Chapter 17. Aortic Stenosis

• History: angina, dyspnea, syncope.
• Physical examination: midsystolic murmur; small and slow rising carotid pulse contour (parvus et tardus).
• Echocardiography: thickened immobile aortic valve leaflets; increased peak transaortic jet velocity and mean gradient; reduced valve area.

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 where there is 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 their disease. Other rare causes of aortic stenosis include those associated with connective tissues diseases such as systemic lupus erythematosus and ochronosis.

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 is attributed to valve disease and not 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 restore 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 very difficult to tease out the extent by which wall stress (afterload) and contractility are contributing to a noted decline in ejection fraction.

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 concepts of continuity disease, 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. Additionally, 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 now 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.

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, which impairs coronary “diastolic suction,” both contributing to 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.

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, which 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.

Physical Examination

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.

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, where the later in systole the peak intensity occurs, generally the stenosis severity is more severe.

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. Additionally, 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 in excluding significant aortic stenosis solely based on murmur intensity or pitch.

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 those of the murmur of mitral regurgitation; however, the shape and configuration of the murmur do not change. This is known as the Gallavardin phenomenon.

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 and blood pressure, 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 all other valve murmurs except for 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.

Carotid Pulse

The carotid artery pulse wave contour in those with aortic stenosis is characterized as small and slow rising (parvus et tardus). However, in older individuals with reduced arterial compliance, this finding is abrogated by increased reflected waves in the aorta. One may also appreciate a carotid shudder.

Heart Sounds

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.

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, in a ventricle with reduced wall compliance and increased end-diastolic pressure.

Apical Impulse

The apical impulse, which in aortic stenosis is generally also 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.

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.

Electrocardiogram

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

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.

Echocardiography

Echocardiography is the principal clinical tool used for the evaluation of aortic stenosis. Appropriate use criteria deem echocardiography appropriate when clinical evaluation provides “reasonable suspicion of valvular or structural heart disease or re-evaluation of known valvular heart disease 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 every 3 years in those with mild and every 1 year in those with moderate to severe valvular stenosis. 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.

Anatomic Evaluation

Although most outcome data in those with aortic stenosis are based on 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. 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 for those circumstances where Doppler measurements are unreliable.

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).

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).

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.

When either V1 is > 1.5 m/s or V2 is < 3.0 m/s, the proximal velocity should be included in the simplified Bernoulli equation: ΔP = 4(V22 – V12). 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.

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:

The calculation of flow across the LVOT assumes the outflow tract to be cylindrical in shape with its area 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 “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 area. The ratio between the anatomic and effective orifice areas is called the contraction coefficient.

Based on the principal measures of hemodynamic severity, the American Heart Association/American College of Cardiology and European Society of Cardiology (ESC) guidelines categorize aortic stenosis, in those with normal cardiac output/transvalvular flow, as mild, moderate, or severe (Table 17–1). The aortic valve area 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 do so because it is difficult to integrate the relationship of weight in association to body “size” versus “adiposity.”

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 the effective orifice area calculation. The dimensionless index is defined as the ratio of the LVOT velocity to that of the transaortic jet velocity. Traditionally a value < 0.25 has been used to indicate severe aortic stenosis. The dimensionless index is however, highly variable depending on the size of the LVOT diameter and as such it has been proposed that the cut-off value for severe aortic stenosis be modified based on the LVOT diameter with values of ≤ 0.35, ≤ 0.30 and ≤ 0.25 in those with small (≤ 1.9 cm), average (2.0-2.2 cm) and large (≥ 2.3 cm) LVOT diameters, respectively.

Energy Loss Coefficient (ELCo)

The correction 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), most significant when the valve area is < 1.2 cm2 and the aorta cross-sectional area is < 3.0 cm.

EOA indicates effective orifice area derived by the continuity equation, and Aa indicates 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.

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 aortic valve replacement is being considered. Cardiac catheterization should not be routinely performed for the evaluation of the hemodynamic severity of aortic stenosis but should be performed in cases where echocardiographic data is 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).

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 Langston dual-lumen catheter. Note, Doppler echocardiography derives a maximum instantaneous gradient at a single point in time and by principal 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 (Figure 17–4). Mean gradients obtained by both Doppler and cardiac catheterization correlate well but for when there is significant pressure recovery where again Doppler derived values of the mean pressure gradient will be greater than those derived by cardiac catheterization.

Valve Area

During cardiac catheterization, cardiac output is measured using primarily either the Fick or thermodilution principal, and the pressure gradient is 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 ΔP = 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 aortic valve area. 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).

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. Although there is a weak correlation between the extent of valve calcification and hemodynamic severity of stenosis, the extent of calcification is predictive of event-free survival (survival without dyspnea, angina, syncope, heart failure, or need for valve replacement).

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

• The evaluation of the LVOT geometry 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 and root calcification, which may impact both the technical success and risk of implantation
• Allowing the prediction of postimplantation aortic regurgitation

The principal parameters of stenosis severity, as discussed earlier, are directly related to transvalvular flow. As such, clinicians managing patients with aortic stenosis may face situations where stenosis severity is characterized as severe by area but not by gradient criteria. After excluding errors of measurement, errors of assumption, LVOT diameter related inconsistencies; low flow may account for diminished gradients despite severe aortic stenosis by AVA determination. Low-flow states (left ventricular stroke volume index < 35 mL/m2) may be associated with either a low left ventricualr ejection fraction (EF) (low EF area-gradient mismatch) or a preserved EF (normal EF area-gradient mismatch). Less commonly, one notes the gradient in the “severe” range, while the AVA remains in the “nonsevere” range (reverse area-gradient mismatch). Deciphering the true severity of aortic stenosis in the presence of area-gradient mismatch is imperative to the understanding of patient prognosis and to guide therapeutic decisions.

Low EF Area-Gradient Mismatch

This is also known as low-flow, low-gradient (LF/LG) aortic stenosis with a depressed EF.

• Effective orifice area < 1.0 cm2
• Left ventricular EF < 45%
• Mean pressure gradient < 30–40 mm Hg

Contemporary clinical protocol is to attempt to increase flow across the aortic valve with a dobutamine infusion and to evaluate the ventricular response and transvalvular hemodynamics. One of three scenarios will evolve:

1. True or fixed severe aortic stenosis: Those in whom dobutamine can induce a > 20% increase in stroke volume with an associated increase in transvalvular gradient and no or little change in AVA.

2. Pseudo or relative severe aortic stenosis: Those in whom dobutamine can induce a > 20% increase in stroke volume with an associated increase in AVA and no or little change in transvalvular gradient.

3. Indeterminate aortic stenosis: Those in whom dobutamine is not able to increase stroke volume (no contractile reserve) with no change in AVA or transvalvular gradient.

The changes in valve area and gradient imposed during a dobutamine infusion are largely dependent on the extent of flow augmentation achieved which can vary considerably between individuals. To overcome the inter-individual variability in flow augmentation it has been proposed to calculate an AVA at a normal flow rate. This variable is called the projected AVA (AVAproj) and is derived as follows:

Where: VC (valve compliance)

and Q (mean flow)

The AVAproj may better differentiate true from pseudo aortic stenosis than traditional dobutamine stress Doppler indices. An AVAproj ≤1.0 cm2 suggests true severe aortic stenosis.

Normal EF Area-Gradient Mismatch

This is also known as paradoxical low-flow, low-gradient (PLF/LG) aortic stenosis.

• Effective orifice area < 1.0 cm2
• Left ventricular EF > 50% and left ventricular stroke volume index < 35 mL/m2
• Mean pressure gradient < 30–40 mm Hg

This scenario is the result of the interaction of a diastolic component whereby generally a thick ventricle with a small cavity is noted, a myocardial component whereby there is intrinsic myocardial dysfunction despite the persevered EF as noted with myocardial/strain imaging, and a valvular-vascular component imposing an increased global ventricular hemodynamic burden resulting from resistance in series by the valve stenosis and decreased systemic arterial compliance and increased vascular impedance. It has been proposed to characterize the valvular-vascular component through an index of valvuloarterial impedance (Zva). The Zva is defined as ratio of the estimated left ventricular systolic pressure (systolic blood pressure + mean pressure gradient) to the stroke volume index. The Zva can be thought of as the cost in mm Hg for each mL of blood ejected. Other hemodynamic subgroups of aortic stenosis include those with normal-flow (> 35 mL/m2) and low-gradient (NF/LG) aortic stenosis, which carries a good prognosis and considered an earlier form of the disease, and low-flow/high-gradient (LF/HG) aortic stenosis, which carries a worse prognosis intermediate between the NF/LG and the LF/LG subgroups.

Reverse Area-Gradient Mismatch

This may be noted when inappropriate assumptions or liberties are taken when applying the simplified Bernoulli equation to Doppler-derived blood flow velocities in an effort to estimate the transvalvular gradient, such as failure to include V1 when significant or, as noted earlier, failing to recall the viscous friction component in those with anemia. More commonly, this dilemma results secondary to the phenomenon of pressure recovery, where downstream to the obstructed orifice as the blood flow velocity/kinetic energy decreases some of the kinetic energy will be converted to potential energy with associated increases in pressure. Pressure recovery is greatest in those in whom the ascending aorta diameter measures < 3.0 cm causing discordance between Doppler and catheter-derived gradients. Pressure recovery is insignificant when the aortic diameter is > 3.0 cm. In addition eccentric jets lead to increase pressure loss across the aortic valve which leads to increased Doppler and catheter derived gradients despite a less than severe reduction in anatomic orifice area.

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 than medical therapy.

Medical Therapy

There is no effective medical therapy for 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 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 by in large 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 (ACE) inhibitors. Initiation of such therapies should begin at low doses and slowly increased. The concern is diuretic-induced reduction in preload lowering cardiac output, resulting in a drop in systemic arterial pressure. This situation can also be imposed by ACE inhibitors. β-Blockers should be used with great caution or avoided entirely because 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.

Valve Replacement

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 aortic valve replacement is not undertaken. Half the 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 17–5). 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, those who, prior to valve replacement, had 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 ideal post–valve replacement outcome. Valve replacement may be either surgical or via a transcatheter approach.

Surgical Aortic Valve Replacement

Surgical aortic valve 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 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. Heterograft valves have the primary advantage of a low thromboembolism rate without anticoagulation obviating its long-term use. 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). 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, must be considered along with the complex decision facing young women considering pregnancy.

Transcatheter Aortic Valve Replacement (TAVR)

Despite the dismal prognosis, many symptomatic patients either are 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 aortic valve replacement. In addition, TAVR may be an alternative to surgical valve replacement in those deemed surgical candidates but who are stratified as having a very high surgical risk. As the technology evolves and experience broadens, there may be other patient populations for whom TAVR replaces the surgical approach.

Currently, TAVR is primarily performed through transfemoral arterial access. If delivery through the femoral artery is not possible, some have advocated using a subclavian approach; however, currently more common is a transapical approach through an intercostal thoracotomy. Although there are a number of transcatheter valves in development at the present time, the Edwards SAPIEN (Edwards Lifesciences Inc., Irvine, CA) and CoreValve (Medtronic Inc., Minneapolis, MN) valves are the only valves approved for clinical use. In high-risk patients not deemed surgical candidates 1 year following TAVR, there was a 20% absolute reduction in mortality, significantly fewer cardiac symptoms, and lower New York Heart Association functional class, when compared with 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 equivalent. The incremental risk of TAVR versus either medical or surgical therapy includes vascular complications, heart block, a slight increase in neurologic events, and more perivalvular regurgitation.

Asymptomatic Patients

In distinct contrast to the universal recommendation for valve replacement in those with symptomatic severe aortic stenosis, the management of the asymptomatic patient remains controversial. As noted earlier, the decision to proceed with valve replacement occurs when the risk of native aortic valve stenosis exceeds the procedural risk combined with the long-term risk of prosthetic heart valve disease. The primary concern in the strategy of watchful waiting is the risk of sudden death and the fact that symptoms are subjective and influenced by the patient's lifestyle and may be underreported.

The contemporary literature suggests that the risk of sudden death in the asymptomatic adult patient with severe aortic stenosis is approximately 1% per year. Conversely, in low-risk patients, there is an operative mortality of 1–3% and a 2–3% per year risk for a prosthesis-related complication such as thromboembolism, endocarditis, valve failure, bleeding (if anticoagulation is required), or death. Therefore, in general, surgical valve replacement risk exceeds any potential benefit to those with truly asymptomatic severe aortic stenosis and normal left ventricular systolic function.

Patients may either not seek medical attention immediately following the onset of symptoms or truncate their lifestyle so as to negate symptoms. Additionally, there is frequently some wait time until a valve replacement can be scheduled while the patient is symptomatic. These individuals are at increased risk, and the ideal situation is to better stratify risk in these “asymptomatic” patients and potentially offer valve replacement to those deemed at greatest risk. Features on the baseline echocardiogram including EF, left ventricular wall thickness, peak transaortic jet velocity, and the rate of hemodynamic progression are independent predictors of outcome. A noteworthy proportion of those who claim to be asymptomatic have an abnormal exercise test defined as exercise limiting symptoms and/or a fall in blood pressure below baseline, and these patients have a worse outcome. The added value of exercise-induced changes in echocardiographically derived valve hemodynamics is contentious, but reports state an incremental and independent prognostic value to an exercise-induced increase in mean gradient > 20 mm Hg even in those with a normal exercise stress test—the “truly” asymptomatic. The extent of valve calcification, very severe stenosis, and plasma brain natriuretic peptide levels may also be helpful in refining risk. Both the North American and European valve disease guidelines primarily based on expert consensus (level of evidence C) make recommendations for valve replacement in those with asymptomatic severe aortic stenosis, but there is variability in the strength of these recommendations (Table 17–2).

Low EF Area-Gradient Mismatch (LF/LG Aortic Stenosis)

Patients with LF/LG aortic stenosis have a poor prognosis with medical management. As noted earlier, deciphering the true severity of aortic stenosis in the presence of area-gradient mismatch is imperative in the evaluation of patient prognosis and to guide the appropriate management of patients. In general, in those with true or fixed severe aortic stenosis, valve replacement should be performed and can be done with an acceptable operative risk. Those with indeterminate aortic stenosis, because of the absence of contractile reserve (the inability to increase stroke volume ≥ 20% with a dobutamine infusion), have an abysmal prognosis with medical management, but also a high operative risk reported in some series (up to 30%). However, those who survive surgery generally show an improvement in functional capacity, ventricular function, and overall survival. The management of those with LF/LG aortic stenosis and the absence of contractile reserve is controversial. In those with significant valve calcification, a mean gradient > 20 mm Hg, and the absence of a large area of left ventricular scar, valve replacement should be considered. Note that the literature on the risks and benefits of valve replacement in these patients is based on surgical valve replacement, and over time, we may find that TAVR offers a lower procedural risk alternative for these patients.

Normal EF Area-Gradient Mismatch (PLF/LG Aortic Stenosis)

These individuals present with a low valve area and low gradient despite a preserved left ventricular EF. There is controversy in how best to manage these patients, and the mere presence of a low gradient cannot exclude severe aortic stenosis in some of these patients who would have a poor outcome if treated medically and would benefit from valve replacement. How best to characterize and select those with PLF/LG aortic stenosis who are most likely to benefit from valve replacement remains challenging. The use of stress echocardiography (supine bicycle or dobutamine) to calculate the AVAproj may help to predict stenosis severity and guide therapeutic decision making.

As noted earlier, the prognosis of those with severe symptomatic 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 > 4.0 m/s, 66% if the jet velocity is between 3.0 an 4.0 m/s, and 84% for those with a jet velocity < 3.0 m/s. Understanding the strong impact that stenosis severity and other clinical predictors, such as functional capacity and the rate of hemodynamic progression, have on outcome is very useful when counseling patients about their prognosis and to help tailor the frequency of follow-up.