Aortic regurgitation results from abnormalities of the aortic leaflets, their supporting structures in the aortic root and annulus, or both. Rheumatic heart disease remains the most common cause of severe AR worldwide. However, diseases involving the aortic root and ascending aorta have become more frequent causes of AR in the western hemisphere.
Abnormalities of the aortic cusps that may result in AR include congenital leaflet abnormalities, such as bicuspid, unicuspid, or quadricuspid valves or rupture of a congenitally fenestrated valve; other congenital defects such as subaortic membranes; rheumatic heart disease with fusion of the commissures and retraction of the aortic valve leaflets due to scarring and fibrosis; myxomatous infiltration of the aortic valve; tumors; infective endocarditis; atherosclerotic degeneration; connective tissue disorders such as Marfan syndrome; ingestion of ergot-derived compounds; inflammatory diseases such as aortitis; antiphospholipid syndrome; and the use of anorectic drugs. Other systemic disorders that may affect the aortic valve include lupus erythematosus, giant cell arteritis, Takayasu arteritis, ankylosing spondylitis, Jaccoud arthropathy, Whipple disease, and Crohn disease.1
Diseases that primarily affect the annulus or aortic root include idiopathic aortic root dilatation, degeneration of the extracellular matrix as an isolated condition or associated with Marfan syndrome or congenitally bicuspid aortic valves, Ehlers-Danlos syndrome, osteogenesis imperfecta, syphilitic aortitis, aortitis noted with other connective tissue diseases such as ankylosing spondylitis, giant cell
arteritis, the Behçet syndrome, psoriatic arthritis, other forms of arthritis associated with ulcerative colitis, relapsing polychondritis, and the Reiter syndrome. Aortic root enlargement causes AR by annular dilatation, resulting in leaflet separation and loss of coaptation. Bicuspid aortic valves are commonly associated with dilatation of the aortic root as well as congenital leaflet abnormality because of abnormalities in the aortic matrix.22
Similarly, ankylosing spondylitis can result in abnormalities of both the leaflets and the aortic root. It is important to note that chronic AR by itself may lead to progressive aortic root dilatation over time.
In chronic AR, a combined preload and afterload excess is imposed on the left ventricle. The excess preload reflects the volume overload that is directly related to the severity of AR. Left ventricular afterload is also increased because the elevated end-diastolic volume increases LV wall stress. In addition, the increased stroke volume that is ejected into the high-impedance aorta often creates systolic hypertension, which in turn further increases LV afterload. The combination of preload and afterload excess with severe AR ultimately leads to progressive LV dilatation with resultant systolic dysfunction. Left ventricular dysfunction may be associated with symptoms of heart failure, such as dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea.
In early, compensated severe AR, the left ventricle adapts to the volume overload by development of eccentric hypertrophy, with replication of sarcomeres in series and elongation of myocytes and myofibers. This eccentric hypertrophy helps to maintain the ratio of the LV cavity radius to wall thickness, thereby regulating the LV wall stress to normal levels (Laplace's law:
[Ventricular Pressure × Radius]/[Wall Thickness × 2]). Increased systolic wall stress and afterload lead to further concentric hypertrophy. The systolic function is thus preserved as a result of the combination of chamber dilatation and hypertrophy. Despite the large regurgitant volume with increases in preload and afterload, these compensatory changes seek to maintain normal LV systolic function and allow patients to remain asymptomatic for many years. However, with progressive LV dilatation, preload reserve may be exhausted, leading to an afterload mismatch and deterioration of systolic function.23-25
This process is initially reversible, and LV systolic function can improve after restoration of normal loading conditions by AVR. With time, however, myocardial contractile dysfunction may develop, at which point there is the risk of irreversible LV dysfunction.
With progression of LV dysfunction, LV end-diastolic pressure increases, resulting in elevated left atrial and pulmonary artery capillary wedge pressures. Patients experience dyspnea, initially with exercise and then ultimately at rest as heart failure ensues. Angina can also occur because of a reduction in coronary flow reserve.
The findings on physical examination in patients with chronic AR are primarily related to the increased stroke volume and widened pulse pressure. The peripheral pulses demonstrate an abrupt rise of the upstroke and a quick collapse (water-hammer or Corrigan pulse). A bisferiens pulse may be palpable. “Pistol shot” sounds may be heard over the femoral arteries. Capillary pulsations can be appreciated at the fingertips, lips, and tongue. Systolic blood pressure is generally elevated and diastolic pressure is low with a widened pulse pressure. The apical impulse is diffuse, hyperdynamic, and displaced laterally and inferiorly. A rapid filling wave can often be palpated at the apex. A systolic thrill may be heard at the base of the heart, the suprasternal notch, and the carotid arteries as a result of the increased stroke volume. At times, a carotid shudder is palpable.
The intensity of the S2
may be increased or decreased depending on the etiology of the AR. A loud closure sound is associated with a dilated aortic root and a soft S2
with abnormally thickened and retracted leaflets. Aortic ejection sounds can be heard in young patients with bicuspid valves.24
may be present as a manifestation of LV dilatation and does not necessarily indicate a failing left ventricle.25
The classic murmur of AR is a high-frequency, blowing, and decrescendo diastolic murmur, usually heard in the aortic area but also audible in the left third and fourth intercostal spaces along the sternal border. The murmur is best heard with the diaphragm of the stethoscope while the patient is sitting up and leaning forward after deep expiration. The murmur is increased by maneuvers that increase peripheral vascular resistance, such as squatting or isometric exercise. The murmur decreases with maneuvers that decrease blood pressure, such as standing, amyl nitrate inhalation, or the strain phase of the Valsalva maneuver. Mild degrees of AR result in a murmur only in early diastole. As the severity of AR increases, the murmur becomes more holodiastolic. However, when the left ventricle decompensates, the gradient between the left ventricle and the aorta at end diastole is diminished, shortening the murmur.25,26
The Austin-Flint murmur, a mid to late diastolic rumble heard best at the apex, is similar to the murmur heard in mitral stenosis (MS) but occurs in patients with no mitral valve (MV) abnormalities. This murmur is low-pitched and has been postulated to represent physiologic MS caused by the rapid increase in LV diastolic pressure and by the high-pressure jet of AR impeding the opening of the MV.26
Others have surmised that the vibrations caused by the AR jet being directed at the anterior mitral leaflet and the LV free wall could be mistakenly appreciated on auscultation as a diastolic rumble.24
Diagnostic Testing for Acute AR
Acute AR is often a catastrophic illness. Because the ventricle has not had time to compensate, diagnosis is often difficult. In these patients, tachypnea and tachycardia are common and pulmonary edema is possible. With acute reduction in forward stroke volume, cardiac output is maintained by compensatory tachycardia. The patient may present in cardiogenic shock. The precordium is usually quiet. The S1
is soft because of the early closure of the MV and a short diastolic murmur. Early closure of the MV noted on echocardiography is a poor prognostic sign and should prompt rapid surgical correction. Rapid diagnosis and prompt surgical correction for acute severe AR are imperative because medical therapy (eg, therapies that reduce heart rate) can often worsen hemodynamics. Aortic balloon counterpulsation is absolutely contraindicated.27
Chest Radiography. In patients with acute AR, chest radiography reveals minimal cardiac enlargement. The aortic root and arch are normal. Pulmonary vascular congestion is noted. In patients with chronic AR, chest radiography demonstrates an enlarged cardiac silhouette with LV dilatation. The ascending aorta may also be enlarged when an aortic aneurysm or aortic dissection is present. Pulmonary congestion is noted when heart failure has developed. A chest radiograph from a patient with severe AR is shown in .
Chest radiograph of a patient with severe aortic regurgitation showing cardiomegaly and bilateral pleural effusions.
Findings on ECG may be normal early in the disease or show LV hypertrophy with or without associated repolarization abnormalities. Left axis deviation may also be present. With early LV volume overload,
there are prominent Q waves in leads I, aVL, and V3 through V6. As the disease progresses, the prominent initial forces decrease, but the total QRS amplitude increases.1
Echocardiography is the most widely used diagnostic tool to assess LV dimensions, volumes, and ejection fraction. It also allows the morphological assessment of the aortic valve, annulus, and root, thereby helping determine the etiology of AR (). Color-flow and spectral Doppler echocardiography are then used to further quantify the severity of AR () and to identify lesions in the other valves.24
No single method provides an entirely accurate quantitative assessment of the severity of valve regurgitation, and the complex interaction of anatomic and hemodynamic variables can add to these potential difficulties.
Transesophageal echocardiographic short-axis view of a patient with a bicuspid aortic valve. Note that there are 2 leaflets instead of 3 (arrows).
Transesophageal echocardiographic long-axis view with color-flow Doppler imaging in a patient with a bicuspid aortic valve with severe aortic regurgitation (arrow). Ao = aorta; LV = left ventricle.
Although cardiac ultrasonographic techniques provide important clinical information in patients with AR, physicians interpreting the results of such testing should be mindful not only of the clinical findings but also of the advantages and limitations of cardiac ultrasonography. A combination of different parameters is used in quantifying the severity of AR because no single method provides the necessary quantitative information.
If a patient has poor acoustic windows, obtaining quantitative information from the study is unlikely. In such patients, alternative imaging modalities such as transesophageal echocardiography may be considered.
The recent development of real-time 3-dimensional echocardiography shows promise for accurate calculation
of LV volumes and ejection fraction. Although not specifically studied in patients with AR, LV-volume assessment using real-time 3-dimensional echocardiography has been shown to be accurate, rapid, and superior to standard 2-dimensional echocardiographic techniques, particularly in abnormally shaped hearts. The major limitation of this technique is the reduced accuracy in patients with poor acoustic windows.
Cardiac Catheterization. Cardiac catheterization is primarily used to assess coronary anatomy before surgery in patients with the appropriate age and risk factor profile. Invasive assessment of LV function and AR severity is reserved for selected patients in whom noninvasive imaging is inconclusive.
Cardiac Magnetic Resonance Imaging.
Cardiac magnetic resonance imaging provides highly accurate assessment of LV volumes, mass, and ejection fraction; it can also provide excellent visualization of the aortic root and ascending aorta. In addition to providing superb anatomic information, CMR can be used to obtain accurate information regarding regurgitant volumes and flow. Although cine CMR is not as well validated as echocardiography, it can be useful for detecting progressive LV dilatation and for planning the timing of surgery for asymptomatic patients with severe AR. Velocity-encoded imaging is another useful technique that allows quantification of both forward and regurgitant flow.28
Exercise testing is useful as a measure of functional capacity when it is unclear whether symptoms are present. However, exercise LV ejection fraction is often abnormal in asymptomatic patients with severe AR and has not been shown to provide additional prognostic information when resting LV size and function are already known.2
Patients with chronic AR may remain asymptomatic for many years. In patients with normal LV systolic function, published data indicate that the rate of progression to asymptomatic LV systolic dysfunction is less than 3.5% per year; the development of symptoms or LV dysfunction, less than 6% per year; and the risk of sudden death, less than 0.2% per year.2,29
However, the mortality rate is much greater among patients older than 50 years with severe AR, and the higher mortality rate in this age group is an important consideration in the timing of AVR.30
When patients develop LV systolic dysfunction while asymptomatic, most will become symptomatic and require AVR within 2 to 3 years. In asymptomatic patients with LV systolic dysfunction, progression to symptoms is greater than 25% per year.2
Asymptomatic patients with normal LV function generally have a favorable prognosis.30
A progressive increase in LV dimensions or a decline in resting ejection fraction during serial follow-up may identify high-risk patients who require careful monitoring. Patients with even moderate symptoms or evidence of severe LV dilatation are at higher risk and should be considered for early intervention. These findings emphasize the importance of close follow-up of patients with chronic AR, including those who are asymptomatic.2
Asymptomatic patients with severe AR and normal LV size and function should undergo clinical examination and echocardiography yearly unless symptoms arise beforehand. Patients with substantial LV dilatation (end-diastolic dimension >60 mm) require clinical evaluations every 6 months and echocardiographic imaging every 6 to 12 months. Patients with very severe LV dilatation (end-diastolic dimension >70 mm or end-systolic dimension >50 mm) may be considered for AVR (New York Heart Association class II indication for AVR).2
However, body surface area should be considered when assessing the LV dimensions because the very large LV dimensions may never be reached in women or small men.
The benefits of long-term vasodilator therapy in asymptomatic patients with severe AR and normal ejection fraction remain controversial, with no definitive trial proving or disproving its benefit. Vasodilators may be helpful in patients who have symptoms and/or LV dysfunction but are poor surgical candidates because of additional cardiac or noncardiac comorbid conditions. They may also be helpful for improving the hemodynamic profile of patients with severe heart failure before they undergo AVR. Lastly, they have been considered as long-term therapy to prolong the compensated phase of asymptomatic patients with preserved ejection fraction but with substantial LV dilatation2
; definitive data regarding the benefit of long-term vasodilator therapy are lacking. The goal of vasodilator therapy is the reduction of systolic blood pressure. Vasodilators such as hydralazine, nifedipine, or angiotensin-converting enzyme inhibitors are preferred.31-33
β-Blocking agents have no proven benefit and, in theory, could increase the aortic regurgitant volume because the resultant bradycardia would prolong the diastolic-filling interval. Vasodilator therapy is not recommended in patients with mild or moderate AR and normal LV function in the absence of systemic hypertension because the prognosis of these patients is excellent without treatment. Patients should be referred for AVR when symptoms develop, LV dilatation is severe, or the ejection fraction decreases.2,29,30
The management of patients with chronic severe AR is outlined in .2
FIGURE 8. Management strategy for patients with chronic severe aortic regurgitation. AVR = aortic valve replacement; DD = diastolic diameter; echo = echocardiography; EF = ejection fraction; LV = left ventricular; MRI = magnetic resonance imaging; RVG = radionuclide (more ...)