10-14: Aortic Stenosis

There are two common clinical scenarios in which aortic stenosis is prevalent (eFigure 10–37). The first is due to a congenitally abnormal unicuspid or bicuspid valve, rather than tricuspid. Symptoms can occur in young or adolescent individuals if the stenosis is severe, but more often emerge at age 50–65 years when calcification and degeneration of the valve become manifest. A dilated ascending aorta, due to an intrinsic defect in the aortic root media and the hemodynamic effects of the eccentric aortic jet, may accompany the bicuspid valve in about half of these patients. Coarctation of the aorta is also seen in a number of patients with congenital aortic stenosis. Offspring of patients with a bicuspid valve have a much higher incidence of the disease in either the valve, the aorta, or both (up to 30% in some series).

A second pathologic process, degenerative or calcific aortic stenosis, is thought to be related to calcium deposition due to processes similar to those that occur in atherosclerotic vascular disease. Approximately 25% of patients over age 65 years and 35% of those over age 70 years have echocardiographic evidence of aortic valve thickening (sclerosis). About 10–20% of these will progress to hemodynamically significant aortic stenosis over a period of 10–15 years. Certain genetic markers are associated with aortic stenosis (most notably Notch 1), so a genetic component appears a likely contributor, at least in some patients. Other associated genetic markers have also been described.

Aortic stenosis has become the most common surgical valve lesion in developed countries, and many patients are elderly. The risk factors include hypertension, hypercholesterolemia, and smoking. Hypertrophic cardiomyopathy may also coexist with valvular aortic stenosis.

A. Symptoms and Signs

Aortic stenosis produces a progressive afterload increase on the LV. To reduce wall stress, the ventricle hypertrophies by laying sarcomeres on top of each other, and increasing the wall thickness (concentric hypertrophy). At times, severe LVH ensues. Eventually, the hypertrophy may lead to myocardial dysfunction. Since the EF measurement is afterload dependent, it is frequently difficult to sort out whether the low EF is due to increased afterload or to myocardial dysfunction.

Slightly narrowed, thickened, or roughened valves (aortic sclerosis) or aortic dilation may contribute to the typical ejection murmur of aortic stenosis. In mild or moderate cases where the valve is still pliable, an ejection click may precede the murmur and the closure of the valve (S₂) is preserved. The characteristic systolic ejection murmur is heard at the aortic area and is usually transmitted to the neck and apex. In severe aortic stenosis, a palpable LV heave or thrill, a weak to absent aortic second sound, or reversed splitting of the second sound is present (see Table 10–1) (AUDIO 10–17) (AUDIO 10–18). In some cases, only the high-pitched components of the murmur are heard at the apex, and the murmur may sound like mitral regurgitation (the so-called Gallaverdin phenomenon). When the valve area is less than 0.8–1.0 cm² (normal, 3–4 cm²), ventricular systole becomes prolonged and the typical carotid pulse pattern of delayed upstroke and low amplitude is present. A delayed upstroke, though, is an unreliable finding in older patients with extensive arteriosclerotic vascular disease and a stiff, noncompliant aorta. LVH increases progressively due to the pressure overload, eventually resulting in elevation of ventricular end-diastolic pressure (eFigure 10–38). Cardiac output is maintained until the stenosis is severe. LV failure, angina pectoris, or syncope may be presenting symptoms of significant aortic stenosis; importantly, all symptoms tend to first occur with exertion.

B. Redefining Severe Aortic Stenosis

There are four different anatomic syndromes that occur in patients with severe aortic stenosis. The common underlying measure of severe aortic stenosis is an aortic valve area of less than 1.0 cm² and echocardiographic evidence of an immobile aortic valve. In patients with a normal LVEF and normal cardiac output, the threshold for intervention is a peak aortic gradient of greater than 64 mm Hg and mean aortic gradient of greater than 40 mm Hg. In the same situation, super-severe aortic stenosis is defined as a mean gradient of greater than 55 mm Hg or peak aortic velocity greater than 5 m/sec by Doppler.

In some patients with an aortic valve area of less than 1.0 cm² with a low cardiac output and stroke volume, the mean gradient may be less than 40 mm Hg. This can occur when the LV systolic function is poor (low-gradient severe aortic stenosis with low LVEF) or when the LV systolic function is normal (paradoxical low-flow severe aortic stenosis with a normal LVEF). Low flow (low output) in these situations is defined by an echocardiographic stroke volume index of less than 35 mL/min/m². Prognosis in patients with low gradient, low valve area, low output, and a normal LVEF aortic stenosis may actually be worse than in patients with the traditional high gradient, low valve area, normal output, and normal LVEF aortic stenosis. If low-flow severe aortic stenosis is present in the face of a low LVEF, provocative testing with dobutamine or nitroprusside is warranted to increase the stroke volume to discover if a mean aortic valve gradient of at least 40 mm Hg can be demonstrated without increasing the aortic valve area. If the aortic valve area can be made to increase and a mean gradient of greater than 40 mm Hg cannot be demonstrated by inotropic challenge, the presumption is that the low gradient is due to an associated cardiomyopathy and not the aortic valve stenosis. In this latter situation intervention is not indicated. The 2014 AHA/ACC guidelines acknowledge these four situations (Table 10–3). Intervention is indicated in super-severe aortic stenosis even without demonstrable symptoms (grade C) and in any of the other situations when symptoms are present: D1 defines the symptomatic high gradient patient; D2 the symptomatic low-flow, low-gradient patient with low LVEF; and D3 the symptomatic low-flow, low-gradient patient with normal LVEF.

Symptoms of LV failure may be sudden in onset or may progress gradually. Angina pectoris frequently occurs in aortic stenosis due to underperfusion of the endocardium. Of patients with calcific aortic stenosis and angina, half have significant associated CAD. Syncope, a late finding, occurs with exertion as the LV pressure rises, stimulating the LV baroreceptors to cause peripheral vasodilation. This vasodilation results in the need for an increase in stroke volume, which increases the LV systolic pressure again, creating a cycle of vasodilation and stimulation of the baroreceptors that eventually results in a drop in systemic BP, as the stenotic valve prevents further increase in stroke volume. Less commonly, syncope may be due to arrhythmias (usually ventricular tachycardia but sometimes AV block as calcific invasion of the conduction system from the aortic valve may occur).

C. Diagnostic Studies

The ECG reveals LVH or secondary repolarization changes in most patients but can be normal in up to 10%. The chest radiograph may show (1) a normal or enlarged cardiac silhouette, (2) calcification of the aortic valve, and (3) dilation or calcification (or both) of the ascending aorta (see eFigures 10–30 and 10–31). The echocardiogram provides useful data about aortic valve calcification and leaflet opening, the severity of LV wall thickness, and overall ventricular function, while Doppler can provide an excellent estimate of the aortic valve gradient. The 2014 AHA/ACC guidelines provide echocardiography/Doppler criteria for identifying aortic stenosis severity. The peak Doppler gradient is derived by squaring the maximal flow velocity through the valve orifice and multiplying times 4; thus, a 4 m/s maximum velocity gradient translates into a 64 mm Hg peak Doppler gradient. Valve area estimation by echocardiography is less reliable but is a critical component of the diagnosis of aortic stenosis due to issues such as paradoxical low-flow aortic stenosis (low-gradient, low-flow, normal LVEF patients). Likewise, the echocardiography/Doppler can estimate the stroke volume index used to define the low-flow state when the valve area is small but the gradient is less than 40 mm Hg. Cardiac catheterization mostly provides an assessment of the hemodynamic consequence of the aortic stenosis, and the anatomy of the coronary arteries. Catheterization data can be important when there is a discrepancy between symptoms and the echocardiography/Dopper information of aortic stenosis severity. In younger patients and in patients with high aortic gradients, the aortic valve need not be crossed at catheterization. Aortic regurgitation can be semiquantified by aortic root angiography. Some authors have suggested the use of BNP (or NT-proBNP) may provide additional prognostic data in the setting of poor LV function and aortic stenosis. A BNP greater than 550 pg/mL has been associated with a poor outcome in these patients regardless of the results of dobutamine testing. Stress testing can be done cautiously in patients in whom the aortic stenosis severity does not match the reported symptoms in order to confirm the reported clinical status. It should not be done in patients with super-severe aortic stenosis.

Table 10–4 outlines the 2014 guidelines for surgical intervention in aortic stenosis. Valve intervention is warranted in all patients who have symptomatic severe aortic stenosis. There are also times when asymptomatic aortic stenosis should undergo intervention. Asymptomatic patients with severe aortic stenosis (aortic valve area less than 1.0 cm²) should generally undergo intervention according to the following guidelines: (1) they are undergoing other cardiac surgery (ie, CABG), (2) there is evidence for a reduced LVEF (less than 50%), (3) when the mean gradient exceeds 55 mm Hg (peak velocity greater than 5 m/sec), (4) when there is failure of the BP to rise more than 20 mm Hg with exercise, (5) when there is severe valvular calcium, or (6) when there is evidence of a rapid increase in the peak aortic gradient (more than 0.3 m/sec/year). Following the onset of heart failure, angina, or syncope, the prognosis without surgery is poor (50% 3-year mortality rate). Medical treatment may stabilize patients in heart failure, but intervention is indicated for all symptomatic patients with evidence of significant aortic stenosis.

The surgical mortality rate for valve replacement is low, even in older adults, and ranges from 2% to 5%. This low risk is due to the dramatic hemodynamic improvement that occurs with relief of the increased afterload. Mortality rates are substantially higher when there is an associated ischemic cardiomyopathy. Severe coronary lesions are usually bypassed at the same time as aortic valve replacement (AVR), although there are few data to suggest this practice affects outcome. In some cases, a staged procedure with stenting of the coronaries prior to surgery may be considered, especially if a percutaneous AVR approach is being considered. Around one-third to one-half of all patients with aortic stenosis have significant CAD, so this is a common concern. With the success of transcatheter aortic valve replacement (TAVR), the treatment options have greatly expanded for many patients with severe aortic stenosis. For this reason, a Heart Valve Team approach bringing together invasive and noninvasive cardiologists, radiologists, anesthesiologists, and cardiac surgeons is mandatory; clinical factors (such as frailty) and anatomic features (such as a calcified aorta, vascular access, etc) can affect the decision making.

Medical therapy to reduce the progression of disease has not been effective to date. Statins have been assessed in four major clinical trials (SALTIRE [atorvastatin], SEAS [simvastatin plus ezetimibe], ASTRONOMER [rosuvastatin], and PROCAS [rosuvastatin]). None revealed any benefit on the the progression of aortic stenosis or on clinical outcomes despite the association of aortic stenosis with atherosclerosis. If patients with aortic stenosis have concomitant CAD, the guidelines for the use of statins should be followed. Efforts to reduce stenosis progression by blockage of the renin-angiotensin system have also been ineffective. Control of systemic hypertension, though, is an important adjunct, and inadequate systemic BP control is all too common due to unreasonable concerns about providing too much afterload reduction in patients with aortic stenosis. Normal systemic BP is important to maintain as the LV is affected by the total afterload (systemic BP plus the aortic valve gradient).

The interventional options in patients with aortic valve stenosis has expanded with the use of TAVR and depend on the patient’s lifestyle and age. The algorithm to decide when an AVR is appropriate in various situations is outlined in Figure 10–3. The 2017 ACC/AHA valvular guidelines modify this only in that surgical AVR can be considered for any of the indications outlined in the figure, whether asymptomatic or not. TAVR should be reserved only for those patients with symptoms. These newest guidelines point out that TAVR is equivalent to surgical AVR in all of the randomized trials of symptomatic patients. As of 2017, TAVR for aortic stenosis can be applied to all except the lowest risk (less than 4%). The lowest risk patients are being studied in trials randomizing between TAVR and surgical AVR.

In young and adolescent patients, percutaneous balloon valvuloplasty still has a small role. Balloon valvuloplasty is associated with early restenosis in the elderly population, and thus is rarely used except as a temporizing measure. Data suggest aortic balloon valvuloplasty in elderly people has an advantage only in those with preserved LV function, and such patients are usually excellent candidates for surgical AVR. (VIDEO 10–11). The Ross procedure is generally still considered a viable option in younger patients, and it is performed by moving the patient’s own pulmonary valve to the aortic position and replacing the pulmonary valve with a homograft (or rarely a bioprosthetic valve). However, dilation of the pulmonary valve autograft and consequent aortic regurgitation, plus early stenosis of the pulmonary homograft in the pulmonary position, has reduced the enthusiasm for this approach in most institutions. Middle-aged adults generally can tolerate the anticoagulation therapy necessary for the use of mechanical aortic valves, so patients younger than 60 years generally undergo AVR with a bileaflet mechanical valve. If the aortic root is severely dilated as well (greater than 4.5 cm), then the valve may be housed in a Dacron sheath (Bentall procedure) and the root replaced along with the aortic valve. Alternatively, a human homograft root and valve replacement can be used. In patients older than 60 years, bioprosthetic (either porcine or bovine pericardial) valves with a life expectancy of about 10–15 years are routinely used instead of mechanical valves to avoid need for anticoagulation. Data favor the bovine pericardial valve over the porcine aortic valve (AUDIO 10–19). As it is becoming clearer that bioprosthetic valve degeneration in the larger valves can be potentially repaired by percutaneous valve-in-valve TAVR, it is likely that the use of mechanical valves will continue to decline. If the aortic annulus is small, a bioprosthetic valve with a short sheath can be sewn to the aortic wall (the stentless AVR) rather than sewing the prosthetic annulus to the aortic annulus. (Annulus is a relative term when speaking of the aortic valve, since there is no true annulus.) Another popular surgical option when the aorta is enlarged is the use of the Wheat procedure; it involves aortic root replacement above the coronary arteries and replacement of the aortic valve below the coronary arteries. The coronary arteries thus remain attached to the native aorta between the new graft and prosthetic valve rather than being reimplanted onto an artificial sheath or homograft.

In patients with a bicuspid aortic valve, there is an associated ascending aortic aneurysm in about half. If the maximal dimension of the aortic root is greater than 5.5 cm, it is recommended to proceed with root replacement regardless of the severity of the aortic valve disease. It is also appropriate to intervene when the maximal aortic root size is greater than 5.0 cm in diameter if there is a family history of aortic dissection or the aortic root size increases by more than 0.5 cm in 1 year. The aortic valve may be replaced at the same time if at least moderate aortic stenosis is present or may be either left alone or repaired (valve sparing operation). If there is an indication for AVR and the root is greater than 4.5 cm in diameter, root replacement is also recommended.

The use of mechanical versus bioprosthetic AVR has changed over time. A bioprosthetic valve is acceptable for patients at any age for whom anticoagulant therapy is contraindicated, not desired, or cannot be managed, and is preferred in patients over the age of 70. An aortic mechanical valve should be used in patients younger than 50 years of age who can take warfarin (this recommendation is a decrease from age 60 in the recent updated guidelines). Either type of valve is acceptable between the ages of 50 and 70 years depending on patient preference and any issues with warfarin usage.

Anticoagulation is required with the use of mechanical aortic valves, and the international normalized ratio (INR) should be maintained between 2.0 and 3.0 for bileaflet valves. In general, mechanical aortic valves are less subject to thrombosis than mechanical mitral valves and do not need bridging with anticoagulation unless there are other thromboembolic risk factors or there is an older generation AVR. Low-dose aspirin is recommended as well. Some newer bileaflet mechanical valves (On-X) allow for a lower INR range from 1.5 to 2.0. Clopidogrel is recommended for the first 6 months after TAVR in combination with lifelong aspirin therapy. DOACs are not recommended for any mechanical valves but may be used in patients with a bioprosthetic AVR if treating atrial fibrillation or venous thrombosis.

The estimated use of TAVR has grown dramatically, with a gross estimate of over 500,000 implants worldwide. In the United States, the Food and Drug Administration (FDA) has granted approval for two devices, the Edwards SAPIEN and the Medtronic CoreValve, for use in patients with at least a 4% surgical risk (intermediate risk) as measured by the Society of Thoracic Surgeons. These devices are fundamentally stents with a trileaflet bioprosthetic valve constructed within them. There are a variety of implantation approaches, though most valves are placed via a femoral artery approach. Other options include an antegrade approach via transseptal across the atrial septum, via the LV apex with a small surgical incision, via the subclavian arteries, via the carotid, or via a minithoracotomy. The Edwards SAPIEN valve is a balloon-expandable valvular stent, while the CoreValve is a valvular stent that self-expands when pushed out of the catheter sheath. Multiple other devices are in trials, many with excellent early results. These devices will allow for a wider range of aortic valve sizes to be treated; can be delivered with smaller catheters, eliminating the need for femoral artery cutdowns; will allow for repositioning before permanent implantation; and appear to result in less paravalvular regurgitation and less injury to the conduction system. Cost remains a major issue. All of the professional societies stress the importance of a Heart Valve Team when considering aortic stenosis intervention. This is critically important because many patients referred for TAVR have serious comorbid conditions that will not improve with alleviation of the aortic stenosis. A 2017 consensus document from the ACC provides a decision pathway for the use of TAVR. This document summarizes background information and provides a checklist of items to consider when deciding between surgical AVR and TAVR. The importance of quality of life and frailty is emphasized because some of the most elderly or most debilitated patients may not benefit from any procedure. Frailty is a risk factor for death and disability following TAVR and surgical aortic valve replacement. A brief four-item scale encompassing lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia outperformed other frailty scales.

Figure 10–4 outlines the suggested indications for TAVR based on the 2017 updated AHA/ACC guidelines. eTable 10–2 outlines the key clinical trials regarding TAVR and includes the risk categories of the patients, the trials associated with those patients, the mortality observed, and complications. As the patient risk has declined, so has the overall mortality. While the initial trials included only inoperable patients (Partner 1B) or those of very high risk (Partner 1A and CoreValve High Risk), positive results from the Partner 2A intermediate risk study and the NOTION registry in a low-risk population has encouraged application of TAVR to lower and lower risk aortic stenosis patients. The FDA has approved TAVR for use in the intermediate risk category. Ongoing randomized trials, SAPIEN 3 and Evolut R, are actively enrolling patients with the lowest risk to compare surgical AVR to TAVR. Enrollment is complete in these trials but results were not available by the end of 2018.

TAVR is also being used more frequently in “valve-in-valve” procedures to reduce the gradient in patients with prosthetic valve dysfunction (regardless of whether in the aortic, mitral, tricuspid, or pulmonary position). While the results of TAVR in patients with bicuspid aortic valves (as opposed to tricuspid) have been less impressive, newer modifications have improved the success rates in these anatomic situations as well.

• All patients with echocardiographic evidence for mild-to-moderate aortic stenosis (estimated peak valve gradient greater than 30 mm Hg by echocardiography/Doppler) should be referred to a cardiologist for evaluation and to determine the frequency of follow-up.

• Any patients with symptoms suggestive of aortic stenosis (ie, exertional symptoms of chest pressure, shortness of breath, or presyncope) should be seen by a cardiologist.