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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:
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.
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).
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.
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]
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:
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] :
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]
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.
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.
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
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:
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).
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.
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]
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] :
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).
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]
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.
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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