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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.
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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:
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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.
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Dyspnea and Exercise Intolerance
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Response to Maneuvers
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A transient alteration in intracardiac hemodynamics may influence the characteristics of a murmur, helping to further specify its etiology.
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- 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.
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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.
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Second Heart Sound (S2)
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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.
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Fourth Heart Sound (S4)
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Hemodynamic Evaluation
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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).
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Transaortic Velocity and Gradient Calculations
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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).
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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.
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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.
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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.
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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:
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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.
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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.
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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.”
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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.
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Energy Loss Coefficient (ELCo)
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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.
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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.
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Cardiac Catheterization
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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.
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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).
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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.
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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:
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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).
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Cardiac Computed Tomography (CT)
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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).
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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:
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- 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
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