High-gradient aortic stenosis in adults: Indications for valve replacement

INTRODUCTION — 

Aortic valve replacement (AVR) by surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) is the only effective treatment for severe aortic stenosis (AS) [1,2]. Indications for AVR (by SAVR or TAVI) in adults with high-gradient AS are discussed here.

Related issues are discussed separately, including:

●(See "Clinical manifestations and diagnosis of aortic stenosis in adults".)

●(See "Choice of intervention for severe calcific aortic stenosis" and "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement".)

●(See "Low gradient severe aortic stenosis: Management and prognosis".)

●(See "Medical management of symptomatic aortic stenosis" and "Medical management of asymptomatic aortic stenosis in adults" and "Percutaneous balloon aortic valvotomy for native aortic stenosis in adults".)

APPROACH TO IDENTIFYING CANDIDATES FOR VALVE REPLACEMENT — 

The following are the key steps in determining whether a patient with high-gradient severe AS (table 1) is a candidate for AVR. Patients with severe AS should be referred to a multidisciplinary Heart Valve Team for evaluation and management [1,3,4]. The Heart Valve Team includes clinicians with expertise in the assessment and treatment of valve disease, including cardiologists, specialists in advanced cardiovascular imaging, interventional cardiologists, cardiac surgeons, and cardiovascular anesthesiologists. The importance of specialist care was highlighted by an observational study finding an association between cardiac specialist care and lower one-year mortality [5].

●Symptom status – Since symptomatic AS is a key indication for AVR, it is useful to determine if the patient with severe AS has cardiac symptoms. Common symptoms in patients followed for AS are dyspnea on exertion, presyncope or syncope, and exertional angina. However, cardiac symptoms are frequent in older adult patients with severe AS and do not necessarily correspond with AS severity [6]. Many patients with AS have more than one potential cause of cardiac symptoms (eg, coronary artery disease and severe AS). Moreover, among asymptomatic patients with severe AS followed longitudinally, the probability of remaining free of cardiac symptoms while unoperated was only 33 percent at five years [7]. Evaluation of symptoms in patients with AS is discussed in detail separately. (See "Clinical manifestations and diagnosis of aortic stenosis in adults", section on 'Symptoms' and "Clinical manifestations and diagnosis of aortic stenosis in adults", section on 'Asymptomatic sedentary patients'.)

In asymptomatic patients with severe AS, exercise testing is suggested to confirm absence of symptoms, assess exercise tolerance, and assess physiologic changes with exercise (eg, fall in systemic blood pressure with exercise). (See 'Abnormal stress test' below.)

●Severity of AS – Identification of severe AS (generally by echocardiography) is a key step in determining if a patient is candidate for AVR. Severe high-gradient AS is generally identified by an aortic jet velocity over ≥4.0 m/s or mean transvalvular pressure gradient ≥40 mmHg, as well as the typical appearance of the valve with severely reduced leaflet opening (table 1); an aortic valve area (AVA) ≤1.0 cm² is typically seen but is not required to identify high-gradient severe AS (high-gradient severe AS, stage D1). Many patients do not develop symptoms until even more severe valve obstruction is present, while some patients become symptomatic when the stenosis is less severe, particularly if there is coexisting aortic regurgitation. (See "Aortic valve area in aortic stenosis in adults" and "Clinical manifestations and diagnosis of aortic stenosis in adults", section on 'Complications'.)

Some patients who appear to have severe AS (eg, AVA ≤1.0 cm²) have a low transvalvular gradient (mean gradient <40 mmHg) across the aortic valve; these patients may have low-gradient true severe AS or pseudo-severe AS. Diagnosis and evaluation of low-gradient severe AS is discussed separately. (See "Low gradient severe aortic stenosis: Clinical manifestations and diagnosis".)

●Left ventricular ejection fraction (LVEF) – Assessment of LVEF aids in identifying patients with LV dysfunction who may benefit from AVR. Among patients with severe AS, mortality following AVR increases with even borderline and low normal LV dysfunction (LVEF 50 to 59 percent) [8], although major society guidelines have specified LVEF <50 percent as a threshold for intervention [1,2]. (See 'Indications for valve replacement' below and 'Left ventricular systolic dysfunction' below.)

Evaluation of patents with low-flow, low-gradient severe AS with LVEF <50 percent is discussed separately. (See "Low gradient severe aortic stenosis: Clinical manifestations and diagnosis", section on 'Diagnosis and evaluation'.)

●Concurrent indication for cardiac surgery – Determine if there is a concurrent indication for cardiac surgery (eg, coronary artery bypass surgery).

●Estimation of the procedural risk of SAVR or of TAVI is a key step in determining if the patient is a candidate for AVR and in choosing between SAVR and TAVI, as discussed separately. (See "Estimating the risk of valvular procedures" and "Choice of intervention for severe calcific aortic stenosis".)

In addition, AVR (SAVR or TAVI) is appropriate only for patients who are expected to benefit from the procedure. The procedure is generally considered futile for patients with a life expectancy of ≤1 year even with a successful procedure, or if the patient’s quality of life is unlikely to improve with the procedure [1,2].

INDICATIONS FOR VALVE REPLACEMENT — 

Recommendations for AVR (by SAVR or TAVI) for severe high-gradient AS are strongest for patients with cardiac symptoms. A patient's symptom status is reflected in the staging of aortic stenosis (table 1).

Indications for AVR in patients with low-flow, low-gradient AS are discussed separately. (See "Low gradient severe aortic stenosis: Management and prognosis".)

For patients with AS with an indication for AVR, the choice of procedure (SAVR versus TAVI, surgical bioprosthetic versus mechanical AVR, or an alternate approach such as the Ross procedure) depends on patient expected longevity, comorbidities, patient preferences, and other factors, as discussed separately. (See "Choice of intervention for severe calcific aortic stenosis".)

Our approach to valve replacement for AS is largely consistent with the 2020 American College of Cardiology/American Heart Association valve guideline and 2021 European Society of Cardiology valve guideline recommendations [1,2].

For symptomatic patients

●For patients with severe high-gradient AS who have symptoms by history or on exercise testing (stage D1), we recommend AVR (by SAVR or TAVI). Relevant symptoms include exertional dyspnea, heart failure, angina, syncope or presyncope. Valve replacement should be performed promptly after the onset of symptoms. (See 'Symptomatic patients' below.)

For asymptomatic patients

●Asymptomatic AS with concomitant indication for cardiac surgery – For asymptomatic patients with severe AS (stage C) who are undergoing cardiac surgery for a concomitant indication, we suggest SAVR. (See 'Candidates for CABG who may require aortic valve replacement' below.)

●Asymptomatic older patients with low TAVI procedural risk – For asymptomatic patients age 65 years and older with severe high-gradient AS, a low estimated TAVI procedural risk, and with anatomy suitable for transfemoral TAVI, options include early TAVI or close clinical surveillance. (See 'TAVI outcomes' below.)

●With impaired LV systolic function – For asymptomatic patients with severe high-gradient AS and left ventricular ejection fraction (LVEF) <50 percent (stage C2), we suggest AVR. (See 'Left ventricular systolic dysfunction' below.)

●With high risk for progression – For asymptomatic patients with severe high-gradient AS with low AVR (TAVI or SAVR) procedural risk, we suggest AVR if one or more of the following features of high risk for progression are present.

•Abnormal stress test – Reduced exercise capacity (based on age and sex) or fall in systolic blood pressure ≥10 mmHg from baseline to peak exercise. (See 'Abnormal stress test' below.)

•Very severe AS – Very severe high-gradient AS is identified by a maximum aortic velocity ≥4.5 m/s) (See 'Very severe AS' below.)

•Rapidly progressive disease – This is defined as an increase in increase in aortic velocity ≥0.3 m/s per year. (See 'Role of periodic monitoring' below.)

•Elevated BNP – Serum B-type natriuretic peptide (BNP) level >3 times normal. (See 'Role of periodic monitoring' below.)

EVIDENCE

Overview — Recommendations for AVR in patients with severe AS are based upon evidence on the relative risks of AVR (SAVR or TAVI) and conservative management with periodic monitoring.

●The operative mortality of SAVR varies widely depending upon a patient’s clinical presentation and comorbidities and the experience of the heart valve center. (See "Estimating the risk of valvular procedures".)

●Procedural morbidity and mortality for TAVI also vary depending upon patient and institutional factors. (See "Transcatheter aortic valve implantation: Complications" and "Estimating the risk of valvular procedures".)

The presence of a surgical or transcatheter prosthetic heart valve is also associated with appreciable long-term morbidity. Among the complications of prosthetic heart valves are prosthesis dysfunction, paravalvular leak, thrombus formation, thromboembolism, endocarditis, and the problems associated with anticoagulation. The incidence of serious complications depends upon the type of valve and a number of clinical variables, but significant complications occur at a frequency of approximately 3 percent per year, and death due directly to the valve occurs at the rate of approximately 1 percent per year [9-12].

Recommendations for surgical valve replacement for AS are based largely upon comparisons of the natural history of patients with AS to outcomes after SAVR, as discussed below (figure 1). (See "Natural history, epidemiology, and prognosis of aortic stenosis" and "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement".)

Recommendations for TAVI for AS are based upon randomized trial and observational study data, as discussed separately. (See "Choice of intervention for severe calcific aortic stenosis".)

Symptomatic patients — As noted above, symptomatic severe AS is an indication for valve replacement based on evidence showing a beneficial effect on survival (figure 1) [1]. Exertional dyspnea, presyncope/syncope, and angina are the primary symptoms in patients with severe AS. Natural history studies have shown that average survival after the onset of these symptoms is only two to three years. There is a high risk of sudden death in symptomatic patients who are followed conservatively [13]. Although randomized trials comparing surgery with continued medical therapy have not been performed, observational studies have found that corrective surgery in this setting is followed by symptomatic improvement and a substantial increase in survival [1,14-20].

The magnitude of benefit from AVR in patients with symptomatic AS is illustrated by the following observations:

●In a retrospective review of 99 older adults with AS, almost all in New York Heart Association (NYHA) functional class III or IV, follow-up at 55 months revealed that 91 percent of survivors were in NYHA class I or II (table 2) [16].

●In a retrospective study of 144 symptomatic patients, survival at three years was 87 percent in 125 who underwent valve replacement compared with 21 percent in 19 nonoperated patients [17].

A limitation of such retrospective observational studies is that the better outcomes with surgery in symptomatic AS could be at least partly due to selection bias (ie, healthier patients are chosen for surgery). However, the magnitude of difference in outcomes between medically managed patients and those undergoing surgical valve replacement is greater than would be expected based upon patient selection alone.

Asymptomatic severe aortic stenosis — Recommendations for valve replacement in patients with severe AS are based upon consideration of the relative risks of valve replacement versus routine clinical surveillance.

The procedural risk of morbidity and mortality in AVR (TAVI or SAVR) varies widely. If a patient's estimated procedural mortality is not under 2 to 3 percent, then the operative risk may exceed the risk (1 percent per year) of sudden death in an asymptomatic patient who does not undergo surgery. Furthermore, valve replacement does not abolish the risk of sudden death. Thus, the procedural risk of valve replacement (TAVI or SAVR) plus late prosthetic valve complications is weighed against the potential reduction in risk of sudden death and symptomatic decompensation with routine surveillance. The decision about timing of AVR should also consider whether surveillance may be impractical and potential delays in scheduling AVR.

Criteria for valve replacement

Left ventricular systolic dysfunction — In patients with depressed LVEF (LVEF <50 percent) and severe AS, observational data suggest that survival is better in those undergoing AVR compared with those treated medically [1,2,8,21-24]. However, mortality following SAVR increases with even borderline and low normal LV dysfunction (LVEF 50 to 59 percent) compared with LVEF ≥60 percent [8]. The depressed LVEF in many patients is caused by excessive afterload that is corrected by valve replacement [25]. Diastolic dysfunction improves months to years after valve replacement when hypertrophy and fibrosis regress [25].

In patients with severely depressed LV systolic function (ie, LVEF of 20 to 35 percent), symptoms and survival are still improved by valve replacement, although symptoms may not completely resolve [15,26].

Abnormal stress test — For asymptomatic patients with severe AS (stage C1), exercise testing is recommended to confirm (or refute) the absence of symptoms, to evaluate exercise tolerance, and to assess physiologic changes with exercise (eg, fall in systemic blood pressure with exercise) [1,27-32]. An abnormal test result (such as development of symptoms with exercise, a drop or ≤20 mmHg rise in systolic blood pressure, significant ventricular arrhythmias, or the inability to achieve the workload expected for age and sex) suggests an increased risk of adverse events with conservative management.

The presence of a physician is generally suggested during stress testing [33]. When exercise testing is performed, the blood pressure should be carefully monitored and the test stopped if the systolic blood pressure falls more than 10 mmHg or if the patient develops symptoms or complex ventricular arrhythmias (table 3).

Of note, exercise testing should not be performed in symptomatic patients with severe AS due to the risk of complications including syncope, ventricular tachycardia, and death [1].

Studies of exercise testing in patients with asymptomatic moderate and severe AS have found that certain stress test findings (including development of symptoms with exercise, inability to exercise to a functional aerobic capacity of at least 80 percent of predicted, a drop or ≤20 mmHg rise in systolic blood pressure, or significant ventricular arrhythmias) are predictive of adverse events including development of symptoms requiring AVR and sudden cardiac death [27,34]. Scant data are available on which exercise text abnormality has greatest prognostic value, but some studies suggest that exercise-induced symptoms have greater prognostic value that abnormal blood pressure response or ST-segment abnormalities [27]. Due to the combination of LV hypertrophy and diminished coronary flow reserve, the development of ST depression during exercise is a common finding in adults with asymptomatic AS and is not specific for the presence of CAD [35].

The ability of exercise testing to identify asymptomatic patients with severe AS who are likely to develop adverse events was illustrated by a meta-analysis of data from seven studies with a total of 491 patients (mean age 50 to 66 years) [34].

●An abnormal stress test result was defined as development of symptoms such as dyspnea, angina, syncope, or near syncope during exercise; a decrease in blood pressure or a <20 mmHg increase in systolic blood pressure during exercise; <80 percent of normal exercise tolerance; OR ≥2 mm horizontal or downsloping ST-segment depression during exercise.

●In patients with normal stress test results, no sudden deaths were observed after one year of follow-up. In patients with abnormal stress test results, 5 percent had sudden cardiac death.

●Adverse cardiac events (including angina, dyspnea, acute heart failure, sudden death, and symptoms requiring AVR) were observed in 21 percent with normal stress test results and in 66 percent of those with abnormal stress test results.

●No complications from stress testing were observed.

Very severe AS — For asymptomatic patients with very severe AS and low estimated procedural risk (with SAVR or TAVI), we suggest early AVR since symptom onset and adverse outcomes are likely within the next year. The randomized controlled RECOVERY trial found that early SAVR improved survival compared with conservative care [36]. The trial enrolled asymptomatic patients with very severe AS (defined as an aortic valve area [AVA] of ≤0.75 cm² with a maximum aortic velocity ≥ 4.5 m/s or a mean transvalvular pressure gradient ≥50 mmHg) with low operative risk, with 73 randomly assigned to early surgery (within two months of randomization) and 72 patients randomly assigned to conservative care with close follow-up. The mean patient age was 64 years. More than half of the patients had a bicuspid aortic valve, about one-third of the patients had calcific valve disease, and about 5 percent of patients had rheumatic valve disease. The mean EuroSCORE II score was 0.9 percent.

●Sixty-nine of 73 patients in the early surgery group underwent surgery within two months after randomization. Two of 72 patients assigned to conservative care crossed over to early surgery. There was no operative mortality in either group.

●In an intention-to-treat analysis:

•A primary endpoint event (composite of operative mortality and death from cardiovascular causes during median over-six-year follow-up) occurred in one patient (1 percent) in the early surgery group and in 11 of 72 patients (15 percent) in the conservative care group (HR 0.09, 95% CI 0.01-0.67).

•Death from any cause occurred in five patients (7 percent) in the early surgery group and in 15 patients (21 percent) in the conservative care group (HR 0.33, 95% CI 0.12-0.90).

These results support AVR for asymptomatic patients with very severe AS and low procedural risk. Although this study did not study outcomes with TAVI, a similar weighing of procedural risk versus the risk of adverse outcomes with conservative management of very severe AS applies to TAVI. However, these results are not generalizable to patients with moderate or higher SAVR or TAVI procedural risk (due to patient and/or institutional factors). Also, this study is limited by the small number of deaths from any cause during this trial (five in the early surgery group and 15 in the conservative care group). Some of the patients in the conservative care group already met criteria for SAVR based on published guidelines (eg, velocity was over 5 m/s) and some did not undergo AVR promptly when an indication developed.

Improved outcomes with AVR in patients with asymptomatic very severe AS were also suggested by an earlier observational study [37]. Very severe AS was defined as an AVA of ≤0.75 cm² ("critical" AS) accompanied by a peak aortic jet velocity ≥4.5 m/s or a mean transvalvular pressure gradient ≥50 mmHg. Early surgery was performed on 102 patients and a conventional treatment strategy (surgery for symptomatic AS) was followed in 95 patients.

●During a median four-year follow-up, the operated group had no operative mortalities, no cardiac deaths, and three noncardiac deaths, while the conventional treatment group had 18 cardiac and 10 noncardiac deaths.

●For 57 propensity score-matched pairs, the risk of all-cause mortality was significantly lower in the operated group than in the conventional treatment group (HR 0.135, 95% CI 0.030-0.597).

Elevated BNP — Observational studies have shown that elevated B-type natriuretic peptide (BNP) in patients with asymptomatic severe aortic stenosis is a marker for adverse cardiovascular events [38]. This association was illustrated by a study of 387 asymptomatic patients with severe AS [39]. The adjusted risk of aortic valve-related death and heart failure hospitalization increased incrementally with increasing serum BNP level.

TAVI outcomes — Selected asymptomatic patients with severe AS with anatomy suitable for transfemoral TAVI may be candidates for early TAVI. A clinical benefit from early TAVI was suggested by a multicenter randomized trial which enrolled 901 asymptomatic patients aged ≥65 years (mean age 75.8) with severe AS and anatomy suitable for transfemoral TAVI [40]. Asymptomatic status was confirmed largely by treadmill testing. Exclusion criteria included Society of Thoracic Surgeons (STS) predicted 30-day risk of mortality for SAVR greater than 10 percent or left ventricular ejection fraction <50 percent. The study participants had a mean STS score of 1.8 percent. They were randomly assigned to transfemoral TAVI with a balloon-expandable device or standard care including routine clinical surveillance. Median follow-up was 3.8 years.

●Mortality rates were similar in the TAVI and clinical surveillance groups (8.4 versus 9.2 percent; HR 0.93, 95% CI 0.60 to 1.44). Stroke rates were also nominally but not significantly lower in the TAVI group (4.2 versus 6.7 percent; HR 0.62; 95% CI 0.35 to 1.10).

●Unplanned hospitalizations for cardiovascular causes were less frequent in the TAVI group (20.9 versus 41.7 percent; HR 0.43; 95% CI 0.33 to 0.55). Unplanned hospitalization included aortic-valve interventions (TAVI or SAVR) within 6 months after randomization in the clinical surveillance group or aortic-valve reintervention within 6 months after the trial procedure in the TAVI group.

●During a median follow-up of 3.8 years. 87 percent of patients in the clinical surveillance group underwent AVR (TAVI or SAVR). The Kansas City Cardiomyopathy Questionnaire (KCCQ) score (in which higher scores indicate fewer physical limitations) was at least 75 in 94.4 percent of the TAVI group and 80.3 percent in the clinical surveillance group.

●One of the limitations of this trial is that the committee that adjudicated clinical events was aware of treatment group assignments.

SAVR outcomes — Contemporary data on asymptomatic patients with AS undergoing SAVR show low operative mortality and substantial rates of event-free survival, especially in younger low-risk patients. In an observational study of patients ≥60 years old undergoing SAVR from 2001 to 2017 (with risk stratified by EuroSCORE or EuroSCORE II), the 30-day mortality was 1.2 percent for low-risk patients, 4.1 percent for intermediate-risk patients, and 8.3 percent for high-risk patients [41]. Median survival time was 10.9 years in low-risk patients, 7.3 years in intermediate-risk patients, and 5.8 years in high-risk patients.

A meta-analysis comparing early SAVR to conservative management included two randomized controlled trials and 10 observational studies with a total of 4130 patients with asymptomatic severe AS [42].

●Early SAVR was associated with lower all-cause mortality (pooled odds ratio [OR] 0.40, 95% CI 0.35-0.45), cardiovascular mortality (pooled OR 0.33, 95% CI 0.19-0.56), and heart failure hospitalization (pooled OR 0.19, 95% CI 0.10-0.39) than conservative management. However, the risk of stroke (pooled OR 1.30, 95% CI 0.73-2.29) and myocardial infarction (pooled OR 0.49, 95% CI 0.19-1.27) were similar with early SAVR and conservative management.

●A limitation of this analysis is that patients receiving conservative management in the observational studies were older, sicker, and thus had greater risk of surgical complications. However, analysis limited to the two randomized trials [36,43] also showed lower all-cause mortality with early SAVR (pooled OR 0.45, 95% CI 0.25-0.82).

The results of these studies in asymptomatic patients with AS, as well as the high likelihood of symptoms developing during follow-up [7], should be taken into consideration in assessment of the asymptomatic patient.

ROLE OF PERIODIC MONITORING — 

For asymptomatic patients with severe AS who do not have a current indication for AVR, periodic monitoring (including echocardiography every 6 to 12 months) is recommended to assess for development of an indication for valve replacement, since asymptomatic patients with severe AS have low rates of survival free from valve replacement and a high likelihood of development of symptoms during follow-up. (See 'Asymptomatic severe aortic stenosis' above and "Medical management of asymptomatic aortic stenosis in adults", section on 'Serial evaluation'.)

CHOICE OF INTERVENTION

Choice of surgical or transcatheter intervention — When an indication for valve replacement for AS is present, the choice of intervention (SAVR or TAVI) is based upon various considerations, including the estimated risk and benefit of the procedures and comorbid conditions. These issues are discussed in detail separately. (See "Choice of intervention for severe calcific aortic stenosis".)

There are scant data to support percutaneous aortic balloon dilation as a possible option in selected symptomatic patients with severe calcific AS a bridge to SAVR or TAVI [1]. (See "Percutaneous balloon aortic valvotomy for native aortic stenosis in adults".)

Choice of surgical prosthetic valve type — In patients referred for SAVR, the choice between a mechanical or bioprosthetic valve varies with patient age and other factors (table 4) [35]. (See "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement".)

Concomitant coronary revascularization — There are two settings in which AVR and coronary revascularization (including coronary artery bypass graft surgery [CABG] and percutaneous coronary intervention [PCI]) intersect:

●Patients who are candidates for AVR in whom coronary angiography demonstrates significant CAD that could be corrected at the time of valve replacement. The role of coronary angiography prior to surgery and the indications for concurrent CABG at the time of AVR issue are reviewed here. (See 'Candidates for aortic valve replacement who may require coronary revascularization' below.)

●Patients who are candidates for CABG who also have AS that might be corrected at the same surgery. This issue is discussed below. (See 'Candidates for CABG who may require aortic valve replacement' below.)

Candidates for aortic valve replacement who may require coronary revascularization

Coronary angiography prior to valve surgery

Indications — As recommended in the 2020 American College of Cardiology/American Heart Association (ACC/AHA) valve guideline, coronary angiography is indicated before valve intervention in patients with symptoms of angina, objective evidence of ischemia, decreased LV systolic function, and history of CAD or coronary risk factors (including males >40 years of age and postmenopausal females) [1]. A similar recommendation is included in the 2021 European Society of Cardiology valve guidelines [2]. Thus, nearly all adults with an indication for valve replacement for AS require coronary angiography prior to valve intervention. Significant CAD is common in patients with AS, with approximately 40 percent of those undergoing surgical valve replacement for AS requiring concurrent CABG [44].

Many patients with severe AS have angina, but this symptom can be caused by CAD or AS alone. Thus, symptoms do not predict the presence or absence of concurrent coronary disease, and the electrocardiogram and noninvasive stress testing may be nondiagnostic in patients with LV hypertrophy [35]. (See "Medical management of asymptomatic aortic stenosis in adults", section on 'Coronary artery disease' and "Valvular heart disease in older adults".)

In addition, some patients require cardiac catheterization to assess the severity of aortic valve disease for decision making about the timing of aortic valve surgery. Catheterization is appropriate if there is a discrepancy between clinical and echocardiographic examinations with regard to the severity of the stenosis or if echocardiographic data are nondiagnostic [1]. There is a risk of cerebral embolization associated with crossing the aortic valve in patients with severe calcific AS; as a result, this approach should be avoided whenever possible. (See "Hemodynamics of valvular disorders as measured by cardiac catheterization", section on 'Aortic stenosis' and "Stroke after cardiac catheterization".)

Noninvasive coronary angiography — As suggested in the 2020 AHA/ACC valve guideline, for selected patients with low pretest probability of CAD who are candidates for coronary angiography prior to valve intervention, coronary computed tomography angiography (CCTA) can be an option to exclude the presence of significant obstructive CAD [1]. Patients with angina, documented ischemia, or prior history of CAD should proceed directly to invasive coronary angiography rather than CCTA. If any epicardial CAD is detected by CCTA, invasive coronary angiography is required for confirmation and to guide potential revascularization. (See "Cardiac imaging with computed tomography and magnetic resonance in the adult".)

Data are limited in patients with AS [45,46]. The ability of coronary CCTA with a 64-slice scanner to exclude significant CAD was investigated in 70 patients referred for cardiac valve surgery, 31 of whom had AS [46]. The prevalence of significant CAD, defined as the presence of at least one lesion with stenosis diameter of ≥50 percent, was 26 percent. The sensitivity of CCTA was 100 percent.

Revascularization and valve replacement — Coronary artery revascularization (CABG or PCI) is warranted in patients undergoing with significant CAD (≥70 percent reduction in luminal diameter in major coronary arteries or ≥50 percent reduction in luminal diameter in the left main coronary artery) [1].

●With SAVR - Observational data suggest that in patients with significant CAD and aortic stenosis who undergo SAVR, concomitant CABG reduces the risk of perioperative myocardial infarction, perioperative mortality, and late mortality [1]. However, interpretation of the data is complex since patients with AS and CAD who undergo concomitant SAVR and CABG have higher short- and long-term mortality rates than patients with isolated AS (without significant CAD) who undergo AVR, likely due to higher baseline risk [47]. The utility of a hybrid approach (PCI plus SAVR) in selected patients who are not candidates for internal mammary bypass grafting is uncertain [47].

●With TAVI – The role of PCI in patients with CAD and AS who undergo TAVI is discussed separately. (See "Transcatheter aortic valve implantation: Periprocedural and postprocedural management", section on 'Management of coronary artery disease'.)

Candidates for CABG who may require aortic valve replacement — For patients with severe AS (stage C or D (table 1)) undergoing other cardiac surgery, we suggest concomitant SAVR [1].

The decision to proceed with concomitant AVR in patients with moderate AS is based upon consideration the natural history of the disease. Studies in which serial testing was performed have identified two groups of patients: one in which there is a decrease in effective valve area of 0.1 to as much as 0.3 cm² per year; and one comprising more than one-half of patients in which there is little or no progression over a three- to nine-year period. (See "Natural history, epidemiology, and prognosis of aortic stenosis", section on 'Progression of aortic stenosis'.)

Thus, some patients with moderate AS who undergo only CABG will progress to severe AS. Valve replacement at this later time is usually associated with a higher risk of mortality than initially combined surgery. In two series with a total of 229 patients who underwent AVR after prior CABG, the early mortality rate was 13 percent [48,49]. In one of these series, postoperative complications included worsening heart failure in 35 percent and perioperative myocardial infarction in 13 percent, but long-term outcome in survivors was favorable [48]. However, some centers have not noted an increase in early risk with combined surgery (7.4 versus 6.3 percent) [50].

The efficacy of combined SAVR and CABG was addressed in a retrospective study from the Cleveland Clinic of 207 patients who underwent CABG and, on preoperative echocardiography, had mild to moderate AS [51]. Moderate stenosis, defined as a mean transvalvular gradient of 30 to 40 mmHg or a valve area of 1.0 to 1.5 cm², was present in 71 patients (23 percent). The following findings were noted:

●Perioperative mortality was similar in the 129 who underwent CABG alone (3.9 percent) and the 78 patients who underwent combined CABG and valve replacement (3.9 versus 3.8 percent).

●Among the 129 patients who underwent CABG alone, 21 (16 percent) subsequently underwent AVR at a mean of 6.2 years after the initial surgery. The rate was higher in the 23 patients who had moderate stenosis at the time of the initial operation (30 versus 13 percent in those with initially mild stenosis).

●Among the 71 patients who initially had moderate AS, there was a significantly lower mortality rate with combined SAVR and CABG compared with CABG alone (42 versus 78 percent at a mean follow-up of approximately six years; propensity adjusted relative risk 0.43, 95% CI 0.20-0.96). There was no survival benefit from combined surgery in the patients with mild AS.

MEDICAL MANAGEMENT IN PATIENTS AWAITING SURGERY — 

The limited role of medical management in patients awaiting surgery is discussed separately. (See "Medical management of symptomatic aortic stenosis", section on 'Medical management in patients awaiting aortic valve replacement'.)

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 5^th to 6^th 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 10^th to 12^th 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

●Indications for AVR for AS – Indications for aortic valve replacement (AVR) for high-gradient aortic stenosis (AS) are based upon the patient’s symptom status, the severity of AS, other clinical criteria, and whether other cardiac surgery is indicated. A patient’s symptom status is reflected in the staging of aortic stenosis (table 1). (See 'Approach to identifying candidates for valve replacement' above.)

Indications for AVR in patients with low-flow, low-gradient AS are discussed separately. (See "Low gradient severe aortic stenosis: Management and prognosis".)

For patients with AS with an indication for AVR, the choice between surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) is discussed separately. (See "Choice of intervention for severe calcific aortic stenosis".)

●Symptomatic patients – For patients with severe high-gradient AS who have symptoms by history or on exercise testing (stage D1), we recommend AVR (SAVR or TAVI) (Grade 1B). Relevant symptoms include exertional dyspnea, heart failure, angina, syncope or presyncope. Valve replacement should be performed promptly after the onset of symptoms. (See 'Symptomatic patients' above.)

●Asymptomatic patients – AVR is indicated in selected asymptomatic patients with high-gradient severe AS (see 'For asymptomatic patients' above):

•With concomitant indication for cardiac surgery – For asymptomatic patients with severe AS (stage C) who are undergoing cardiac surgery for a concomitant indication, we suggest SAVR (Grade 2C). (See 'Candidates for CABG who may require aortic valve replacement' above.)

•With low TAVI procedural risk – For asymptomatic patients (stage C1) aged 65 years or greater with low estimated TAVI procedural risk and anatomy suitable for transfemoral TAVI, options include early TAVI or close clinical surveillance. (See 'TAVI outcomes' above.)

•With impaired LV systolic function - For asymptomatic patients with severe high-gradient AS and LVEF <50 percent (stage C2), we suggest early AVR. (Grade 2C) (See 'Left ventricular systolic dysfunction' above.)

•With high risk for progression – For asymptomatic patients with severe high-gradient AS with low estimated AVR (TAVI or SAVR) procedural risk, we suggest early AVR if one or more of the following features are present (Grade 2C):

-Abnormal stress test – Exercise stress test showing decreased exercise tolerance or fall in systolic blood pressure by at least 10 mmHg from baseline to peak exercise. (See 'Abnormal stress test' above.)

-Very severe AS – Very severe high-gradient AS is defined as maximum aortic velocity ≥4.5 m/s). (See 'Very severe AS' above.)

-Rapidly progressive disease – This is defined as an increase in aortic velocity ≥0.3 m/s per year). (See 'Role of periodic monitoring' above.)

-Elevated BNP – Serum B-type natriuretic peptide (BNP) level >3 times normal. (See 'Elevated BNP' above.)

●Evidence – Recommendations for surgical valve replacement for AS are based upon comparisons of the natural history of patients with AS to outcomes after SAVR (figure 1). Recommendations for TAVI for AS are based upon randomized trial and observational study data. (See 'Evidence' above and "Choice of intervention for severe calcific aortic stenosis".)

●Indications for coronary angiography prior to AVR – Coronary angiography is indicated before valve intervention in patients with symptoms of angina, objective evidence of ischemia, decreased LV systolic function, history of coronary artery disease (CAD), or coronary risk factors (including males >40 years of age and postmenopausal females). (See 'Indications' above.)

●Indications for concomitant coronary revascularization – Coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is indicated in patients undergoing valve repair or replacement with significant CAD (≥70 percent reduction in luminal diameter in major coronary arteries or ≥50 percent reduction in luminal diameter in the left main coronary artery). (See 'Revascularization and valve replacement' above.)

•Patients with significant CAD undergoing SAVR should receive concomitant CABG. The utility of a hybrid approach (PCI plus SAVR) as an alternative is under investigation.

•Strategies for revascularization in patients with CAD undergoing TAVI are evolving. Observational studies suggest that selective PCI as a staged or concomitant procedure may yield reasonable outcomes.

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges William H Gaasch, MD, who contributed to an earlier version of this topic review.