Etiology

Etiologies of aortic regurgitation (AR) fall into two broad categories: primary leaflet problems and abnormalities of the aortic root. Primary leaflet problems include both congenital and acquired abnormalities. The most common congenital cardiac anomaly is bicuspid aortic valve, which is seen in 0.5% to 2% of the population. Bicuspid aortic valves are predisposed to regurgitation and stenosis and are often associated with ascending aortic dilation, which can also contribute to AR. Quadricuspid aortic valves, which are a much rarer anatomic variant, are more commonly associated with AR than stenosis ( Fig. 103.1 and Video 103.1, A ). Acquired valvular lesions, such as degenerative and calcific changes, endocarditis, and rheumatic valvular disease, can also result in AR ( Fig. 103.2 and Video 103.2, A-G).

Transesophageal echocardiogram images of incidentally discovered quadricuspid aortic valve. A , Short-axis view in systole (see Video 103.1, A ). B, Short-axis view in diastole. C, Long-axis view in diastole with color Doppler demonstrating moderate aortic regurgitation.

Transesophageal echocardiography in a patient with multivalvular rheumatic heart disease, demonstrating both aortic stenosis and regurgitation. A, Short-axis view in systole demonstrates diffuse thickening of the leaflet tips with impaired leaflet opening. Aortic valve area by planimetry is 1.8 cm . B, Short-axis view in diastole (see Video 103.2, A, B ). C, Short-axis view in diastole demonstrating mild, central aortic regurgitation (see Videos 103.2, C , 103.2, D-F )

Dilation and distortion of the aortic annulus, the sinuses of Valsalva, and the sinotubular junction, often collectively called the aortic root, may lead to suboptimal aortic valve leaflet coaptation, resulting in AR. The most common cause of thoracic aortic aneurysm is degenerative change; risk factors include advanced age, hypertension, and smoking. Genetic disorders such as Marfan syndrome, Turner syndrome, and familial thoracic aortic aneurysm syndrome, among others, can cause the sinuses of Valsalva and the ascending aorta to become dilated. Stanford type A aortic dissection can cause AR via multiple mechanisms, including dilation of the aortic root, pressure of a false lumen on one cusp resulting in asymmetrical coaptation, flail caused by disruption of leaflet support at the level of the sinotubular junction and/or annulus, and prolapse of an intimal flap through the annulus ( Figs. 103.3 , A-C , and 103.4 and Video 103.3). Rarely, blunt chest wall trauma can cause a leaflet tear or disruption of leaflet support ( Fig. 103.5 and Video 103.5, A and B ). A more extensive list of AR etiologies is given in Table 103.1 .

Transesophageal echocardiography in a patient with bicuspid aortic valve, previously treated staphylococcal endocarditis, and progressive heart failure symptoms. A , Short-axis view demonstrates that the left and right coronary cusps are fused, with severe thickening of the raphé and the edge of the left coronary cusp. B , Long-axis view illustrates that the right-left cusp is extensively damaged and effectively flail. C , Color Doppler in the long-axis view shows severe aortic regurgitation. The patient underwent aortic valve replacement, and pathologic examination of the valve showed foci of necrotizing inflammation.

A, Proximal aortic dissection with intimal flap spiraling distally down the aorta ( arrows ). B, The intimal flap prolapses across the aortic valve into the left ventricular outflow tract, disrupting normal valve function ( arrow ) and resulting in aortic regurgitation.

Transesophageal echocardiography in a patient with a history of left chest wall trauma from a snowmobile accident, noted to have a new diastolic murmur. A, Long-axis view in diastole demonstrates a subtle abnormality of coaptation, such that the tip of the right coronary cusp is displaced slightly into the left ventricular outflow tract. Notably, the valve appeared morphologically normal in the short-axis view. B, Long-axis view with color Doppler demonstrates severe, eccentric aortic regurgitation directed away from the right coronary cusp. (See Video 103.5, A and B .)

Left ventricular responses to aortic regurgitation

The response of the left ventricle (LV) to AR depends upon the time of AR onset. In acute, severe AR, the LV experiences a sudden increase in end-diastolic volume but is not compliant enough to dilate rapidly. That is, normal LV size in the presence of severe AR is an indication that the AR is acute. The sudden increase in end-diastolic pressure with acute AR usually results in elevated left atrial pressure and pulmonary edema. Afterload also increases, leading to a decrease in stroke volume; tachycardia develops to maintain sufficient cardiac output. As the LV end-diastolic pressure approaches aortic diastolic and coronary perfusion pressures, myocardial ischemia may result.

Echocardiography is indispensable in establishing the etiology of acute, severe AR. The most common causes are infective endocarditis and Stanford type A aortic dissection. Transthoracic echocardiography (TTE) may be able to distinguish between these entities, but it is often appropriate to proceed to transesophageal echocardiography (TEE) for optimal imaging of all valves and the aorta. Because Stanford type A aortic dissection is a surgical emergency, an expeditious diagnosis is critical, and TEE can rapidly establish the presence of a dissection, define its extent, and clarify the mechanism(s) by which it is causing AR. Echocardiography can also be very helpful in identifying two other features of acute, severe AR: premature mitral valve closure (best appreciated on M-mode echocardiography) and diastolic mitral regurgitation.

In chronic AR, the LV adapts to accommodate the increased end-diastolic volume. Chamber compliance increases, and eccentric and concentric hypertrophy occur so that filling pressures remain normal or near-normal. Chamber dilation allows for preserved stroke volume, even though afterload is also increased. Over time, often years, LV systolic function worsens and patients may begin to experience heart failure symptoms such as dyspnea and lower extremity edema.

Prognosis and guideline-based management of aortic regurgitation

The prognosis of chronic AR is closely associated with the degree and pace of LV remodeling, even in the absence of symptoms. Longitudinal studies have shown that initial end-systolic dimension, rate of increase of end-systolic dimension, LV ejection fraction (EF), and rate of decrease of LVEF are independently predictive of symptom development and mortality. Because asymptomatic patients with significant chronic AR can experience poor outcomes, including sudden death, serial echocardiography is indicated to assess for LV dilation and dysfunction. Other indications for echocardiography in patients with AR are listed in Box 103.1 .

The definitive treatment of severe AR is generally surgery. Optimal timing of surgery may be determined by clinical assessment of the patient and echocardiographic evaluation of LV dimensions and systolic function. Indications for aortic valve surgery in AR are listed in Table 103.2 . The left ventricular end-diastolic diameter and end-diastolic volume are expected to decrease in the immediate postoperative period. The EF tends to increase postoperatively in patients with preexisting LV systolic dysfunction, but in those with normal systolic function, it may decrease following surgery because of decreased preload. Patients with preoperative LV systolic dysfunction may have continued improvement in the EF in the months to years following aortic valve surgery. The degree of increase in EF correlates with the decrease in end-diastolic diameter. Patients with severe preoperative symptoms or reduced exercise tolerance and those with severe or long-standing LV dysfunction tend to have higher operative mortality and worse recovery of LV systolic function.

Echocardiography is an invaluable tool for establishing the presence and etiology of AR and its effects on the left ventricle. A combination of transthoracic and transesophageal imaging is often warranted for accurate assessment of LV size and systolic function and optimal visualization of the aortic valve. Patients with AR often require serial echocardiograms to reevaluate the ventricle, as LV remodeling is associated with adverse clinical consequences.

Aortic regurgitation pathophysiology

The pathophysiology of acute and chronic aortic regurgitation (AR) is quite different. The pathophysiology and hemodynamic presentation differs whether AR develops abruptly (acute AR) or over a prolonged time period (chronic AR). Table 104.1 lists the main differences between these two distinct processes.

Acute aortic regurgitation

Acute severe AR is characterized by the abrupt development of severe left ventricular (LV) volume overload in a ventricle, which does not have time to adapt to this acute change. The LV is often normal in size and is consequently exposed to a very high preload as well as an excessive afterload (due to the combination of elevated blood pressure and increased LV wall stress). The excessive load on the left ventricle can cause depression in LV ejection fraction (LVEF) and then a drop in LV stroke volume despite a relatively maintained myocardial contractility. The rapid increase in the regurgitant flow into the LV results in a hemodynamically overloaded LV with an acute rise in the LV end-diastolic pressure as the LV volume is somewhat fixed. This results in a rapid and marked increase not only of the LV end-diastolic pressure but also of the left atrial end-diastolic pressure and pulmonary capillary wedge pressure. This acute volume load causes the ventricle to operate at the extreme of the pressure-volume curve ( Fig. 104.1 ). The development of reflex tachycardia helps maintain cardiac output. In severe cases, the LV end-diastolic pressure can exceed the left atrial pressure and cause premature, presystolic closure of the mitral valve with or without diastolic mitral regurgitation ( Fig. 104.2 ). Thus, patients often present with pulmonary edema and even cardiogenic shock. In patients with preexisting LV hypertrophy (due to pressure overload such as in hypertension and aortic stenosis), acute AR can cause “exaggerated” hemodynamic changes, as these patients often have a small LV cavity, concentric hypertrophy, and a noncompliant left ventricle with a reduced preload reserve. Further deterioration accompanied by depression in the LV function and stroke volume can occur when the LV end-diastolic pressure approaches the aortic diastolic pressure, causing a drop in the gradient from aorta to LV end-diastolic pressure (myocardial perfusion pressure). This may cause subendocardial hypoperfusion and signs and symptoms of myocardial ischemia. With distention and dilation of the left ventricle, there is distention/dilation of the mitral annulus, which can induce functional mitral regurgitation (MR), which then further elevates the left atrial and pulmonary capillary wedge pressures.

A, Schematic presentation of patients with acute severe (middle) and chronic severe (right) aortic regurgitation (AR) as compared with a normal heart (left) . In acute severe AR there is a normal effective forward flow along with an elevated end-diastolic pressure and volume. The ventricle accommodates and shifts to the chronic phase in both dilates and hypertrophies eccentrically to keep the required wall stress at a normal level. B, Pressure volume loops of acute AR (middle) and chronic AR (right) compared with a normal heart (left) . In acute AR there is both volume and pressure overload acting on an unconditioned ventricle and causing a large change in pressure per volume. In chronic AR the accommodated ventricle is able to sustain markedly higher volumes with a more modest change in pressure per volume. See text for further details.

Transesophageal echocardiographic images of a patient with severe acute aortic regurgitation. Left, Color flow Doppler demonstrating severe aortic regurgitation during diastole. Right, In the same view without color Doppler, during diastole preclosure of the mitral valve (arrow) can be seen. Ao, Aorta; LA, left atrium; LV, left ventricle.

Chronic aortic regurgitation

Failure of adequate closure of the aortic cusps causes AR. Factors that affect regurgitant volume are mainly the effective regurgitant orifice and, to a lesser extent, the diastolic pressure gradient between the aorta and the LV. Bradycardia, by prolonging diastole, also increases the regurgitant load. As AR progresses over time, the LV end-diastolic volume rises. It may eventually attain an LV volume at which the preload reserve is reached, meaning that all the sarcomeres within the LV are maximally distended such that any further increase in the LV afterload results in a decreased LV stroke volume. Table 104.2 summarizes the differences in the pathophysiologic features affecting the LV during the chronic phase of aortic and mitral regurgitation. Both AR and MR are volume overload conditions. However, in MR the regurgitant stroke volume flows retrograde into the low-pressure left atrial chamber. Conversely, in AR the sum of the regurgitant volume and the forward stroke volume is ejected forward into the high-pressure aorta during systole. The increase in the ejected forward stroke volume causes systolic hypertension (increased afterload) along with a wide pulse pressure caused by the decrease in diastolic pressure due to a drop in the aortic diastolic pressure. Although MR and AR are both associated with mechanical overload of the left ventricle, the systolic wall stress is higher in patients with AR compared to MR. In fact, wall stress may reach a level similar to that found in patients with aortic stenosis. Systolic wall stress is expressed by the Laplace relation p × r /2 h ( p , LV pressure; r , LV radius; h , wall thickness). In patients with AR, both p and r are increased, and although h is increased as well, it is generally not enough to compensate for the combined increase of both p and r . Consequently, AR increases the volume-pumping requirements of the LV (preload) and it also results in a significant increase in systolic wall stress and LV afterload.

The volume overload accompanying chronic AR causes a series of pathophysiologic events, which include an initial increase in LV end-diastolic volume and pressure that leads to increasing LV compliance, accommodating the increased volume with optimizing filling pressures (see Fig. 104.1; Fig. 104.3 ). The chronic LV volume overload results in chamber enlargement, an eccentric pattern of hypertrophy, and an increase in LV mass that permits the ventricle to eject a large stroke volume, increasing the systolic pressure (increased afterload) to maintain a normal forward stroke volume.

Severe aortic regurgitation increases the volume load on the left ventricle, which, along with decreasing aortic distensibility over time, leads to increased stroke work and wall stress. These maladaptations in turn lead to LV hypertrophy and decreasing LV compliance. As a result of these stressors, the expression of collagen and certain proteins in fibroblasts changes, promoting myocardial fibrosis. See text for more details. LV, Left ventricular; LVH, left ventricular hypertrophy.

(From Goldbarg SH, Halperin JL. Aortic regurgitation: disease progression and management. Nat Clin Pract Cardiovasc Med 5:269–279, 2008.)

In the early phase of chronic AR, compensatory mechanisms keep LVEF and LV fractional shortening in the normal range. Over time, however, the LV dilates and hypertrophies, and the ratio of ventricular wall thickness to cavity radius is maintained. As a consequence, the LV end-diastolic wall stress remains normal. These adaptive mechanisms permit the LV to accommodate large stroke volumes, often with little increase in LV filling pressure. Patients with severe AR have the largest LV end-diastolic volumes that occur in patients with heart failure—also termed cor bovinum ( Fig. 104.4 ). In AR patients, LV end-diastolic volumes can be three or four times normal, which allows these patients to sustain high cardiac outputs. LV compliance is usually also increased, so that the LV end-diastolic pressure (LVEDP) may be only slightly elevated. These compensatory mechanisms allow patients to remain stable for years even in the presence of severe AR. However, this is a progressive condition, and the increased afterload results in an increase in end-systolic dimensions and eventually a reduction in LVEF. The LVEF is low normal in AR, and the end-systolic dimensions are higher when compared with MR patients in whom the LVEF is generally preserved or is even on the higher side. In chronic AR, if wall thickening fails to keep up with the volume overload, there is an increase in wall stress, which then further reduces LV systolic function and the LVEF associated with contractile dysfunction due to myocyte damage. As LV filling pressure rises, symptoms of fatigue and dyspnea appear. Angina develops even in the presence of normal coronary arteries because of the combination of reduced coronary blood flow reserve in the hypertrophied myocardium, lower than normal diastolic pressures, shorter diastolic time (due to increasing heart rate), and elevated LVEDP, which results in a decrease in the gradient (aortic diastolic pressure–LVEDP) for coronary blood flow and myocardial perfusion. These further contribute to progressive deterioration in LV function. Distention and dilation of the left ventricle can also lead to secondary (functional) MR. Subsequently, cardiac output falls and the LV end-diastolic pressure and volume rise. All these contribute to elevation of the left atrial and pulmonary artery wedge pressures, which can cause pulmonary edema and an increase in the pulmonary artery, right ventricular, and right atrial pressures, eventually compromising right ventricular function.

Postexplant images from a patient with chronic severe aortic regurgitation. In this explanted heart, weighing 860 g at explantation (normal 350-400 g), there is pronounced cardiomegaly (top image) , along with left ventricular hypertrophy (bottom image) and moderately increased interstitial and endocardial fibrosis (not shown).

Quantitation of aortic regurgitation

Semiquantitative Methods

Currently, Doppler color flow imaging is widely used to determine the severity of aortic regurgitation despite its limitations and semiquantitative nature. Parasternal long-axis, short-axis, and apical views can nicely demonstrate AR via color Doppler recording. Maximal length and area of the aortic regurgitant jet correlate poorly with aortic angiography. Short-axis jet area at the high left ventricular outflow tract (LVOT) relative to the LVOT area correlates well with angiography. Proportion of either jet area or jet width compared with LVOT area or width in excess of 60% to 65% indicates severe AR. Although this method is appealing, note that it requires careful attention to gain settings and Nyquist limits to avoid over- or underestimating the severity of regurgitation. In general, this method only gives a rough estimate of the severity of AR. This method is of limited utility in patients with eccentric jets, diffuse jets, and jets originating along the entire coaptation line.

Both continuous and pulse wave Doppler techniques are useful for the semiquantitative assessment of AR. Dense continuous-wave Doppler signal implies greater quantity of regurgitation, whereas faint signals generally represent mild regurgitation. Pressure half-time, the time for the pressure gradient to drop by half of its original value, is another measure of severity of AR obtained by continuous-wave Doppler. It is expected that the pressure half-time will be shorter (< 200 msec) in patients with severe AR because of rapid rise in left ventricular pressure from a large amount of regurgitant volume, especially in patients with acute AR. Conversely, in patients with mild AR pressure, half-time is longer (> 500 msec) because of a more gradual rise in left ventricular pressure. Pressure half-time cannot be used alone to determine the severity of AR because it is dependent on chronicity of the regurgitation, systolic blood pressure, and left ventricular compliance. For example, someone may have a short pressure half-time because of underlying severe left ventricular diastolic dysfunction. Another frequently used Doppler technique involves pulse-wave Doppler of the proximal descending thoracic aorta. Significant holodiastolic flow reversals in the descending thoracic aorta, diastolic velocity time integral similar to systolic velocity time integral, and relatively high end-diastolic velocity (> 20 cm/sec) are indicative of moderate to severe AR ( Fig. 105.1 and Video 105.1). In some older patients, diastolic flow reversal is a less reliable indicator of the severity of AR because of a stiff aorta.

Holodiastolic flow reversal in proximal descending thoracic aorta in a patient with severe aortic regurgitation.

It has been proposed that hydrodynamically the smallest area of the aortic regurgitant jet represents vena contracta (VC). From parasternal views, using the zoom function, one can visualize the proximal flow convergence zone, flow at the aortic valve, and flow below the aortic valve. In early to mid-diastole, VC is then measured, defined as the width of the narrowest portion of the aortic regurgitant jet, which occurs immediately distal to the anatomic orifice. VC width greater than 6 mm is indicative of severe AR with a sensitivity of 81% and specificity of 94%. In some patients, a right parasternal transthoracic window or transesophageal echocardiography (TEE) may be required to obtain adequate VC measurement ( Fig. 105.2 and Video 105.2).

Vena contracta width (9 mm) measurement in a patient with chronic severe aortic regurgitation on transesophageal study.

Quantitative Methods

Continuity method utilizes the principle of conservation of mass for determination of aortic regurgitation. Calculation of the regurgitant volume is based on the calculation of the stroke volume through the aortic valve and the stroke volume throughout a second and competent valve (e.g., the mitral valve). Assuming there is no or minimal mitral regurgitation, the volume of AR can be precisely calculated by subtracting the flow through the mitral valve from the LVOT flow. This method uses the combination of two-dimensional (2D) information and Doppler technique. Flow through the mitral annulus and LVOT can be calculated by multiplying mitral annular area and LVOT areas with their corresponding time-velocity integrals (TVI). Assuming a circular mitral annulus and LVOT, the following formulas are used to determine the mitral flow, LVOT flow, and aortic regurgitant volume (RVol) :

<SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='Mitralflow=Mitralannulusarea×TVIatthemitralannuluslevel*’>Mitralflow=Mitralannulusarea×TVIatthemitralannuluslevel∗Mitralflow=Mitralannulusarea×TVIatthemitralannuluslevel*
Mitral flow = Mitral annulus area × TVI at the mitral annulus level *

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