Chapter 31. Pathophysiology of Aortic Valve Disease

Craig M. Jarrett; Samuel Edwards; A. Marc Gillinov; Tomislav Mihaljevic

Introduction

The aortic valve (AV) is a semilunar valve positioned at the end of the left ventricular outflow tract (LVOT) between the left ventricle and aorta. Proper functioning of this valve is critical in maintaining efficient cardiac function. This chapter explores the anatomical and physiologic properties of the AV.

Embryologic Development

Listen

Embryologic development of the AV is closely associated with development of the LVOT. In the primary heart tube, blood travels from the primitive ventricle into the bulbous cordis and out the aortic roots. The midportion of the bulbous cordis, the conus cordis, develops into the outflow tracts of the ventricles. The distal portion of the bulbous cordis, the truncus arteriosus (TA), develops into the proximal portion of the aorta and pulmonary arteries. During the fifth week of development, pairs of opposing swellings appear in the conus cordis and TA (Fig. 31-1). These conotruncal, or bulbar, ridges grow toward each other and fuse to form the aorticopulmonary (AP) septum. The AP septum divides the conus cordis into the left and right ventricular outflow tracts and the TA into the ascending aorta and pulmonary trunk.

Figure 31-1

View Full Size||Download Slide (.ppt)

Schematic representation of development of the left and right ventricular outflow tracts and aortic and pulmonary valves. (Top left) Cross-section through the cordis showing the conotruncal ridges beginning to develop. (Top right) Aorticopulmonary septum forming from fusion of the conotruncal ridges and subendocardial swellings beginning to develop into the aortic and pulmonary valve leaflets. (Bottom left) Left and right ventricular outflow tracts separated by the aorticopulmonary septum and further development of the subendocardial swellings. (Bottom right) Aortic and pulmonary valves in the adult. (Reproduced with permission of the Cleveland Clinic, Cleveland, OH.)

When partitioning of the TA is nearly completed, the AV begins to develop from three swellings of subendocardial tissue (see Fig. 31-1). Two swellings arising from the fused truncal ridges develop into the right and left AV leaflets. A third dorsal swelling develops into the posterior leaflet. These swellings are reshaped and hollowed out to form the three thin-walled cusps of the fully developed AV. The pulmonary valve develops in a similar manner.

Anatomy

Listen

The AV separates the terminal portion of the LVOT from the aorta. The normal AV consists of three semilunar leaflets or cusps projecting outward and upward into the lumen of the ascending aorta (Fig. 31-2). The space between the free edge of each leaflet and the points of attachment to the aorta comprise the sinuses of Valsalva. Because the coronary arteries arise from two of the three sinuses, the sinuses and the respective leaflets are named the right coronary, left coronary, and posterior (noncoronary) sinuses and leaflets. The ostia of coronary arteries arise from the upper part of the sinuses, with the ostium of the left coronary artery positioned slightly higher than the ostium of the right. The leaflets are separated from one another at the aorta by the right-left, right-posterior, and left-posterior commissures (Fig. 31-3). The area adjacent to the left-posterior commissure is the fibrous continuity, which interconnects the aorta and the mitral valve annulus. The area beneath this commissure is the aortomitral curtain, which is an important anatomical landmark for root enlargement procedures. The posterior leaflet attaches above the posterior diverticulum of the LVOT and opposes the right atrial wall. The right-posterior commissure is positioned directly above the penetrating atrioventricular bundle and membranous septum. The right-left commissure opposes the posterior commissure of the pulmonary valve and the two associated aortic cusps oppose the right ventricular infundibulum. The lateral part of the left coronary sinus is the only part of the AV that is not closely related to another cardiac chamber and is in direct relationship with the free pericardial space.

Figure 31-2

View Full Size||Download Slide (.ppt)

Anatomical relationship between the aortic valve leaflets and surrounding structures. (Reproduced with permission of the Cleveland Clinic, Cleveland, OH.)

Figure 31-3

View Full Size||Download Slide (.ppt)

Anatomical relationship between the aortic valve and surrounding structures. (Reproduced with permission of the Cleveland Clinic, Cleveland, OH.)

The AV leaflets meet centrally along a line of coaptation, at the center of which are the thickened nodules of Arantius. Because of the semilunar shape of the leaflets, the AV does not have a true annulus in the traditional sense of a ringlike attachment. Instead, the leaflets have semilunar attachments along a hollow cylinder or cuff of tissue interconnecting the left ventricular (LV) chamber and the proximal aorta (Fig. 31-4).1 The distal border of the cuff is the sinotubular junction, which is defined by imaginary lines connecting the commissures. The proximal border is the ventriculoarterial (VA) junction, which has both hemodynamic and anatomic parts. The hemodynamic VA junction is marked by the semilunar attachments of the leaflets, whereas, the anatomic VA junction is marked by the circular attachment of the proximal aorta and the muscular and membranous ventricular septums.

Figure 31-4

View Full Size||Download Slide (.ppt)

Schematic representation of the aortic valve cuff. The sinotubular junction marks the distal border. The ventriculoarterial junction, which has both hemodynamic and anatomic parts, marks the proximal border. (Reproduced with permission of the Cleveland Clinic, Cleveland, OH.)

The valve leaflets consist of three layers of endothelially invested connective tissue of distinctly different density and composition. There is no demarcation between the outer layers of the aortic and ventricular sides of the leaflets and outer layers of the corresponding aortic and ventricular walls; that is, leaflet endothelial cells form a continuum with aortic and ventricular endothelial cells (Fig. 31-5).2,3 Endothelial cells of both the aortic and ventricular surfaces of the AV are arranged circumferentially. Beneath the endothelium, there are extensions of the aortic intima and ventricular endocardium, termed the arterialis and ventricularis, respectively. The next layer is the lamina fibrosa, which is composed of dense collagen mostly in a circumferential pattern. Because of the thickness and density of this layer, it is the strongest layer and important for bearing the stress of diastolic pressure. The middle layer, referred to as the spongiosa, forms the core of the leaflets at their bases. It is made of loose connective tissue consisting of water and glycosaminoglycans with sparse fibers and cellularity. The semifluid nature of this layer gives the leaflet considerable plasticity.

Figure 31-5

View Full Size||Download Slide (.ppt)

Schematic representation of a cross-section through the aortic valve leaflet showing the continuity of endocardial and endothelial components with the aortic valve. Inset illustrates the radial and circumferential axes of the valve leaflet. (Reproduced with permission of the Cleveland Clinic, Cleveland, OH.)

Mechanics of Movement

Listen

The AV passively opens and closes in response to pressure differences between the left ventricle and aorta during the cardiac cycle. Pressure generated from ventricular contraction leads to valve opening, and the subsequent relatively higher pressure of the aorta leads to valve closure. The mechanical properties of the AV allow it to open with minimal transvalvular gradient and close completely with minimal flow reversal.

Opening

Pressure differences between the aorta and the ventricle coupled with compliance of the aortic root cause aortic root dilation and constriction during the cardiac cycle. This dynamic motion of the root plays an important role in opening and closure of the AV. During late diastole, as blood fills the ventricle, a 12% expansion of the aortic root occurs 20 to 40 msec before AV opening.4,5 The leaflets begin to open as a result of root dilation even before any generation of positive pressure from ventricular contraction. Root dilation alone opens the leaflets about 20%.6 As pressure rises in the LVOT, tension across the leaflets produced from root dilation lessens. As pressure continues to rise, the pressure difference across the leaflets is minimal, and no tension is present within the leaflet.4 This loss of tension allows the aortic root to further dilate and allows the valve to open rapidly at the beginning of ejection. Under normal circumstances, the AV presents little or no obstruction to flow because the specific gravity of the leaflets is equal to that of blood.7 These mechanisms permit rapid opening of the valve and minimal resistance to ejection.8

Closure

Closure of the AV is an elegant mechanism, which has interested investigators since the time of Leonardo da Vinci.9 A principal theory involved in closure is vortex theory, which recognizes the importance of the sinuses of Valsalva in valve closure.10 As ejection occurs, blood creates small eddy currents or vortices along the aortic wall. At the end of ejection and before valve closure, these vortices fill the sinuses and balloon the leaflets away from the aortic wall toward the aortic axis. After the pressure difference across the open AV equalizes, a small flow reversal forces the leaflets completely closed. Apposition of the valve leaflets occurs briskly and the ensuing second heart sound occurs after complete closure of the AV. Upon closing, the elastic leaflets stretch and recoil to generate compression and expansion of blood. The subsequent pressure changes produce the second heart sound; the sound is not produced by physical apposition of the valve leaflets.11

Aortic Stenosis

Listen

Aortic stenosis (AS) is incomplete opening of the AV, which restricts blood flow out of the left ventricle during systole.

Prevalence and Etiology

In developed countries, AS is the most prevalent valvular heart disease in adults. Observational echocardiography studies demonstrate that 2% of people 65 years of age or older have isolated calcific AS, whereas 29% exhibit age-related AV sclerosis without stenosis.12 AS is more common in men and prevalence increases with age. In patients aged 65 to 75 years, 75 to 85 years, and greater than 85 years, the prevalence of AS is 1.3, 2.4, and 4%, respectively.13 The most common causes of AS are acquired degenerative disease, bicuspid AV, and rheumatic heart disease.

Acquired Aortic Stenosis

The most common cause of AS is degenerative calcification of the AV, which typically occurs in septuagenarians and octogenarians. Progressive calcification, initially along the flexion lines at the leaflet bases, leads to immobilization of the cusps. The characteristic pathologic findings are discrete, focal lesions on the aortic side of the leaflets that can extend deep into the aortic annulus. The deposits may involve the sinuses of Valsalva and the ascending aorta. Although long considered to be the result of years of mechanical stress on an otherwise normal valve, it is now understood that the mechanical stress leads to proliferative and inflammatory changes, with lipid accumulation, upregulation of angiotensin-converting enzyme (ACE) activity, and infiltration of macrophages and T lymphocytes in a process similar to atherosclerosis.13–18 The risk factors for the development of calcific AS are also similar to those for atherosclerosis and include elevated serum levels of low-density lipoprotein (LDL) cholesterol, diabetes, smoking, and hypertension.13 Therefore, coronary artery disease is commonly present in patients with AS. Age-related AV sclerosis is associated with an increased risk of cardiovascular death and myocardial infarction (MI).

Calcific AS is also observed in a number of other conditions, including Paget's disease of bone and end-stage renal disease.19 Ochronosis with alkaptonuria is another rare cause of AS, which also can cause a rare greenish discoloration of the AV.20

Bicuspid Aortic Stenosis

A calcified bicuspid AV represents the most common form of congenital AS. Bicuspid AVs are present in approximately 2% of the general population. Gradual calcification of the bicuspid AV results in significant stenosis most often in the fifth and sixth decades of life, earlier in unicommissural than in bicuspid valves and earlier in men than women. The abnormal architecture of the unicommissural or bicuspid AV induces turbulent flow, which injures the leaflets and leads to fibrosis, increased rigidity, leaflet calcification, and narrowing of the AV orifice.21 Bicuspid valves are often associated with dilatation of the ascending aorta related to accelerated degeneration of the aortic media that in some cases may progress to aneurysm formation. Recent work suggests that a DNA transcriptional error in the gene encoding endothelial nitric oxide synthetase may be implicated in the genetic abnormality that leads to bicuspid AV.22 It appears that the microfibrils within the AV and the aortic root are defective in structure in patients with bicuspid AV disease. This leads to a decrease in mechanical support for the valve, thereby contributing to accelerated "wear and tear," and hence degenerative changes in the valve matrix.

Rheumatic Aortic Stenosis

In Western countries, rheumatic AS represents the least common form of AS in adults.23 Rheumatic AS is rarely an isolated disease and usually occurs in conjunction with mitral valve stenosis.24 Rheumatic AS is characterized by diffuse fibrous leaflet thickening with fusion, to a variable extent, of one or more commissures. The early stage of rheumatic AS is characterized by edema, lymphocytic infiltration, and revascularization of the leaflets, whereas the later stages are characterized by thickening, commissural fusion, and scarred leaflet edges.25

Pathophysiology

In adults with calcific disease, the AV slowly thickens over time. Early, it causes little hemodynamic disturbance as the valve area is reduced from the normal 3 to 4 cm2 to 1.5 to 2 cm2.13 Past this point, hemodynamically significant obstruction of LV outflow develops with a concomitant increase in LV pressure and lengthening of the LV ejection time. The elevated LV pressure increases wall stress. Wall stress is normalized by increased wall thickness and LV hypertrophy (LVH). As it hypertrophies, the left ventricle becomes less compliant and LV end-diastolic pressure (LVEDP) increases without chamber dilatation. This reflects diastolic dysfunction and the ventricle becomes increasingly dependent on atrial systole for filling.26 Hence, if a patient develops an atrial arrhythmia, he or she can rapidly decompensate.

Although adaptive, the concentric hypertrophy that develops has adverse consequences. LVH, increased systolic pressure, and prolonged ejection time all contribute to an increase in myocardial oxygen consumption. Increased diastolic pressure increases endocardial compression of the coronary arteries, reducing coronary flow reserve (or maximal coronary flow).27 Prolonged ejection also results in decreased time in diastole and therefore reduced myocardial perfusion time. The increased demand of the hypertrophied ventricle and decreased delivery capacity can yield subendocardial ischemia with activity. This can result in angina and LV dysfunction. LVH also makes the heart more susceptible to ischemic injury. Severe LVH is only partly reversed by AV replacement (AVR) and is associated with decreased long-term survival even after initially successful surgery.28

In late stages of severe AS, the left ventricle decompensates with resulting dilated cardiomyopathy and heart failure. Cardiac output (CO) declines and the pulmonary artery pressure rises, leading to pulmonary hypertension.

Myocardial hypertrophy in patients with AS is characterized by increased gene expression for collagen I and II, and fibronectin that is associated with activation of the renin-angiotensin system.22 Reduction in renin-angiotensin parallels regression of hypertrophy after AVR.29 Experimental studies have indicated a role of apoptotic mechanisms in the progression to LVH and heart failure in patients with AS.30 For 50% of patients who present with symptoms of congestive heart failure (CHF), mean survival is less than 1 year.31

Hemodynamics

The severity of AS can be assessed by measuring the AV orifice area (AVA), mean pressure gradient, and peak jet velocity. AVA is calculated by using CO, heart rate (HR), systolic ejection period (SEP), and mean pressure gradient in the Gorlin formula, which describes the fundamental relationships linking the area of an orifice to the flow and pressure drop across the orifice. The Gorlin formula is:

CO can be measured using the Fick or thermodilution technique. SEP is the time from AV opening to closure. The normal AVA is 2.6 to 3.5 cm2 in adults. Valve areas of less than 1.0 cm2 represent severe AS. In low-output states, the Gorlin formula may systematically predict smaller valve areas than are actually present. Several reports also indicate that the AVA from the Gorlin formula increases with increases in CO.32

In patients with AS, the transvalvular pressure gradient can be measured by simultaneous catheter pressure measurements in the left ventricle and proximal aorta. The peak-to-peak gradient, measured as the difference between peak LV pressure and peak aortic pressure, is used commonly to quantify the valve gradient.

Invasive measurements of AS severity have been largely replaced by echocardiographic measurements, which are currently the clinical standard. The Doppler acquired jet velocity is converted to a gradient using the Bernoulli equation, which is:

Gradient = 4 × (velocity)2

Transesophageal echocardiography (TEE) is an alternative method for assessment of AVA that uses planimetry of the systolic short-axis view of the AV (Fig. 31-6).33 Planimetry of the valve area is challenging because the valve orifice is a complex, three-dimensional shape, and area measurements assume the valve orifice lies entirely within the image plane.

Figure 31-6

View Full Size||Download Slide (.ppt)

Transesophageal echocardiographic image of aortic stenosis resulting from severe degenerative calcification. Transverse section of the aortic root at the level of the aortic valve orifice showing the aortic ring (arrow), the sinuses of Valsalva (asterisks), and a significantly reduced aortic valve orifice area of 0.44 cm2 (dotted line).

Clinical Presentation

Symptoms

The cardinal symptoms of AS are angina pectoris, syncope, and symptoms of CHF (dyspnea, orthopnea, and paroxysmal nocturnal dyspnea).34 Although the mechanisms of angina and heart failure are well understood, the mechanism of syncope is less clear. A common theory is that the augmented stroke volume that usually accompanies exercise is limited by the narrowed outflow orifice. With exercise-induced reduction in peripheral arterial resistance, blood pressure drops, leading to cerebral hypoperfusion and syncope.35 Syncope also may be the result of dysfunction of baroreceptor mechanisms and a vasodepressor response to the increased LV systolic pressure during exercise. Besides these cardinal symptoms, patients also commonly present with more subtle symptoms, such as fatigue, decreased exercise tolerance, and dyspnea on exertion.36

Another rare presentation of AS is gastrointestinal bleeding secondary to angiodysplasia occurring predominantly in the right colon as well as the small bowel or stomach. This complication arises from shear-stress–induced platelet aggregation with reduction in high-molecular-weight multimers of von Willebrand factor and increases in proteolytic subunit fragments. These abnormalities correlate with the severity of AS and are correctable by AVR.37 Other late manifestations of severe AS include atrial fibrillation and pulmonary hypertension. Infective endocarditis can occur in younger patients with AS; it is less common in elderly patients with a severely calcified valve.

Patients who develop severe AS have a long period of asymptomatic progression in which morbidity and mortality is relatively low (Fig. 31-7). Sudden death from AS before the onset of symptoms is estimated to be approximately 1% per year.38 With the onset of symptoms, survival is dramatically reduced without surgical intervention. Of the 35% of patients who present with angina, 50% survive for 5 years. Of the 15% who present with syncope, 50% survive for 3 years, and mean survival for those who present with CHF is 2 years.34

Figure 31-7

View Full Size||Download Slide (.ppt)

Natural history of aortic stenosis. (From Ross J, Braunwald E. Aortic stenosis. Circulation 1968; 38(suppl 5):61-67.)

Signs

AS is frequently first diagnosed before symptom onset by auscultation of a murmur on physical exam. Classically, AS causes a systolic crescendo-decrescendo murmur, heard loudest at the right upper sternal border. Another sign of AS is a delayed second heart sound (S2) because of prolongation of the systolic ejection time. S2 also may be single when the aortic component is absent, and if the aortic component is audible, this may give rise to a paradoxical splitting of S2.

The classic pulsus parvus (small pulse) is a sign of severe AS or decompensated AS and occurs when stroke volume and systolic and pulse pressures fall. A wide pulse pressure is also characteristic of AS. Prolongation of the ejection phase with slow rise in the arterial pressure also gives rise to the pulsus tardus (late pulse). Pulsus parvus et tardus is diagnosed by palpation.

LVH is evident as a sustained apical thrust or heave. This sign is present only when failure occurs because until failure occurs, the hypertrophy is not accompanied by dilatation, and the apical impulse is not displaced. Conversely, absence of an apical thrust (except in muscular patients, or those with emphysema or adiposity) suggests mild or moderate AS. Other physical findings of significant AS include a prominent atrial kick and prominence of the jugular venous a wave secondary to decreased right ventricular compliance caused by right ventricular hypertrophy.39

Electrocardiogram

Most patients with severe AS present with QRS complex or ST-T interval abnormalities reflecting LVH. Patients with a higher gradient are more likely to show a "strain" or "systolic overload" pattern. The conduction abnormalities may result from septal trauma secondary to high intramyocardial tension from hypoxic damage to the conducting fibers or from extension of valvular calcifications into the fibrous septum.

Roentgenogram

The roentgenographic characteristics of compensated AS include concentric hypertrophy of the left ventricle without cardiomegaly, poststenotic dilatation of the aorta, and calcification of the valve cusps. With decompensation, there is cardiomegaly in the posteroanterior projection and pulmonary venous congestion. It is important to recognize that a routine chest x-ray may be within normal limits in patients with hemodynamically compensated AS. The rounding of the lower-left heart border may be subtle, the poststenotic aortic dilatation may be equivocal, and the valvular calcification may be invisible on the posteroanterior view. Of equal importance, the presence of cardiomegaly in a normotensive patient with isolated AS indicates decompensated AS.

Echocardiography

Echocardiography is the diagnostic tool of choice for confirming the diagnosis of AS and quantification of disease severity. Echocardiography is used to define: (1) the severity and etiology of AS; (2) coexisting valvular abnormalities; and (3) cardiac chamber size and function.

The development of diastolic dysfunction in patients with AS can lead to symptom development, and may increase late mortality after AVR.28,40 Hence, the quantification of diastolic dysfunction is important in the assessment of AS. LV filling pressures can be assessed by combining transmitral flow velocity and annular velocity obtained at the level of the mitral annulus with tissue Doppler (E/E').41 In patients with normal LV function (LVF), stress echocardiography is used to determine if symptom development during exercise is due to diastolic dysfunction.42 Diastolic dysfunction in patients with normal LVF may cause exercise intolerance for several reasons: (1) elevated LV diastolic and pulmonary venous pressures increase the work of breathing and cause dyspnea; (2) patients with LVH exhibit a limited ability to use the Frank-Starling mechanism during exercise, resulting in a decrease in CO during exercise; and (3) elevated LV diastolic and pulmonary venous pressures result in abnormalities in the diastolic properties of the ventricle.

When AS is suspected, an initial Doppler echocardiogram can confirm the diagnosis and assess the severity. Periodic re-examination, every 5 years for mild AS, every 2 years for moderate AS, and annually for severe AS, is recommended to identify worsening stenosis, LV dysfunction, LVH, and mitral regurgitation.43 Although AS is best understood as a disease continuum, severity can be graded by echocardiographic evaluation of hemodynamics. The current guidelines use definitions based on the AVA, mean pressure gradient, and peak jet velocity (Table 31-1).

Table 31-1 Classification of Aortic Stenosis Severity

View Table||Download (.pdf)

Table 31-1 Classification of Aortic Stenosis Severity

Indicator

Mild

Moderate

Severe

Aortic valve area (cm2)

>1.5

1.0–1.5

<1.0

Aortic valve area index (cm2 per m2)

<0.6

Mean pressure gradient (mm Hg)

<25

25–40

>40

Peak jet velocity (m/sec)

<3.0

3.0–4.0

>4.0

Adapted from Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, et al: 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008; 52(13):e1-142.

Exercise Testing

Traditionally, severe AS has been regarded as a relative contraindication to exercise testing. Exercise testing should be avoided in symptomatic patients with AS as well. Recent studies have indicated that quantitative exercise Doppler echocardiography can be performed safely in asymptomatic patients and may be useful for identifying patients who at higher risk of becoming symptomatic and/or requiring AVR. Several studies have shown that asymptomatic patients with severe AS who become symptomatic on exercise stress testing, have a higher rate of cardiac death or progression to AVR.44,45 Dobutamine stress echocardiography is occasionally used in severe AS, specifically to assess contractile reserve in patients with moderate to severe AS with a low AV gradient and depressed LVF.46,47

Cardiac Catheterization

Although Doppler echocardiography is well validated, cardiac catheterization remains the gold standard for measuring the transvalvular gradient. Because coronary artery disease is common in patients with AS, coronary angiography is usually performed in patients with severe AS to assess coronary anatomy and evaluate the need for combined AVR and myocardial revascularization. Right-sided heart catheterization is also used to calculate the AVA based on the Gorlin equation, as described earlier. Cardiac catheterization can also provide an assessment of ejection fraction (EF) through ventriculography and also may provide information about the presence or absence of other valve lesions.

Computed Tomography

Computed tomography (CT) can be used to assess progression of AS. Electrocardiographically gated multidetector row CT has shown high accuracy and reproducibility in quantifying AV calcification and its progression48 and estimating AVA by planimetry.49 The quantification of calcification may develop into clinical applications with respect to the prognostic relevance of AV sclerosis, as well as the problem of calcification of bioprostheses after surgery.

Magnetic Resonance Imaging

Cardiac magnetic resonance imaging (MRI) has emerged as an alternative noninvasive imaging modality for AS.50 Similar to echocardiography, cardiac MRI records images throughout the cardiac cycle. Cardiac MRI uses a range of pulse sequences to assess structural heart disease. The steady-state free precession (SSFP) cine pulse sequence is commonly used in cardiac MRI and provides detailed images of AV leaflet number, leaflet thickening, valve calcification, and commissural fusion. This sequence is also useful for assessing the effects of AS, including LVH and LVF.51 MRI is useful when acoustic windows in the echocardiogram are poor or there are discordant imaging and catheterization results.52,53 MRI has also been used to demonstrate improvement in LVF, myocardial metabolism, and diastolic function, as well as reduced hypertrophy after AVR for AS.54

Management

Symptomatic Patients

There is no effective medical therapy for AS. Given the biologic similarity of the calcific lesions of AS to atherosclerosis, there has been substantial effort to investigate the role of lipid-lowering agents in slowing the progression of AS, but to date prospective randomized trials have not found any benefit.55,56 Prophylactic antibiotics are recommended before any dental or surgical procedures as a prevention strategy for endocarditis.43 Management of CHF from AS has traditionally consisted of diuretics and ionotropes. Beta-blockers are avoided as reduced inotropy may lead to decreased CO in an overloaded ventricle. Classically, vasodilators are avoided in AS because their administration can lead to hypotension, syncope, and reduced coronary perfusion.

Percutaneous balloon valvuloplasty (valvotomy) is effective in congenital AS, but in adults the valve tends to re-stenose, and the procedure has no effect on long-term mortality.17 Currently, valvuloplasty is recommended only as a possible bridge to surgical intervention or a palliative measure.43 AV repair for AS has yielded poor results compared with AVR.57

The definitive treatment for severe AS is AVR, and onset of symptoms is the primary indication for AVR. As the risk of asymptomatic severe AS is perceived to be low, symptom onset remains the primary indication. Survival after successful AVR is reduced in younger patients but mimics that of the normal population in older patients.28,58,59

Percutaneous AVR represents a novel, less invasive approach to the treatment of AS. This approach has been applied successfully in high-risk patients with severe symptomatic AS who were not deemed candidates for conventional surgery.60

Asymptomatic Patients

AVR in asymptomatic patients is currently controversial. Current guidelines recommend AVR for patients with symptomatic AS, for patients with asymptomatic moderate or severe AS who also require coronary revascularization or surgery of the aorta, and for patients with severe AS and reduced EF.43 As AVR has become a safer procedure and technology for assessing disease severity has improved, it is likely that an identifiable high-risk subset of asymptomatic patients with severe AS could benefit from AVR. Studies show that asymptomatic patients with an aortic jet velocity greater than 4 m/sec,36 patients with high rates of aortic jet velocity progression and valve calcification,61 and those with small AVAs and LVH38 progress to symptom development quickly and will soon require AVR. Exercise stress testing, as described earlier, is also useful to stratify high-risk patients.

A number of recent studies have explored the potential benefit of AVR in asymptomatic patients. In studies of propensity matched cohorts of asymptomatic patients with severe AS, those who had AVR had significantly improved survival.62,63 It has also been shown that, among patients undergoing AVR for severe AS, LVH is only partly reversed and is associated with decreased long-term survival even after initially successful surgery. This suggests that intervening before development of LVH may improve outcomes.28 In summary, there is increasing evidence that AVR can be beneficial in a subset of asymptomatic patients with severe AS.

Aortic Regurgitation

Listen

Aortic regurgitation (AR) is the diastolic reflux of blood from the aorta into the left ventricle due to failure of coaptation of the valve leaflets at the onset of diastole.

Prevalence and Etiology

AR has numerous causes, which can be grouped according to the structural components of the valve apparatus affected. AR may be caused by primary disease of the aortic leaflets and/or disease of the aortic root.

Aortic leaflet calcific degeneration, myxomatous degeneration, infective endocarditis, rheumatic disease, a bicuspid AV, and anorectic medications, such as fenfluramine and phentermine, all lead to distortion of the valve leaflets and prevent proper coaptation.64–67 Aortic root dilatation caused by aortic dissection; trauma; chronic systemic hypertension; aortitis from syphilis, viral syndromes, or other systemic arteritides (eg, giant cell and Takayasu); and connective tissue disorders, such as Marfan's syndrome, Reiter's disease, Ehlers-Danlos syndrome, osteogenesis imperfecta, and rheumatoid arthritis, leads to improper leaflet coaptation and consequent AR.68–73 AR is seen most commonly in combination with AS due to calcific or rheumatic disease in which some degree (usually mild) of AR is present in the vast majority of patients. However, AR secondary to aortic dilation is now more common than primary valve disease in patients undergoing AVR for pure AR.74

Pathophysiology

The pathophysiology of AR varies according to the onset and duration of the disease process.

Acute Aortic Regurgitation

AR that presents in the acute setting is typically caused by aortic dissection, endocarditis, or trauma. By definition, acute AR is a significant aortic incompetence of sudden onset across a previously competent AV. The blood returned to the left ventricle in diastole causes a sudden increase in LV end-diastolic volume (LVEDV) and reduces the effective or forward stroke volume. LVEDV only increases mildly (20 to 30%) because the ability of the left ventricle to dilate acutely is limited. This leads to a rapid increase in LVEDP. This increase is greatest in the less compliant, concentrically thickened, hypertrophic myocardium seen in those with AS or chronic systemic hypertension. Increased LVEDP results in increased mean LA and pulmonary venous pressures and produces varying degrees of pulmonary edema.75 The rapid rise in LVEDP also blunts or abolishes the normally widened pulse pressure seen in chronic AR.76 In the acute setting, two compensatory mechanisms attempt to maintain an effective CO: an increase in contractility attributable to the Frank-Starling mechanism and an increase in HR. The maintenance of an appropriate effective CO depends on the adequacy of these mechanisms, especially systolic pump function.

Chronic Aortic Regurgitation

In contrast, chronic AR is a slow, insidious process, which sets in motion numerous compensatory mechanisms. The diastolic regurgitant flow in AR increases LVEDV, LVEDP, and wall stress. Adaptive signals lead to an increase in myocyte length and addition of sarcomeres in series in a pattern of remodeling known as eccentric hypertrophy. Typically there is a modest increase in LV wall thickness such that the ratio of wall thickness to radius is close to normal. Chamber enlargement in the setting of normal systolic function increases total stroke volume and maintains forward stroke volume (total stroke volume minus regurgitant volume).77 The increased total stroke volume coupled with a normal to slightly elevated LVEDP is responsible for the wide pulse pressure seen in chronic AR. Forward stroke volume in AR is increased by any physiologic change that decreases afterload or increases HR. Increasing HR increases forward stroke volume by itself, but it also decreases diastolic filling time and hence regurgitant flow time and volume. The peripheral vasodilatation and increased HR that accompany exercise increase forward stroke volume in this manner.78 This also illustrates the physiologic basis for vasodilator therapy in the treatment of AR, and explains why bradycardia and use of negative chronotropic agents should be avoided.

As AR progresses, the hypertrophic response becomes inadequate, 79 and/or the preload reserve is eventually exhausted.80 Thereafter, any further increase in afterload creates afterload mismatch and results in a reduction in EF. Although the hypertrophied myocardium may provide adequate compensation for many years, eventually maladaptive signals, which lead to decreased myocyte survival and fibrosis, predominate. The myocardium becomes incapable of sustaining the increased work load imposed upon it and heart failure ensues.

Myocardial ischemia in AR, which can result from both decreased coronary artery perfusion and increased myocardial oxygen demand, may lead to further impairment of LVF. The decrease in diastolic coronary perfusion that occurs with a severe reduction in aortic diastolic pressure is only partially compensated by increased coronary arterial flow during systole. In severe AR, there may even be reversal of coronary arterial flow. Superimposed CAD only exacerbates the effect of decreased diastolic coronary perfusion pressure. On the other hand, increased LV muscle mass, wall tension, and systolic ventricular pressure all contribute to increased myocardial oxygen demand. The subsequent ischemia caused by decreased perfusion and increased oxygen demand can lead to cell death and fibrosis, and chronically, can contribute to systolic dysfunction.

Clinical Presentation

Symptoms

The presentation varies depending on the acuity of onset, severity of regurgitation, compliance of the ventricle and aorta, and hemodynamic conditions present at the time. Acute AR can be debilitating and life threatening if not treated emergently, whereas chronic AR is usually well tolerated for years. Severe acute AR commonly presents catastrophically with sudden cardiovascular collapse. Patients also often present with ischemic chest pain caused by decreased coronary blood flow coupled with rapidly increased myocardial oxygen consumption.

Patients with chronic, compensated AR remain asymptomatic for prolonged periods of time while the left ventricle gradually enlarges. Symptoms of heart failure, such as exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, usually develop gradually only after considerable ventricular hypertrophy and decompensation. Patients with severe AR may experience palpitations during emotional stress or exertion; an uncomfortable awareness of each heartbeat, especially at the ventricular apex; angina pectoris; nocturnal angina; or atypical chest pain syndromes, such as thoracic pain owing to pounding of the heart against the chest wall.81

Signs

Physical examination findings of AR vary with the chronicity of the disease process. Many of the classic findings of chronic AR are a result of the widened pulse pressure. They include a "water-hammer pulse" (Corrigan pulse), head bobbing with each heartbeat (De Musset sign), capillary pulsations in the lips and fingers (Quincke pulses), pulsus bisferiens, "pistol shot sounds" on auscultation of the femoral artery (Traube sign), pulsations of the uvula (Müller sign). Although interesting, these signs are not necessarily clinically useful. The classic auscultatory finding of AR is an immediate to early diastolic, blowing, decrescendo murmur. It is best heard with the diaphragm at the left sternal border while the patient is sitting, leaning forward, and holding respiration in deep exhalation. The murmur is often better heard along the right sternal border when AR is caused primarily by root disease.82 When it is soft, isometric exercise, such as handgrip, can increase its intensity by increasing aortic diastolic pressure. In severe AR, the murmur may be holodiastolic. S1 is usually soft because the mitral leaflets are close to each other at the onset of systole. S2 is usually single because the AV does not close properly, or because LV ejection time is prolonged and P2 is obscured by the early diastolic murmur. Other findings, if present, are associated with CHF, for example, rales, S3, etc.81 As discussed, the pulse pressure in acute AR is not widened, hence many of the classic signs of chronic AR are not seen in the acute setting. Instead, signs of CHF predominate.

Electrocardiogram

The increased LV mass in chronic AR leads to left axis deviation and increased QRS complex amplitude. A strain pattern and reduction in the total QRS complex amplitude in patients with chronic severe AR is highly predictive of severe depression of EF resulting from inadequate hypertrophy.83 Q waves in leads I, V1, and V3 through V6 are indicative of diastolic volume overload.84 LV conduction defects occur late in the course and are usually associated with LV dysfunction. Overall, ECG is an inaccurate predictor of AR severity.

Roentgenogram

The chest radiograph typically shows a "normal"-sized heart with pulmonary edema, although there may be some enlargement of all cardiac chambers and the main pulmonary artery. The aorta may be dilated if aortic root disease is the cause of AR. There may be signs of pulmonary emboli in AR caused by endocarditis when there is concomitant tricuspid valve endocarditis.

Echocardiography

Echocardiography is the most useful diagnostic modality in both the initial diagnosis and continued monitoring of patients with AR. Transthoracic echocardiography (TTE) is the most commonly used imaging tool. TTE provides noninvasive assessment of the AV and aortic anatomy; the presence, severity, and etiology of regurgitation; and the size and function of the left ventricle. TEE is used when the patient's body habitus does not allow for adequate assessment with TTE and to evaluate the AV and ascending aorta in patients with suspected aortic dissection (Fig. 31-8).

Figure 31-8

View Full Size||Download Slide (.ppt)

Transesophageal echocardiographic images of aortic regurgitation due to acute aortic dissection. (Top) Showing dilated annulus, prolapse of aortic valve leaflet (dotted arrow), and intimal flap (solid arrow). (Bottom) Color Doppler showing regurgitant flow.

Two-dimensional (2D) echocardiography with Doppler color-flow mapping has been used routinely to assess the severity of AR.85–87 The color-flow jets are typically composed of three components: (1) a proximal flow convergence zone (area of acceleration into the orifice); (2) the vena contracta (the narrowest and highest-velocity region of the jet); and (3) the distal jet itself in the LV cavity. Assessment of the severity of AR is determined qualitatively by jet width and vena contracta width, and quantitatively by regurgitant volume, regurgitant fraction, and regurgitant orifice area (Table 31-2). The regurgitant orifice area is calculated by dividing the regurgitant volume by the velocity time integral of the AR jet calculated by continuous wave Doppler.88 Measurement of LV dimensions, such as end-systolic and end-diastolic volumes and wall thickness, are useful for determining LV changes and function. Additional echocardiographic findings in AR include premature closure of the mitral valve, diastolic fluttering of the anterior mitral leaflet from regurgitant flow, and less commonly, diastolic fluttering of the posterior mitral leaflet.89

Table 31-2 Classification of Aortic Regurgitation Severity

View Table||Download (.pdf)

Table 31-2 Classification of Aortic Regurgitation Severity

Indicator

Mild

Moderate

Severe

Angiographic grade

3-4+

Jet width

<25% LVOT

25–65% LVOT

>65% LVOT

Vena contracta width (cm)

<0.3

0.3–0.6

>0.6

Regurgitant volume (mL per beat)

<30

30–59

≥60

Regurgitant fraction (%)

<30

30–49

≥50

Regurgitant orifice area (cm2)

<0.10

0.10–0.29

≥0.30

Exercise Stress Testing

Exercise stress testing can provide valuable information in patients with AR, especially in those whose symptoms are equivocal or difficult to assess. In the management of AR, the presence of symptoms with exercise testing is equivalent to symptoms at rest because both circumstances warrant AVR.

Cardiac Catheterization

Cardiac catheterization is less frequently used to assess the severity of AR. It is most commonly used during preoperative assessment of coronary anatomy in patients requiring AV repair or replacement. The amount of regurgitant flow can be determined by calculating the angiographic stroke volume minus a measured fixed stroke volume. The difference between these two measured volumes divided by the angiographic stroke volume determines the regurgitant fraction. LVEDP is measured directly and EF is estimated roughly.

Computed Tomography

CT can be used to assess the severity of AR by measurement of the regurgitant orifice area, but currently the results are inferior to echocardiography.90 Several studies have demonstrated the utility of CT to detect moderate and severe AR, but inaccuracies are seen with lesser degrees of AR.91–93

Magnetic Resonance Imaging

With the recent advancements in MRI technology, MRI cineangiography is able to provide some of the same information provided by TTE and TEE. MRI in some aspects provides superior resolution of the valves and better quantification of regurgitant flow and LVF. The regurgitant volume can be calculated by quantitative assessment, wherein aortic flow is subtracted from the ventricular stroke volume measured by the volumetric technique. It also can be assessed using flow mapping downstream from the AV by measuring the retrograde volume flow after valve closure. This method is more reproducible and is used more frequently for follow-up studies. However, MRI is costly, and expertise is not available in most centers. Future improvements in technology may reduce costs and increase its availability, thereby making it a standard imaging modality along with or in substitution for echocardiography.94–96

Management

Acute AR is treated by early AV repair or replacement, depending on the etiology. With inadequate time for the left ventricle to compensate by eccentric hypertrophy, progressive CHF, tachycardia, and diminished CO occur rapidly. Vasodilators and inotropic agents, which augment forward flow and reduce LVEDP, may be helpful to manage the patient temporarily before surgery.

Compensated chronic AR is well tolerated by most patients.97–99 Current recommendations for the management of chronic AR depend on the presence of symptoms, LVF, and LV dimensions. Patients with symptoms or EFs less than or equal to 50% should undergo AV repair or replacement.100 Surgery is currently not recommended for patients who are asymptomatic, even with severe chronic AR. However, these patients must have normal LVF and LV dimensions. In asymptomatic patients with normal LVF, it is reasonable to perform surgery with an LV end-diastolic dimension (LVEDD) approaching 75 mm or an LV end-systolic dimension (LVESD) approaching 55 mm.100

After surgery, LVEDV and LVEDP decrease significantly and with the decrease in preload, EF also decreases.101 LV size and function eventually return to normal if the operation is timed correctly.102–113 The best postoperative predictor of recovery in systolic function is reduction in LVEDD because the magnitude of reduction correlates well with the magnitude of increase in EF.102 Importantly, 80% of the total reduction in LVEDD after AVR occurs within 10 to 14 days after surgery.102,107,114 Additional changes postoperatively include regression of myocardial hypertrophy, normalization of mass-to-volume ratio, increase in diastolic coronary perfusion, and decrease in peak systolic wall stress.102,114,115

Despite surgery, LV dilation and/or impaired LVF may continue in some patients. The best predictors of persistent LV dilation are greater preoperative LVESD and end-diastolic radius to wall thickness ratio.116,117 In addition to these measures, greater preoperative LVEDD and duration of LV dysfunction, and reduced EF and fractional shortening predict persistent LV dysfunction.102,106,118–121

Medical management with chronic vasodilator therapy is indicated in patients with severe AR who have symptoms or LV dysfunction, and are poor candidates for surgery. Vasodilator therapy may be beneficial in asymptomatic patients with severe AR, normal LVF, and LV dilation. Other than these instances, chronic therapy with vasodilators is not indicated in patients with AR.

In asymptomatic patients with normal LVF, the overall rate of progression to symptoms or LV dysfunction averages 4.5% per year and the mortality rate is 0.2% per year.100 Predictors for the development of future symptoms, LV dysfunction, or death include age, LVESV, LVEDV, and EF during exercise.97,122–125 Currently, there is insufficient evidence to determine if EF during exercise is a reliable predictor because exercise EF is dependent on too many factors, such as myocardial contractility,126 severity of volume overload,97,126–128 and exercise-induced changes in preload and PVR.128

References

Listen

1. Anderson RH, Devine WA, Ho SY, Smith A, McKay R: The myth of the aortic annulus: the anatomy of the subaortic outflow tract. Ann Thorac Surg 1991; 52(3):640-646. [PubMed: 1898167]

2. Broom ND: The Third George Swanson Christie memorial lecture. Connective tissue function and malfunction: a biomechanical perspective. Pathology 1988; 20(2):93-104. [PubMed: 3211601]

3. Deck JD: Endothelial cell orientation on aortic valve leaflets. Cardiovasc Res 1986; 20(10):760-767. [PubMed: 3791342]

4. Deck JD, Thubrikar MJ, Schneider PJ, Nolan SP: Structure, stress, and tissue repair in aortic valve leaflets. Cardiovasc Res 1988; 22(1):7-16. [PubMed: 3167931]

5. Thubrikar M, Harry R, Nolan SP: Normal aortic valve function in dogs. Am J Cardiol 1977; 40(4):563-568. [PubMed: 910719]

6. Gnyaneshwar R, Kumar RK, Balakrishnan KR: Dynamic analysis of the aortic valve using a finite element model. Ann Thorac Surg 2002; 73(4): 1122-1129. [PubMed: 11996252]

7. Zimmerman J: The functional and surgical anatomy of the aortic valve. Isr J Med Sci 1969; 5(4):862-866. [PubMed: 5820535]

8. Mercer JL: The movements of the dog's aortic valve studied by high speed cineangiography. Br J Radiol 1973; 46(545):344-349. [PubMed: 4715157]

9. Robicsek F: Leonardo da Vinci and the sinuses of Valsalva. Ann Thorac Surg 1991; 52(2):328-335. [PubMed: 1863165]

10. Bellhouse BJ, Reid KG: Fluid mechanics of the aortic valve. Br Heart J 1969; 31(3):391. [PubMed: 5401830]

11. Sabbah HN, Stein PD: Investigation of the theory and mechanism of the origin of the second heart sound. Circ Res 1976; 39(6):874-882. [PubMed: 1000782]

12. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, et al: Burden of valvular heart diseases: a population-based study. Lancet 2006; 368(9540):1005-1011. [PubMed: 16980116]

13. Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS: Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. NEJM 1999; 341(3):142-147. [PubMed: 10403851]

14. Ghaisas NK, Foley JB, O'Briain DS, Crean P, Kelleher D, et al: Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement. J Am Coll Cardiol 2000; 36(7):2257-2262. [PubMed: 11127470]

15. O'Brien KD, Shavelle DM, Caulfield MT, McDonald TO, Olin-Lewis K, et al: Association of angiotensin-converting enzyme with low-density lipoprotein in aortic valvular lesions and in human plasma. Circulation 2002; 106(17):2224-2230. [PubMed: 12390952]

16. Olsson M, Thyberg J, Nilsson J: Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves. Arterioscleros Thromb Vasc Biol 1999; 19(5):1218-1222. [PubMed: 10323772]

17. Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O'Brien KD: Characterization of the early lesion of 'degenerative' valvular aortic stenosis. Histological and immunohistochemical studies. Circulation 1994; 90(2): 844-853. [PubMed: 7519131]

18. Rajamannan NM, Gersh B, Bonow RO: Calcific aortic stenosis: from bench to the bedside—emerging clinical and cellular concepts. Heart Br Card Soc 2003; 89(7):801-805. [PubMed: 12807865]

19. Hultgren HN: Osteitis deformans (Paget's disease) and calcific disease of the heart valves. Am J Cardiol 1998; 81(12):1461-1464. [PubMed: 9645898]

20. Hangaishi M, Taguchi J, Ikari Y, Ohno M, Kurokawa K, et al: Aortic valve stenosis in alkaptonuria. Images in cardiovascular medicine. Circulation 1998; 98(11):1148-1149. [PubMed: 9736602]

21. Fedak PW, Verma S, David TE, Leask RL, Weisel RD, et al: Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation 2002; 106(8):900-904. [PubMed: 12186790]

22. Fielitz J, Hein S, Mitrovic V, Pregla R, Zurbrugg HR, et al: Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease. J Am Coll Cardiol 2001; 37(5):1443-1449. [PubMed: 11300459]

23. Roberts WC: Anatomically isolated aortic valvular disease. The case against its being of rheumatic etiology. Am J Med 1970; 49(2):151-159. [PubMed: 5452937]

24. Passik CS, Ackermann DM, Pluth JR, Edwards WD: Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases. Mayo Clin Proc 1987; 62(2):119-123. [PubMed: 3807436]

25. Roberts WC, Ko JM: Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation 2005; 111(7):920-925. [PubMed: 15710758]

26. Hess OM, Ritter M, Schneider J, Grimm J, Turina M, et al: Diastolic stiffness and myocardial structure in aortic valve disease before and after valve replacement. Circulation 1984; 69(5):855-865. [PubMed: 6231136]

27. Marcus ML, Doty DB, Hiratzka LF, Wright CB, Eastham CL: Decreased coronary reserve: a mechanism for angina pectoris in patients with aortic stenosis and normal coronary arteries. NEJM 1982; 307(22):1362-1366. [PubMed: 6215582]

28. Mihaljevic T, Nowicki ER, Rajeswaran J, Blackstone EH, Lagazzi L, et al: Survival after valve replacement for aortic stenosis: implications for decision making. J Thorac Cardiovasc Surg 2008; 135(6):1270-1278; discussion 1278-1279. [PubMed: 18544369]

29. Walther T, Schubert A, Falk V, Binner C, Walther C, et al: Left ventricular reverse remodeling after surgical therapy for aortic stenosis: correlation to Renin-Angiotensin system gene expression. Circulation 2002; 106(12 Suppl 1): I23-26.

30. Yussman MG, Toyokawa T, Odley A, Lynch RA, Wu G, et al: Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers apoptotic cardiomyopathy. Nat med 2002; 8(7):725-730. [PubMed: 12053174]

31. Pellikka PA, Nishimura RA, Bailey KR, Tajik AJ: The natural history of adults with asymptomatic, hemodynamically significant aortic stenosis. J Am Coll Cardiol 1990; 15(5):1012-1017. [PubMed: 2312954]

32. Tardif JC, Rodrigues AG, Hardy JF, Leclerc Y, Petitclerc R, et al: Simultaneous determination of aortic valve area by the Gorlin formula and by transesophageal echocardiography under different transvalvular flow conditions. Evidence that anatomic aortic valve area does not change with variations in flow in aortic stenosis. J Am Coll Cardiol 1997; 29(6): 1296-1302. [PubMed: 9137227]

33. Blumberg FC, Pfeifer M, Holmer SR, Kromer EP, Riegger GA, et al: Transgastric Doppler echocardiographic assessment of the severity of aortic stenosis using multiplane transesophageal echocardiography. Am J Cardiol 1997; 79(9):1273-1275. [PubMed: 9164904]

34. Ross J Jr, Braunwald E: Aortic stenosis. Circulation 1968; 38(1 Suppl): 61-67.

35. Schwartz LS, Goldfischer J, Sprague GJ, Schwartz SP: Syncope and sudden death in aortic stenosis. Am J Cardiol 1969; 23(5):647-658. [PubMed: 5771033]

36. Otto CM, Burwash IG, Legget ME, Munt BI, Fujioka M, et al: Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation 1997; 95(9):2262-2270. [PubMed: 9142003]

37. Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, et al: Acquired von Willebrand syndrome in aortic stenosis. NEJM 2003; 349(4):343-349. [PubMed: 12878741]

38. Pellikka PA, Sarano ME, Nishimura RA, Malouf JF, Bailey KR, et al: Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 2005; 111(24): 3290-3295. [PubMed: 15956131]

39. Selzer A: Changing aspects of the natural history of valvular aortic stenosis. NEJM 1987; 317(2):91-98. [PubMed: 3295554]

40. Gjertsson P, Caidahl K, Farasati M, Oden A, Bech-Hanssen O: Preoperative moderate to severe diastolic dysfunction: a novel Doppler echocardiographic long-term prognostic factor in patients with severe aortic stenosis. J Thorac Cardiovasc Surg 2005; 129(4):890-896. [PubMed: 15821660]

41. Maurer MS, Spevack D, Burkhoff D, Kronzon I: Diastolic dysfunction: can it be diagnosed by Doppler echocardiography? J Am Coll Cardiol 2004; 44(8):1543-1549. [PubMed: 15489083]

42. Agricola E, Oppizzi M, Pisani M, Margonato A: Stress echocardiography in heart failure. Cardiovasc Ultrasound 2004; 2:11. [PubMed: 15285780]

43. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, et al: 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008; 52(13):e1-142.

44. Amato MC, Moffa PJ, Werner KE, Ramires JA: Treatment decision in asymptomatic aortic valve stenosis: role of exercise testing. Heart Br Card Soc 2001; 86(4):381-386. [PubMed: 11559673]

45. Das P, Rimington H, Chambers J: Exercise testing to stratify risk in aortic stenosis. Eur Heart J 2005; 26(13):1309-1313. [PubMed: 15820999]

46. deFilippi CR, Willett DL, Brickner ME, Appleton CP, Yancy CW, et al: Usefulness of dobutamine echocardiography in distinguishing severe from nonsevere valvular aortic stenosis in patients with depressed left ventricular function and low transvalvular gradients. Am J Cardiol 1995; 75(2):191-194. [PubMed: 7810504]

47. Monin JL, Quere JP, Monchi M, Petit H, Baleynaud S, et al: Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics. Circulation 2003; 108(3):319-324. [PubMed: 12835219]

48. Melina G, Scott MJ, Cunanan CM, Rubens MB, Yacoub MH: In-vitro verification of the electron beam tomography method for measurement of heart valve calcification. J Heart Valve Dis 2002; 11(3):402-407; discussion 408. [PubMed: 12056735]

49. Alkadhi H, Wildermuth S, Plass A, Bettex D, Baumert B, et al: Aortic stenosis: comparative evaluation of 16-detector row CT and echocardiography. Radiology 2006; 240(1):47-55. [PubMed: 16709791]

50. Cawley PJ, Maki JH, Otto CM: Cardiovascular magnetic resonance imaging for valvular heart disease: technique and validation. Circulation 2009; 119(3):468-478. [PubMed: 19171869]

51. Cranney GB, Lotan CS, Dean L, Baxley W, Bouchard A, et al: Left ventricular volume measurement using cardiac axis nuclear magnetic resonance imaging. Validation by calibrated ventricular angiography. Circulation 1990; 82(1):154-163. [PubMed: 2364511]

52. Caruthers SD, Lin SJ, Brown P, Watkins MP, Williams TA, et al: Practical value of cardiac magnetic resonance imaging for clinical quantification of aortic valve stenosis: comparison with echocardiography. Circulation 2003; 108(18):2236-2243. [PubMed: 14568899]

53. John AS, Dill T, Brandt RR, Rau M, Ricken W, et al: Magnetic resonance to assess the aortic valve area in aortic stenosis: how does it compare to current diagnostic standards? J Am Coll Cardiol 2003; 42(3):519-526. [PubMed: 12906983]

54. Beyerbacht HP, Lamb HJ, van Der Laarse A, Vliegen HW, Leujes F, et al: Aortic valve replacement in patients with aortic valve stenosis improves myocardial metabolism and diastolic function. Radiology 2001; 219(3): 637-643. [PubMed: 11376247]

55. Cowell SJ, Newby DE, Prescott RJ, Bloomfield P, Reid J, et al: A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. NEJM 2005; 352(23):2389-2397. [PubMed: 15944423]

56. Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, et al: Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. NEJM 2008; 359(13):1343-1356. [PubMed: 18765433]

57. Craver JM: Aortic valve debridement by ultrasonic surgical aspirator: a word of caution. Ann Thorac Surg 1990; 49(5):746-752; discussion 752-743. [PubMed: 2339931]

58. Lindblom D, Lindblom U, Qvist J, Lundstrom H: Long-term relative survival rates after heart valve replacement. J Am Coll Cardiol 1990; 15(3): 566-573. [PubMed: 2303624]

59. Gillinov AM, Lytle BW, Hoang V, Cosgrove DM, Banbury MK, et al: The atherosclerotic aorta at aortic valve replacement: surgical strategies and results. J Thorac Cardiovasc Surg 2000; 120(5):957-963. [PubMed: 11044322]

60. Kapadia SR, Goel SS, Svensson L, Roselli E, Savage RM, et al: Characterization and outcome of patients with severe symptomatic aortic stenosis referred for percutaneous aortic valve replacement. J Thorac Cardiovasc Surg 2009; 137(6):1430-1435. [PubMed: 19464460]

61. Rosenhek R, Binder T, Porenta G, Lang I, Christ G, et al: Predictors of outcome in severe, asymptomatic aortic stenosis. NEJM 2000; 343(9):611-617. [PubMed: 10965007]

62. Pai RG, Kapoor N, Bansal RC, Varadarajan P: Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement. Ann Thorac Surg 2006; 82(6):2116-2122. [PubMed: 17126122]

63. Varadarajan P, Kapoor N, Bansal RC, Pai RG: Survival in elderly patients with severe aortic stenosis is dramatically improved by aortic valve replacement: results from a cohort of 277 patients aged > or = 80 years. Eur J Cardiothoracic Surg 2006; 30(5):722-727. [PubMed: 16950629]

64. Carabello BA: Progress in mitral and aortic regurgitation. Prog Cardiovasc Dis 2001; 43(6):457-475. [PubMed: 11431801]

65. Fedak PW, Verma S, David TE, Leask RL, Weisel RD, et al: Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation 2002; 106(8):900-904. [PubMed: 12186790]

66. Maurer G: Aortic regurgitation. Heart 2006; 92(7):994-1000. [PubMed: 16775114]

67. Tonnemacher D, Reid C, Kawanishi D, Cummings T, Chandrasoma P, et al: Frequency of myxomatous degeneration of the aortic valve as a cause of isolated aortic regurgitation severe enough to warrant aortic valve replacement. Am J Cardiol 1987; 60(14):1194-1196. [PubMed: 2961237]

68. Carter JB, Sethi S, Lee GB, Edwards JE: Prolapse of semilunar cusps as causes of aortic insufficiency. Circulation 1971; 43(6):922-932. [PubMed: 5578866]

69. Emanuel R, Ng RA, Marcomichelakis J, Moores EC, Jefferson KE, et al: Formes frustes of Marfan's syndrome presenting with severe aortic regurgitation. Clinicogenetic study of 18 families. Br Heart J 1977; 39(2):190-197. [PubMed: 836734]

70. Heppner RL, Babitt HI, Bianchine JW, Warbasse JR: Aortic regurgitation and aneurysm of sinus of Valsalva associated with osteogenesis imperfecta. Am J Cardiol 1973; 31(5):654-657. [PubMed: 4698138]

71. Roberts WC: Aortic dissection: anatomy, consequences, and causes. Am Heart J 1981; 101(2):195-214. [PubMed: 7008565]

72. Roldan CA: Valvular disease associated with systemic illness. Cardiol Clin 1998; 16(3):531-550. [PubMed: 9742329]

73. Roldan CA, Chavez J, Wiest PW, Qualls CR, Crawford MH: Aortic root disease and valve disease associated with ankylosing spondylitis. J Am Coll Cardiol 1998; 32(5):1397-1404. [PubMed: 9809954]

74. Roberts WC, Ko JM, Moore TR, Jones WH 3rd: Causes of pure aortic regurgitation in patients having isolated aortic valve replacement at a single US tertiary hospital (1993 to 2005). Circulation 2006; 114(5):422-429. [PubMed: 16864725]

75. Rahimtoola SH: Recognition and management of acute aortic regurgitation. Heart Dis Stroke 1993; 2(3):217-221. [PubMed: 8137029]

76. Reimold SC, Maier SE, Fleischmann KE, Khatri M, Piwnica-Worms D, et al: Dynamic nature of the aortic regurgitant orifice area during diastole in patients with chronic aortic regurgitation. Circulation 1994; 89(5): 2085-2092. [PubMed: 8181132]

77. Grossman W, Jones D, McLaurin LP: Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 1975; 56(1):56-64. [PubMed: 124746]

78. Slordahl SA, Piene H: Haemodynamic effects of arterial compliance, total peripheral resistance, and glyceryl trinitrate on regurgitant volume in aortic regurgitation. Cardiovasc Res 1991; 25(10):869-874. [PubMed: 1747880]

79. Gaasch WH: Left ventricular radius to wall thickness ratio. Am J Cardiol 1979; 43(6):1189-1194. [PubMed: 155986]

80. Ross J Jr: Afterload mismatch in aortic and mitral valve disease: implications for surgical therapy. J Am Coll Cardiol 1985; 5(4):811-826. [PubMed: 3882814]

81. DeGowin RL, DeGowin EL, Brown DD, Christensen J: DeGowin & DeGowin's Diagnostic Examination. New York: McGraw-Hill; 1994.

82. Bonow RO. Valvular Heart Disease, 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2000.

83. Scognamiglio R, Fasoli G, Bruni A, Dalla-Volta S: Observations on the capability of the electrocardiogram to detect left ventricular function in chronic severe aortic regurgitation. Eur Heart J 1988; 9(1):54-60. [PubMed: 3345770]

84. Schamroth L, Schamroth CL, Sareli P, Hummel D: Electrocardiographic differentiation of the causes of left ventricular diastolic overload. Chest 1986; 89(1):95-99. [PubMed: 2934232]

85. Aurigemma G, Whitfield S, Sweeney A, Fox M, Weiner B: Color Doppler mapping of aortic regurgitation in aortic stenosis: comparison with angiography. Cardiology 1992; 81(4-5):251-257.

86. Bouchard A, Yock P, Schiller NB, Blumlein S, Botvinick EH, et al: Value of color Doppler estimation of regurgitant volume in patients with chronic aortic insufficiency. Am Heart J 1989; 117(5):1099-1105. [PubMed: 2711970]

87. Enriquez-Sarano M, Bailey KR, Seward JB, Tajik AJ, Krohn MJ, et al: Quantitative Doppler assessment of valvular regurgitation. Circulation 1993; 87(3):841-848. [PubMed: 8443904]

88. Perry GJ, Helmcke F, Nanda NC, Byard C, Soto B: Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol 1987; 9(4):952-959. [PubMed: 3558992]

89. Chia BL: Mitral valve fluttering in aortic insufficiency. J Clin Ultrasound 1981; 9(4):198-200. [PubMed: 6793640]

90. LaBounty TM, Glasofer S, Devereux RB, Lin FY, Weinsaft JW, et al: Comparison of cardiac computed tomographic angiography to transesophageal echocardiography for evaluation of patients with native valvular heart disease. Am J Cardiol 2009; 104(10):1421-1428. [PubMed: 19892062]

91. Feuchtner GM, Dichtl W, Muller S, Jodocy D, Schachner T, et al: 64-MDCT for diagnosis of aortic regurgitation in patients referred to CT coronary angiography. Am J Roentgenol 2008; 191(1):W1-7.

92. Feuchtner GM, Dichtl W, Schachner T, Muller S, Mallouhi A, et al: Diagnostic performance of MDCT for detecting aortic valve regurgitation. Am J Roentgenol 2006; 186(6):1676-1681. [PubMed: 16714658]

93. Jassal DS, Shapiro MD, Neilan TG, Chaithiraphan V, Ferencik M, et al: 64-slice multidetector computed tomography (MDCT) for detection of aortic regurgitation and quantification of severity. Invest Radiol 2007; 42(7):507-512. [PubMed: 17568273]

94. Benjelloun H, Cranney GB, Kirk KA, Blackwell GG, Lotan CS, et al: Interstudy reproducibility of biplane cine nuclear magnetic resonance measurements of left ventricular function. Am J Cardiol 1991; 67(16): 1413-1420. [PubMed: 2042573]

95. Cranney GB, Lotan CS, Dean L, Baxley W, Bouchard A, et al: Left ventricular volume measurement using cardiac axis nuclear magnetic resonance imaging. Validation by calibrated ventricular angiography. Circulation 1990; 82(1):154-163. [PubMed: 2364511]

96. Dulce MC, Mostbeck GH, O'Sullivan M, Cheitlin M, Caputo GR, et al: Severity of aortic regurgitation: interstudy reproducibility of measurements with velocity-encoded cine MR imaging. Radiology 1992; 185(1):235-240. [PubMed: 1523315]

97. Bonow RO, Lakatos E, Maron BJ, Epstein SE: Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation 1991; 84(4):1625-1635. [PubMed: 1914102]

98. Ishii K, Hirota Y, Suwa M, Kita Y, Onaka H, et al: Natural history and left ventricular response in chronic aortic regurgitation. Am J Cardiol 1996; 78(3):357-361. [PubMed: 8759822]

99. Tornos MP, Olona M, Permanyer-Miralda G, Herrejon MP, Camprecios M, et al: Clinical outcome of severe asymptomatic chronic aortic regurgitation: a long-term prospective follow-up study. Am Heart J 1995; 130(2):333-339. [PubMed: 7631617]

100. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, et al: 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008; 118(15):e523-661.

101. Boucher CA, Bingham JB, Osbakken MD, Okada RD, Strauss HW, et al: Early changes in left ventricular size and function after correction of left ventricular volume overload. Am J Cardiol 1981; 47(5):991-1004. [PubMed: 7223671]

102. Bonow RO, Dodd JT, Maron BJ, O'Gara PT, White GG, et al: Long-term serial changes in left ventricular function and reversal of ventricular dilatation after valve replacement for chronic aortic regurgitation. Circulation 1988; 78(5 Pt 1):1108-1120.

103. Bonow RO, Rosing DR, Maron BJ, McIntosh CL, Jones M, et al: Reversal of left ventricular dysfunction after aortic valve replacement for chronic aortic regurgitation: influence of duration of preoperative left ventricular dysfunction. Circulation 1984; 70(4):570-579. [PubMed: 6478563]

104. Borer JS, Herrold EM, Hochreiter C, Roman M, Supino P, et al: Natural history of left ventricular performance at rest and during exercise after aortic valve replacement for aortic regurgitation. Circulation 1991; 84(5 Suppl): III133-139.

105. Borer JS, Rosing DR, Kent KM, Bacharach SL, Green MV, et al: Left ventricular function at rest and during exercise after aortic valve replacement in patients with aortic regurgitation. Am J Cardiol 1979; 44(7):1297-1305. [PubMed: 159618]

106. Carabello BA, Usher BW, Hendrix GH, Assey ME, Crawford FA, et al: Predictors of outcome for aortic valve replacement in patients with aortic regurgitation and left ventricular dysfunction: a change in the measuring stick. J Am Coll Cardiol 1987; 10(5):991-997. [PubMed: 3668112]

107. Carroll JD, Gaasch WH, Zile MR, Levine HJ: Serial changes in left ventricular function after correction of chronic aortic regurgitation. Dependence on early changes in preload and subsequent regression of hypertrophy. Am J Cardiol 1983; 51(3):476-482. [PubMed: 6218744]

108. Clark DG, McAnulty JH, Rahimtoola SH: Valve replacement in aortic insufficiency with left ventricular dysfunction. Circulation 1980; 61(2): 411-421. [PubMed: 7351067]

109. Fioretti P, Roelandt J, Sclavo M, Domenicucci S, Haalebos M, et al: Postoperative regression of left ventricular dimensions in aortic insufficiency: a long-term echocardiographic study. J Am Coll Cardiol 1985; 5(4):856-861. [PubMed: 3156174]

110. Gaasch WH, Andrias CW, Levine HJ: Chronic aortic regurgitation: the effect of aortic valve replacement on left ventricular volume, mass and function. Circulation 1978; 58(5):825-836. [PubMed: 151609]

111. Schwarz F, Flameng W, Langebartels F, Sesto M, Walter P, et al: Impaired left ventricular function in chronic aortic valve disease: survival and function after replacement by Bjork-Shiley prosthesis. Circulation 1979; 60(1):48-58. [PubMed: 445734]

112. Taniguchi K, Nakano S, Hirose H, Matsuda H, Shirakura R, et al: Preoperative left ventricular function: minimal requirement for successful late results of valve replacement for aortic regurgitation. J Am Coll Cardiol 1987; 10(3):510-518. [PubMed: 3624657]

113. Toussaint C, Cribier A, Cazor JL, Soyer R, Letac B: Hemodynamic and angiographic evaluation of aortic regurgitation 8 and 27 months after aortic valve replacement. Circulation 1981; 64(3):456-463. [PubMed: 7261277]

114. Schuler G, Peterson KL, Johnson AD, Francis G, Ashburn W, et al: Serial noninvasive assessment of left ventricular hypertrophy and function after surgical correction of aortic regurgitation. Am J Cardiol 1979; 44(4):585-594. [PubMed: 158302]

115. Fujiwara T, Nogami A, Masaki H, Yamane H, Kanazawa S, et al: Coronary flow characteristics of left coronary artery in aortic regurgitation before and after aortic valve replacement. Ann Thorac Surg 1988; 46(1):79-84. [PubMed: 2968072]

116. Gaasch WH, Carroll JD, Levine HJ, Criscitiello MG: Chronic aortic regurgitation: prognostic value of left ventricular end-systolic dimension and end-diastolic radius/thickness ratio. J Am Coll Cardiol 1983; 1(3): 775-782. [PubMed: 6219153]

117. Kumpuris AG, Quinones MA, Waggoner AD, Kanon DJ, Nelson JG, et al: Importance of preoperative hypertrophy, wall stress and end-systolic dimension as echocardiographic predictors of normalization of left ventricular dilatation after valve replacement in chronic aortic insufficiency. Am J Cardiol 1982; 49(5):1091-1100. [PubMed: 6461239]

118. Bonow RO, Picone AL, McIntosh CL, Jones M, Rosing DR, et al: Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function. Circulation 1985; 72(6):1244-1256. [PubMed: 4064269]

119. Fioretti P, Roelandt J, Bos RJ, Meltzer RS, van Hoogenhuijze D, et al: Echocardiography in chronic aortic insufficiency. Is valve replacement too late when left ventricular end-systolic dimension reaches 55 mm? Circulation 1983; 67(1):216-221. [PubMed: 6847800]

120. Michel PL, Iung B, Abou Jaoude S, Cormier B, Porte JM, et al: The effect of left ventricular systolic function on long term survival in mitral and aortic regurgitation. J Heart Valve Dis 1995; 4(Suppl 2):S160-168; discussion S168-169.

121. Stone PH, Clark RD, Goldschlager N, Selzer A, Cohn K: Determinants of prognosis of patients with aortic regurgitation who undergo aortic valve replacement. J Am Coll Cardiol 1984; 3(5):1118-1126. [PubMed: 6707364]

122. Borer JS, Hochreiter C, Herrold EM, Supino P, Aschermann M, et al: Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aortic regurgitation and normal left ventricular performance. Circulation 1998; 97(6):525-534. [PubMed: 9494022]

123. Scognamiglio R, Rahimtoola SH, Fasoli G, Nistri S, Dalla Volta S: Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function. NEJM 1994; 331(11):689-694. [PubMed: 8058074]

124. Siemienczuk D, Greenberg B, Morris C, Massie B, Wilson RA, et al: Chronic aortic insufficiency: factors associated with progression to aortic valve replacement. Ann Intern Med 1989; 110(8):587-592. [PubMed: 2930091]

125. Tarasoutchi F, Grinberg M, Spina GS, Sampaio RO, Cardoso LF, et al: Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology. J Am Coll Cardiol 2003; 41(8): 1316-1324. [PubMed: 12706927]

126. Shen WF, Roubin GS, Choong CY, Hutton BF, Harris PJ, et al: Evaluation of relationship between myocardial contractile state and left ventricular function in patients with aortic regurgitation. Circulation 1985; 71(1):31-38. [PubMed: 3964721]

127. Greenberg B, Massie B, Bristow JD, Cheitlin M, Siemienczuk D, et al: Long-term vasodilator therapy of chronic aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial. Circulation 1988; 78(1):92-103. [PubMed: 3289791]

128. Kawanishi DT, McKay CR, Chandraratna PA, Nanna M, Reid CL, et al: Cardiovascular response to dynamic exercise in patients with chronic symptomatic mild-to-moderate and severe aortic regurgitation. Circulation 1986; 73(1):62-72. [PubMed: 3940670]

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.

Send Email

Jump to a Section

Figure 31-1

Figure 31-2

Figure 31-3

Figure 31-4

Figure 31-5

Opening

Closure

Prevalence and Etiology

Acquired Aortic Stenosis

Bicuspid Aortic Stenosis

Rheumatic Aortic Stenosis

Pathophysiology

Hemodynamics

Figure 31-6

Clinical Presentation

Symptoms

Figure 31-7

Signs

Electrocardiogram

Roentgenogram

Echocardiography

Exercise Testing

Cardiac Catheterization

Computed Tomography

Magnetic Resonance Imaging

Management

Symptomatic Patients

Asymptomatic Patients

Prevalence and Etiology

Pathophysiology

Acute Aortic Regurgitation

Chronic Aortic Regurgitation

Clinical Presentation

Symptoms

Signs

Electrocardiogram

Roentgenogram

Echocardiography

Figure 31-8

Exercise Stress Testing

Cardiac Catheterization

Computed Tomography

Magnetic Resonance Imaging

Management

Pop-up div Successfully Displayed