Mrs. R is a 92-year-old woman with history of severe aortic stenosis (AS), hypertension (HTN), atrial flutter, and nonobstructive coronary artery disease (CAD). She first developed symptoms around 2 years ago that were characterized by mild dyspnea on exertion and fatigue, and was appropriately referred for further therapy with either a surgical or transcatheter aortic valve replacement (TAVR). However, the patient at the time refused any further intervention for fear of complications given her advanced age.

She returned to the clinic 2 years later with now severe dyspnea even on minimal exertion, significant fatigue, dizziness, lower extremity edema, and weight loss. Physical examination revealed a frail elderly woman. The carotid pulse was slow and decreased in amplitude. On cardiac auscultation a soft S₂ was heard along with a late-peaking systolic murmur that was best heard at the right upper sternal border and radiated to the carotids.

Repeat echocardiography revealed a heavily calcified aortic valve with limited mobility (Figure 15-1). Doppler assessment of the aortic valve yielded a peak velocity of 5.4 m/sec, a mean gradient of 62 mm Hg, and a calculated aortic area of 0.6 cm², making the diagnosis of critical AS (Figure 15-2). The left ventricle (LV) showed moderate concentric hypertrophy with preserved ejection fraction (EF), but with evidence of diastolic dysfunction. Because of her significant, activity-limiting symptoms, the patient agreed to undergo further therapy. She was deemed high surgical risk because of high frailty score. She was therefore, referred for transcatheter aortic implantation with an Edwards SAPIEN 3 prosthesis. The procedure was successfully completed. However, the patient experienced a prolonged hospital course because of her advanced disease, significantly delayed intervention since symptom onset, and frailty. She has since recovered with markedly improved symptoms, and the latest echocardiogram shows a normally functioning prosthetic valve with a peak velocity to 2.8 m/sec, and mean gradient of 16 mm Hg (Figure 15-3).

Aortic stenosis (AS) is the most frequent valvular heart disease. The prevalence of AS in the general population increases with age, and has been reported to occur in up to 9.8% of individuals aged 80 to 89 years.¹ The disease is usually caused by calcific degeneration of a trileaflet valve, or by progressive calcification of a congenitally abnormal valve, such as a bicuspid or unicuspid valve (Figure 15-4). Worldwide, however, rheumatic heart disease is still the most common etiology, and is usually accompanied by mitral disease. Traditional risk factors for atherosclerosis, such as HTN, smoking, and dyslipidemia, have been associated with the development of both calcific AS, and its predecessor, aortic sclerosis.²

A normal effective aortic valve area is about 3.0 to 4.0 cm² in adults. As the severity of the AS progresses, the valve area narrows, and the transvalvular pressure gradient increases. To compensate for the increased afterload obstruction, the LV undergoes concentric hypertrophy, and is thus able to maintain wall stress and cardiac output, at least for a while. Further progression of the stenosis severity and hypertrophy can lead to decreased compliance of the LV and the development of diastolic dysfunction. The progressive increase of LV hypertrophy and wall stress parallels an increase in oxygen demand, which cannot be met by the reduced coronary flow reserve. This supply-demand mismatch can result in angina, even if the epicardial coronary arteries are normal. Eventually, the compensatory mechanisms fail, and systolic dysfunction develops in the face of constant pressure overload.

Typically, patients with AS have a long latent period in which they are asymptomatic. There is a wide degree of variability in the actual degree of obstruction that would lead to symptoms in an individual patient, in part because of body size and physical fitness. In general, symptoms rarely develop until the AS is severe (defined as an area <1 cm², velocity >4 m/sec, and/or mean gradient >40 mm Hg), and even then, the patient might remain free of symptoms. In one series of asymptomatic patients with AS, survival free of death or valve replacement indicated by the development of symptoms was 5% at 2 years of follow-up.³ On the other hand, other reports have shown a more aggressive progressive course of severe AS, with a high likelihood of developing symptoms within the following 3 to 5 years.⁴ When symptoms do initially develop, they might be vague and nonspecific, such as decreased exercise tolerance, exertional dizziness, and dyspnea on exertion. The development of the classic clinical symptoms of AS, which include angina, syncope, and HF, signals a poor prognosis and decreased survival rate over the next 2 to 5 years, unless aortic valve replacement is performed.⁵

In asymptomatic patients, an abnormal physical examination might be the first clue to the presence of AS. A hallmark finding of severe AS is pulsus parvus et tardus, a carotid pulse that is diminished and delayed. This might be absent in the elderly, however, because of increased vasculature rigidity. The typical auscultatory findings include a systolic ejection murmur that is best heard over the right upper sternal border and radiates to the carotids. As the severity of the AS increases, the duration of the murmur becomes longer and peaks later. The intensity of the murmur is generally not a reflection of the severity of AS. Also, with severe AS, the aortic component of S₂ may become soft or even absent because the aortic valve is calcified and immobile.

An electrocardiogram (ECG) of a patient with severe AS will often show LV hypertrophy (85% of patients). Chest radiography might be normal in these patients, or might show AV and aortic root calcifications, or cardiomegaly and pulmonary congestion if there is LV dysfunction.

The test of choice to establish the diagnosis of AS, determine the cause, and assess the severity, is a transthoracic echocardiogram (TTE). Two-dimensional echocardiography and M-mode can help determine the morphology of the aortic valve, and can often delineate if it is trileaflet or bicuspid. The aortic valve is usually thickened and calcified, with limited leaflet excursion during systole and reduced orifice size (Figures 15-1, 15-2, 15-3, 15-4). In cases where TTE is equivocal or technically limited, a transesophageal echo may be useful (Figure 15-5). In the absence of HF, the LV cavity size is usually normal, and the LV wall is typically concentrically hypertrophied. Initially, the left ventricular ejection fraction (LVEF) is preserved, but as the disease progresses, systolic dysfunction and a drop in EF are seen.

Doppler echocardiography measures the velocity and pressure gradient across the diseased valve (Figure 15-6), and allows the calculation of the aortic area. The classification of the severity of the AS is dependent on the Doppler echo findings; the more severe the AS, the higher the velocity and pressure gradient, and the smaller the aortic area. In patients with low cardiac output, such as those secondary to LV dysfunction, the low flow across the valve might lead to low velocity and pressure gradient. This in turn will lead to an underestimation of the severity of the AS. On the other hand, the poor LV contraction can lead to poor leaflet mobility of a calcified aortic valve, and the illusion of a tight aortic area. This might be erroneously interpreted as severe AS, the so-called pseudo AS. In such cases of low-flow, low-gradient AS, the administration of low dose dobutamine may aid in the differentiation between true AS and pseudo AS, as well as the assessment of LV contractile reserve.

AS remains the most common cause of LV outflow tract obstruction. Other causes include stenosis at the supravalvular level, which is uncommon and usually a part of a congenital disorder such as Williams syndrome. Or it could be secondary to stenosis at the subvalvular level, such as a discrete fibromuscular membrane present below the aortic valve (Figure 15-7), or, in extreme cases, a tunnel-like obstruction of the LV outflow tract.

Asymptomatic patients with AS should be followed closely with serial clinical examinations, and assessment of any developing symptoms. Serial echocardiograms should be done, the frequency of which is determined by the severity of the stenosis. Once the patient develops severe AS, then more frequent clinical follow-up is recommended. Aortic valve replacement (AVR) is usually kept on hold until the patient develops symptoms. However, in specific situations, early AVR might be reasonable in asymptomatic severe AS patients. Patients with very severe asymptomatic AS (velocity 5.0 m/sec or greater, or mean pressure gradient 60 mm Hg or higher) and low surgical mortality, might benefit from early surgical AVR.⁵

No medical therapies are currently recommended to halt the progression of AS. Medical treatment of concomitant HTN or dyslipidemia is recommended according to standard guideline-directed therapy.

In symptomatic severe AS, or asymptomatic severe AS with secondary LV dysfunction (EF <50%), AVR is the treatment of choice. Once symptoms secondary to severe AS develop, outcomes are extremely poor unless the outflow obstruction is relieved. Even in patients with a low LVEF and severe AS, survival is better in those who undergo AVR compared to those treated medically.^5,6 The choice of intervention includes surgical or transcatheter AVR (TAVR). Whenever intervention is recommended and the surgical risk is low, surgical AVR is recommended. The choice between mechanical or bioprosthetic valve depends on the patient’s age, ability to take and maintain therapeutic anticoagulation, and the patient’s preference. In patients with severe symptomatic AS who are unable to undergo surgical AVR due to a prohibitive surgical risk or who have a high surgical risk, and who have an expected survival of >1 year after intervention, TAVR is recommended to improve survival and reduce symptoms (Figure 15-8).^7,8 Recently, TAVR has also been shown to be beneficial and comparable to open surgery in intermediate-risk patients.⁹

Frequency of follow-up for asymptomatic AS patients depends on the severity of the stenosis, and the presence of comorbidities. The more severe the AS, the closer the follow-up is scheduled, so that patients with severe AS should be evaluated every 6 months to 1 year with repeat TTE. It is hard to predict when patients with severe AS will develop symptoms, and thus the frequent clinical visits are geared to pick up insidious symptoms that might be missed by the patient.

In patients with severe symptomatic AS, treatment with surgical or TAVR results in improved survival rates, reduced symptoms, and improved exercise capacity. Thus, AVR is indicated in all symptomatic patients in the absence of serious comorbid conditions that limit life expectancy or quality of life.

Following the placement the prosthetic valve, regular clinical follow-up is indicated. A TTE is checked after the surgery, and repeated whenever there is a clinical change suggestive of valve dysfunction. Because of the high incidence of bioprosthetic valve dysfunction after 10 years, an annual TTE after that is recommended.⁵

Mr. P is a 51-year-old man with no significant past medical history, presented to the emergency department for evaluation of a few days history of dyspnea on minimal exertion that progressed to orthopnea. On presentation, he was found to be in florid HF with pulmonary edema. His symptoms rapidly improved upon diuresis. Mr. P admitted to a fairly sedentary lifestyle, and so previous symptoms such as exercise-induced dyspnea could not be elucidated. Physical examination revealed bounding peripheral pulses, a laterally displaced LV apical impulse, loud S₂, and a grade III/VI holodiastolic murmur heard best at the right upper sternal border while the patient was sitting up and leaning forward.

Workup revealed a large ascending aortic aneurysm extending from the root to the proximal transverse arch, measuring 6 cm in diameter (Figure 15-9). TTE revealed a significantly dilated LV cavity (LV end-diastolic diameter of 6.7 cm, and an LV end-diastolic volume of 263 mL) (Figure 15-10), severe systolic LV dysfunction (EF of 35%), and evidence of severe aortic regurgitation (AR). Further assessment of the aortic valve showed it to be trileaflet with no inherent evident disease. However, the dilated aortic root caused malcoaptation of the leaflets. Echocardiographic features of severe AR are noted (Figures 15-11 and 15-12).

Because of his severe, symptomatic AR with large ascending aneurysm, and detrimental cardiac sequelae, manifested by a dilated heart with depressed systolic function, Mr. P was referred for urgent cardiac surgery. He underwent aortic root and valve replacement using a 27-mm mechanical valve within a 30-mm Valsalva graft, and replacement of the ascending aorta and proximal transverse arch with a 26-mm Dacron graft. Postoperative echocardiography shows a well-seated, mechanical valve in the aortic position with a peak velocity of 1.6 m/sec, mean gradient of 5 mm Hg, and no evidence of AR. Mr. P is out of the hospital now and continues to recover at home.

Aortic regurgitation (AR) is caused by blood flow leaking back through the aortic leaflets due to an inadequate closure line. This could be due to a primary disease of the leaflets (Figures 15-13 and 15-14), or due to abnormalities of the aortic root or ascending aorta (Figure 15-9), or a combination of both (Figure 15-15) (Table 15-1). Worldwide, rheumatic heart disease remains the leading cause of AR. In the Western hemisphere, however, abnormalities of the aortic root and bicuspid aortic valves, are the more common causes of AR.^2,10