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]
Acquired causes:

Rheumatic fever
Infective endocarditis
Collagen vascular diseases
Degenerative aortic valve disease
Traumatic
Postsurgical (including post-transcatheter aortic valve replacement)
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 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
Other 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.

Pathophysiology
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.

Etiology
Acute 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. With the development and clinical adoption of transcatheter aortic valve replacement (TAVR)
techniques, post-TAVR AR has emerged as a common and potentially important cause of both acute and chronic AR.
[8]
AR may also develop as a complication of left ventricular assist device (LVAD) implantation. [9]
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.[10]
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.
[11]
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.
Behet disease causes cardiac complications in less than 5% of patients, but potential findings include proximal aortitis
with AR, as well as coronary artery disease.[12]
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). [13]
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. [14]
Systemic lupus erythematosus can cause valvular fibrosis and consequent dysfunction, including AR. [15] Lupus is also
associated with Libman-Sacks endocarditis, resulting in sterile, verrucous valvular vegetations that can cause AR. [16, 17]
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.[18]

Whipple disease has been reported in the literature in association with AR or aortic valve endocarditis. [19]
Connective tissue disorders that can cause significant AR include the following:

Marfan syndrome
Ehlers-Danlos syndrome
Floppy aortic valve
Aortic valve prolapse
Sinus of Valsalva aneurysm
Aortic annular fistula

Epidemiology
Occurrence 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. [20]
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. [21] 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.[22]

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. [22]
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.[21] The greater prevalence of AR in men may reflect, in part, the preponderance of underlying
conditions, such as Marfan syndrome[23] or bicuspid aortic valve, in males.[24]
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.[21] However, there are many exceptions to this observation. Patients with bicuspid
aortic valve and, especially, those with Marfan syndrome tend to present much earlier.[23, 24]

Following TAVR
TAVR has emerged as an important treatment for aortic valve disease, primarily aortic stenosis. Paravalvular AR is
common after TAVR, occurring to some degree in approximately 70% of cases and being graded as moderate or severe
in approximately 15%.[8]

Prognosis
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 year

Rate of progression to asymptomatic LV dysfunction - Less than 3.5% per year
Rate 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[25] :

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 endsystolic 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. [26]
Following TAVR
Multiple studies have shown that the presence of greater than mild AR following TAVR is associated with significantly
increased morbidity and mortality. Compared with patients who have no or mild AR, patients with moderate or severe
AR after TAVR may have more than double the risk of mortality.[8]

Clinical Presentation
History
Acute aortic regurgitation
The typical presentation of severe acute AR includes sudden, severe shortness of breath; rapidly developing heart
failure; and chest pain if myocardial perfusion pressure is decreased or an aortic dissection is present. [5]

Chronic aortic regurgitation

Patients with chronic AR often have a long-standing asymptomatic period that may last for several years. A
compensatory tachycardia may develop to maintain a large forward stroke volume, leading to a decreased diastolic
filling period. As a result, patients may be asymptomatic even with exercise. Over time, however, chronic volume
overload leads to LV dysfunction as the LV dilates. Significant deterioration of LV function may begin prior to the
development of symptoms in up to 25% of patients, highlighting the importance of periodic echocardiographic
surveillance.[4]
Among patients with asymptomatic LV dysfunction, more than 25% of them develop symptoms within 1 year. Once
symptoms arise, cardiac function usually worsens more rapidly and mortality may exceed 10% per year.
Symptoms of severe chronic AR include the following:
Palpitations - Often described as the sensation of having forceful heart beats, due to widened pulse pressure with
hyperdynamic circulation

Uncomfortable awareness of the heartbeat

Shortness of breath - May not worsen with exertion in the early stages due to compensatory tachycardia with
shortened diastole

Chest pain - Occurs if increased LV end-diastolic pressure compromises coronary perfusion pressure
gradients
Sudden cardiac death - This is uncommon (< 0.2% per year), however, in asymptomatic patients with
preserved LV function

Physical Examination
Many classical physical examination findings have been described in patients with severe chronic AR. However, these
findings may be only minimally present (if at all) in patients with severe acute AR.

Acute aortic regurgitation

Cases of acute AR may be fulminant and lead to cardiogenic shock; patients who have CHF or shock associated with
severe AR often appear gravely ill. Other symptoms of acute AR include the following:

Tachycardia
Peripheral vasoconstriction
Cyanosis
Pulmonary edema
Arterial pulsus alternans; normal LV impulse
Early diastolic murmur (lower pitched and shorter than in chronic AR) may be present. An Austin-Flint murmur, which is
caused by the regurgitant flow causing vibration of the mitral apparatus, is lower pitched and short in duration. The
decrescendo diastolic murmur is heard best with the patient leaning forward in full expiration in a quiet room. It is the
cardiac murmur most commonly missed.
A murmur at the right sternal border is associated more often with dissection than it is with any other cause of aortic
regurgitation.

Chronic aortic regurgitation

Manifestations of severe chronic AR are often the result of widened pulse pressure (ie, an exaggerated difference
between systolic and diastolic blood pressure) because (1) elevated stroke volume exists during systole and (2) the
incompetent aortic valve allows the diastolic pressure within the aorta to fall significantly.
Diastolic pressures are often lower than 60 mm Hg, with pulse pressures often exceeding 100 mm Hg, although
younger patients with more compliant vessels may have a less widened pulse pressure. Associated physical
examination findings include the following:

Becker sign - Visible systolic pulsations of the retinal arterioles

Corrigan pulse ("water-hammer" pulse) - Abrupt distention and quick collapse on palpation of the peripheral
arterial pulse
de Musset sign - Bobbing motion of the patient's head with each heartbeat
Hill sign - Popliteal cuff systolic blood pressure 40 mm Hg higher than brachial cuff systolic blood pressure
Duroziez sign - Systolic murmur over the femoral artery with proximal compression of the artery, and diastolic
murmur over the femoral artery with distal compression of the artery
Mller sign - Visible systolic pulsations of the uvula
Quincke sign - Visible pulsations of the fingernail bed with light compression of the fingernail
Traube sign ("pistol-shot" pulse) - Booming systolic and diastolic sounds auscultated over the femoral artery
On palpation, the point of maximal impulse may be diffuse or hyperdynamic but is often displaced inferiorly and toward
the axilla. Peripheral pulses are prominent or bounding. Auscultation may reveal an S 3 gallop if LV dysfunction is
present.
The murmur of AR occurs in diastole, usually as a high-pitched sound that is loudest at the left sternal border. The
duration of the murmur correlates better with the severity of AR than does the loudness of the murmur. A functional
systolic flow murmur may also be present because of increased stroke volume, although concurrent aortic stenosis may
also be present.[5]
An Austin-Flint murmur may be present at the cardiac apex in severe AR; it is a low-pitched, mid-diastolic rumbling
murmur due to blood jets from the AR striking the anterior leaflet of the mitral valve, which results in premature closure
of the mitral leaflets.
In many cases, physical examination also reveals findings relating to the underlying cause of AR. For example, there
may be various embolic phenomena in patients with AR due to infective endocarditis, or the patient may have skeletal
features suggestive of Marfan syndrome or a spondyloarthropathy if AR is due to these conditions.

Diagnostic Considerations

Physical examination findings suggesting a widened pulse pressure may also be seen in other conditions of
hyperdynamic circulation, including the following:

Thyrotoxicosis
Severe anemia
Pregnancy
Thiamine deficiency (wet beriberi)
Arteriovenous fistula - Such as patent ductus arteriosus or peripheral arteriovenous malformations
Volume depletion
Sympathetic overdrive

Differential Diagnoses

Acute Coronary Syndrome

Blunt Abdominal Trauma
Heart Failure
Infective Endocarditis
Mitral Regurgitation
Mitral Stenosis
Myocardial Infarction
Pulmonic Regurgitation
Tricuspid Stenosis

Approach Considerations
Laboratory testing in patients with AR should be guided by the clinical scenario. For example, in patients with AR due to
suspected infective endocarditis, peripheral blood counts and cultures may help to clarify the diagnosis and to identify
the causative organism. Specific serologic tests may assist in the diagnosis of rheumatologic causes. Laboratory
assessment of renal and hepatic function may play an important role in determining a patient's eligibility for certain
vasodilator or other drug therapy.
Laboratory studies for AR include the following:

Complete blood count (CBC)

Prothrombin time (PT)/activated partial thromboplastin time (aPTT)
Type and screen
Electrolytes
Myocardial muscle creatine kinase isoenzyme (CK-MB)
Cardiac troponin
Lactate dehydrogenase
Early surgical intervention is recommended in cases of AR caused by infective endocarditis, and emergent intervention
is warranted in cases caused by aortic dissection.

Imaging for Aortic Regurgitation

Transthoracic echocardiography
Transthoracic echocardiography should be performed in all patients with suspected AR and should be performed
periodically in patients with confirmed AR of significant severity.[27]
Echocardiography is a highly accurate test in AR, with sensitivity and specificity well in excess of 90%. In addition,
echocardiographic parameters are used to determine the optimal timing of surgery in many cases. [4] Important
echocardiographic findings in AR include the following:

Aortic valve structure and morphology - Bileaflet versus trileaflet, flail, thickening
Presence of vegetations or nodules - May require transesophageal echocardiography in selected cases
Severity of AR
Color Doppler jet width
Vena contracta width - In severe AR, the vena contracta width is usually more than 65% of the width of the LV
outflow tract
Regurgitant volume, fraction, and orifice area
Premature closure of the mitral valve (seen in severe AR) and opening of the aortic valve (with severely
elevated LV end-diastolic pressure)
Pressure half-time - Usually less than 300-350 ms with significant AR
Associated lesions of the aorta - Including dilation, aneurysm, dissection, or ectasia
LV structure and function
LV hypertrophy and dilation
Ejection fraction (EF) and end-systolic dimension - These are key determinants of outcome; surgery is
recommended if the EF is 55% or less or if the end-systolic dimension is more than 55 mm [4]

Echocardiographic assessment of AR following TAVR is much more challenging because the AR is usually paravalvular
and occurs in the context of acute hemodynamic changes, as well as prosthetic materials that may impair image quality.
Proposed TEE criteria for identifying significant AR include a regurgitant jet extending below the LV outflow tract,
multiple AR jets, holodiastolic flow reversal in the descending aorta, and circumferential extent of the jet in short axis
(>10% moderate, 30% severe).[8] Further research is needed to validate these criteria for clinical application.
Exercise treadmill testing
Exercise treadmill testing may be used to guide recommendations for surgical therapy in patients with severe chronic
AR and equivocal symptoms.[4] However, the role of stress echocardiography in patients with AR remains uncertain, and
further studies may be needed before it can be recommended for routine clinical use. [28]

Chest radiography
Standard chest radiography may show evidence of structural abnormalities (aortic dilation, prosthetic valve
dislodgement, aortic valvular calcification) or functional compromise (pulmonary edema, cardiomegaly).

In acute aortic regurgitation, the following may be seen:

Minimal cardiac enlargement

Normal aortic root/arch
Pulmonary venous pattern increased
In chronic aortic regurgitation, the following may be seen:

Marked cardiac enlargement

Prominent aortic root/arch
Normal pulmonary venous pattern

Radionuclide imaging
Radionuclide imaging may provide complementary clinical information, including the AR regurgitant fraction and the
LV/right ventricular (RV) stroke volume ratio. In the absence of mitral regurgitation and tricuspid regurgitation, an LV/RV
stroke volume ratio of 2.5 or more denotes severe aortic regurgitation.
Demonstration of a fall in the EF with exercise is one of the most important indications for surgery in patients who are
asymptomatic.

Aortic angiography
Aortic angiography, which may be performed during a cardiac catheterization procedure, may provide useful information
regarding the severity of the patient's AR. Traditional angiographic grading is as follows:

Mild (1+) - A small amount of contrast enters the LV during diastole and clears with each systole
Moderate AR (2+) - Contrast enters the LV with each diastole, but the LV chamber is less dense than the aorta
Moderately severe AR (3+) - The LV chamber is equal in density to the ascending aorta.
Severe AR (4+) - Complete, dense opacification of the LV chamber occurs on the first beat, and the LV is more
densely opacified than the ascending aorta
Assessment of the anatomy of the aorta and coronary ostia usually produces normal findings, except for the visible
reflux of dye from the aortic root into the ventricle.

Cardiac CT scanning and magnetic resonance imaging (MRI)

Cardiac computed tomography (CT) scanning and magnetic resonance imaging (MRI) have not yet achieved
widespread adoption in the management of AR, although support in the literature is increasing for the potential clinical
use of these imaging techniques.[29, 30, 31]

Electrocardiography
Electrocardiographic findings are nonspecific but may include evidence of the following:

LV hypertrophy
Left axis deviation
Left atrial enlargement
LV volume overload pattern - Prominent Q waves in leads I, aVL, and V 3 to V6 and relatively small r waves in V1
LV conduction defects - Typically late in the disease process

Cardiac Catheterization
Cardiac catheterization is not always required in all patients with chronic AR but may provide extremely valuable clinical
information, especially in patients who are contemplating surgery. Class I indications for cardiac catheterization under
current ACC/AHA guidelines include the following[4] :

Assessment of coronary anatomy prior to aortic valve surgery in patients with risk factors for coronary artery
disease

Assessment of severity of AR, LV function, or aortic root size when noninvasive tests are inconclusive or are
discordant with clinical findings

Histologic Findings
Histologic valvular findings in patients with AR depend on the ARs cause. Patients with congenital abnormalities can
usually be easily characterized noninvasively or grossly at the time of surgery or during pathologic inspection.
Aortic root dilation may be present in up to 25% of patients with AR due to bicuspid valve. Many patients with a bicuspid
aortic valve have concurrent aortopathy, including connective tissue and cellular abnormalities, that predisposes these
individuals to aortic dilation, aneurysm, and dissection. [10]

Treatment and Management

Emergency Department Care
General requirements in emergency department care for patients with AR include the following:

Provide adequate airway management

Intubate when necessary
Consider prompt surgical intervention in acute AR

Acute aortic regurgitation

Administer a positive inotrope (eg, dopamine, dobutamine) and a vasodilator (eg, nitroprusside). Administration of
vasodilators may be appropriate to improve systolic function and to decrease afterload.
The administration of cardiac glycosides (eg, digoxin) for rate control may in rare cases be necessary. Avoid betablockers in the acute setting.

Chronic aortic regurgitation

Consider antibiotic prophylaxis for patients with endocarditis when performing procedures likely to result in bacteremia.
The administration of pressors and/or vasodilators may be appropriate.

Vasodilator Therapy
In severe chronic AR, vasodilator therapy may be used in select conditions to reduce afterload in patients with systolic
hypertension, in order to minimize wall stress and optimize LV function. In normotensive patients, however, vasodilator
therapy is not likely to reduce regurgitant volume (preload) significantly and thus may not be of clinical benefit. [32]
The current ACC/AHA guidelines say the following about vasodilator therapy:

Vasodilator therapy is indicated for long-term treatment in patients who have severe chronic AR and symptoms
of LV dysfunction but who are not candidates for surgery.

Vasodilator therapy is reasonable for short-term therapy in patients with severe LV dysfunction and heart
failure symptoms, in order to improve their hemodynamic profile before surgery

Vasodilator therapy is acceptable for long-term therapy in asymptomatic patients with severe AR and LV
dilation with normal EF
Under the current guidelines, vasodilator therapy is not indicated for the following:

Long-term therapy in asymptomatic patients with less than severe AR and normal EF
Long-term therapy in asymptomatic patients with LV dysfunction who are candidates for surgery
Long-term therapy in symptomatic patients with less than severe LV dysfunction who are candidates for
surgery
The 2012 European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS)
guidelines recommend short-term use of vasodilators and inotropic agents to improve the condition of patients with
severe heart failure before proceeding with valve surgery. In patients with severe chronic AR and heart failure,
vasodilators are useful in the treatment of those who have hypertension, those in whom surgery is contraindicated, or
patients whose LV dysfunction persists postoperatively.[33]

Antibiotic Prophylaxis
Under current ACC/AHA guidelines, the prophylactic use of antibiotics prior to dental procedures is no longer routinely
recommended for all patients with AR. [4]However, select patient groups for whom prophylactic antibiotic therapy prior to
dental procedures may be reasonable include the following:

Patients with prosthetic material in their heart - Such as an artificial valve or a valve repaired with prosthetic
material
Patients with prior infective endocarditis
Patients who, following cardiac transplantation, have valve regurgitation due to a structurally abnormal valve
Patients with congenital heart disease (CHD) who meet any of the following criteria: (1) Cyanotic CHD that has
not been repaired or has been incompletely repaired (including patients with palliative shunts and conduits); (2)
repaired CHD using prosthetic material, for the first 6 months postprocedurally (ie, prior to endothelialization of the

material); or (3) repaired CHD but the patient is at risk for inhibited endothelialization (ie, with residual defects at or
adjacent to the site of the prosthetic material)

Valve Surgery
Surgical treatment of AR usually requires replacement of the diseased valve with a prosthetic valve, although valvesparing repair is increasingly possible with advances in surgical technique and technology. Such improvements have
also enabled many patients, even those with severe LV dysfunction, to undergo valve surgery instead of cardiac
transplantation.[34, 35, 36]
Under current ACC/AHA guidelines, aortic valve surgery is recommended for patients with severe chronic AR under the
following circumstances[4] :

Patient is symptomatic
Patient is asymptomatic, with a resting EF 55%
Patient is asymptomatic, with LV dilation (LV end-systolic dimension [LVESD] >55 mm)
Surgery is recommended in the ESC/EACTS guidelines for the following patients [33] :

Patients with severe AR with symptom onset

Patients with LV dysfunction or marked LV dilation, after exclusion of other possible causes
Asymptomatic patients with severe AR and impaired LV function (EF < 50%)
Under the ESC/EACTS guidelines, surgery should also be considered if the LV end-diastolic dimension (LVEDD) is >70
mm or the LVESD is >50 mm (or >25 mm/m2 body surface area in patients with small body size).
Additional circumstances in which aortic valve surgery may be reasonable include the following:

Patient has moderate AR and is undergoing coronary artery bypass surgery or other surgery involving the
ascending aorta

Patient has severe AR with no symptoms, normal EF, and less severe LV dilation (LVESD >50 mm or LVEDD
>70 mm), if the patient experiences (1) progressive LV dilation on serial imaging studies, (2) deteriorating exercise
tolerance, or (3) abnormal hemodynamic responses to exercise, such as an inability to augment blood pressure during
a treadmill study
In patients undergoing aortic valve surgery for bicuspid aortic valve disease who also have a dilated or aneurysmal
ascending aorta with a diameter of more than 4.5 cm, concurrent aortic root repair or replacement is indicated.
Aortic valve surgery is generally not indicated in asymptomatic patients with normal EF and less LV dilation (LVESD <
50 mm or LVEDD < 70 mm).

Mechanical versus bioprosthetic aortic valves

For patients undergoing aortic valve replacement, careful consideration should be given to the relative risks and benefits
of mechanical versus bioprosthetic valves.
Traditionally, mechanical valves have been thought to be more durable, but they require long-term anticoagulation
therapy with warfarin due to an increased risk of thrombosis. The use of bioprosthetic valves avoids the need for longterm warfarin, but they carry a greater risk of long-term deterioration and a need for reoperation. [37]
In some cases, the choice of valve is apparent; eg, a homograft is often preferred to a mechanical valve in the setting of
active infective endocarditis.
While further discussion is beyond the scope of this article, the reader is referred to the current ACC/AHA guidelines,
which include major criteria for aortic valve selection, as well as recommendations for antithrombotic therapy (including
aspirin for all prosthetic valve recipients along with long-term anticoagulation with warfarin for selected patients). [4]

Transcatheter aortic valve replacement as a treatment

Transcatheter aortic valve replacement (TAVR) has emerged as an important therapy for aortic stenosis (with or without
AR) and now is being evaluated for use in patients with predominantly AR. TAVR involves the implantation of a
bioprosthetic aortic valve using a catheter that is inserted peripherally, typically through the femoral artery, and
implanted without requiring a median sternotomy (ie, without open heart surgery). Initial reports are promising but
further studies are needed before TAVR becomes clinically available.[38]

TAVR as a cause
Management of AR that is the result of TAVR, typically following its use for aortic stenosis, depends on the severity and
hemodynamic impact of the AR. Once a determination is made that the patient is likely to benefit from intervention,
potential corrective measures (each of which carries unique risks include the following: [8]

Balloon postdilation - In cases of valve malapposition or underexpansion

Snare technique - Use of a snare catheter to reposition a deeply implanted valve
Interventional closure - Use of a vascular plug to seal a localized AR jet
Valve-in-valve implantation - Deployment of a second prosthetic valve

Diet and Activity

No specific dietary recommendations exist pertaining purely to AR. However, for patients with hypertension or
hypervolemia (including peripheral edema or other heart failure symptoms), salt restriction may provide significant
clinical benefit.
Current recommendations regarding activity in patients with AR are based mostly on expert opinion, because there is a
paucity of clinical trial data, including no convincing evidence to suggest that even strenuous periodic exercise worsens
LV function in patients with AR.
Patients who are asymptomatic and have a normal EF may safely participate in normal daily activities as well as mild
exercise and some forms of competitive exercise. However, isometric exercise is discouraged. The short-term safety of
more vigorous exercise (eg, competitive athletics) may be estimated through the use of stress testing at a comparable
level of exertion, but the long-term effects of such exercise are not known.

Long-Term Monitoring
Asymptomatic patients with severe chronic AR require ongoing clinical surveillance with periodic echocardiography. This
is because significant LV dysfunction in many cases may arise even before the patient becomes symptomatic.
After the initial study, clinical evaluation and a repeat echocardiogram are recommended in 3 months. The
recommended frequency of subsequent follow-up evaluations is based on the stability of the LVESD and LVEDD, as
follows:

For patients with an end-systolic dimension (ESD) below 45 mm or an end-diastolic dimension (EDD) below
60 mm and stable dimensions, clinical evaluation is recommended every 6-12 months and repeat echocardiography is
recommended every 12 months
For patients with an ESD below 45 mm or an EDD below 60 mm and increasing dimensions, clinical
evaluation and repeat echocardiography are recommended in 3 months
For patients with an ESD of 45-50 mm or an EDD of 60-70 mm and stable dimensions, clinical evaluation is
recommended every 6 months and repeat echocardiography is recommended every 12 months
For patients with an ESD of 45-50 mm or an EDD of 60-70 mm and increasing dimensions, clinical evaluation
and repeat echocardiography are recommended in 3 months
For patients with an ESD of 50-55 mm or an EDD of 70-75 mm and stable dimensions, clinical evaluation and
repeat echocardiography are recommended every 6 months
For patients with an ESD of 50-55 mm or an EDD of 70-75 mm and increasing dimensions, clinical evaluation
and repeat echocardiography are recommended in 3 months
For patients with an ESD below 55 mm or an EDD below 75 mm, surgery is recommended

Approach Considerations
In severe acute aortic regurgitation (AR), surgical intervention is usually indicated, but the patient may be supported
medically with dobutamine to augment cardiac output and shorten diastole and with sodium nitroprusside to reduce
afterload in hypertensive patients.
Vasodilator therapy may be used on an inpatient or outpatient basis under conditions described in the current ACC/AHA
guidelines.[4]
All patients with an artificial heart valve should receive antibiotic prophylaxis prior to dental procedures. For
antithrombotic therapy, all patients with an artificial heart valve should receive daily aspirin, and many should also
receive oral anticoagulation therapy with warfarin according to the ACC/AHA guidelines. [4]
Although diuretics, nitrates, and digoxin are sometimes used to help control symptoms in patients with AR, not enough
data in the clinical literature justify routinely recommending or discouraging these therapies. Also, no data support drug
therapy of any class in patients with less than severe AR. [4]
Intra-aortic balloon counterpulsation, which can be used to provide temporary mechanical circulatory support, is
contraindicated in patients with severe AR.

Inpatient/outpatient care
Inpatient care is required for most patients with severe acute aortic regurgitation (AR), particularly patients with
symptoms or evidence of hemodynamic decompensation. Patients with severe chronic AR may be followed as
inpatients or outpatients, depending on the stage of their disease and severity of their symptoms and LV dysfunction.

Transfer
For patients who are hospitalized for severe AR in facilities without appropriate cardiovascular and surgical expertise,
transfer may be justified to optimize clinical outcomes. For outpatients with stable but severe AR, longitudinal care by a
cardiologist with appropriate expertise is recommended.
Proceed to Medication

Medicaton
Irbesartan (Avapro)

Irbesartan inhibits the vasoconstrictor and aldosterone-secreting effects of angiotensin II by blocking the binding of
angiotensin II to receptors.
View full drug information

Olmesartan (Benicar)
Olmesartan inhibits the vasoconstrictor and aldosterone-secreting effects of angiotensin II by blocking the binding of
angiotensin II to receptors.
View full drug information

Telmisartan (Micardis)
Telmisartan inhibits the vasoconstrictor and aldosterone-secreting effects of angiotensin II by blocking the binding of
angiotensin II to receptors.

Calcium channel blockers

Class Summary
Calcium channel blockers inhibit the movement of calcium ions across the cell membrane, depressing impulse
formation (automaticity) and conduction velocity.
View full drug information

Nifedipine (Procardia, Adalat, Nifedical)

Produces significant fall in arterial pressure, reduces LV volume and mass, increases EF, and delays need for AVR in
asymptomatic patients with severe AR and normal LV systolic function. Effective vasodilator therapy requires adjustment
of dosage to decrease arterial pressure.
View full drug information

Diltiazem (Cardizem, Dilacor, Cartia XT, Tiazac)

During depolarization, diltiazem inhibits calcium ions from entering slow channels and voltage-sensitive areas of
vascular smooth muscle and myocardium. It produces vasodilation but causes less reflex tachycardia than nifedipine
does. Diltiazem may be useful if patients develop excessive hypotension with nifedipine.
View full drug information

Amlodipine (Norvasc)
Amlodipine has a longer duration of action than nifedipine or diltiazem and requires less frequent dosing. Experience
with this agent in pulmonary hypertension is not as extensive as that with other agents. Amlodipine has fewer effects on
conduction and infrequently causes atrioventricular (AV) block.

Cardiovascular, Other
Class Summary
The effects of digoxin include an increase in the force and velocity of myocardial systolic contraction (positive inotropic
action), a slowing of the heart rate, and a decrease in conduction velocity through the atrioventricular (AV) node
(vagomimetic effect). The use of this drug in patients with heart failure has been associated with 25% reduction in the
frequency of hospitalization for heart failure. However, digoxin use is not associated with a mortality benefit.
View full drug information

Digoxin (Lanoxin)
The effects of digoxin include an increase in the force and velocity of myocardial systolic contraction (positive inotropic
action), a slowing of the heart rate, and a decrease in conduction velocity through the atrioventricular (AV) node
(vagomimetic effect). The use of this drug in patients with heart failure has been associated with 25% reduction in the
frequency of hospitalization for heart failure. However, digoxin use is not associated with a mortality benefit.

Diuretics
Class Summary
Diuretics increase urine flow. These agents are ion-transport inhibitors that decrease the reabsorption of sodium at
different sites in the nephron. Diuretics have major clinical uses in managing disorders involving abnormal fluid retention
(edema) or in treating hypertension, in which their diuretic action causes decreased blood volume.
View full drug information

Furosemide (Lasix)
Like torsemide and bumetanide, furosemide is a potent loop diuretic. Compared with all other classes of diuretics, loop
diuretics have the highest efficacy in mobilizing sodium and chloride from the body, inhibiting the Na+, K+, and Clcotransport in the ascending limb of the loop of Henle.

Furosemide and other loop diuretics are indicated in the treatment of edema associated with CHF, cirrhosis of the liver,
and renal disease, including nephrotic syndrome. They may be used alone or with other antihypertensive agents to treat
hypertension.
View full drug information

Bumetanide
Bumetanide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn,
inhibits sodium and chloride reabsorption in the ascending loop of Henle. This agent does not appear to act in the distal
renal tubule.

Adrenergic Agonists
Class Summary
These agents act directly on alpha- and beta-receptors, producing effects similar to those that occur following
stimulation of sympathetic nerves or the release of the hormone epinephrine from the adrenal medulla.
View full drug information

Dobutamine (Dobutrex)
Dobutamine is a synthetic direct-acting catecholamine and beta-receptor agonist. It increases cardiac contractility and
output in CHF. At therapeutic doses, it is mainly an inotropic agent, while producing comparatively mild chronotropic and
vasodilative effects. As compared with other sympathomimetic drugs, dobutamine does not significantly increase
myocardial oxygen demands, which is its major advantage compared with other direct-acting catecholamines.

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