Contemporary Reviews in Cardiovascular Medicine

Valvular Heart Disease

Aortic Regurgitation
Raffi Bekeredjian, MD; Paul A. Grayburn, MD

Abstract—Aortic regurgitation (AR) is characterized by diastolic reflux of blood from the aorta into the left ventricle (LV).
Acute AR typically causes severe pulmonary edema and hypotension and is a surgical emergency. Chronic severe AR
causes combined LV volume and pressure overload. It is accompanied by systolic hypertension and wide pulse pressure,
which account for peripheral physical findings, such as bounding pulses. The afterload excess caused by systolic
hypertension leads to progressive LV dilation and systolic dysfunction. The most important diagnostic test for AR is
echocardiography. It provides the ability to determine the cause of AR and to assess the severity of AR and its effect
on LV size, function, and hemodynamics. Many patients with chronic severe AR may remain clinically compensated
for years with normal LV function and no symptoms. These patients do not require surgery but can be followed carefully
for the onset of symptoms or LV dilation/dysfunction. Surgery should be considered before the LV ejection fraction falls
below 55% or the LV end-diastolic dimension reaches 55 mm. Symptomatic patients should undergo surgery unless
there are excessive comorbidities or other contraindications. The primary role of medical therapy with vasodilators is
to delay the need for surgery in asymptomatic patients with normal LV function or to treat patients in whom surgery
is not an option. The goal of vasodilator therapy is to achieve a significant decrease in systolic arterial pressure. Future
therapies may focus on molecular mechanisms to prevent adverse LV remodeling and fibrosis. (Circulation. 2005;112:
125-134.)
Key Words: aorta 䡲 echocardiography 䡲 valves 䡲 ventricles

A ortic regurgitation (AR) is characterized by diastolic

reflux of blood from the aorta into the left ventricle (LV)
associated with modest increases in aortic root size but not
AR when age is included in the model.3,4 The Strong Heart
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due to malcoaptation of the aortic cusps. Its clinical presen- Study5 showed an overall prevalence of AR of 10% in a
tation is variable and depends on a complex interplay of a Native American population. Most cases were of mild sever-
number of factors, including acuity of onset, aortic and LV ity; age and aortic root diameter, but not gender, were
compliance, hemodynamic conditions, and severity of the independent predictors of AR in this study.
lesion. Although chronic AR is generally well tolerated for
many years, acute AR may lead to rapid cardiac decompen- Etiology
sation and, if untreated, to early death.1 This review focuses AR results from malcoaptation of the aortic leaflets due to
on the clinical manifestations of AR, evaluation of its severity abnormalities of the aortic leaflets, their supporting structures
and hemodynamic consequences, and its treatment. (aortic root and annulus), or both. Diseases that primarily
affect the leaflets include bicuspid aortic valve and other
Prevalence congenital abnormalities, atherosclerotic degeneration, infec-
The prevalence of chronic AR and incidence of acute AR are tive endocarditis, rheumatic heart disease, connective tissue
not precisely known. Singh et al2 reported the prevalence of or inflammatory diseases, antiphospholipid syndrome, and
chronic AR detected by color Doppler echocardiography in a use of anorectic drugs.6 –12 The leaflets can also be affected by
large unselected adult population (the Framingham Offspring trauma, due either to chest wall or deceleration injury, or a jet
Study). The overall prevalence AR in men was 13% and in lesion, due to dynamic or fixed subaortic stenosis. Diseases
women 8.5%. However, most of the AR in this population that primarily affect the annulus or aortic root include
was trace or mild in severity; moderate or severe AR was rare idiopathic aortic root dilation, aortoannular ectasia, Marfan
(Table 1). Multiple logistic regression analysis revealed age syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta,
and male gender to be predictors of AR. Interestingly, aortic dissection, syphilitic aortitis, or various connective
hypertension did not predict AR on multivariate analysis, tissue diseases.13 A bicuspid aortic valve is commonly asso-
confirming results of earlier studies that hypertension is ciated with dilation of the aortic root in addition to the

From the Department of Cardiology, University of Heidelberg, Heidelberg, Germany (R.B.), and Department of Internal Medicine, Cardiology Section,
Baylor University Medical Center, Dallas, Tex (P.A.G.).
Correspondence to Paul A. Grayburn, MD, Baylor Heart and Vascular Institute, 621 N Hall St, Suite H030, Dallas, TX 75226. E-mail
paulgr@baylorhealth.edu
© 2005 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.104.488825

125
 126 Circulation July 5, 2005

TABLE 1. Prevalence of AR in the Framingham In early, compensated severe AR, the LV adapts to the
Offspring Study volume overload by eccentric hypertrophy, in which sarco-
Age, y meres are laid down in series and myofibers are elongat-
ed.25,26 Eccentric hypertrophy preserves LV diastolic compli-
26 –39 40 – 49 50 –59 60 – 69 70 – 83 ance, such that LV filling pressures remain normal or mildly
Men (n⫽91) (n-352) (n⫽433) (n⫽359) (n⫽91) increased despite a large regurgitant volume. In addition,
None 96.7% 95.4% 91.1% 74.3% 75.6% eccentric hypertrophy increases LV mass, such that the LV
Trace 3.3% 2.9% 4.7% 13.0% 10.0% volume/mass ratio is normal, and LV ejection fraction
Mild 0% 1.4% 3.7% 12.1% 12.2%
(LVEF) is maintained by increased preload. The slope of the
LV pressure volume relationship (elastance or Emax), a load-
ⱖModerate 0% 0.3% 0.5% 0.6% 2.2%
independent measure of myocardial function, is normal.27
Women (n⫽93) (n⫽451) (n⫽515) (n⫽390) (n⫽90)
Over time, progressive LV dilation and systolic hypertension
None 98.9% 96.6% 92.4% 86.9% 73.0% increase wall stress and the volume/mass ratio. As this
Trace 1.1% 2.7% 5.5% 6.3% 10.1% occurs, there is a phase during which LVEF is still normal,
Mild 0% 0.7% 1.9% 6.0% 14.6% but Emax decreases, indicating early myocardial dysfunction
ⱖModerate 0% 0% 0.2% 0.8% 2.3% that is largely masked by increased preload. At this stage,
By multivariate analysis, only age and gender predicted AR prevalence. LVEF still increases after successful valve replacement.27
Adapted from Singh et al.2 Eventually, the increase in wall stress leads to overt LV
systolic dysfunction, manifested by a decline in LVEF and
severely reduced Emax. In chronic severe AR, end-systolic
congenital leaflet abnormality.14,15 Ankylosing spondylitis
wall stress can be as high as in aortic stenosis.28 Marked LV
can cause disease of both the leaflets and the aortic root.
hypertrophy (cor bovinum) develops with increased LV
Finally, chronic severe AR of any cause can lead to progres-
volume and mass and spherical geometry.29
sive enlargement of the aortic root and further worsening of
In decompensated severe AR, LV systolic dysfunction is
AR over time.
accompanied by decreased LV diastolic compliance as a
Acute AR is most commonly caused by bacterial endocar-
result of hypertrophy and fibrosis, leading to high filling
ditis, aortic dissection, or blunt chest trauma.16 –18 Other less
pressures and heart failure symptoms. Exertional dyspnea is
common causes of acute AR include nonbacterial endocardi-
the most common manifestation, but angina can also occur
tis,19 laceration of the aorta,20 and complications of invasive because of a reduction in coronary flow reserve with predom-
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procedures such as aortic valvuloplasty and percutaneous inantly systolic coronary flow.30,31 In experimental animals,
balloon dilatation of aortic coarctation.21 Fortunately, acute the transition from a compliant (chronic compensated AR) to
AR, which has a poor prognosis, is rare. a stiff (decompensated AR) LV chamber appears to involve
The prevalence of chronic AR is much higher, and its upregulation of several cardiac fibroblast genes.32,33 Acute
causes are different. In a prospective study of 104 patients AR leads to rapid decompensation due to low forward cardiac
with chronic AR, 35% had unknown causes, 26% idiopathic output and pulmonary congestion. There is not time for
root dilation, 13% congenital abnormalities, 12% rheumatic compensatory LV dilation to occur, and severe hypotension
heart disease, 10% infective endocarditis, and 7% degenera- occurs rather than the systolic hypertension that is character-
tive valve disease.22 A different study of 246 patients dem- istic of chronic severe AR. The different stages of AR are
onstrated 40% degenerative causes, 28% congenital causes, shown in Figure 1.
19% aortic root enlargement, 6% rheumatic causes, 3%
aortitis, and 3% endocarditis.23 These numbers only represent Physical Findings
a rough estimate because demographic changes in population A variety of physical signs have been described for AR. On
age, geographic location, and socioeconomic status may auscultation, a high-frequency, decrescendo diastolic murmur
affect prevalence of different diseases, such as rheumatic is typically heard over the third or fourth intercostal space at
heart disease. the left sternal border. In some patients, a mid and late
diastolic apical rumble (Austin-Flint murmur) is heard, pos-
Pathophysiology sibly because of vibration of the anterior mitral leaflet as it is
Chronic severe AR imposes a combined volume and pressure struck by a posteriorly directed AR jet.34 A systolic ejection
overload on the LV. The volume overload is a consequence of murmur due to high ejection volumes should be present in
the regurgitant volume itself and is therefore directly related significant AR. Further findings on auscultation are soft or
to the severity of the leak. Thus, whereas mild AR produces absent second heart sound and presence of a third heart
only minimal volume overload, severe AR can produce sound. In acute AR, the diastolic murmur may be absent
massive LV volume overload and progressive chamber dila- because of rapid equilibration of aortic and LV diastolic
tion. The pressure overload results from systolic hyperten- pressures. The only clue may be an absent second heart sound
sion, which occurs as a result of increased total aortic stroke in the setting of severe hypotension and pulmonary edema.
volume, because both the regurgitant volume and the forward In chronic severe AR, the elevated stroke volume and
stroke volume are ejected into the aorta during systole.24 systolic hypertension produce a variety of interesting physical
Systolic hypertension can contribute to a cycle of progressive findings. Among these are the bounding carotid pulse (Cor-
dilation of the aortic root and subsequent worsening of AR. rigan’s pulse), head bobbing (de Musset’s sign), pulsation of
 Bekeredjian and Grayburn Aortic Regurgitation 127

Figure 1. Different stages of AR. Top left, In mild

AR, LV size, function, and hemodynamics are nor-
mal. Top right, In acute severe AR, there is equili-
bration of aortic and LV pressures (80/40 mm Hg
in this example). Left atrial pressure is elevated,
leading to pulmonary edema. Bottom left, In
chronic severe, compensated AR, the LV may
begin to dilate, but LVEF is often maintained in the
normal range by increased preload. There is sys-
tolic arterial hypertension and a wide pulse pres-
sure. However, LV filling pressures are normal or
only slightly elevated, such that dyspnea is absent.
Bottom right, In decompensated chronic severe
AR, the LV is dilated and hypertrophied, and LV
function is often depressed as a result of afterload
excess. Forward output is decreased, leading to
fatigue and other low-output symptoms. Fibrosis
and hypertrophy decrease LV compliance, leading
to increased filling pressures and dyspnea.

the uvula (Muller’s sign), and pistol shot sounds over the functional class, comorbidity index, atrial fibrillation, LV
femoral artery with compression (Traube’s sign). During end-systolic diameter, and ejection fraction (EF). As shown
compression with a glass slide, capillary pulsations can be in Figure 2, patients with greater NYHA functional class or
seen on the fingernail (Quincke’s sign). LV end-diastolic diameters ⬎25 mm/m2 had an adverse
prognosis. Taken together, these studies indicate that asymp-
Progression and Natural History tomatic patients with normal LV function generally have a
Progression of AR involves a complicated interaction of favorable prognosis and indicate that decline in LVEF with
several variables, including AR severity, aortic root pathol- exercise or serial follow-up may identify patients who will
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ogy, and the adaptive response of the LV. AR severity may

worsen as a result of progressive leaflet pathology and/or
further dilation of the aortic root. In addition, LV dilation
occurs gradually and progressively, depending on the severity
of AR, hemodynamic factors, and the degree of eccentric
hypertrophy and remodeling, which may vary from patient to
patient and may be related to genetic factors. Reimold et al35
have shown that quantitative measures of AR severity by
echocardiography worsen over time. Padial et al36 showed
that patients with more rapidly progressive increases in aortic
root size also tend to have significant worsening of AR
severity and LV dilation.
A few studies have investigated the mortality and morbid-
ity of chronic AR if left without surgical treatment. Bonow et
al37 studied 104 asymptomatic patients with severe AR and
normal LVEF. The rate of attrition (defined as death, symp-
toms, or asymptomatic LV dysfunction) was ⬍5%/y over
11-year follow-up. The rate of sudden death was only 0.4%/y.
At 11 years, 58% of patients remained asymptomatic with
normal LV systolic function. Borer et al22 found similar
results in 104 different patients monitored for a mean of 7.3
years. The rate of attrition was 6.2%/y and was predicted by
the change in LVEF or LVEF adjusted for wall stress from
rest to exercise. At 5 years, 75% of patients remained free of Figure 2. Top, Survival of patients with chronic severe AR by
symptoms (NYHA class). Survival in asymptomatic patients (class I)
death, symptoms, or LV dysfunction. Dujardin et al23 inves- is no different than expected (P⫽0.38). However, patients with
tigated the fate of 246 patients with moderately severe or class II symptoms have a significantly worse survival (P⫽0.02), and
severe AR with a mean follow-up time of 7 years. Unlike the patients with class II to IV symptoms have a markedly worse sur-
2 prior studies, these patients were not all asymptomatic with vival (P⬍0.001). Bottom, Survival for patients stratified by LV end-
systolic dimension (LVESD). Patients with LV end-systolic dimen-
normal LV systolic function. The 10-year mortality rate was sion ⬍25 mm/m2 have a markedly worse survival (P⬍0.001).
34%, with independent predictors of survival being age, Adapted from Dujardin et al.23
 128 Circulation July 5, 2005

TABLE 2. Natural History of AR Anatomy of the Aortic Root and Leaflets

Echocardiographic evaluation of the anatomy of the aortic
Asymptomatic patients with normal LV systolic function
root, annulus, and leaflets is important in defining the
Progression to symptoms and/or LV dysfunction ⬍6%/y
etiology and severity of AR. As noted earlier, disorders such
Progression to asymptomatic LV dysfunction ⬍3.5%/y as aortic root dilation, bicuspid aortic valve, endocarditis,
Sudden death ⬍0.2%/y degenerative aortic valve disease, and dissection of the
Asymptomatic patients with LV systolic dysfunction ascending aorta have different implications with regard to
Progression to symptoms ⬎25%/y treatment. Although it is common to see mild AR with a
Symptomatic patients structurally normal aortic valve and supporting apparatus, it is
Mortality rate ⬎10%/y rare for severe AR to occur without major lesions of the
Adapted with permission from ACC/AHA guidelines.38
leaflets or the aortic root. Figure 3 shows echocardiographic
examples of different causes of AR.
require surgical intervention. Patients with even moderate Color Flow Mapping
symptoms or evidence of LV dilation are at higher risk and Doppler color flow mapping is widely used to identify the
should be considered for early intervention. The American presence of AR and estimate its severity. In general, color
College of Cardiology/American Heart Association Guide- flow jets are composed of 3 distinct segments. The proximal
lines for Management of Patients with Valvular Heart Dis- flow convergence zone is the area of flow acceleration into
ease have nicely summarized the natural history of chronic
the orifice, the vena contracta is the narrowest and highest-
AR (Table 2).38
velocity region of the jet at or just downstream from the
Echocardiography orifice, and the jet itself occurs distal to the orifice in the LV
The most important diagnostic test for evaluation of AR is cavity in the case of AR. Measurement of jet area or
echocardiography. It allows (1) assessment of the anatomy of penetration into the LV cavity is not accurate in assessing AR
the aortic leaflets and the aortic root, (2) detection of the severity. Perry et al40 compared the ratio of AR jet width to
presence and severity of AR, and (3) characterization of LV LV outflow tract (LVOT) width in a parasternal long-axis
size and function. The American Society of Echocardiogra- view to angiography. A jet width/LVOT width ⬍25% is
phy guidelines for quantification of valvular regurgitation specific for mild AR, whereas a jet width/LVOT width ratio
emphasize the need to integrate all of this information to ⬎65% is specific for severe AR (Figure 4). This works best
properly evaluate patients with AR.39 when the regurgitant orifice is relatively round in shape.
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Figure 3. Echocardiographic images from different patients with AR due to different pathologies. Top left, Parasternal long-axis view
showing a dilated aortic root (arrows) due to aortoannular ectasia. Top right, Parasternal long-axis view showing large, mobile vegeta-
tion (arrow) on the aortic valve in a patient with infective endocarditis. Bottom left, Parasternal short-axis view showing a bicuspid aor-
tic valve with characteristic elliptical opening (arrow). Bottom right, Parasternal long-axis view of a patient with acute AR due to aortic
dissection. Intimal flap is shown by arrows.
 Bekeredjian and Grayburn Aortic Regurgitation 129

Figure 4. Color flow images from

parasternal long-axis views in patients
with mild (left) and severe (right) AR. Jet
width is ⬍25% of LVOT width in mild
AR. This jet is eccentric; width is mea-
sured at the origin of the jet adjacent to
the leaflets. In severe AR, jet width is
usually ⬎50% of LVOT width. A jet
width/LVOT width ⬎65% (as in this
patient) is specific for severe AR.39

When it is elliptical, as in bicuspid aortic valves, this ratio can proximal isovelocity surface area (PISA) region that is as
lead to underestimation of AR severity.41 The short-axis view large as possible. The surface area of the PISA region is 2␲r2,
is helpful in identifying such cases. where r is the radius from the alias line to the orifice. Peak
regurgitant flow is obtained by multiplying this value by the
Vena Contracta Imaging aliasing velocity, and effective regurgitant orifice area is the
Vena contracta is defined as the narrowest central flow region
peak regurgitant flow divided by the peak velocity obtained
of a jet. In AR, it can be measured in a parasternal long-axis
by continuous wave Doppler. The PISA method has been
or short-axis view in a color Doppler mode. Animal studies
shown to work in AR but is less accurate in eccentric jets or
have shown good correlation of vena contracta width and
aortic root dilation.46
severity of AR.42 Clinical studies have confirmed the useful-
ness of this measurement for judging AR severity.43,44 Quantitative Doppler Flow Measurements
Tribouilloy et al43 demonstrated in a study with 79 patients AR volume and fraction can be calculated by comparing flow
that a vena contracta width of ⱖ6 mm correlates well with at the aortic level (total stroke volume) with that at the mitral
severe AR, having a sensitivity of 95% and a specificity of valve level (forward stroke volume).39 The total stroke
90%. Conversely, a vena contracta width ⬍0.3 cm is specific volume is generally measured in the LVOT by multiplying
for mild AR. Willett et al44 compared vena contracta width by the LVOT area times the velocity time integral of pulsed
transesophageal echocardiography to simultaneous aortic Doppler LVOT flow. The mitral stroke volume is measured
flow probe measurements of regurgitant volume and fraction in similar fashion but is more prone to error because of
in an intraoperative setting. Figure 5 shows an example of the
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difficulty in accurately measuring the mitral annulus and

vena contracta in a patient with moderate AR. placing the pulsed Doppler sample volume at the level of the
Jet Eccentricity annulus. Effective regurgitant orifice area can be calculated
Eccentricity of the regurgitant jet may contribute to the by dividing the regurgitant volume by the velocity time
understanding of mechanisms of aortic valve dysfunction.45 A integral of the AR jet obtained from continuous wave
centrally directed jet entrains fluid on all sides and generally Doppler. This method, although tedious, provides quantita-
appears larger and wider than eccentric jets directed anteri- tive measures of AR severity. The cut points for AR severity
orly toward the ventricular septum or posteriorly toward the measured by regurgitant volume, regurgitant fraction, and
anterior mitral leaflet. This should be taken into account when effective regurgitant orifice area are shown in Table 3.39
AR severity is graded.
Supportive Findings
Proximal Isovelocity Surface Area Method A number of echocardiographic findings provide supporting
It is less common to identify a clear proximal flow conver- evidence for AR severity. By M-mode echocardiography,
gence in AR compared with MR. However, when it is early mitral valve closure indicates increased LV filling
present, the Nyquist velocity should be shifted toward the pressures and is often present in severe AR, unless masked by
direction of the jet to produce a clearly visible, round tachycardia.47 The continuous wave Doppler spectral signal

Figure 5. Vena contracta images of AR jet

by transesophageal echocardiography in
long-axis (left) and short-axis (right) views.
The vena contracta is seen as the narrow-
est part of the jet as it emerges from the
regurgitant orifice. The short-axis view is
difficult to orient precisely in the plane of
the vena contracta but is useful in deter-
mining whether the jet is central and round
(in which case the long-axis vena con-
tracta accurately describes AR severity) or
markedly elliptical, as in bicuspid aortic
valves (in which the long-axis vena con-
tracta may underestimate AR severity).
Reprinted from Willett et al,44 copyright
2001, with permission from the American
College of Cardiology Foundation.
 130 Circulation July 5, 2005

TABLE 3. Application of Specific and Supportive Signs, and Quantitative Parameters in the Grading of Aortic Regurgitation Severity
Mild Moderate Severe
Specific signs for AR severity Central jet, width ⬍25% of LVOT† Signs of AR ⬎mild present Central jet, width ⱖ65% of LVOT†
Vena contracta ⬍0.3 cm† but no criteria for severe AR Vena contracta ⬎0.6 cm†
No or brief early diastolic flow reversal in
descending aorta
Supportive signs Pressure half-time ⬎500 ms Intermediate values Pressure half-time ⬍200 ms
Normal LV size* Holodiastolic aortic flow reversal in
descending aorta
Moderate or greater LV enlargement‡
Quantitative parameters§
RVol, mL/beat ⬍30 30–44 45–59 ⱖ60
RF, % ⬍30 30–39 40–49 ⱖ50
EROA, cm2 ⬍0.10 0.10–0.19 0.20–0.29 ⱖ0.30
*LV size applied only to chronic lesions.
†At a Nyquist of 50 – 60 cm/s.
‡In the absence of other etiologies of LV dilatation.
§Quantitative parameters can help sub-classify the moderate regurgitation group into mild-to-moderate and moderate-to-severe regurgitation as shown.
AR indicates aortic regurgitation; EROA, effective regurgitant orifice area; LV, left ventricle; LVOT, left ventricular outflow tract; RVol, regurgitant volume; and RF,
regurgitant fraction.
Table reprinted with permission of the American Society of Echocardiography from Zoghbi et al,39 Table 6.

of the AR jet provides clues to the severity of the leak. With the pressure half-time. Conversely, moderate AR into a stiff
severe AR, diastolic pressure will decrease rapidly in the LV, especially in the acute or subacute setting, may signifi-
aorta, thus leading to a shorter pressure half-time or more cantly shorten pressure half-time. Thus, pressure half-time
rapid deceleration slope (Figure 6).48,49 As a general rule, an and early mitral closure should be considered markers of the
AR pressure half-time ⬍200 ms indicates severe AR, hemodynamic consequences of AR rather than the regurgitant
whereas a pressure half-time ⬎500 ms suggests mild AR.39 volume itself. A complete echocardiographic study provides
LV end-diastolic pressure can be calculated as the diastolic measurements of the severity of the leak (regurgitant volume,
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blood pressure minus the end-diastolic pressure gradient fraction, and orifice area) and the hemodynamic effects of AR
calculated from the modified Bernoulli equation (Figure 6).48 (LV volumes, pressure half-time, LV end-diastolic pressure).
Importantly, the rate of deceleration of AR velocities simply Another important supportive sign of severe AR is diastol-
reflects the rate of equilibration of the diastolic pressure ic flow reversal in the descending aorta. Although brief early
gradient between the aorta and LV. In chronic compensated diastolic flow reversal is often seen in normal subjects,
AR, a large regurgitant volume may not significantly shorten holodiastolic flow reversal usually indicates at least moderate

Figure 6. Continuous wave Doppler of

AR jet in a patient with moderate AR and
a long-standing history of hypertension.
The slope of velocity deceleration is fairly
steep, with a pressure half-time (PHT) of
315 ms. LV end-diastolic pressure
(LVEDP) can be calculated by converting
end-diastolic velocity (measured at the R
wave peak) to pressure gradient by 4V2
and subtracting this value from the dia-
stolic blood pressure (BP). Patients with
chronic compensated AR may have a
relatively flat slope, reflecting a compliant
LV with a normal or only slightly elevated
LVEDP.
 Bekeredjian and Grayburn Aortic Regurgitation 131

AR.50 Diastolic flow reversal in the descending aorta is best sedentary lifestyle. In such patients, exercise testing may be
measured with pulsed-wave Doppler from a suprasternal very useful in eliciting symptoms or determining functional
probe position. capacity. Some studies have suggested that an exercise-
induced decrease in LVEF is a predictor of poor outcome that
LV Size and Geometry warrants surgery.22,55–57 However, most of these studies
Echocardiography is useful in measuring LV dimensions,
included patients who already had symptoms, LV dilation, or
volumes, and LVEF, all of which are important determinants
decreased resting LVEF. Thus, it is not clear that exercise
of the need for surgery in chronic severe AR. Serial progres-
LVEF is helpful in determining the need for surgery in
sion of LV dilation predicts the need for surgery.37 Because asymptomatic patients with normal LV size and function.38
LV chamber dilation and systolic dysfunction can occur from
other causes (ie, cardiomyopathy), it is important to establish Surgical Treatment
a link between severity of AR and LV dysfunction. This can In acute AR, immediate surgical intervention is necessary
be difficult at times and underscores the need for accurate, because the acute volume overload results in life-threatening
careful quantification of AR severity. Repeated echocardiog- hypotension and pulmonary edema.1 Vasodilator therapy with
raphy to assess progression of LV dilation and severity of AR sodium nitroprusside may stabilize the patient during trans-
is recommended every 2 to 3 years in stable asymptomatic port to the operating department. Aortic balloon counterpul-
patients with normal LV size and function.38 In asymptomatic sation is contraindicated because it worsens AR. ␤-Blockers
patients with LV dilation, more frequent echocardiography should be avoided in acute AR because they prolong diastole
(every 6 to 12 months) is indicated.38 and may worsen AR. Atrial pacing to increase heart rate
might be of theoretical benefit58,59; however, this does not
Cardiac Catheterization have an established role in clinical practice. Several studies
Even if echocardiography accurately identifies severity of AR have demonstrated that emergency aortic valve replacement
and degree of LV function, catheterization may be needed to can be performed with low operative mortality and good
evaluate coronary anatomy in patients requiring surgical long-term results in acute AR.60 – 62
intervention. As a general rule, men aged ⬎35 years, pre- In contrast to acute AR, patients with chronic AR may be
menopausal women aged ⬎35 years with risk factors for asymptomatic for many years or even their entire life.
coronary artery disease, or postmenopausal women should Therefore, the critical issue is to determine if and when
undergo preoperative coronary arteriography.38 Supravalvu- surgical intervention is required. There are no randomized
lar aortography provides a semiquantitative approach to grade controlled trials to guide surgical decision making. However,
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AR during heart catheterization. Visual grading of AR reasonable guidelines have been proposed on the basis of the
severity is based on the amount of contrast that appears in the aforementioned natural history of AR, retrospective studies,
LV after aortography. Mild or 1⫹ AR is contrast appearing in and expert opinion.38 The operative mortality for isolated
the LV but clearing with each beat. Moderate or 2⫹ AR is aortic valve replacement is ⬇4%.63– 65 It is higher with
faint opacification of the entire LV over several cardiac concomitant aortic root replacement or coronary bypass
cycles. Moderately severe or 3⫹ AR is opacification of the surgery or if there are substantial comorbidities, including
entire LV with the same intensity as in the aorta. Severe or advanced age. As shown in Table 2, the death rate for
4⫹ AR is opacification of the entire LV on the first heart beat asymptomatic patients with normal LV size and function is
with an intensity higher than in the aorta. Unfortunately, this ⬍0.2%/y. Therefore, asymptomatic patients with normal LV
method is subjective, depends on the amount of contrast size and systolic function do not require surgery but should be
injected and the size of the LV, and correlates poorly with monitored carefully for development of symptoms, LV dys-
regurgitant volume, particularly in patients with dilated function, or progressive LV dilation. In contrast, symptomatic
LVs.51 patients with chronic severe AR have a mortality ⬎10%/y
Cine MRI can also be used to detect and quantify AR.52–54 and therefore should undergo surgery unless there are exces-
Phase velocity encoding is used to calculate forward stroke sive comorbidities or a condition with a known short life
volume through the aortic valve. Total LV stroke volume is expectancy. The more difficult issue is when to operate on
determined from LV end-diastolic and end-systolic volumes, asymptomatic patients to prevent irreversible LV dysfunction
which are measured by summing the volumes of a stack of from occurring. Outcomes are better in patients with an
slices of known thickness (typically 8 to 10 mm) through the LVEF ⬎55% or an end-systolic LV diameter ⬍55 mm (or
LV from base to apex. The difference between aortic and LV ⬍25 mm/m2).23,38,66,67 This has been termed the “55 rule.”67
stroke volumes is the regurgitant volume. Although cine Careful, serial echocardiographic follow-up is necessary to
magnetic resonance is not as well validated as echocardiog- identify patients for surgery before their LV values reach
raphy for quantification of AR severity, it provides highly these thresholds.
accurate measurements of LV volumes, mass, and EF and Surgery for symptomatic patients with severe AR has been
therefore could be useful for detecting progressive LV dila- shown to reduce LV volumes, LV mass, and wall stress and
tion and timing of operation for asymptomatic severe AR. to increase LVEF.68 –71 Even patients with dilated LV or low
LVEF can benefit from surgery. Chaliki et al72 reported the
Role of Exercise Testing results of surgery in 450 patients with severe AR. Operative
Many asymptomatic patients with valvular heart disease have mortality was 14%, 6.7%, and 3.7% for those with LVEF
gradually and imperceptibly reduced their activities or lead a ⬍35%, 36% to 49%, and ⱖ50%, respectively (Figure 7).
 132 Circulation July 5, 2005

Figure 7. Data from Chaliki et al72 show

survival in patients after aortic valve
replacement as a function of preopera-
tive LVEF. LoEF indicates markedly
reduced LV function; MedEF, moderately
reduced LV function; and Nl EF, normal
LV function. Reprinted with permission.

Moreover, surgical survivors with low preoperative LVEF hypertrophy and preserve LV systolic function. Endocarditis
had improved symptoms and LV function. Thus, it is almost prophylaxis is important for all patients with AR.
never “too late” to operate in chronic severe AR, although Future developments in interventional cardiology may
patients with severe LV dysfunction and a systolic blood offer new alternatives for patients with severe AR who are not
pressure ⬍120 mm Hg may be at particularly high risk.73 considered surgical candidates. Percutaneous transcatheter
implantation of a heart valve prosthesis may be possible in
Medical Therapy such patients, although this is still investigational at this
The regurgitant volume in AR is determined by the regurgi- time.84
tant orifice area, the square root of the diastolic pressure
gradient across the valve, and the duration of diastolic flow Conclusions
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(which may not be holodiastolic if the LV is stiff and pressure On the basis of available evidence and consensus opinion,
equilibrates early).74 Medical therapy is not able to signifi- surgery is indicated for patients with severe AR who either
cantly reduce regurgitant volume in chronic severe AR (1) are symptomatic or (2) have evidence of increasing LV
because the regurgitant orifice area is relatively fixed and the size or decreasing LVEF. It appears that it is best to operate
diastolic blood pressure is already low.74 Further reducing before LV end-diastolic diameter increases to ⬎55 mm or
diastolic blood pressure might adversely affect coronary 25 mm/m2 or before LVEF falls to ⬍55%. This underscores
perfusion and should be avoided. Moreover, the square root the importance of careful quantification of AR severity and
function dictates that a 25% reduction in diastolic pressure LV function. The role of medical therapy, particularly vaso-
gradient would only achieve a 13% reduction in regurgitant dilators, is primarily to decrease systolic hypertension and
volume.74 Therefore, the main goal of medical therapy is to delay the onset of LV dysfunction in asymptomatic patients.
reduce the systolic hypertension associated with chronic
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