Medical management of symptomatic aortic stenosis

INTRODUCTION — Aortic valve replacement (AVR, including surgical aortic valve replacement and transcatheter aortic valve implantation [TAVI]) is the mainstay of treatment of symptomatic aortic stenosis (AS). AVR offers substantial improvements in symptoms and life expectancy. Medical therapy may not prolong life in patients with AS and has limited utility in treating symptoms.

In patients who are awaiting AVR, medical therapy to optimize hemodynamics in the preoperative setting may be needed. When severe symptoms are present, it may be prudent to admit the patient to the hospital and perform AVR urgently, as there is a high risk of cardiac death once severe symptoms are present.

Longer-term palliative medical management of symptomatic AS is appropriate for patients who are not candidates for aortic valve intervention due to coexisting medical conditions and in patients who decline aortic valve intervention. TAVI enables AVR in many patients with prohibitive or high operative risk for surgical AVR. However, TAVI may not be feasible in some patients due to anatomic factors or may not be appropriate in patients with a limited life expectancy due to other comorbidities or extreme frailty.

This topic will discuss medical management of patients with symptomatic AS and possible indications for aortic valvotomy. Indications for AVR, surgical and transcatheter methods of AVR, and management of asymptomatic AS are discussed separately. (See "Indications for valve replacement for high gradient aortic stenosis in adults" and "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement" and "Medical management of asymptomatic aortic stenosis in adults" and "Choice of intervention for severe calcific aortic stenosis".)

SETTINGS — Aortic valve replacement (AVR) is recommended for patients with symptomatic AS (see "Indications for valve replacement for high gradient aortic stenosis in adults"). However, patients with symptomatic AS in the following settings may require temporary or indefinite medical management. Decisions regarding management (including surgical AVR, transcatheter aortic valve implantation [TAVI], and medical management) should involve a multidisciplinary heart team and a patient-centered approach.

Comorbid conditions — AVR may not be appropriate in some patients with symptomatic AS due to certain severe comorbid conditions, such as malignancy with limited life expectancy, or extreme frailty. In some cases, AVR may be deferred only temporarily while a treatable condition (eg, infection) is managed and controlled.

High-risk patients — Some patients are not candidates for surgical valve replacement due to a very high risk for operative mortality and morbidity. Some of these patients may be candidates for TAVI, but others may not be able to undergo TAVI due to anatomic reasons (annulus size, vascular access, etc) or the potential benefit of TAVI may be low due to a high level of comorbidities or frailty. (See "Estimating the risk of valvular procedures" and "Choice of prosthetic heart valve for surgical aortic or mitral valve replacement" and "Choice of intervention for severe calcific aortic stenosis".)

Patient preference — Some patients with symptomatic AS may decline both surgical AVR and TAVI despite comprehensive counseling on the potential benefits and risks of AVR and deferral of intervention.

Care should be taken to ensure that AVR is offered to all appropriate patients with symptomatic AS with a full discussion of estimated risks and benefits. Patients seen at centers without cardiac surgery or a TAVI program should be promptly referred to a heart valve center of excellence that performs AVR. Of concern are reports that substantial numbers of patients with symptomatic AS with reasonable estimated operative risks are not referred for aortic valve surgery [1,2]. Patients may also experience disparities in access to TAVI and surgical AVR depending on race and socioeconomic status. (See "Indications for valve replacement for high gradient aortic stenosis in adults" and "Estimating the risk of valvular procedures".)

Patients awaiting valve replacement — In general, medical intervention prior to AVR should be minimized in patients with symptomatic AS. Most medical interventions that alter hemodynamic conditions carry the risk of destabilizing the patient. Patients with the onset of mild symptoms may be scheduled electively for valve replacement. However, those who develop heart failure, angina, or syncope attributed to AS should undergo expedited evaluation for valve replacement and may require hospitalization. The management of critically ill patients is discussed below. (See 'Critically ill patients awaiting valve replacement' below.)

Pregnancy — Management of pregnant patients with symptomatic AS is discussed separately. (See "Bicuspid aortic valve: Management during pregnancy", section on 'Bicuspid aortic stenosis'.)

MEDICAL MANAGEMENT

Severe symptomatic inoperable AS

General considerations — Aortic valve replacement (AVR) for symptomatic AS effectively treats symptoms and prolongs life and should be considered in all patients. When valve replacement is not possible or is refused by the patient, medical therapy may not prolong life and has potential harm. The goals of medical therapy are to treat concurrent cardiovascular conditions, prevent or treat superimposed diseases that often exacerbate the effects of valve obstruction, maintain optimal hemodynamic conditions, and treat symptoms. In addition, the physician should provide both the patient and family or caregiver counseling about the expected disease course, treatment options, and end-of-life preferences.

●No endocarditis prophylaxis is indicated for patients with AS without prior history of infective endocarditis. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

●Adults with symptomatic severe AS should engage in only mild physical activity, as symptoms will be precipitated by even moderate physical exertion. Patients with symptomatic severe AS should not participate in competitive sports [3].

●Since patients with calcific aortic valve disease commonly have concurrent atherosclerotic disease, including coronary artery disease, evaluation for and management of associated cardiovascular risk factors (eg, hyperlipidemia) is recommended. (See "Medical management of asymptomatic aortic stenosis in adults", section on 'Coronary artery disease' and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

●At present, statin therapy solely to treat or prevent progression of AS (ie, in the absence of coexisting atherosclerotic vascular disease or other indications) cannot be recommended. However, most of these patients are older and meet criteria for statin therapy, as above. (See "Medical management of asymptomatic aortic stenosis in adults", section on 'Prevention of disease progression' and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

●Medical therapy for coronary artery disease, and atrial fibrillation should be continued in adults with AS, both in those with and without symptoms. An appropriate goal for patients with atrial fibrillation is rate control and anticoagulation, as discussed separately. (See "Medical management of asymptomatic aortic stenosis in adults" and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy" and "Atrial fibrillation in adults: Selection of candidates for anticoagulation".)

Management of adverse hemodynamic conditions and symptoms — Even in the absence of an acute illness, adults with severe symptomatic inoperable AS may have fewer symptoms and less frequent hospitalizations with treatment of hypertension and maintenance of a normal volume status.

Management of hypertension — Treatment of hypertension in severe symptomatic AS is recommended but can be challenging. Concomitant hypertension and AS present a "double load" to the left ventricle (LV), which may adversely affect the ventricle. [4]. The combination of hypertension and AS may lead to development of symptoms as an earlier stage of AS [5]. However, no specific treatment regimen for patients with AS with hypertension has been established.

Various medical therapies pose a risk of destabilizing the patient with AS:

●Diuretics reduce preload, on which the patient may depend for maintenance of cardiac output. Therefore, diuretics should be used with caution.

●Beta blockers reduce contractility, which may pose a risk for the overloaded LV. While low dose beta blockers may be considered in patients with asymptomatic hypertension (particularly in the setting of atrial fibrillation), beta blockers should be avoided in patients with symptomatic AS and heart failure.

●Vasodilators (such as hydralazine, nitroglycerin, and nifedipine) in the presence of a fixed valvular stenosis may reduce systemic blood pressure and reduce coronary artery perfusion pressure. These agents should be avoided or used with caution. (See 'Critically ill patients awaiting valve replacement' below.)

Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) tend to be well tolerated in patients with moderate and asymptomatic severe AS, although there are few data on management of hypertension in symptomatic patients with severe AS.

Despite these concerns, hypertension should be treated according to standard recommended therapy, with antihypertensive agents started at a low dose and gradually titrated upward as needed with appropriate clinical monitoring [6-9]. Treatment with an ACE inhibitor or ARB is often preferred given possible beneficial effects on the ventricle as well as antihypertensive effects [6,10]. Since experience in AS patients is limited, calcium channel blockers should be used with caution [11].

Management of heart failure — For management of patients who have had symptoms of heart failure, we suggest a combination of a diuretic and an ACE inhibitor or ARB. These should be started at low doses with gradual titration.

Treatment is improved if patients are educated and involved in following daily weights and signs of decompensation. In addition, patients should be educated about the effects of sodium intake, changes in elevation with travel, and other factors that may lead to clinical decompensation. Frequent physician or nurse visits are needed for patient monitoring.

Prevention and treatment of concurrent conditions — Many adults with severe symptomatic AS have relatively stable symptoms with decompensation triggered by an intercurrent illness such as influenza, anemia, pulmonary embolism, etc. Optimal preventative care can prevent recurrent hospitalizations. These measures include pneumococcal vaccination, annual influenza vaccination, routine preventative care examinations, and treatment of any noncardiac conditions.

When clinical decompensation occurs, in addition to treating the disease process, patients may be effectively managed by supportive care during the acute illness. Medical therapy focuses on decreasing cardiac workload by reducing fever, controlling heart rate and blood pressure, correction of anemia, and administration of oxygen. Volume status should be carefully monitored with cautious replacement of fluid or gentle diuresis, as needed. With severe AS, patients are very sensitive to small changes in preload. An increase in LV volume in a non-compliant hypertrophied LV results in a rise in diastolic pressure and symptoms of pulmonary congestion. Conversely, when filling volumes are too low, the small LV does not fill adequately with a fall in forward stroke volume and signs of low output failure.

Medical management in patients awaiting aortic valve replacement — In general, medical intervention prior to AVR should be minimized in patients with severe or symptomatic AS. Most medical interventions carry a risk of destabilizing the patient:

●Diuretics reduce preload, on which the patient may depend for maintenance of cardiac output.

●Vasodilators in the presence of a fixed valvular stenosis may excessively reduce systemic blood pressure and reduce coronary artery perfusion pressure.

●Positive inotropic agents such as dobutamine must be used with caution; tachycardia (with reduced cardiac output) and myocardial ischemia (due to increased oxygen demand) may occur.

Critically ill patients awaiting valve replacement — Some critically ill patients with AS are hemodynamically unstable prior to surgical aortic valve replacement or transcatheter aortic valve implantation (TAVI) and at high risk for mortality during the procedure. This is especially true in patients with LV dysfunction, who may present with heart failure, and those with coronary disease, who may present with unstable angina. For some of these patients, palliative care may be appropriate, depending on age, comorbidities, technical factors, patient values, and other factors. Others may benefit from urgent valve replacement. It may be desirable to stabilize such patients prior to transcatheter or surgical valve replacement, but these are precisely the patients at highest risk of further decompensation with medical intervention. The limited data available are equivocal whether outcomes are improved with medical therapy or balloon aortic dilation prior to intervention, compared to proceeding directly to TAVI. (See "Percutaneous balloon aortic valvotomy for native aortic stenosis in adults".)

The decision to proceed with TAVI versus consideration of balloon dilation is best made by a Heart Valve Team. TAVI may be appropriate in selected patients, but balloon dilation may be considered for short-term improvement in hemodynamics and clinical symptoms [12].

Although data are limited, nitroprusside may be useful in improving ventricular performance prior to surgery and thus reduce surgical risk. The use of nitroprusside was evaluated in a study of 25 patients with severe AS and depressed LV function who were not hypotensive; nitroprusside was administered during continuous hemodynamic monitoring with a pulmonary artery catheter [13]. During nitroprusside treatment, there were significant increases in cardiac index (1.60 to 2.52 L/min per m²) and stroke volume (from 32 to 54 mL) and significant reduction in mean arterial pressure (81 to 69 mmHg) and systemic vascular resistance. Five patients died in the hospital and 13 underwent successful AVR.

Although no complications occurred, the use of vasodilator therapy in such patients is associated with a risk of hypotension and hemodynamic collapse, and it is unclear from this uncontrolled study whether the surgical outcomes were improved [14]. This approach should be undertaken only with careful hemodynamic monitoring by experienced clinicians.

A potential alternative approach is use of dobutamine in such patients, although use of nitroprusside or dobutamine in critically ill patients with AS requires intensive monitoring.

POSSIBLE INDICATIONS FOR AORTIC BALLOON DILATION — Percutaneous aortic balloon dilation (previously termed percutaneous aortic balloon valvotomy) is a procedure in which one or more balloons are placed across the stenotic aortic valve and inflated [15]. The aim is to relieve the stenosis, presumably by fracturing calcific deposits within the valve leaflets. Stretching of the annulus and separation of the calcified commissures also may contribute. Early changes after successful balloon dilation include a moderate reduction in the transvalvular pressure gradient and an often dramatic improvement in symptoms; however, the post-procedure valve area rarely exceeds 1.0 cm² [15,16].

Serious complications (stroke, aortic regurgitation, myocardial infarction) occur in approximately 10 to 20 percent of patients [15-17]. Furthermore, restenosis and clinical deterioration occur in most cases within 6 to 12 months and the long-term outcome resembles the natural history of untreated AS [16,18]. Repeat balloon dilation can be performed, but most patients fail within six months [19].

Based upon these observations, the 2020 American College of Cardiology/American Heart Association (ACC/AHA) guidelines suggest that balloon aortic dilation may be considered as a bridge to transcatheter aortic valve implantation (TAVI) or surgical AVR in patients with severe symptomatic AS, although moving directly to transcatheter AVR also is an option [20]. However, balloon dilation is not a substitute for valve replacement in adults, although selected young adults without valve calcification represent an exception. (See "Subvalvar aortic stenosis (subaortic stenosis)" and "Bicuspid aortic valve: Intervention for valve disease or aortopathy in adults", section on 'Balloon valvotomy'.)

Although the evidence is not well established, the guidelines noted two specific settings in adults in which balloon dilation might be reasonable [20]:

●As a bridge to transcatheter or surgical aortic valve replacement (AVR) in hemodynamically unstable patients at high risk for morbidity and mortality with AVR. However, mortality remains high in these patients [21]. Most centers now recommend proceeding directly to TAVI in patients with a high or prohibitive surgical risk [22,23]. (See 'Critically ill patients awaiting valve replacement' above.)

●Use for palliation in patients with serious comorbid conditions that prevent performance of AVR.

In addition, there are two other settings in which balloon dilation has been considered:

●As a bridge to delivery of a baby in symptomatic pregnant patients with severe AS who typically have a congenitally abnormal aortic valve. Although there are case reports suggesting success with this approach, balloon dilation can induce aortic regurgitation even with an experienced operator. (See "Bicuspid aortic valve: Management during pregnancy".)

●In patients who require urgent noncardiac surgery. However, the ACC/AHA guidelines concluded that most asymptomatic patients with severe AS can undergo urgent noncardiac surgery at relatively low risk with careful intraoperative and postoperative management, including monitoring of anesthesia and careful attention to fluid balance [20,24,25]. If preoperative correction of AS is warranted, this should be addressed by surgical AVR or TAVI, not balloon dilation [20]. (See "Noncardiac surgery in adults with aortic stenosis".)

ROLE OF PALLIATIVE CARE — Given the life-limiting nature of severe AS, as well as the high symptom burden associated with severe AS, palliative care consultation is valuable in this population, particularly if the AS is associated with other significant morbidities and/or if the patient is not a candidate for surgical or transcatheter aortic valve implantation (TAVI).

Palliative care focuses on quality of life in people with life-limiting conditions, is provided alongside rather than instead of active medical therapy, and is ideally not delayed until end stages of illness. It can and does include end-of-life planning and care, but is meant to be initiated earlier in the course of illness. Palliative care is partly founded on the principles of shared decision making, and its practitioners are highly skilled at ascertaining patients’ views and preferences and helping the patients and family or caregiver understand how various medical options will or will not facilitate the patient in reaching their goals of care. (See "Benefits, services, and models of subspecialty palliative care".)

The principles of palliative care and decision making in advanced heart failure and other cardiovascular diseases also apply to patients with severe AS who have concomitant heart failure, who are older adults and frail, or who have other chronic conditions that may limit their prognosis with or without surgical or percutaneous valve replacement [26-31]. (See "Palliative care for patients with advanced heart failure: Indications and systems of care".)

In particular, older adults with functional limitations or comorbidities for whom TAVI is being considered could benefit from consultation with palliative care providers with advanced communication skills to promote shared decision making [32]. These providers can facilitate ascertainment of patients’ goals and preferences, assess patient knowledge and understanding of their disease, and discuss prognosis and foreseeable outcomes with medical options. In many of these patients, TAVI will either not be advisable, or the patients themselves will decide against it as being unlikely to help them achieve their goals. For example, if the patient’s goals are to improve cognitive function, mobility, and independence, TAVI may not help significantly with these goals.

Even with optimal care, adults with severe symptomatic inoperable AS will have exacerbations of symptoms and frequent hospitalizations. Symptoms of dyspnea and chest pain are treated as described above, within the end-of-life care parameters set by the patient. Dizziness and presyncope typically are exertional and can be avoided by decreasing physical activity and instructing the patient to stop and sit (or lie) down when symptoms occur. Palliative care includes symptomatic treatment for symptoms of dyspnea and angina. In addition, end-of-life discussions and counseling are appropriate. (See "Palliative care for patients with advanced heart failure: Indications and systems of care".)

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

●Limited role of medical therapy for AS – Symptomatic aortic stenosis (AS) is an indication for aortic valve replacement (AVR) and medical therapy has limited utility in treating symptoms. However, medical management may be required in patients who are not candidates for surgery (either due to comorbid conditions or patient preference to decline valve replacement). (See 'Settings' above.)

●Management of critically ill patients with severe AS – In critically ill patients with severe AS, attempts to medically stabilize the patient should be undertaken with caution. These patients generally require prompt aortic valve intervention (either surgical valve replacement or transcatheter aortic valve implantation [TAVI]). In selected patients with AS, aortic balloon dilation is an option for short term improvement in hemodynamics but has largely been replaced by TAVI. (See 'Critically ill patients awaiting valve replacement' above.)

●Palliative care – Palliative care for severe symptomatic inoperable AS includes the following (see 'Medical management' above):

•Prevention and treatment of concurrent cardiovascular conditions such as atrial fibrillation and coronary artery disease.

•Management of adverse hemodynamic loading conditions and symptoms. Careful treatment of hypertension is appropriate. For patients with heart failure, we suggest a combination of a diuretic and an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). These should be started at low doses with gradual titration.

•End-of-life discussions and counseling. (See 'Role of palliative care' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Stephanie Cooper, MD, who contributed to earlier versions of this topic review.