Aortic Regurgitation

Background

Aortic regurgitation (AR) is the diastolic flow of blood from the aorta into the left ventricle (LV). Regurgitation is due to incompetence of the aortic valve or any disturbance of the valvular apparatus (eg, leaflets, annulus of the aorta) resulting in the diastolic flow of blood into the left ventricular chamber. (See Pathophysiology and Etiology.)

Valvular abnormalities that may result in AR can be caused by the following (see Etiology, Presentation, and Workup):

Congenital causes - Bicuspid aortic valve is the most common congenital cause[1]

Rheumatic feverInfective endocarditisCollagen vascular diseasesDegenerative aortic valve disease

Abnormalities of the ascending aorta, in the absence of valve pathology, may also cause AR. Such abnormalities may occur with the following conditions:

Longstanding, uncontrolled hypertensionMarfan syndromeIdiopathic aortic dilationCystic medial necrosisSenile aortic ectasia and dilationSyphilitic aortitisGiant cell arteritisTakayasu arteritisAnkylosing spondylitisWhipple diseaseOther spondyloarthropathies

Aortic regurgitation may be a chronic disease process or it may occur acutely, presenting as heart failure.[2] The most common cause of chronic aortic regurgitation used to be rheumatic heart disease, but presently it is most commonly caused by bacterial endocarditis.[3] In developed countries, it is caused by dilation of the ascending aorta (eg, aortic root disease, aortoannular ectasia). (See Presentation and Workup.)

Three fourths of patients with significant aortic regurgitation survive 5 years after diagnosis; half survive for 10 years. Patients with mild to moderate regurgitation survive 10 years in 80-95% of the cases. Average survival after the onset of congestive heart failure (CHF) is less than 2 years. (See Prognosis, Treatment, and Medication.)

Acute aortic regurgitation is associated with significant morbidity, which can progress from pulmonary edema to refractory heart failure and cardiogenic shock.

Patient education

The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines for valvular heart disease, including for AR, are available to the public online for free.[4] Additionally, educational and support organizations, such as the National Marfan Foundation and the Bicuspid Aortic Foundation, exist for many of the underlying conditions.

NextPathophysiology

Incompetent closure of the aortic valve can result from intrinsic disease of the cusp, diseases of the aorta, or trauma. Diastolic reflux through the aortic valve can lead to left ventricular volume overload. An increase in systolic stroke volume and low diastolic aortic pressure produces an increased pulse pressure. The clinical signs of AR are caused by the forward and backward flow of blood across the aortic valve, leading to increased stroke volume.[5]

The severity of AR is dependent on the diastolic valve area, the diastolic pressure gradient between the aorta and LV, and the duration of diastole.

The pathophysiology of AR depends on 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 and altering coronary flow dynamics. 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. Decreased myocardial perfusion may lead to myocardial ischemia.

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 volume overload that leads to a series of compensatory changes, including LV enlargement and eccentric hypertrophy. LV dilation occurs through the addition of sarcomeres in series (resulting in longer myocardial fibers), as well as through the 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 result 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 worsen 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.

PreviousNextEtiologyAcute aortic regurgitation

Infective endocarditis may lead to destruction or perforation of the aortic valve leaflet. A bulky vegetation can also interfere with proper coaptation of the valve leaflets or lead to frank prolapse or disruption of a leaflet (flail leaflet).[3, 6, 7]

Another cause of acute AR, chest trauma, may lead to a tear in the ascending aorta and disruption of the aortic valve support apparatus.

In acute ascending aortic dissection (type A), the retrograde proximal dissection undermines the suspensions of the aortic valve leaflets. Varying levels of aortic valve malcoaptation and prolapse occur. Prosthetic valve malfunction can also lead to AR.

Chronic aortic regurgitation

Bicuspid aortic valve is the most common congenital lesion of the human heart. Although it leads more often to progressive aortic stenosis than to AR, it is nonetheless the most common cause of isolated AR requiring aortic valve surgery. In patients with bicuspid aortic valve, an associated aortopathy may be present, resulting in aortic dilation and/or dissection that worsens the AR.[8]

Certain weight loss medications, such as fenfluramine and dexfenfluramine (commonly referred to as Phen-Fen), may induce degenerative valvular changes that result in chronic AR.

Rheumatic fever, a common cause of AR in the first half of the 20th century, has become less common in the United States, although it remains prevalent in some immigrant populations. Fibrotic changes cause thickening and retraction of the aortic valve leaflets, resulting in central valvular regurgitation. Leaflet fusion may occur, leading to concurrent aortic stenosis. Associated rheumatic mitral valve disease is almost always present.

Ankylosing spondylitis often causes an aortitis, which most frequently involves the aortic root, with associated AR.[9] Further extension of the subaortic fibrotic process into the intraventricular septum may result in conduction system disease. Coronary and more distal aortic abnormalities are also seen in this condition.

Behçet disease causes cardiac complications in less than 5% of patients, but potential findings include proximal aortitis with AR, as well as coronary artery disease.[10]

Giant cell arteritis is a systemic vasculitis that typically affects the extracranial branches of the carotid artery but that may also cause aortic inflammation and AR (as well as coronary artery disease and LV dysfunction).[11]

Rheumatoid arthritis uncommonly causes granulomatous nodules to form within the aortic valve leaflets. In rare cases, this may lead to clinical AR, although it is more commonly an incidental finding postmortem.[12]

Systemic lupus erythematosus can cause valvular fibrosis and consequent dysfunction, including AR.[13] Lupus is also associated with Libman-Sacks endocarditis, resulting in sterile, verrucous valvular vegetations that can cause AR.[14, 15]

Takayasu arteritis, in addition to having aortic valvular (and coronary) involvement, can produce an aortitis. The aortitis may increase the risk of prosthetic valve detachment, leading some to advocate for concurrent aortic root replacement in patients undergoing valve surgery.[16]

Whipple disease has been reported in the literature in association with AR or aortic valve endocarditis.[17]

Connective tissue disorders that can cause significant AR include the following:

Marfan syndromeEhlers-Danlos syndromeFloppy aortic valveAortic valve prolapseSinus of Valsalva aneurysmAortic annular fistulaPreviousNextEpidemiologyOccurrence in the United States

Although rheumatic heart disease is overall the most common cause of AR worldwide, congenital and degenerative valve abnormalities are the most common cause in the United States, 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.[18]

In the Framingham study (with an original cohort of 5209 patients aged 28-62 y and an additional cohort of 5124 patients), AR of any severity was found in 13% of men and 8.5% of women.[19] Prevalence and severity increased with age; when stratified by decades of life, AR of moderate or greater severity was seen in less than 1% of patients in all strata younger than 70 years.

International occurrence

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.[20]

Race-, sex-, and age-related demographics

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.[20]

AR is seen more commonly in men than in women. In the cohort from the Framingham study, AR was found in 13% of men and 8.5% of women.[19] The greater prevalence of AR in men may reflect, in part, the preponderance of underlying conditions, such as Marfan syndrome[21] or bicuspid aortic valve, in males.[22]

Chronic aortic regurgitation often begins in patients when they are in their late 50s and is documented most frequently in patients older than 80 years. In general, the prevalence and severity of AR increase with age, although severe chronic AR is uncommon before age 70 years.[19] However, there are many exceptions to this observation. Patients with bicuspid aortic valve and, especially, those with Marfan syndrome tend to present much earlier.[21, 22]

PreviousNextPrognosis

The prognosis for patients with severe AR depends on the presence or absence of LV dysfunction and symptoms.[4] In asymptomatic patients with normal EF, the following has been found:

Rate of progression to symptoms or LV dysfunction - Less than 6% per yearRate of progression to asymptomatic LV dysfunction - Less than 3.5% per yearRate of sudden death - Less than 0.2% per year

In asymptomatic patients with decreased EF, the rate of progression to symptoms is greater than 25% per year, while in symptomatic patients, the mortality rate is over 10% per year.

The strongest predictors of outcome are echocardiographic parameters (EF and LV end-systolic dimension), underscoring the crucial role of serial echocardiography in the management of patients with severe AR.

Severe acute AR, if left untreated, is likely to lead to considerable morbidity and mortality from either the underlying cause (typically infective endocarditis or aortic dissection) or from hemodynamic decompensation of the LV.

Potential complications in patients with severe chronic AR include progressive LV dysfunction and dilation, congestive heart failure, myocardial ischemia, arrhythmia, and sudden death. Additional complications may arise as a result of the patient's underlying condition (such as aortic root dissection in a patient with a bicuspid aortic valve and a severely dilated aortic root).

Morbidity and mortality

Severe acute 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 that potentially can cause myocardial ischemia and even sudden cardiac death. In most cases, early (if not emergent) surgical intervention is warranted.

Severe chronic AR tends to follow a more gradual clinical course. This 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 severe chronic AR, the linearized yearly rates of major events have been estimated as follows[23] :

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

The presence of symptoms has been found to predict yearly mortality risk, as follows:

Asymptomatic - 2.8%New York Heart Association (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, as stated earlier, the most important predictors of mortality (and of postoperative LV function) are not symptoms but 2 crucial echocardiographic parameters; specifically, LV ejection fraction and LV end-systolic dimension.[4]

Risk of coronary artery disease

A study by Atalar et al found that in patients with rheumatic valve disease, the prevalence of AR was inversely proportional to the prevalence of significant coronary artery disease. The investigators, who conducted a retrospective analysis of more than 1000 patients with rheumatic valve disease, also found that, while the presence of coronary artery disease was particularly low in patients with AR, it was unusually high in those with aortic stenosis.[24]

PreviousProceed to Clinical Presentation , Aortic Regurgitation