Aortic Regurgitation 

Aortic regurgitation (AR) is the abnormal retrograde flow of blood through the aortic valve during cardiac diastole.

AR may be caused by either valvular or aortic root pathology. Valvular abnormalities that may result in AR include bicuspid aortic valve (the most common congenital cause), rheumatic fever, infective endocarditis, collagen vascular diseases, and degenerative aortic valve disease.

Abnormalities of the ascending aorta, in the absence of valve pathology, may also cause AR, such as may occur with longstanding uncontrolled hypertension, Marfan syndrome, idiopathic aortic dilation, cystic medial necrosis, senile aortic ectasia and dilation, syphilitic aortitis, giant cell arteritis, Takayasu arteritis, ankylosing spondylitis, Whipple disease, and other spondyloarthropathies.

AR causes a volume load of the left ventricle (LV); in diastole, the LV fills antegrade from the left atrium and retrograde from the aorta through the leaky aortic valve. The pathophysiology depends upon whether the AR is acute or chronic. In acute AR, the LV does not have time to dilate in response to the volume load, whereas in chronic AR, the LV may undergo a series of adaptive (and maladaptive) changes.

Acute aortic regurgitation

Acute AR of significant severity leads to increased blood volume in the LV during diastole. The LV does not have sufficient time to dilate in response to the sudden increase in volume. As a result, LV end-diastolic pressure increases rapidly, causing an increase in pulmonary venous pressure. As pressure increases throughout the pulmonary circuit, the patient develops dyspnea and pulmonary edema. In severe cases, heart failure may develop and potentially deteriorate to cardiogenic shock. Early surgical intervention should be considered (particularly if AR is due to aortic dissection, in which case surgery should be performed immediately).

Chronic aortic regurgitation

Chronic AR causes gradual left ventricular (LV) volume overload that leads to a series of compensatory changes, including LV enlargement and eccentric hypertrophy. LV dilation occurs through addition of sarcomeres in series (resulting in longer myocardial fibers) as well as rearrangement of myocardial fibers. As a result, the LV becomes larger and more compliant, with greater capacity to deliver a large stroke volume that can compensate for the regurgitant volume. The resulting hypertrophy is necessary to accommodate the increased wall tension and stress that results from LV dilation (Laplace law).

During the early phases of chronic AR, the LV ejection fraction (EF) is normal or even increased (due to the increased preload and the Frank-Starling mechanism). Patients may remain asymptomatic during this period. As AR progresses, LV enlargement surpasses preload reserve on the Frank-Starling curve with the EF falling to normal and then subnormal levels. The LV end-systolic volume rises and is a sensitive indicator of progressive myocardial dysfunction. Eventually, the LV reaches its maximal diameter and diastolic pressure begins to rise, resulting in symptoms (dyspnea) that may be worse during exercise. Increasing LV end-diastolic pressure may also lower coronary perfusion gradients, causing subendocardial and myocardial ischemia, necrosis, and apoptosis. Grossly, the LV gradually transforms from an elliptical to a spherical configuration.

Frequency

United States

Worldwide, rheumatic heart disease is the most common cause of AR. In the United States, congenital and degenerative valve abnormalities are most common, with the age of detection peaking at 40-60 years. Estimates of the prevalence of AR of any severity range from 2-30%, but only 5-10% of patients with AR have severe disease, resulting in an overall prevalence of severe AR of less than 1% in the general population.^[1]

In the Framingham study (with an original cohort of 5,209 patients aged 28-62 y and an additional cohort of 5,124 patients), AR of any severity was found in 13% of men and 8.5% of women.^[2] Prevalence and severity both increased with age; when stratified by decades of life, AR of moderate or greater severity was seen in less than 1% in all strata younger than 70 years.

International

The prevalence of AR internationally is not well known. However, the international prevalence of underlying conditions has been described elsewhere. For example, rheumatic heart disease remains highly prevalent in many Asian, Middle Eastern, and North African countries.^[3]

Mortality/Morbidity

Acute severe AR carries a very high short-term rate of morbidity and mortality owing to the imposition of a greatly increased regurgitant volume upon a relatively noncompliant LV. Increased LV end-diastolic pressure leads to elevated left atrial and pulmonary pressures with resulting pulmonary edema, as well as decreased coronary perfusion gradients potentially causing myocardial ischemia and even sudden cardiac death. In most cases, early (if not emergent) surgical intervention is warranted.

Chronic severe AR tends to follow a more gradual clinical course that is typically characterized initially by a long, relatively asymptomatic period. However, once symptoms ensue, the patient's clinical status may deteriorate relatively rapidly. Thus, current guidelines recommend surgical intervention before symptoms develop, usually based on echocardiographic parameters.

With conservative (medical) management of chronic severe AR, the linearized yearly rates of major events have been estimated as follows:^[4]

• Death from any cause, 4.7%
• Congestive heart failure, 6.2%
• Aortic valve surgery, 14.6%

The presence of symptoms predicted yearly mortality risk, as follows:

• Asymptomatic, 2.8%
• NYHA Class I, 3.0%
• NYHA Class II, 6.3%
• NYHA Class III-IV, 24.6%

Although these types of data suggest that a symptom-triggered approach to surgical intervention may be feasible, multiple studies have shown that the most important predictors of mortality (and of postoperative LV function) are not symptoms but 2 crucial echocardiographic parameters: LV ejection fraction and LV end-systolic dimension.^[5]

Race

The prevalence of AR appears to be similar across racial populations in the United States, although internationally there is significant variation in the prevalence of predisposing conditions such as rheumatic heart disease.^[3]

Sex

Aortic regurgitation is seen more commonly in men than in women. As discussed above in the Framingham cohort, AR was found in 13% of men versus 8.5% of women.^[2] The greater prevalence of AR in men may reflect, in part, the male preponderance of underlying conditions such as Marfan syndrome^[6] or bicuspid aortic valve^[7] .

Age

In general, the prevalence and severity of AR increase with age, although severe chronic AR is uncommon before aged 70 years.^[2] However, there are many exceptions to this observation. Patients with bicuspid aortic valve and especially Marfan syndrome tend to present much earlier.^{[6, 7]}