Over the past century, there has been a linear climb in record life expectancy and an overall aging of the human race. Therefore, we are faced with an epidemic of aging and age-associated disease, not the least of which is valvular heart disease. Aortic stenosis, the narrowing of the aortic valve orifice caused by failure of the leaflets to open normally, is now the most common indication for valve replacement in North America and Europe.

The pathogenesis of aortic stenosis is most commonly progressive calcification and degeneration of a trileaflet or congenitally bicuspid valve. Although once thought to be a degenerative process, it is now recognized that calcific aortic stenosis is in fact an active disease process that shares similarities to atherosclerosis and involves inflammation, lipid accumulation, and calcification of the leaflets. The mechanisms by which some valves degenerate and become stenotic while others remain relatively normal are unknown but are probably related to genetic polymorphisms. Those with end-stage renal disease, Paget disease, or severe familial hypercholesterolemia may present with calcific aortic stenosis at a younger age and are susceptible to more rapid progression of stenosis severity.

Rheumatic valve disease is a rare cause of aortic stenosis in industrialized nations. However, for indigenous populations within these countries as well as in developing countries, there remains a significant prevalence of rheumatic valve disease. In contrast to calcific aortic valve stenosis, the rheumatic valve shows adhesion, leaflet retraction, and commissural fusion. Along or just a few millimeters away from the free margins of the valve leaflets, small sessile nodules develop that also contribute to leaflet malcoaptation. Therefore, the rheumatic aortic valve invariably will leak. Rheumatic aortic valve disease is almost never present in isolation, and there is invariably concomitant mitral valve disease. A patient with aortic stenosis and a perfectly normal mitral valve should be considered as having another cause for his or her disease. Other rare causes of aortic stenosis include connective tissues diseases such as systemic lupus erythematosus and ochronosis.

A. History

Those with acquired aortic stenosis generally have a long latent period before the onset of the salient clinical manifestations of the disease: effort-related dyspnea (heart failure), angina, and syncope. The most common initial clinical manifestations are a gradual decline in functional capacity and effort-related dyspnea. Regardless of the initial presenting symptom(s), it is imperative to ensure that the pathophysiologic mechanism of the symptoms is attributed to valve disease and not a manifestation of another mechanism such as concomitant coronary artery or lung disease because the onset of even mild symptoms attributed to aortic stenosis heralds a dramatic increase in the mortality rate for these patients if the valve is not replaced. Symptoms are therefore the guidepost for intervention, and understanding them is the key to understanding and managing the disease.

The primary determinants of left ventricular systolic function are contractility and afterload. The load on individual myocardial fibers can best be described as left ventricular wall stress and defined by the Laplace equation:

With acquired aortic stenosis, the obstruction will commonly progress gradually over time. Left ventricular adaptation to increases in systolic pressure is the parallel replication of sarcomeres to increase its thickness (concentric hypertrophy) in an effort to normalize wall stress and maintain systolic performance. As the severity of stenosis progresses, the increase in wall thickness may become insufficient to offset the rise in pressure (“afterload mismatch”), resulting in a rise in wall stress and a decline in ventricular function. The presence of aortic stenosis may also result in true depression of myocardial contractility, the exact mechanism of which is unclear but likely related to a loss of contractile elements secondary to reduced coronary blood flow. Thus, a decline in ejection fraction results from the interplay of varying degrees between excessive afterload and true myocardial depression. Those in whom the decline in function is largely attributed to afterload mismatch are more likely to experience restored ventricular function following aortic valve replacement. The evaluation of left ventricular ejection phase indices should be related to the global wall tension; however, clinically, it is difficult to tease out the extent to which wall stress (afterload) and contractility are contributing to a noted decline in ejection fraction.

1. Dyspnea and Exercise Intolerance

The increase in left ventricular wall thickness, although imposed in an effort to maintain wall stress and systolic performance, does have maladaptive physiologic consequences. The increase in wall thickness makes it harder to fill the ventricle, and therefore, higher filling pressures are required to achieve any given volume and end-diastolic volume will be required to increase to allow the maintenance of a normal ejection fraction (a rightward shift in the ventricular diastolic pressure-volume relationship) (Figure 17–1). In alignment with the concept of hemodynamic continuity, when the mitral valve opens, the left atrium is now exposed to the hemodynamic milieu of the left ventricle. The increased ventricular diastolic pressure is transmitted to atrium and further back into the pulmonary veins and lungs, resulting in pulmonary congestion and an increased work of breathing. In addition, with outflow obstruction, there is a prolongation of the ejection phase; this, in conjunction with an exercise-induced increase in heart rate, will result in a reduction of the diastolic filling time, and the ventricle will reach its limit of “preload reserve.” Once limits of preload reserve are met, stroke volume becomes directly related to ventricular pressure (see Figure 17–1), resulting in an inability to increase cardiac output and further contributing to the presence of dyspnea and exercise intolerance.

Figure 17-1. Left ventricular (LV) pressure-volume (P-V) loops. As LV pressure increases, stroke volume (SV) would decrease if the end-diastolic volume were fixed (loop 2). The ventricle, however, adapts by increasing end-diastolic volume to maintain a normal SV (loop 3). Eventually, the limits of preload reserve are met whereby increases in LV pressure result in a decline in SV (SV is now directly related to LV pressure; loop 4). (Reproduced with permission from Ross J. Afterload mismatch in aortic and mitral valve disease: Implications for surgical therapy. J Am Coll Cardiol. 1985;5(4):811826.)

2. Angina

Angina results from myocardial ischemia, which occurs when there is an imbalance between myocardial oxygen requirements/demand and myocardial oxygen supply. Although epicardial coronary artery disease often coexists with aortic stenosis, symptoms of angina frequently occur in those without epicardial coronary artery disease. Oxygen demand is best estimated clinically by the product of heart rate and wall stress, and as noted earlier, eventually the extent of hypertrophy cannot keep up with pressure demands of the ventricle and wall stress increases. In the absence of epicardial coronary artery disease, myocardial oxygen supply may also be decreased secondary to the rise in left ventricular end-diastolic pressure and a delayed rate of ventricular relaxation, with impaired coronary “diastolic suction” contributing to both reduced coronary perfusion and a decline in coronary flow reserve needed to offset increased oxygen demands during stress or exercise. In addition, with exercise and increased heart rates, there is reduced diastolic coronary perfusion time. Recently, coronary microvascular dysfunction has also been proposed as a mechanism of angina in patients with severe aortic stenosis as determined by adenosine-stress cardiac magnetic resonance.

3. Syncope

Syncope is a transient loss of consciousness due to cerebral hypoperfusion. Syncope in those with aortic stenosis usually occurs during exercise. There are two primary mechanisms, not mutually exclusive, that have been theorized to cause syncope. First, the narrowed aortic valve does not permit the appropriate increase in cardiac output necessary to offset the associated reduction in total peripheral resistance associated with exercise, resulting in a drop in blood pressure. Second, the very high ventricular pressure that develops with exercise when sensed by ventricular mechanoreceptors triggers a reflexive vasodepressor response, also leading to a decline in blood pressure. Less commonly, exercise can result in either ventricular or supraventricular arrhythmias, which can lead to a reduction in cardiac output and, consequently, a drop in blood pressure.

B. Physical Examination

1. Murmur

The character of a murmur can be described by its timing and shape, intensity and pitch, and location and radiation, along with changes in these characteristics imposed by transient changes in intracardiac hemodynamics.

A. Timing and Shape

The murmur of valvular aortic stenosis is a midsystolic murmur, which begins after the first heart sound and ends before the aortic (A₂) component of the second heart sound. During systole, as blood flow velocity accelerates across the valve, the intensity of the murmur increases, and as blood flow velocity decelerates, the intensity diminishes. Therefore, there is a classic “crescendo-decrescendo” configuration or shape to the murmur of valvular aortic stenosis. Further insights into the configuration of the murmur may help to discern the severity of disease; the later in systole the peak intensity occurs, generally the more severe is the stenosis.

B. Intensity and Pitch

The intensity of the aortic stenosis murmur relates to the quantity and velocity of transaortic blood flow along with the ability to transmit sound through the chest. The pitch of the murmur relates to the pressure gradient and size of the “aperture” with which the blood flows through. In general, as the stenosis severity increases, the intensity and pitch of the murmur will increase. However, in those with a thick ventricle and low end-diastolic volume or in the presence of a decline in cardiac function, both of which may result in a low stroke volume, the intensity and pitch of the murmur may be lower than expected for the given severity of stenosis. In addition, the ability to transmit the sound through the chest is impaired in those with a pericardial effusion, emphysema, or obesity. Therefore, one should be cautious of excluding significant aortic stenosis solely based on murmur intensity/pitch.

C. Location/Radiation

The murmur of aortic stenosis typically is heard loudest in the “aortic area,” the right second interspace at the sternal border, and will often radiate into the carotids and along a line from the aortic area toward the left ventricular apex. At the apex, the intensity and pitch of the murmur may change to more resemble that of the murmur of mitral regurgitation; however, the shape/configuration of the murmur does not change. This is known as the Gallavardin phenomenon.

D. Response To Maneuvers

A transient alteration in intracardiac hemodynamics may influence the characteristics of a murmur helping to further specify its etiology.

• Isometric handgrip: Increases systemic vascular resistance, decreasing the intensity of the murmur of aortic stenosis.

• Standing/Valsalva maneuver (phase II): Decreases ventricular filling, reducing the intensity of the murmur of aortic stenosis and most other valve murmurs, except that of hypertrophic cardiomyopathy and the duration of the murmur of mitral valve prolapse.

• Squatting: Increases ventricular filling but also increases systemic vascular resistance. Its effect on the murmur of aortic stenosis is therefore generally neutral; however, it will reduce the intensity of the murmur of hypertrophic cardiomyopathy.

• Cycle length: The intensity of the murmur of aortic stenosis may vary from beat to beat in those with atrial fibrillation or premature contractions, increasing in intensity in the beats following a longer R-R interval where diastolic filling time is increased.

2. Carotid Pulse

The carotid artery pulse wave contour in those with aortic stenosis is characterized as small and slow rising (parvus et tardus). One may also appreciate a carotid shudder.

3. Heart Sounds

A. Second Heart Sound (S2)

The presence of significant aortic stenosis may result in paradoxical splitting of the second heart sound where the A₂ component of S₂ is delayed, resulting in S₂ being more split during expiration than inspiration. Reduced movement of the aortic valve may render A₂ inaudible where only a single second heart sound can be appreciated.

B. Fourth Heart Sound (S4)

As noted earlier, left ventricular hypertrophy imposed by the increase in wall stress reduces ventricular wall compliance. The fourth heart sound is a low-pitch sound heard coincident with late diastolic filling, due to atrial contraction, of a ventricle with reduced wall compliance and increased end-diastolic pressure.

4. Apical Impulse

The apical impulse, which in aortic stenosis is generally the point of maximal impulse, remains in its normal position but is sustained due to prolongation of the ejection time. The atrial component of ventricular filling may also be palpable. With simultaneous palpation of the apical and carotid impulses, normally one will appreciate little delay in their peaks; however, they become separated in time proportional to the severity of stenosis.

C. Diagnostic Studies

The clinical severity of aortic stenosis is largely an operational classification based on the presence or absence of symptoms as discussed earlier. However, the indications for consideration of either a surgical or percutaneous aortic valve replacement rely on an estimate of stenosis severity.

1. Electrocardiogram

Left ventricular hypertrophy is the primary finding noted in those with aortic stenosis. Other common findings include left atrial abnormality along with ST- and T-wave abnormalities. There are, however, no electrocardiogram findings that are either sensitive or specific for aortic stenosis.

2. Chest Radiography

With isolated aortic stenosis, the cardiac silhouette is generally normal in size with possible rounding of the left heart border consistent with concentric left ventricular hypertrophy. There may be signs of left atrial enlargement and pulmonary venous hypertension. The aortic shadow may become enlarged, and valve calcification may be appreciated.

3. Echocardiography

Echocardiography is the principal clinical tool used for the evaluation of aortic stenosis, and currently still remains the gold standard imaging modality for the assessment of aortic stenosis despite the advances in other cardiac imaging modalities. Appropriate use criteria deem transthoracic echocardiography appropriate on the initial evaluation of a patient when clinical evaluation provides “unexplained murmur or abnormal heart sounds, reasonable suspicion of valvular or structural heart disease, history of rheumatic heart disease, known systemic or acquired heart disease associated with valvular heart disease, first-degree family history of bicuspid aortic valve, or exposure to medications that could result in the development of valvular heart disease, syncope without other symptoms or signs of cardiovascular disease, hypotension or hemodynamic instability with suspected cardiac etiology, respiratory failure, or initial heart failure evaluation to exclude valvular cause.” Re-evaluation of known valvular heart disease with echocardiography is appropriate “with a change in clinical status or cardiac exam or to guide therapy.” Routine surveillance in the absence of a change in clinical status or cardiac examination is deemed appropriate at intervals of 6 months to 1 year when the aortic velocity is ≥ 4.0 m/s, 1–2 years when the aortic velocity is between 3.0 and 3.9 m/s, and 3–5 years when the aortic velocity is between 2.0 and 2.9 m/s. The echocardiogram should include not only anatomic and hemodynamic measures of stenosis severity, but also an assessment of the left ventricular response to the pressure load, insights into whether there is dilation of the ascending aorta, and assessment for the presence of coexisting valve regurgitation and other cardiac abnormalities. Myocardial imaging and a measure of global longitudinal peak systolic strain may detect adverse ventricular consequences to the hemodynamic load despite a preserved left ventricular ejection fraction.

A. Anatomic Evaluation

Although most outcome data in those with aortic stenosis are based on the measures of the hemodynamic severity and physiologic orifice area, the anatomic evaluation of the valve is gaining increased importance in the evolving era of percutaneous valve replacement in guiding patient selection and procedural planning. From primarily the transthoracic parasternal views, or transesophageal imaging if the transthoracic images are suboptimal, the number of leaflets, extent of calcification, leaflet thickening, and mobility should be evaluated. An anatomic measure of the geometric valve area can be obtained by planimetry, either from echocardiography or cardiac CT. The fundamental limitations to accurate and reproducible measurements of the geometric orifice area are image attenuation secondary to leaflet calcification and the spatial integration of images required to ensure planimetry of the minimal opening area at the leaflet tips (Figure 17–2). It is for these reasons that the measure of geometric orifice area is reserved clinically primarily for those circumstances where Doppler measurements are unreliable. This holds true for classification of disease severity, however as we will discuss planimetry for procedural planning by cardiac CT has now become routine.

Figure 17-2. Planimetry of the aortic valve. A: Short-axis image of the aortic valve and a calculated anatomic valve area by planimetry. Leaflet calcification and image attenuation limit accurate delineation of the leaflet borders. B: Long-axis image of the aortic valve noting that slight alteration in the tomographic slice obtained through the aortic valve will result in marked variation in the valve area calculated by planimetry. (AV VTI, aortic valve velocity time integral)

B. Hemodynamic Evaluation

The principal measures of the hemodynamic severity include peak transaortic jet velocity, peak instantaneous and mean pressure gradients, and valve area (effective orifice area by the continuity equation).

(1) Transaortic Velocity and Gradient Calculations

The principle of conservation of energy states that the total amount of energy in a closed system remains constant. Energy can change its location and form, but can be neither created nor destroyed. With respect to flow, as the flow stream approaches a narrowed orifice, its kinetic energy increases and potential energy decreases. Distal to the narrowed orifice, pressure is lost in part due to the dissipation of kinetic energy as heat. This creates a pressure gradient across the valve orifice. Continuous wave Doppler is used to determine the maximum jet velocity through the stenotic valve. Meticulous imaging from multiple acoustic windows is required to ensure that flow velocities are acquired with a parallel intercept angle to the direction of flow, limiting the error of underestimation of the peak velocity. The Bernoulli equation is then applied to the highest jet velocity obtained to calculate the peak instantaneous gradient (Figure 17–3).

Figure 17-3. Continuous wave Doppler of aortic stenosis.

Bernoulli equation:

deltaCap.gif P = pressure gradient, ρ = mass density of blood, V₁ and V₂ = velocity proximal and distal to obstruction respectively, R = viscous resistance, µ = viscosity

Under most physiologic conditions, the latter two terms (flow acceleration and viscous friction) are negligible and can be ignored and V₂>>> V₁ and thus V₁ can be ignored. Therefore, under most physiologic conditions, a simplified Bernoulli equation can be applied to the peak velocity obtained to derive the peak instantaneous gradient.

Simplified Bernoulli equation: deltaCap.gifP = 4(V₂)²

When either V₁ is more than 1.5 m/s or V₂ is less than 3.0 m/s, the proximal velocity should be included in the simplified Bernoulli equation: . The final term, R(µ), represents energy losses due to viscous friction. Failing to recall this component may result in an overestimation of gradient in those who are anemic.

The mean gradient is obtained by averaging the instantaneous gradients over the ejection period. Because it is not possible to match each point on the ejection curve between the proximal and distal velocity profiles, it is not possible to “correct” the mean gradient when V₁ is significant, and in these circumstances, the measure of mean gradient should not be used to grade stenosis severity.

(2) Aortic Valve Area

Valve area calculations are based on the continuity equation, which assumes the principle of conservation of mass where flow across the left ventricular outflow tract (LVOT) is assumed equal to flow across the aortic valve (AV). Stroke volume is calculated as the product of the cross-sectional area (CSA) and velocity time integral (VTI). Therefore aortic valve area (AVA) is calculated as:

AVA = (CSA_LVOT × VTI_LVOT)/VTI_AV

The calculation of flow across the LVOT assumes the outflow tract is cylindrical in shape with the area of the LVOT therefore equal to π multiplied by its radius squared (πr²); thus, an error in the calculation of LVOT diameter will be exponentially amplified. Note that the calculation of AVA is essentially the estimation of the “flow or effective orifice area” and not the true anatomic/geometric orifice area. As blood flows toward a narrowed orifice, there is flow convergence beyond the anatomic orifice. The narrowest point of the flow stream, the vena contracta, is located just distal to the anatomic orifice, and its area is smaller than the anatomic orifice. The ratio between the anatomic and effective orifice areas is called the correction coefficient.

Based on the principal measures of hemodynamic severity, the American Heart Association/American College of Cardiology guidelines categorize aortic stenosis in those with a normal transaortic flow volume as mild, moderate, or severe (Table 17–1).

Table 17–1. Categories of Aortic Stenosis Based on the Principal Measures of Hemodynamic Severity

	Transaortic Jet Velocity	Mean Gradient (mm Hg)	AVA (cm2)	Indexed AVA (cm2/m2)
Mild	2.0–2.9	<20	1.51–2.0
Moderate	3.0–3.9	20–39	1.0–1.5
Severe	≥4.0	≥40	≤1.0	≤0.6

AVA, aortic valve area.

The AVA should be indexed for body surface area in smaller individuals so as not to overestimate the severity of stenosis based on the valve area calculation. The role of indexed AVA in the obese is unclear, and it is not our practice to use this because it is difficult to integrate the relationship of weight in association to body “size” versus “adiposity.”

(3) Dimensionless Index

As noted earlier, an error in the measure of the LVOT diameter will be exponentially amplified notwithstanding the assumption that the LVOT is cylindrical in shape. Therefore, a proposed LVOT independent measure of stenosis severity, the dimensionless index, can be helpful to either confirm or dispute stenosis severity classification based on the effective orifice area calculation. The dimensionless index is defined as the ratio of the LVOT velocity to that of the transaortic jet velocity, and a value of less than 0.25 indicates severe aortic stenosis.

(4) Energy Loss Coefficient (Elco)

The coefficient increases as the extent of pressure recovery (discussed later) increases. The magnitude of pressure recovery is determined by the ratio between the effective orifice area and the cross-sectional area of the ascending aorta (measured at the sinotubular junction) and is most significant when the valve area is less than 1.2 cm² and the aorta cross-sectional area is less than 3.0 cm.

ELCo = (EOA × Aa)/(Aa − EOA)

where EOA = effective orifice area derived by the continuity equation and Aa = cross-sectional area of the aorta measured 1 cm distal to the sinotubular junction.

The ELCo then provides a value of valve area derived by Doppler echocardiography more equivalent to the valve area derived by the Gorlin equation, which is more representative of the actual energy loss caused by the stenosis and thus the burden it imposes on the ventricle.

4. Cardiac Catheterization

The fundamental role of cardiac catheterization in those with aortic stenosis is to evaluate for the presence of coexisting coronary artery disease in those with symptoms of angina pectoris, helping clarify its pathophysiologic mechanism, and in whom AV replacement is being considered. Cardiac catheterization should not be routinely performed for the evaluation of the hemodynamic severity of aortic stenosis except for cases where echocardiographic data are of poor quality or when there remains a discrepancy between the clinical and echocardiographic determinations of stenosis severity.

The principal measures of the hemodynamic severity of aortic stenosis as assessed by cardiac catheterization include peak-to-peak and mean pressure gradients and valve area (derived by the Gorlin equation).

A. Pressure Gradients

The transvalvular pressure gradient is calculated by placing one catheter into the left ventricle and a second into the proximal aorta. The difference in the pressure from simultaneous recordings from each catheter represents the peak-to-peak pressure gradient. Single-catheter techniques may include a pullback gradient and the use of a dual-lumen catheter. Note that Doppler echocardiography derives a maximum instantaneous gradient at a single point in time and by principle assumes that the pressure drop across the valve is irretrievably lost while the invasive measure derives a peak-to-peak gradient with the upstream pressure partially recovered. Therefore, the invasively derived measure of the peak pressure gradient is always lower than the Doppler-derived measure, and this difference is accentuated as the extent of pressure recovery increases (Figure 17–4). Mean gradients obtained by both Doppler and cardiac catheterization correlate well.

Figure 17-4. Top: Simultaneous left ventricular and aortic pressure tracings. Bottom: Doppler echocardiographyderived transaortic velocity profile. AO, aortic pressure; LV, left ventricle; MIG, maximum instantaneous gradient (the gradient that is derived by applying the Bernoulli equation to the peak jet velocity obtained by Doppler echocardiography); PPG, peak-to-peak gradient (the gradient obtained with invasive catheterization).

B. Valve Area

During cardiac catheterization cardiac output is measured using primarily either the Fick or thermodilution principal and the pressure gradient measured as discussed earlier with values obtained used to calculate valve area using the Gorlin equation:

where CO = cardiac output, SEP = systolic ejection period (in seconds), HR = heart rate, and deltaCap.gifP = pressure gradient (mean). The presence of a measure of flow/cardiac output in the numerator of the Gorlin equation highlights the flow dependence on the derived values of AVA. Note that the valve area derived from the Gorlin equation is derived from recovered pressures, and as such, its value is higher than Doppler-derived valve areas by the continuity equation. The current guidelines, however, make no distinction between invasive and Doppler echocardiographic measurements in the characterization of stenosis severity by valve area and pressure gradients (see earlier discussion regarding the energy loss coefficient).

5. Cardiac Computed Tomography (CT)

Cardiac CT can be used to calculate the geometric valve area by planimetry and to quantify the extent and distribution of valve calcification, and although echocardiography remains the gold standard imaging modality, cardiac CT is becoming integral in the care of the patients with moderate to severe aortic stenosis (Figures 17–5 and 17–6). When echocardiography leaves the severity of the diagnosis inconclusive or is discordant between imaging and clinical suspicion, cardiac CT can be an invaluable tool to help classify severity, as it offers evaluation independent of hemodynamics of the patient. Cardiac CT quality continues to improve at an impressive rate. With upgrades in hardware, software, and scanning protocols which optimize gating and slice thickness, reconstruction image resolution continues to improve. These advances all aid in improving the accuracy of cardiac CT and limit the exposure of radiation to the patient. Quantification of AV calcification is strongly, but nonlinearly, associated with the hemodynamic severity of aortic stenosis, and the extent of calcification is predictive of event-free survival (survival without dyspnea, angina, syncope, heart failure, or need for valve replacement). Therefore, the measurement of AV calcium load should be considered for both diagnostic and prognostic purposes. Despite a similar degree of stenosis severity, women have lower valve calcium scores compared to men even after indexing for their smaller body size. For aortic stenosis severity purposes, the interpretation of the calcium load is thus different for men and women, where a score of more than 1300 AU for women and more than 2000 AU for men is considered severe.

Figure 17-5. A: Left; Cardiac CT showing the structures of the left ventricular outflow tract and aorta, along with the heavy calcifications (radio-opaque) on the aortic valve. B: right; Cross-sectional view of aortic valve on cardiac CT. Gating protocols allowing for the valve to be viewed at its opening during systole to allow for planimetry of the valve.

Figure 17-6. Cross-sectional view of a bicuspid aortic valve on cardiac CT. Gating protocols allowing for the valve to be viewed at its opening during systole to allow for planimetry of the valve. Note the diminished AVA along with the heavy (radio-opaque) calcifications.

In contemporary clinical practice, cardiac CT, in conjunction with two- and three-dimensional echocardiography, now has an essential role in the evaluation of patients being considered for a percutaneous valve replacement primarily for:

• The evaluation of the annular area and perimeter required for the appropriate selection of prosthetic valve size

• The assessment of the peripheral vasculature and suitability for arterial access

• The assessment of the geometric relationship/distance between the aortic annulus and the coronary ostia to ensure that the implanted valve, when in position, does not blanket the coronary ostia

• Characterizing the extent of valve, root, and LVOT calcification, which may impact the technical success, risk of implantation, and paravalvular regurgitation

• Allowing the prediction of post-implantation aortic regurgitation

• Determining the feasibility of transaortic transcatheter aortic valve replacement when the transfemoral route is not feasible

DohertyJU, KortS, MehranR, SchoenhagenP, SomanP. ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2017;70(13):16471672. 28870679

PawadeT, ShethT, GuzzettiE, DweckMR, ClavelMA. Why and how to measure aortic valve calcification in patients with aortic stenosis. JACC Cardiovasc Img.2019;12:18351848. 31488252

Aortic stenosis is a mechanical problem requiring a mechanical solution where the only effective treatment is valve replacement. The optimal time for valve replacement is therefore at the inflection point where the procedural risk and the long-term consequences of prosthetic heart valve disease become less then medical therapy.

A. Medical Therapy

There is no effective medical therapy for the treatment or cure of aortic stenosis. Because aortic stenosis is an active disease process that shares similarities and risk factors with atherosclerosis, there has been intellectual enthusiasm for aggressive atherosclerotic risk factor modification and the use of cholesterol-lowering drugs in an effort to slow stenosis progression and reduce the necessity for valve replacement. To date, studies evaluating the use of cholesterol-lowering therapies overall have not shown salutary effects with respect to disease progression or need for valve replacement.

In those with symptomatic aortic stenosis who are not candidates for valve replacement, medical therapy is directed at the relief of symptoms because there is no therapy that prolongs life. Treatment of the patient with heart failure may include the cautious use of diuretics and angiotensin-converting enzyme inhibitors. Initiation of such therapies should begin at low doses and be slowly increased. The concern is that diuretic-induced reduction in preload will lower cardiac output, resulting in a drop in systemic arterial pressure, adding to that imposed by angiotensin-converting enzyme inhibitors. β -Blockers should be used with great caution or avoided entirely as they may unmask the left ventricle’s dependence on adrenergic support for pressure generation and thereby cause heart failure. Digoxin use is reserved primarily for those with left ventricular dysfunction and/or atrial fibrillation. Hypertension should be treated with careful titration of pharmacotherapy and frequent patient monitoring to avoid hypotension.

The latest guidelines have eliminated the need for antibiotic prophylaxis to prevent infective endocarditis in those with native valvular aortic stenosis. However, endocarditis prophylaxis remains essential in patients who have undergone aortic valve replacement.

B. Valve Replacement

1. Symptomatic Patients

As noted earlier, survival in aortic stenosis abruptly declines once the classic symptoms of angina, effort syncope, or congestive heart failure appear. Fifty percent of patients with aortic stenosis in whom angina pectoris develops are dead within 5 years of its onset if AV replacement is not undertaken. Half of patients with syncope will be dead within 3 years and 50% of patients with congestive heart failure will be dead within 2 years without valve replacement (Figure 17–7). The exact pathophysiologic changes that produce the onset of symptoms and begin this rapid downhill course are unknown. The development of symptoms is a class I indication for valve replacement, and following successful valve replacement, symptoms and quality of life improve and survival, in general, is similar to an age-matched population. However, patients who, prior to valve replacement, have severe left ventricular hypertrophy, poor functional capacity, or a large area of myocardial scar and who, after valve replacement, have untreated coexisting coronary artery disease or suboptimal prosthesis hemodynamics are at risk for a less than ideal post-valve replacement outcome. Valve replacement may be either surgical or via a transcatheter approach.

Figure 17-7. The natural history of aortic stenosis. There is little change in survival until the symptoms of angina, syncope, or heart failure develop. (Reproduced with permission from Ross J Jr, Braunwald E. Aortic stenosis. Circulation. 1968;38[1 Suppl: 6167.)

A. Surgical Aortic Valve Replacement

Surgical AV replacement is done primarily through a midline sternotomy, but in those without coexisting coronary artery disease requiring bypass or a chest wall deformity, valve replacement may be approached through a “mini-sternotomy”—minimally invasive valve surgery. The advantage of the minimally invasive approach is less blood loss, a faster recovery time, and a better cosmetic outcome at the expense of less surgical “exposure.” There are a number of different types of valve prostheses including mechanical, stented, and stentless heterografts, xenografts, and homografts.

Mechanical valves used in the aortic position are primarily bileaflet valves, which are durable and provide a good hemodynamic profile particularly at the larger valve sizes. The primary drawback of mechanical valves is the need for lifelong anticoagulation and the associated risk of bleeding. However, new-generation heart valves may permit less aggressive anticoagulation regimens. The On-X bileaflet mechanical valve is the first and currently only heart valve that allows patients, beginning 3 months after their surgery, to be managed with an international normalized ratio of 1.5–2.0 along with low-dose aspirin. This regimen was associated with a 65% overall reduction in bleeding events with no increase in stroke rate.

Heterograft valves have the primary advantage of a low thromboembolism rate without anticoagulation. For any given prosthesis size, the stentless heterograft valves have a better hemodynamic profile when compared to the more commonly used stented bioprostheses. The primary drawback of heterograft valves is their reduced durability when compared to the mechanical valves. Homografts and pulmonary autografts (Ross procedure) are rarely used in the adult population because the operation is technically more challenging and the rate of structural valve failure appears to exceed that of the heterograft valves. The decision of which type of valve prosthesis is best suited for any given patient is based on a number of patient-related factors, such as the bleeding risk with anticoagulation or the need for anticoagulation in those already at high risk for thromboembolism (presence of atrial fibrillation, prior thromboembolism, or a hypercoagulable state). Age can be a factor as well, in a younger population for example, if medical co-morbidities and risk factors permit, a consideration of mechanical valve over bioprosthetic may be considered for durability. Those with renal failure, particularly if on dialysis, or hypercalcemia are at increased risk for structural valve failure with a bioprosthetic valve. The risk of a possible reoperation, if required, also must be considered along with the complex decision facing young women considering pregnancy.

B. Transcatheter Aortic Valve Replacement (Tavr)

Despite the dismal prognosis, many symptomatic patients are either not referred, generally because of age and the perception of surgical risk, or are declined as candidates for surgical valve replacement. TAVR now provides an option for those with severe symptomatic aortic stenosis and a life expectancy in excess of 1 year who have been deemed to have a surgical risk that would preclude AV replacement. Initially, TAVR was an alternative to surgical valve replacement in those deemed surgical candidates but were stratified to have a high surgical risk. However, the FDA has expanded the indication now for patients who are not only high, but also intermediate and low surgical risk. The determination of surgical risk is based on a risk model from the Society of Thoracic Surgeons (STS) to estimate 30-day mortality. The score equals the predicted mortality expressed as a percentage. Patients deemed high surgical risk generally have an STS score greater than 8%. Increased operator experience and new-generation heart valves and delivery systems have resulted in lower TAVR-associated risk, making TAVR similar to surgical AV replacement with respect to death or disabling stroke in intermediate-risk patients. Intermediate-risk patient are generally those with an STS score between 4% and 8%. In the low-risk category, there have been trials to show that TAVR has been noninferior and occasionally shows lower rate of complications such as disabling stroke, complications due to bleeding, acute kidney injury, and atrial fibrillation as a result of transcatheter approach versus surgical approach. It should be noted however that there are higher rates of post-replacement aortic regurgitation and the need for permanent pacemakers after TAVR, especially with self-expanding valves.

TAVR is primarily performed through transfemoral arterial access. If delivery through the femoral artery is not possible, a transthoracic approach may be used (transapical or transaortic access route). Transsubclavian, transcaval, and transcarotid approaches have also been described. Although there are several transcatheter valves in development, at present, the Edwards SAPIEN 3 ultra (Edwards Lifesciences Inc., Irvine, CA) and EvolutPro/Pro Plus (Medtronic Inc., Minneapolis, MN) valves are the only valves approved for clinical use (Figure 17–8). In high-risk patients not deemed to be surgical candidates 1 year after TAVR, there was a 20% absolute reduction in mortality, significantly fewer cardiac symptoms, and lower New York Heart Association functional class with either the SAPIEN valve or the CoreValve when compared to those who received standard medical therapy. When high-risk patients were randomized to either surgical or transcatheter valve replacement, the 30-day mortality was lower with TAVR and the 1-year mortality was equivalent. The risks of TAVR include death, vascular complications, heart block requiring a pacemaker, neurologic events, and paravalvular regurgitation. Therefore, in high-risk patients who are still candidates for surgery, the European Society of Cardiology guidelines on valvular heart disease state that the decision “should be individualized and TAVR considered as an alternative to surgery in those patients for whom the heart team favors TAVR based on the individual’s risk profile and anatomic suitability.”

Figure 17-8. A: The Edward SAPIEN balloon expandable valve (Edwards Lifesciences, Irvine, CA) incorporates a stainless-steel frame, bovine pericardial leaflets, and a fabric sealing cuff. B: The SAPIEN XT THV (Edwards Lifesciences) uses a cobalt chromium alloy frame and is compatible with lower profile delivery catheters. C: The Medtronic CoreValve (Medtronic, Minneapolis, MN) incorporates a self-expandable frame, porcine pericardial leaflets, and a pericardial seal. (Reproduced, with permission, from Webb J, Wood D. J Am Coll Cardiol. 2012;60:483492. Copyright © American College of Cardiology Foundation.)

The concept of the multidisciplinary approach and the TAVR heart team has been one of the greatest collaborative successes in the field of cardiovascular diseases. The team encompasses the patient at its center and involves the referring physician, imaging and interventional cardiologist, cardiac surgeon, valve clinic coordinator, anesthesiologist, and the cardiac and operating room staff. The patients are investigated clinically through assessing their frailty, STS score, imaging studies, cardiac catheterization, and assessment of social support. A plan is then conducted and conveyed to the patient and family.

Finally, there has been a shift from transesophageal echocardiography–guided/general anesthesia support for TAVR to a minimalist approach of local anesthesia with Perclose and transthoracic echocardiography. This has led to a decreased hospital stay, lesser morbidity, and lower cost at no penalty of increased mortality or morbidity.

C. Balloon Aortic Valvuloplasty (Bav)

Occasionally there will be circumstances in which patients with severe symptomatic aortic stenosis who would otherwise require TAVR or SAVR are unable to have valve replacements done. A possible alternative procedure to improve the stenotic lesion would be the balloon valvuloplasty. This is a nonsurgical, catheter-based technique in which balloon expansion at the stenotic aortic valve can fracture and force the calcified leaflets open. This of course comes with the obvious risk of causing aortic insufficiency which can be a contraindication to performing the procedure. Balloon aortic valvuloplasties can be useful procedures in a variety of clinical situations, for example, in patients who require urgent noncardiac surgery in whom their surgical risk otherwise would be too elevated due to their severe aortic stenosis. Other candidates to consider would be those who otherwise would have a contraindication or would be at elevated risk for SAVR or TAVR procedures. Occasionally a role for hemodynamic stabilization in those with decompensated heart disease due to obstruction of the aortic valve may find some relief from BAV procedure.

As noted earlier, the prognosis of those with severe symptomatic and asymptomatic aortic stenosis, in the absence of valve replacement, is very poor. However, the age-adjusted survival following valve replacement is excellent, even in the elderly who are free of other cardiac or systemic diseases. Asymptomatic patients generally have a good prognosis, with the strongest predictor of clinical outcome (death or valve replacement) being stenosis severity. The likelihood of remaining alive without valve replacement at 2 years is approximately 20% in those with a peak jet velocity greater than 4.0 m/s, 66% if the jet velocity is between 3.0 and 4.0 m/s, and 84% for those with a jet velocity less than 3.0 m/s. Understanding the strong impact of stenosis severity along with other clinical predictors, such as functional capacity and the rate of hemodynamic progression, an outcome is useful when counseling patients about their prognosis and to help tailor the frequency of follow-up. As well, there are ongoing studies evaluating the prognosis without and with interventions in symptomatic and asymptomatic moderate aortic stenosis.