prognosis of low gradient aortic stenosis".)

●No proven preventative therapy – Among patients with asymptomatic AS, there are no medical therapies that have been proven to delay progression of disease (see 'Prevention of disease progression' above).

●Monitoring – In patients with stage B mild AS, echocardiography is recommended every three to five years. In patients with stage B moderate AS, echocardiography is recommended every one to two years. In patients with stage C1 severe asymptomatic AS, echocardiography is recommended every 6 to 12 months. (See 'Serial evaluation' above.)

●Cardiovascular risk reduction – In patients with aortic valve disease, conventional coronary risk factors should be evaluated and treated based upon accepted guidelines for adults, including treatment of hypertension and statin therapy as appropriate for primary or secondary prevention. (See 'Risk factor reduction' above.)

●Management of noncardiac surgery – Since clinical deterioration can occur in patients with asymptomatic AS during the hemodynamic stress associated with noncardiac surgery, preoperative evaluation (including echocardiography of murmurs suggestive of AS) is indicated. (See 'Noncardiac surgery' above.)

  1. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021; 143:e72.
  2. Nakatsuma K, Taniguchi T, Morimoto T, et al. B-type natriuretic peptide in patients with asymptomatic severe aortic stenosis. Heart 2019; 105:384.
  3. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 2005; 111:3290.
  4. Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med 2000; 343:611.
  5. Rosenhek R, Zilberszac R, Schemper M, et al. Natural history of very severe aortic stenosis. Circulation 2010; 121:151.
  6. Kang DH, Park SJ, Rim JH, et al. Early surgery versus conventional treatment in asymptomatic very severe aortic stenosis. Circulation 2010; 121:1502.
  7. Nakatsuma K, Taniguchi T, Morimoto T, et al. Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry. J Am Heart Assoc 2017; 6.
  8. Lindman BR, Clavel MA, Mathieu P, et al. Calcific aortic stenosis. Nat Rev Dis Primers 2016; 2:16006.
  9. Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: a disease of the valve and the myocardium. J Am Coll Cardiol 2012; 60:1854.
  10. Bing R, Dweck MR. The quest for an aortic stenosis cure. Heart 2020; 106:1790.
  11. Lee S, Lee SA, Choi B, et al. Dipeptidyl peptidase-4 inhibition to prevent progression of calcific aortic stenosis. Heart 2020; 106:1824.
  12. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2009; 119:1541.
  13. Pohle K, Mäffert R, Ropers D, et al. Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors. Circulation 2001; 104:1927.
  14. Palta S, Pai AM, Gill KS, Pai RG. New insights into the progression of aortic stenosis: implications for secondary prevention. Circulation 2000; 101:2497.
  15. Rallidis L, Naoumova RP, Thompson GR, Nihoyannopoulos P. Extent and severity of atherosclerotic involvement of the aortic valve and root in familial hypercholesterolaemia. Heart 1998; 80:583.
  16. Agmon Y, Khandheria BK, Meissner I, et al. Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study. J Am Coll Cardiol 2001; 38:827.
  17. Shavelle DM, Takasu J, Budoff MJ, et al. HMG CoA reductase inhibitor (statin) and aortic valve calcium. Lancet 2002; 359:1125.
  18. Novaro GM, Tiong IY, Pearce GL, et al. Effect of hydroxymethylglutaryl coenzyme a reductase inhibitors on the progression of calcific aortic stenosis. Circulation 2001; 104:2205.
  19. Bellamy MF, Pellikka PA, Klarich KW, et al. Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community. J Am Coll Cardiol 2002; 40:1723.
  20. Rosenhek R, Rader F, Loho N, et al. Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis. Circulation 2004; 110:1291.
  21. Aronow WS, Ahn C, Kronzon I, Goldman ME. Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons. Am J Cardiol 2001; 88:693.
  22. Thiago L, Tsuji SR, Nyong J, et al. Statins for aortic valve stenosis. Cochrane Database Syst Rev 2016; 9:CD009571.
  23. Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med 2005; 352:2389.
  24. Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008; 359:1343.
  25. Otto CM. Calcific aortic stenosis--time to look more closely at the valve. N Engl J Med 2008; 359:1395.
  26. Chan KL, Teo K, Dumesnil JG, et al. Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation 2010; 121:306.
  27. van der Linde D, Yap SC, van Dijk AP, et al. Effects of rosuvastatin on progression of stenosis in adult patients with congenital aortic stenosis (PROCAS Trial). Am J Cardiol 2011; 108:265.
  28. Rahimi K, Mohseni H, Kiran A, et al. Elevated blood pressure and risk of aortic valve disease: a cohort analysis of 5.4 million UK adults. Eur Heart J 2018; 39:3596.
  29. O'Brien KD, Probstfield JL, Caulfield MT, et al. Angiotensin-converting enzyme inhibitors and change in aortic valve calcium. Arch Intern Med 2005; 165:858.
  30. Nadir MA, Wei L, Elder DH, et al. Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis. J Am Coll Cardiol 2011; 58:570.
  31. Stewart RA, Kerr AJ, Cowan BR, et al. A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis. Am Heart J 2008; 156:348.
  32. Aurigemma GP, Keaney JF Jr. Renin-angiotensin system inhibition for aortic stenosis "A II, Bruté?". J Am Coll Cardiol 2011; 58:577.
  33. Skolnick AH, Osranek M, Formica P, Kronzon I. Osteoporosis treatment and progression of aortic stenosis. Am J Cardiol 2009; 104:122.
  34. Innasimuthu AL, Katz WE. Effect of bisphosphonates on the progression of degenerative aortic stenosis. Echocardiography 2011; 28:1.
  35. Gersony WM, Hayes CJ, Driscoll DJ, et al. Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect. Circulation 1993; 87:I121.
  36. Roberts WC, Oluwole BO, Fernicola DJ. Comparison of active infective endocarditis involving a previously stenotic versus a previously nonstenotic aortic valve. Am J Cardiol 1993; 71:1082.
  37. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; 116:1736.
  38. Kadem L, Dumesnil JG, Rieu R, et al. Impact of systemic hypertension on the assessment of aortic stenosis. Heart 2005; 91:354.
  39. Zile MR, Gaasch WH. Heart failure in aortic stenosis - improving diagnosis and treatment. N Engl J Med 2003; 348:1735.
  40. Kang TS, Park S. Antihypertensive Treatment in Severe Aortic Stenosis. J Cardiovasc Imaging 2018; 26:45.
  41. Gosavi S, Channa R, Mukherjee D. Systemic Hypertension in Patients with Aortic Stenosis: Clinical Implications and Principles of Pharmacological Therapy. Cardiovasc Hematol Agents Med Chem 2015; 13:50.
  42. Routledge HC, Townend JN. ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity? J Hum Hypertens 2001; 15:659.
  43. Bang CN, Greve AM, Rossebø AB, et al. Antihypertensive Treatment With β-Blockade in Patients With Asymptomatic Aortic Stenosis and Association With Cardiovascular Events. J Am Heart Assoc 2017; 6.
  44. Badano L, Cassottano P, Bertoli D, et al. Changes in effective aortic valve area during ejection in adults with aortic stenosis. Am J Cardiol 1996; 78:1023.
  45. Bermejo J, García-Fernández MA, Torrecilla EG, et al. Effects of dobutamine on Doppler echocardiographic indexes of aortic stenosis. J Am Coll Cardiol 1996; 28:1206.
  46. Burwash IG, Forbes AD, Sadahiro M, et al. Echocardiographic volume flow and stenosis severity measures with changing flow rate in aortic stenosis. Am J Physiol 1993; 265:H1734.
  47. Chambers JB, Sprigings DC, Cochrane T, et al. Continuity equation and Gorlin formula compared with directly observed orifice area in native and prosthetic aortic valves. Br Heart J 1992; 67:193.
  48. Shah SP, Kumar A, Draper TS, Gaasch WH. Hypertension in patients with severe aortic stenosis: emphasis on antihypertensive treatment and the risk of syncope. Curr Hypertens Rev 2014; 10:149.
  49. Kvidal P, Bergström R, Hörte LG, Ståhle E. Observed and relative survival after aortic valve replacement. J Am Coll Cardiol 2000; 35:747.
  50. Julius BK, Spillmann M, Vassalli G, et al. Angina pectoris in patients with aortic stenosis and normal coronary arteries. Mechanisms and pathophysiological concepts. Circulation 1997; 95:892.
  51. Hasdai D, Lev EI, Behar S, et al. Acute coronary syndromes in patients with pre-existing moderate to severe valvular disease of the heart: lessons from the Euro-Heart Survey of acute coronary syndromes. Eur Heart J 2003; 24:623.
  52. Redfors B, Pibarot P, Gillam LD, et al. Stress Testing in Asymptomatic Aortic Stenosis. Circulation 2017; 135:1956.
  53. Bonow RO, Nishimura RA, Thompson PD, Udelson JE. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 5: Valvular Heart Disease: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2385.
  54. Chockalingam A, Venkatesan S, Subramaniam T, et al. Safety and efficacy of angiotensin-converting enzyme inhibitors in symptomatic severe aortic stenosis: Symptomatic Cardiac Obstruction-Pilot Study of Enalapril in Aortic Stenosis (SCOPE-AS). Am Heart J 2004; 147:E19.
  55. Pibarot P, Messika-Zeitoun D, Ben-Yehuda O, et al. Moderate Aortic Stenosis and Heart Failure With Reduced Ejection Fraction: Can Imaging Guide Us to Therapy? JACC Cardiovasc Imaging 2019; 12:172.
  56. Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation 2005; 111:920.
  57. Tashiro T, Pislaru SV, Blustin JM, et al. Perioperative risk of major non-cardiac surgery in patients with severe aortic stenosis: a reappraisal in contemporary practice. Eur Heart J 2014; 35:2372.
Topic 8117 Version 29.0

References

1 : 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

2 : B-type natriuretic peptide in patients with asymptomatic severe aortic stenosis.

3 : Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up.

4 : Predictors of outcome in severe, asymptomatic aortic stenosis.

5 : Natural history of very severe aortic stenosis.

6 : Early surgery versus conventional treatment in asymptomatic very severe aortic stenosis.

7 : Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry.

8 : Calcific aortic stenosis.

9 : Calcific aortic stenosis: a disease of the valve and the myocardium.

10 : The quest for an aortic stenosis cure.

11 : Dipeptidyl peptidase-4 inhibition to prevent progression of calcific aortic stenosis.

12 : Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics.

13 : Progression of aortic valve calcification: association with coronary atherosclerosis and cardiovascular risk factors.

14 : New insights into the progression of aortic stenosis: implications for secondary prevention.

15 : Extent and severity of atherosclerotic involvement of the aortic valve and root in familial hypercholesterolaemia.

16 : Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study.

17 : HMG CoA reductase inhibitor (statin) and aortic valve calcium.

18 : Effect of hydroxymethylglutaryl coenzyme a reductase inhibitors on the progression of calcific aortic stenosis.

19 : Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community.

20 : Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis.

21 : Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons.

22 : Statins for aortic valve stenosis.

23 : A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis.

24 : Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.

25 : Calcific aortic stenosis--time to look more closely at the valve.

26 : Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial.

27 : Effects of rosuvastatin on progression of stenosis in adult patients with congenital aortic stenosis (PROCAS Trial).

28 : Elevated blood pressure and risk of aortic valve disease: a cohort analysis of 5.4 million UK adults.

29 : Angiotensin-converting enzyme inhibitors and change in aortic valve calcium.

30 : Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis.

31 : A randomized trial of the aldosterone-receptor antagonist eplerenone in asymptomatic moderate-severe aortic stenosis.

32 : Renin-angiotensin system inhibition for aortic stenosis "A II, Bruté?".

33 : Osteoporosis treatment and progression of aortic stenosis.

34 : Effect of bisphosphonates on the progression of degenerative aortic stenosis.

35 : Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect.

36 : Comparison of active infective endocarditis involving a previously stenotic versus a previously nonstenotic aortic valve.

37 : Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group.

38 : Impact of systemic hypertension on the assessment of aortic stenosis.

39 : Heart failure in aortic stenosis - improving diagnosis and treatment.

40 : Antihypertensive Treatment in Severe Aortic Stenosis.

41 : Systemic Hypertension in Patients with Aortic Stenosis: Clinical Implications and Principles of Pharmacological Therapy.

42 : ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity?

43 : Antihypertensive Treatment Withβ-Blockade in Patients With Asymptomatic Aortic Stenosis and Association With Cardiovascular Events.

44 : Changes in effective aortic valve area during ejection in adults with aortic stenosis.

45 : Effects of dobutamine on Doppler echocardiographic indexes of aortic stenosis.

46 : Echocardiographic volume flow and stenosis severity measures with changing flow rate in aortic stenosis.

47 : Continuity equation and Gorlin formula compared with directly observed orifice area in native and prosthetic aortic valves.

48 : Hypertension in patients with severe aortic stenosis: emphasis on antihypertensive treatment and the risk of syncope.

49 : Observed and relative survival after aortic valve replacement.

50 : Angina pectoris in patients with aortic stenosis and normal coronary arteries. Mechanisms and pathophysiological concepts.

51 : Acute coronary syndromes in patients with pre-existing moderate to severe valvular disease of the heart: lessons from the Euro-Heart Survey of acute coronary syndromes.

52 : Stress Testing in Asymptomatic Aortic Stenosis.

53 : Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 5: Valvular Heart Disease: A Scientific Statement From the American Heart Association and American College of Cardiology.

54 : Safety and efficacy of angiotensin-converting enzyme inhibitors in symptomatic severe aortic stenosis: Symptomatic Cardiac Obstruction-Pilot Study of Enalapril in Aortic Stenosis (SCOPE-AS).

55 : Moderate Aortic Stenosis and Heart Failure With Reduced Ejection Fraction: Can Imaging Guide Us to Therapy?

56 : Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation.

57 : Perioperative risk of major non-cardiac surgery in patients with severe aortic stenosis: a reappraisal in contemporary practice.

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟